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Biomedical subjects

M Kotler

Publications and source records attributed to M Kotler.

At least 91 records · Page 5Linked to original sources
PubMed1995

Avian sarcoma leukemia virus protease linked to the adjacent Gag polyprotein is enzymatically active.

The activity of avian sarcoma leukemia virus (ASLV) protease (PR) prior to its release from the precursor protein was determined by introducing mutations at the cleavage site between PR and the adjacent upstream nucleocapsid (NC) protein. Gag DNA fragments containing these mutations were cloned into expression vectors and introduced into Escherichia coli in which the ASLV proteins were expressed. The dipeptide NC-PR containing these mutations did not undergo autoprocessing when expressed in bacterial cells and the fused proteins were devoid of enzymatic activity. However, when the whole Gag polyprotein containing these mutations was expressed in bacterial cells, other PR cleavage sites in the viral Gag polyprotein underwent normal cleavage, indicating that the release of free PR is not a prerequisite for correct processing of the ASLV Gag precursor.

Animals↗
PubMed1995

Ribosomal frameshifting at the Gag-Pol junction in avian leukemia sarcoma virus forms a novel cleavage site.

The Gag and Gag-Pol precursors of avian sarcoma leukemia virus (ASLV) are translated from viral genomic-size mRNA at a molar ratio of about 20:1. Translation of Gag is terminated at the stop codon UAG located at the carboxyl-terminus of the viral protease (PR), whereas a ribosomal frameshift occurring at the carboxyl-terminus of Gag allows translation of the Gag-Pol precursor. To determine how PR is released from the Gag-Pol precursor, a single base (A or T) was inserted at the Gag-Pol junction in order to adjust the translation into a single reading frame. These mutations allow processing of the viral precursor when expressed in bacterial cells, but cause cessation of viral production after transfection of avian cells. The viral PR released from the large precursor is one amino acid longer than PR cleaved from the Gag polyprotein and is terminated by an Ile instead of a Leu residue.

Alpharetrovirus↗
PubMed1995

Thymoma with pericardial tamponade.

Thymomas are tumors of the anterior mediastinum. They are most often seen in adults aged 45 to 50 years. These tumors are routinely asymptomatic for prolonged periods of time. The most common presentation is discovery on routine chest x-ray. We therefore present a case report of an elderly woman who presented with symptoms of dyspnea caused by a malignant thymoma. To our knowledge, symptomatic pericardial tamponade due to a thymoma with a massive pericardial effusion has not been described previously.

Aged↗
PubMed1995

Clonal dominance of RadLV-induced lymphomas.

RadLV-induced leukemogenesis begins with the emergence of a pleioclonal population of preleukemic (PL) cells, which subsequently gives rise to a monoclonal lymphoma. We have recently found that the pleioclonal-->monoclonal transition may occur early during the PL latency and long before the eruption of a full blown lymphoma. We sought to find out what causes one PL clone to become dominant. Our working hypothesis was that a dominant clone(s) at the PL stage has the ability to inhibit the development of other, recessive clones. Since some premalignant characteristics of a progenitor clone are probably maintained in the descending lymphoma, we studied whether tumors that developed after injection of a high dose (HD) of PL cells were dominant over tumors that developed after injection of a limiting dose (LD) of PL cells. To identify dominant clones, HD and LD lymphomas were mixed in a co-culture and the outgrowth of one clone over the other was determined by T beta-TCR rearrangement analysis. A checker-board combination of seven lymphomas revealed a dominance hierarchy scale. Lymphomas induced directly by the virus (without transfer) were dominant over both HD and LD lymphomas. High dose lymphomas were dominant over LD lymphomas and LD lymphomas were always recessive. The speed at which a dominant lymphoma outgrew the co-culture suggested that dominance is acquired through the ability of the prevailing cells to actively suppress the growth of recessive cells.

Animals↗
PubMed1995

Valproic acid in ultra-rapid cycling: a case report.

Valproic acid has been proven to be efficient in the treatment of bipolar affective disorders as an adjunctive agent to lithium and carbamazepine. Recently, its efficacy in rapid cycling states has attracted interest. We present the case of a male patient with bipolar affective disorder who developed an extreme state of ultra-rapid cycling (48-h cycles). Only the addition of valproic acid therapy to prior lithium treatment succeeded in curtailing the ultra-rapid cycling. Several issues regarding ultra-rapid cycling and valproate's efficacy in bipolar disorder are discussed.

Bipolar Disorder↗
PubMed1995

Nightmares related to fluoxetine treatment.

Sleep disturbances are found in most depressive patients. Serotonin reuptake inhibitors, such as fluoxetine hydrochloride, seem to improve sleep by changing the depressive affect and the underlying biological mechanisms. Insomnia is an occasional adverse effect of the medication, but it was shown that only 2-3% of the patients with fluoxetine-induced insomnia discontinued the drug for this reason. We could not find any report of nightmares or night terrors under fluoxetine treatment. We report on four patients who experienced nightmares on fluoxetine monotherapy.

Adult↗
PubMed1995

Point mutation in avian sarcoma leukaemia virus protease which increases its activity but impairs infectious virus production.

The retrovirus protease (PR), an aspartic PR, is composed of two identical subunits, each containing a conserved tripeptide sequence present at the active site of the enzyme. Asp-Ser-Gly is found in avian sarcoma leukaemia viruses (ASLV) and Asp-Thr-Gly in mammalian oncoretroviruses. We have mutated the conserved sequence at the active site of ASLV PR by converting the Ser and Gly residues to Thr and Ala, respectively. Replacement of Gly with Ala yielded an ASLV PR devoid of proteolytic activity. The Ser to Thr conversion did not alter the substrate specificity of the enzyme. Both wild-type and mutated PRs correctly cleaved viral precursors expressed in bacterial cells, as well as synthetic peptides homologous to ASLV and human immunodeficiency virus type 1 cleavage sites. Bacterially produced ASLV PR with Thr instead of Ser had increased enzymatic activity, as shown by hydrolysis of synthetic peptides. However, this mutation reduced the production of reverse transcriptase-containing particles and infectious virus following transfection of permissive cells with virus DNA.

Alpharetrovirus↗
PubMed1995

The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes.

Recently, melatonin was found to be the most potent physiological free radical scavenger known to date. In this work, we attempted to define the role this neurohormone plays in the regulation of apoptosis, since the effect of bcl-2, the main gene implicated in its inhibition, acts via an antioxidant mechanism. We investigated the role of melatonin in cell death of thymus, a well known model for the study of apoptosis. Two sets of experiments were carried out: in vivo experiments, performed with Wistar rats, and in vitro experiments, performed with primary cultures of young Wistar rat thymocytes treated with glucocorticoids in order to induce apoptosis. Morphometrical studies in semithin sections of thymus and analysis of DNA fragmentation by gel electrophoresis show that physiological apoptosis occurring in thymus of 65 days old rats, is prevented by the daily administration of melatonin beginning when the rats were 25 days old. Also, we found that at a concentration of 10(-7) M, melatonin decreases by 35% the percentage of apoptotic cells induced by glucocorticoids in cultured thymocytes of 25 day old rats. 10(-9) M melatonin decreases cell death by 20%. Finally, melatonin at 10(-11) M did not have any effect. Several hypothesis are discussed to explain this effect: direct interaction of melatonin with glucocorticoid receptors in the thymus; induction of interleukin-4 release; direct genomic action modulating the expression of apoptosis-inhibiting genes; an effect on nitric oxide synthase; and finally, the antioxidant action of melatonin. Since apoptosis is a possible mechanism involved in neuronal death shown in several neurodegenerative diseases such as Parkinson or Alzheimer's diseases, investigative efforts should be directed to the possible role of melatonin in inhibiting cell death in tissues other that the thymus. Melatonin might be a potent therapeutic agent in some of these conditions.

Aging↗
PubMed1995

Obsessive-compulsive disorder limited to pregnancy.

The relationship between obsessive-compulsive disorder and pregnancy is reviewed in the light of recent reports concerning the frequent onset and exacerbation of obsessive-compulsive disorder during pregnancy. We present the case of a young woman who developed obsessive-compulsive disorder during a pregnancy and recovered completely after delivery. Five years afterwards she is still symptom-free. Several possible explanations for this unusual occurrence are discussed.

Adult↗
PubMed1995

Parental loss and family violence as correlates of suicide and violence risk.

Seventy-nine psychiatric inpatients were administered a battery of psychometric instruments that obtained information about early parental loss, exposure to family violence, and behavioral problems in themselves and in their first-degree relatives. These variables were correlated with suicide and violence risk measures. Suicide risk significantly correlated with all family variables whereas violence risk correlated with behavioral problems both in oneself and in one's first-degree relatives. Moreover, suicidal and/or violent patients had experienced maternal loss significantly more frequently than the nonsuicidal/nonviolent patients. In the suicidal/violent group, age of patient at death of parents was significantly lower than in the nonsuicidal/nonviolent group. Finally, family violence was significantly correlated with behavioral problems in self and in first-degree relatives. Findings are interpreted according to the authors' theoretical model of aggression regulation.

Adolescent↗
PubMed1994

Olfactory sensitivity in major depressive disorder and obsessive compulsive disorder.

Olfactory sensitivity to two odorants, isoamyl acetate and androsterone, was assessed in 14 obsessive compulsive disorder (OCD) patients, nine major depressive disorder (MDD) patients, and 16 sex- and age-matched healthy controls. Tests were performed during a drug-free period, and 3 and 6 weeks after initiation of antidepressant drug therapy. No difference in olfactory sensitivity, to either odorant, was found between OCD patients and controls at any time. In MDD patients, a significant increase in the sensitivity to isoamyl acetate was observed 6 weeks after initiation of treatment, compared to controls.

Adult↗
PubMed1994

Radiation leukemogenesis: quantitative relationship between pre-leukemic cells in the thymus and lymphoma induction.

Fractionated irradiation of C57BL/6 mice induces a population of pre-leukemic (PL) cells that progress into mature thymic lymphomas after a latency of 4 to 6 months. Transfer of graded numbers of thymocytes from an irradiated mouse into recipient mice indicated that PL cells first appear in the thymus 6 weeks after irradiation. The initial proportion of the thymic PL cells is > or = 10(-5) and their frequency continuously increases with time, reaching > or = 10(-3) 10 weeks after irradiation. The PL cell population that emerges early during the pre-malignant latency consists of pleioclonal T lymphocytes. However, within 4 weeks a dominant PL clone can be detected which becomes the progenitor of a clonal lymphoma 9 to 15 weeks later. These results suggest that radiation leukemogenesis involves continuous accumulation of pleioclonal PL cells in the thymus, one of which is then selected for further maturation into frank lymphoma.

Animals↗
PubMed1994

Effects of alprazolam on increases in hormonal and anxiety levels induced by meta-chlorophenylpiperazine.

The effects of alprazolam, a triazolobenzodiazepine, on hormonal and behavioral responses induced by meta-chlorophenylpiperazine (MCPP), a serotonin receptor agonist, were investigated in 10 healthy men. Alprazolam (0.5 mg) or placebo was given 1 hour before MCPP (0.5 mg/kg) or placebo. Cortisol, prolactin, and growth hormone (GH) release, MCPP and alprazolam plasma levels, anxiety level, and panic symptoms were measured over 210 minutes. MCPP was found to increase cortisol, prolactin, GH, and anxiety levels. Alprazolam decreased cortisol and GH levels but had no effect on prolactin. When used in combination with MCPP, alprazolam blunted MCPP-induced cortisol and GH release, and it blocked the anxiogenic effects of MCPP.

Adult↗
PubMed1994

Psychiatric aspects of hyperemesis gravidarum.

Hyperemesis gravidarum is a potentially dangerous disorder of pregnancy characterized by severe and protracted vomiting. It is suggested that psychosocial factors may have a role in determining whether the pregnant woman experiences a transient spell of mild vomiting or progresses towards the much rarer but more significant pernicious vomiting. Psychotherapy, hypnotherapy and behavior therapy have been reported to contribute to the treatment of patients with hyperemesis gravidarum. A review of the etiological factors as well as of the therapeutic approaches is presented.

Behavior Therapy↗
PubMed1993

Death without warning? A clinical postmortem study of suicide in 43 Israeli adolescent males.

Forty-three consecutive Israeli male suicides, 18 to 21 years of age, that occurred during compulsory military service were studied using preinduction assessment data, service records, and extensive postmortem interviews with family and peers. At preinduction, subjects, as a group, appeared above average in intelligence, physical fitness, and measures predictive of successful adaptation to military service. Active duty performance was generally satisfactory. Ascertained post mortem, 53.5% met formal criteria for major depressive disorder; most cases, however, appeared recent and reactive. Narcissistic and/or schizoid traits were common. Substance abuse was absent and antisocial personality disorder was rare (4.7%). Furthermore, in eight patients (18.6%) no Axis I diagnosis could be made; half of these also lacked any significant Axis II pathology. These findings, at partial variance with US studies, suggest a complex relationship between suicide and mental disorder. The striking failure of intensive screening and preventive measures to prevent these suicides highlights unresolved questions of etiology and intervention.

Adaptation, Psychological↗
PubMed1993

An epidemiologic study of Gilles de la Tourette's syndrome in Israel.

OBJECTIVES: The goal of this study was to estimate the lifetime prevalence of Gilles de la Tourette's syndrome (GTS) in adolescents aged 16 to 17 years. DESIGN: Population-based epidemiologic study. SUBJECTS: Eighteen thousand three hundred sixty-four males and 9673 females aged 16 to 17 years screened for induction into the Israel Defense Force. RESULTS: Of the 28,037 individuals screened, 12 met diagnostic criteria for GTS. The point prevalence in this population was 4.3 +/- 1.2 (mean +/- SE) per 10,000. The 95% confidence interval for this estimate is 1.9 to 6.7 per 10,000. The point prevalence was 4.9 +/- 1.6 per 10,000 for males (95% confidence interval, 1.8 per 10,000) and 3.1 +/- 1.8 per 10,000 for females (95% confidence interval, 0 to 6.6 per 10,000). The rate of obsessive-compulsive disorder (OCD) was significantly elevated among the subjects with GTS (41.7%) compared with the population point prevalence of OCD (3.4) in those without GTS. In contrast, the rate of attention deficit hyperactivity disorder was only 8.3% compared with the population point prevalence of 3.9% in those individuals without GTS. CONCLUSIONS: The prevalence estimates from this population-based study are in agreement with previous results based on surveys of younger children. The sex ratio observed in this study is not as large as reported in previous studies and remains to be explored in other studies of adolescents and adults.

Adolescent↗