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Biomedical subjects

M Kotler

Publications and source records attributed to M Kotler.

At least 73 records · Page 4Linked to original sources
PubMed1997

Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects.

Only in the past decade has a role of heredity in substance abuse been established as a result of extensive twin and family studies. More recently, several candidate genes have been investigated for their possible role in alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse have not been investigated in man, although animal studies suggest that quantitative trait loci (QTLs) can be identified that predispose mice both to morphine and alcohol preference. Central dopaminergic pathways figure prominently in drug-mediated reinforcement suggesting that dopamine receptors are likely candiadates for association with substance abuse in man. In addition, we recently reported an association between a human personality trait, Novelty Seeking and the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking is also more pronounced in substance abusers, who score higher in this dimension than control subjects. The twin role of dopamine receptors in mediating Novelty Seeking and drugreinforcement prompted us to examine a group of Israeli heroin addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7-repeat allele is significantly over-represented in the opioid-dependent cohort and confers a relative risk of 2.46. To our knowledge this is the first report of an association between a specific genetic polymorphism and opioid addiction.

Adult↗
PubMed1997

The treatment of comorbid premature ejaculation and panic disorder with fluoxetine.

Premature ejaculation is a common sexual disturbance among men. Both open-label and double-blind studies have demonstrated the effectiveness of serotonergic medications for this disorder. These studies support the hypothesis that the serotonergic system has an important role in the modulation of sexual response, especially attainment of orgasm. Serotonergic dysfunction also has been linked to the pathogenesis of panic disorder. Several studies have demonstrated the efficacy of serotonergic drugs in this disorder. The purpose of the present study was to examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for the treatment of comorbid premature ejaculation and panic disorder, in 10 men in an open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the study. Parameters pertaining to sexual function and measures of anxiety were examined. Improvement of premature ejaculation was noted as of week 2 of the study, whereas measures of panic and sexual satisfaction became statistically significant only as of week 4. Further studies with larger samples and longer periods of follow-up are needed in order to determine the usefulness of fluoxetine for the treatment of comorbid premature ejaculation and panic disorder.

Adult↗
PubMed1997

Life events in childhood, adolescence and adulthood and the relationship to panic disorder.

The aim of this study was to explore the association between stressful life events (SLE) and the development of panic disorder (PD) in an Israeli sample. A total of 44 PD patients and a matched control group were studied with regard to SLE over the life cycle (in childhood, adolescence, adulthood and the year preceding the outbreak of the disorder). The major findings were as follows. (i) With regard to the total number of life events experienced in childhood and adolescence, the PD group had experienced significantly more life events than the control group. (ii) No differences were detected in the total amount of SLE between the PD group and the control group with regard to adulthood and the year preceding the outbreak of the disorder, although the PD group had more life events relating to loss in adulthood, whereas in the year before the outbreak of PD life events relating to 'love and family', negative and loss events were more prevalent. These results expand previous findings by demonstrating that SLE in childhood and adolescence may contribute to the development of PD in adulthood.

Adolescent↗
PubMed1997

Human immunodeficiency virus type 1 (HIV-1) protein Vif inhibits the activity of HIV-1 protease in bacteria and in vitro.

Human immunodeficiency virus type 1 (HIV-1) Vif is required for productive infection of T lymphocytes and macrophages. Virions produced in the absence of Vif have abnormal core morphology and those produced in primary T cells carry immature core proteins and low levels of mature capsid (M. Simm, M. Shahabuddin, W. Chao, J. S. Allan, and D. J. Volsky, J. Virol. 69:4582-4586, 1995). To investigate whether Vif influences the activity of HIV-1 protease (PR), the viral enzyme which is responsible for processing Gag and Gag-Pol precursor polyproteins into mature virion components, we transformed bacteria to inducibly express truncated Gag-Pol fusion proteins and Vif. We examined the cleavage of polyproteins consisting of matrix to PR (Gag-PR), capsid to PR (CA-PR), and p6Pol to PR (p6Pol-PR) and evaluated HIV-1 protein processing at specific sites by Western blotting using antibodies against matrix, capsid, and PR proteins. We found that Vif modulates HIV-1 PR activity in bacteria mainly by preventing the release of mature MA and CA from Gag-PR, CA from CA-PR, and p6Pol from p6Pol-PR, with other cleavages being less affected. Using subconstructs of Vif, we mapped this activity to the N-terminal half of the molecule, thus identifying a new functional domain of Vif. Kinetic study of p6Pol-PR autocatalysis in the presence or absence of Vif revealed that Vif and N'Vif reduce the rate of PR-mediated proteolysis of this substrate. In an assay of in vitro proteolysis of a synthetic peptide substrate by purified recombinant PR we found that recombinant Vif and the N-terminal half of the molecule specifically inhibit PR activity at a molar ratio of the N-terminal half of Vif to PR of about 1. These results suggest a mechanism and site of action of Vif in HIV-1 replication and demonstrate novel regulation of a lentivirus PR by an autologous viral protein acting in trans.

Escherichia coli↗
PubMed1997

Anger, impulsivity and suicide risk.

BACKGROUND: To examine the relationship between anger, impulsivity and suicidality. METHODS: Thirty psychiatric inpatients admitted for suicidal behavior were compared with 30 nonsuicidal psychiatric inpatients and 32 healthy controls on measures of anger, impulsivity and suicide risk. RESULTS: The three groups were similar on demographic variables, but the suicidal group scored higher on the suicide risk scale, impulsivity scale and anger scale. Anger and impulsivity correlated significantly with suicide risk. High anger and impulsivity contributed synergistically to the suicide risk. Whereas anger was specific to both psychiatric groups, suicidals and nonsuicidals, only impulsivity was specific to the suicidal group. CONCLUSIONS: These findings may have important implications for therapists and primary prevention workers, and may pave the way for the recognition of risk factors and for effective intervention in patients with a high suicide risk.

Adult↗
PubMed1997

Sumatriptan-associated myocardial infarction: report of case with attention to potential risk factors.

Vascular headaches are a relatively common phenomenon. Increasing numbers of patients with headache are being considered for treatment with the selective serotonin-receptor agonist sumatriptan succinate because of its potential for pronounced therapeutic efficacy in selected patients. Sumatriptan-associated myocardial infarction occurred in a 50-year-old woman with a history of migraine headaches. Cardiac risk factors that must be considered in all patients with migraine before initiation of therapy include concomitant ergotamine use, postmenopausal state, male gender older than 40 years, family history of heart disease, cigarette smoking, hypertension, diabetes mellitus, as reviewed in this report.

Female↗
PubMed1996

Regulation of the aminolevulinate synthase gene in the Syrian hamster Harderian gland: changes during development and circadian rhythm and role of some hormones.

The Syrian hamster Harderian gland has been advocated as a model to study the porphyrin biosynthetic pathway, since it shows by far the highest porphyrin concentration known to date. Another particular characteristic is the sexual dimorphism at both the morphological and the biochemical levels. We found a variation in the ALV-S (aminolevulinate synthase) gene expression according to sex, with females exhibiting much higher mRNA levels than do males. After castration, ALV-S mRNA rose considerably in males, this increase being inhibited by darkness or treatment with melatonin. Treatment with hCG or progesterone did not vary the ALV-S mRNA levels in females. Castrated males, however, showed a much larger increase when they were treated with hCG. No variations have been found in the expression of the ALV-S gene in female HG throughout the estrous cycle. During development, males and females showed similar ALV-S mRNA levels until they were 20 days old. Afterwards, they started showing gender-associated differences. In females, ALV-S mRNA levels rose during the first 3 months of life, and thereafter they decreased progressively with aging. A circadian rhythm has been found in the gene expression of ALV-S mRNA in females, showing very low levels in the morning and reaching a peak during the first hours of darkness. It was an endogenous rhythm, probably regulated at the transcriptional level. It is proposed that the light-dark period duration modulates this rhythm through the suprachiasmatic nucleus which in turn acts on the pineal secretion of melatonin that regulates ALV-S gene expression.

5-Aminolevulinate Synthetase↗
PubMed1996

A preliminary study of possible psychoactive effects of intravenous forskolin in depressed and schizophrenic patients. Short communication.

Forskolin is a unique activator of adenylate cyclase that bypasses membrane receptors and directly raised levels of the second messenger cyclic AMP. Depressed patients and schizophrenic patients with negative symptoms have been reported to have reduced cyclic AMP levels. In the first study of forskolin in psychiatry, we gave iv forskolin in a 75 minute infusion to four depressed and five schizophrenic patients. All four depressed patients showed a transient mood elevation or stimulation, as did two of the five schizophrenic patients.

Adult↗
PubMed1996

Type of trauma, severity of posttraumatic stress disorder core symptoms, and associated features.

Sixty-six persons with posttraumatic stress disorder (PTSD) exposed to battlefield experience, civilian terrorism, and work and traffic accidents were studied to assess the differential outcome of the various types of trauma as measured by PTSD core symptoms and associated features of depression, anxiety, interpersonal sensitivity, and somatization. The participants were assessed on a PTSD scale, Impact of Events Scale, and four Symptom Check List subscales. The results showed that the battle-experience group was more severely affected than the other groups. Time elapsed since the trauma was significantly positively correlated to PTSD core symptoms and associated features. Only the time elapsed since the trauma-not the division into type of trauma groups-was significantly correlated with severity. Education and army rank were found to be protecting variables.

Accidents, Occupational↗
PubMed1996

Coping styles and suicide risk.

A total of 30 psychiatric in-patients admitted because of suicidal behaviour were compared with 30 non-suicidal psychiatric in-patients and 32 healthy controls on measures of suicide risk and coping styles. The three groups were similar with regard to demographic variables, but the suicidal group scored higher on the suicide risk scale. Suicidal patients were significantly less likely to use the coping styles of minimization and mapping. They were unable to de-emphasize the importance of a perceived problem or source of stress. They also lacked the ability to obtain new information required to resolve stressful life events. Four coping styles correlated negatively with the suicide risk (minimization, replacement, mapping and reversal), while another three (suppression, blame and substitution) correlated positively. These findings may have important implications for therapists and primary prevention workers, and might pave the way towards recognition of the role played by coping styles in predicting suicide and its use for cognitive intervention in these high-risk patients.

Adaptation, Psychological↗
PubMed1996

A p6Pol-protease fusion protein is present in mature particles of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) protease (PR) and p6(Pol) are translated as part of the Gag-Pol polyprotein after a ribosomal frameshift. PR is essential to virus replication and is responsible for cleaving Gag and Gag-Pol precursors, but the role of p6(Pol) in HIV-1 infection is poorly understood. Here, we report that (i) PR is present in mature HIV-1 virions primarily as a p6(Pol)-PR fusion protein; (ii) HIV-1 PR cleaves viral precursor proteins expressed in bacterial cells at the Phe-Leu bond (positions 1639 to 1642) located at the junction of the NC and p6(Pol) proteins, releasing the p6(Pol)-PR fusion protein; and (iii) purified p6(Pol)-PR fusion protein undergoes autocleavage in vitro at at least three sites.

Amino Acid Sequence↗
PubMed1996

A combined clinical approach to treating and understanding prolonged combat stress reaction.

Over the last decade combat stress reaction (CSR) has received increasing attention in Israel and abroad. The treatment of prolonged CSR is known to be complicated and unrewarding, and the majority of cases became chronic. The authors describe the difficulties of diagnosing delayed and prolonged CSR and present a model of combined treatment approach through a case study.

Adult↗