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Biomedical subjects

M Kotler

Publications and source records attributed to M Kotler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hemispheric function in disorganized type schizophrenia: performance on the quality extinction test.

We assessed hemisphere function in right-handed male chronic, disorganized type schizophrenic patients (N = 60, age range 18-45 years) using the Quality Extinction Test (QET), in comparison to 20 right-handed male healthy controls in the same age range. The QET analysis discriminated between the disorganized schizophrenic patients and the controls. QET results indicated that chronic schizophrenic patients were less sensitive to tactile stimuli in both hands as compared to controls. Furthermore, the sensitivity to tactile stimuli of the left hand was less than that of the right hand in the schizophrenic patients. In contrast, in the normal controls the sensitivity was similar in both hands. These results indicate possible right hemisphere dysfunction together with disturbance in interhemispheric transmission through the corpus callosum in chronic, disorganized type schizophrenic patients.

Adolescent↗
PubMed2000

Administration of high-dose ketoconazole, an inhibitor of steroid synthesis, prevents posttraumatic anxiety in an animal model.

Acute psychological stress is the presumed immediate cause of post-traumatic stress disorder (PTSD), and may also contribute to other anxiety disorders. Abnormal activity of the hypothalamic-pituitary-adrenal (HPA) axis has been tentatively implicated in some of the features of these disorders. Ketoconazole (KTCZ), an imidazole derivative, is a potent inhibitor of gonadal and adrenal steroidogenesis. The aim of this study was to explore the effects of KTCZ blockade of adrenal steroidogenesis, and consequent elevation of adreno-corticotropic hormone (ACTH), on a model of chronic post-traumatic anxiety in rats. Amelioration of anxious behaviors after reduction of corticosterone would suggest that corticosterone (and by implication cortisol in humans) is an important mediator of anxious symptoms: exacerbation of such behaviors would suggest that corticosterone elevations are only secondary, and possibly implicate corticotropin releasing hormone (CRH) and/or ACTH in the pathogenesis of anxious symptoms. We exposed rats for 10 min to cat scent, a prima facie valid model for acute psychological stress, with and without high dose KTCZ for 14 days. Treatment with KTCZ abolished the chronic behavioral effects of acute exposure to a cat scent. Lower levels of anxious behavior in KTCZ-treated and exposed rats were accompanied by lower plasma corticosterone, ACTH and prolactin (PRL) levels compared to untreated exposed rats. Results in this model implicate corticosterone, but not ACTH, in the pathogenesis of chronic anxiety following acute psychological stress.

Animals↗
PubMed2000

Elevated circulatory level of GABA(A)--antagonistic neurosteroids in patients with combat-related post-traumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a multisystem neurobiological disorder with chronic alterations in various neurochemical systems. Levels of the GABA(A)--antagonistic neurosteroids plasma dehydroepiandrosterone (DHEA) and its sulphate derivate, dehydroepiandrosterone sulphate (DHEAS) may be relevant to depressive and anxiety disorders, including PTSD. METHODS: We assessed the circulatory levels of morning plasma DHEA and DHEAS in 21 male outpatients with untreated chronic combat-related PTSD (CR-PTSD), and 18 healthy control male subjects. RESULTS: Compared with the control subjects, the PTSD patients showed significantly higher plasma DHEA and DHEAS levels. CONCLUSIONS: Chronic CR-PTSD may be associated with increased circulatory level of neuroactive steroids with inhibitory activity at the GABA(A) receptors. Neurosteroid-induced decreased GABAergic tone may be relevant to the symptomatology and pathophysiology of chronic PTSD, as well as to the frequent co-morbidity of PTSD with depression and anxiety disorders.

Adult↗
PubMed2000

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT).

Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol O-methyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT x 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR x D4DR (F = 6.18, P = 0.03) and COMT x 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry (2000) 5, 96-100.

Adolescent↗
PubMed2000

An interaction between the catechol O-methyltransferase and serotonin transporter promoter region polymorphisms contributes to tridimensional personality questionnaire persistence scores in normal subjects.

Persistence (RD2) is a subscale of the reward dependence trait, one of the three major personality factors assessed by the Tridimensional Personality Questionnaire (TPQ). Subjects with high RD2 scores are characterized as industrious, hard-working, ambitious, perfectionistic. TPQ scores were examined in 577 normal subjects inventoried for two common genetic polymorphisms, the catechol O-methyltransferase (COMT) valine to methionine (val to met) amino acid substitution that determines high and low enzyme activity, and the serotonin transporter promoter region 44 bp deletion (5-HTTLPR) linked in some studies to harm avoidance or neuroticism. When TPQ RD2 scores are grouped by COMT and 5-HTTLPR polymorphisms and analyzed by two-way ANOVA, significant main effects for COMT (F = 2. 98, p = 0.05) and 5-HTTLPR (F = 4.27, p = 0.04) and a significant interaction COMT x 5-HTTLPR (F = 6.18, p = 0.002) are observed. In the presence of COMT homozygosity (val/val or met/met genotypes), the presence of the short 5-HTTLPR allele raises RD2 scores. The effect of these two polymorphisms on RD2 was also examined using a within-families design. Siblings in our data set who shared identical genotypes had significantly correlated RD2 scores (intraclass coefficient = 0.34, F = 2.03, p = 0.002, n = 67), whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for RD2 scores (intraclass coefficient = 0.105, F = 1.23, p = 0.16, n = 92).

Adolescent↗
PubMed2000

Normalization of heart rate variability in post-traumatic stress disorder patients following fluoxetine treatment: preliminary results.

BACKGROUND: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone. OBJECTIVES: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients. METHODS: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram. RESULTS: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.

Adult↗
PubMed2000

Unusual combination: polydipsia with hypernatremia in a schizophrenic patient.

OBJECTIVE: The authors describe a patient with an unusual combination of polydipsia and isolated hypernatremia without any other changes of electrolytes. The patient had two attacks of hypernatremia which were successfully treated with clozapine. Some speculations about possible mechanisms of this unusual combination are discussed.

Drinking↗
PubMed2000

Medical confidentiality in the new Israeli Patients' Rights Act (1996): does it add or detract?

Medical confidentiality is dealt with in various laws in Israel. The 1996 Israel Patient's Rights Act approaches the subject of confidentiality in an extensive and fairly detailed manner which includes several innovations in relation to previous laws. This article will review the old and the new legislations on confidentiality, and will analyze and discuss the implications and potential problems for psychiatric clinical practice. The new Act will also be examined in light of the World Health Organization guidelines on Mental Health Care Laws.

Confidentiality↗
PubMed2000

The patient's right to know, in the 1996 Israel law for the rights of the patient: the pains of progress.

The 1996 Israel Law for Patients' Rights, Sections 21 and 22, introduces to the field of health legislation two new entities: internal examination committees and quality-control committees. The former are to be established when there is a need to investigate unusual, irregular or exceptional events related to diagnosis and/or treatment. Furthermore, the 1996 Law directs the internal examination committee to reveal its findings to the patient or to his representatives. This approach has evoked strong controversy up until the present time. On the other hand, the quality-control committees which produce privileged information have been smoothly integrated into psychiatric practice. This paper presents the history of the creation of these two committees based on law, and examines their effect on the daily practice of medicine and the reaction of the physicians' guild to their activation. It also discusses the effect of the implementation of these committees on the level of mutual trust between therapist and patient, and on medical morality and its relationship to the social phenomenon known as defensive medicine. Feasible solutions for controversial issues are presented. These include participation of patients or their representatives in the internal examination committees, privileged peer reviews, increased utilization of quality control committees and of ethics committees.

Humans↗
PubMed1999

Homicidal behavior in schizophrenia associated with a genetic polymorphism determining low catechol O-methyltransferase (COMT) activity.

Although aggressive, violent, and dangerous behavior in man has multifactorial causes, genetic factors are estimated by twin and adoption studies to substantially contribute to the development of such conduct. Recently, homozygosity of a low enzyme activity variant of the catechol O-methyltransferase (COMT) gene was reported to be associated with aggressive behavior in a group of schizophrenic patients. We observe a similar tendency in a group of 30 schizophrenic patients who were confined to a maximum-security psychiatric facility for homicide. Significant excess (46.7% versus 21.0%) homozygosity of the low activity COMTmet/met genotype was observed in 30 mostly male (28 of 30) homicidal schizophrenic patients compared with 415 control subjects (Pearson chi(2) = 10.53, P = 0.005, df = 2). No difference in COMT genotype was found between 62 nonviolent schizophrenic patients and the 415 control subjects (chi(2) = 0.963, P > 0.1, df = 2). A trend for excess (46.7% versus 25.8%) homozygosity of the low activity COMTmet/met genotype was also observed when the homicidal schizophrenic subjects were compared directly with the nonviolent schizophrenic patients (chi(2) = 4.03, P = 0.1, df = 2). Similarly, an excess of the low activity COMTmet allele was observed in homicidal versus nonviolent schizophrenic patients (chi(2) = 2.92, P = 0.087, df = 2). Similar results were obtained if only male subjects were examined. No significant difference was found between control (257 Ashkenazi and 152 non-Ashkenazi Jews) COMT genotypes in the two principal ethnic groups examined (chi(2) = 3.79, P > 0.1, df = 2). Finally, no association was observed between homicidal behavior in schizophrenic patients and the dopamine D4 exon III repeat length polymorphism (D4DR) and the serotonin transporter promoter-region polymorphism (5-HTTLPR). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:628-633, 1999.

Adult↗
PubMed1999

Peptides derived from HIV-1 Vif: a non-substrate based novel type of HIV-1 protease inhibitors.

The retroviral protease (PR) is absolutely essential for completion of human immunodeficiency virus multiplication cycle, and cannot be replaced by any cellular function. Thus PR, like reverse transcriptase, is an ideal target for the development of anti-AIDS therapy. A large number of human immunodeficiency virus type-1 (HIV-1) PR inhibitors have been developed, and several are currently used as anti-AIDS drugs. These inhibitors are mainly based on the natural PR cleavage sites within the viral Gag and Gag-Pol precursors. The major difficulty encountered while using anti-HIV therapeutic agents in patients has been the rapid emergence of drug-resistant viral strains. Most of the mutations which convert the PR into inhibitor-resistant are located within the substrate binding subsites of the enzyme. Recently, it has been shown that the HIV-1 auxiliary protein Vif, and especially the N-terminal half of Vif (N'-Vif) specifically interacts with the viral PR and inhibits its activity. We now show that efficient inhibition of HIV-1 PR activity can be achieved using Vif-derived peptides. Based on the above model we have performed peptide mapping of N'-Vif in order to find a small peptidic lead compound which inhibits PR activity. The screening revealed that peptides derived from two regions in Vif spanning from residues 30-65 and 78-98 inhibit PR activity in vitro, specifically bind HIV-PR and inhibit HIV-1 production in vivo. Further mapping of these regions revealed the lead compounds Vif81-88 and Vif88-98. These peptides specifically inhibit and bind HIV-1 PR, but do not affect pepsin and rous sarcoma virus protease. In contrast to other known PR inhibitors, these peptides are not substrate-based and their sequences do not resemble the sequences of the natural PR substrates (cleavage sites). Moreover, the Vif-derived peptides themselves are not cleaved by HIV-1 PR. Conversion of the lead peptides into small backbone cyclic peptidomimetics is taking place nowadays in order to turn these lead compounds into metabolically stable selective novel type of HIV-PR non-substrate-based inhibitors.

Amino Acid Sequence↗
PubMed1999

Sensitization of resting T cells to autologous natural-killer-cell-mediated lysis by phytohemagglutinin.

Natural killer (NK) cells are non-T, non-B cell lymphocytes that lyse a variety of tumor and virus-infected cells. In this study, we demonstrated that phytohemagglutinin (PHA) rendered resistant autologous T cells extremely sensitive to natural-killer(NK)-cell-mediated lysis. The sensitization was very rapid and concentration-dependent (0.01-1 microg/ml); 62% and 95% of autologous T cells were lysed by interleukin-2-activated NK cells 5 min and 18 h respectively after treatment with PHA (1 microg/ml). The maximal decrease in the level of MHC class I molecules observed on T cells was 22%. Induction of susceptibility to NK-mediated lysis was correlated with the expression of activation markers on T cells treated for relatively long intervals (more than 18 h) with high concentrations of PHA (more than 0.1 microg/ml). Sensitization of T cells required RNA and protein synthesis, although DNA synthesis was not essential. We propose that this unique system is suitable for studying the mechanisms involved in recognition and killing of target cells by NK cells.

Adenocarcinoma↗
PubMed1999

Low persistence in euthymic manic-depressive patients: a replication.

BACKGROUND: A previous study which compared euthymic Israeli bipolars in a public hospital clinic to US normative data suggested that low Persistence scores on the Tridimensional Personality Questionnaire (TPQ) may be a temperament marker for manic-depressive illness. The current study attempts to replicate that finding. METHODS: A new sample of 25 euthymic Israeli bipolars in private treatment was compared to Israeli normal controls matched for gender and ethnic background. All subjects completed Hebrew versions of the TPQ. RESULTS: Patients scored lower than controls on the Novelty Seeking and Persistence Scales. LIMITATIONS AND CONCLUSIONS: Though sample and effect size are both small, the finding of low Persistence is consistent with that of the earlier study.

Affect↗
PubMed1999

Identification of the major intestinal fatty acid transport protein.

While intestinal transport systems for metabolites such as carbohydrates have been well characterized, the molecular mechanisms of fatty acid (FA) transport across the apical plasmalemma of enterocytes have remained largely unclear. Here, we show that FATP4, a member of a large family of FA transport proteins (FATPs), is expressed at high levels on the apical side of mature enterocytes in the small intestine. Further, overexpression of FATP4 in 293 cells facilitates uptake of long chain FAs with the same specificity as enterocytes, while reduction of FATP4 expression in primary enterocytes by antisense oligonucleotides inhibits FA uptake by 50%. This suggests that FATP4 is the principal fatty acid transporter in enterocytes and may constitute a novel target for antiobesity therapy.

Binding, Competitive↗
PubMed1999

Natural killer (NK) cells prevent virus production in cell culture.

Natural killer (NK) cells (CD3-/CD16+/CD56+ lymphocytes) play an important role in early immune defense against viral infection, a fact which is of prime significance for heavily immunosuppressed patients after bone marrow transplantation. In this study we demonstrate that NK cells preferentially lyse human colon adenocarcinoma (Colo-205) tumor cells infected with herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV) and autologous T cells infected with VV. This phenomenon was assessed by the viral infectious center (IC) method and compared with the results obtained by means of the standard 51Cr-release assay. Using the IC assay, we found that NK cells lyse virus infected cells at an early stage of infection, thereby preventing viral dissemination to neighboring cells. 51Cr-release assay verified by propidium iodide (PI) penetration showed that the early effects of NK mediated anti-viral activity are not the result of membrane damage. The effect of NK cells on HSV-1 infected Colo-205 cells appears to be independent of the level of expression of major histocompatibility complex (MHC) class I molecules while the killing of autologous VV-infected T cells correlates with a reduction in MHC class I expression. Our results suggest that additional factors besides MHC play a role in the regulation of NK cell-mediated lysis of virus infected cells. This may be of clinical importance in patients who are heavily immunosuppressed after bone marrow transplantation.

Antigens, Viral↗
PubMed1999

The effect of long-term antipsychotic treatment on the body weight of patients suffering from chronic schizophrenia: clozapine versus classical antipsychotic agents.

The aim of this study was to evaluate the effect of long-term clozapine treatment on body weight changes in neuroleptic-resistant chronic schizophrenic patients and to compare it with that of classical antipsychotic agents. The body mass index (BMI) of 96 neuroleptic-resistant chronic schizophrenic patients was calculated before the beginning and after long-term (mean +/- SD 1.7 +/- 1.3 years) clozapine treatment. These data were compared to the BMI of 98 chronic schizophrenic patients maintained on classical antipsychotic agents for a similar duration (mean +/- SD 1.9 +/- 1.6 years). A significant elevation in BMI was detected in both groups during these periods (P < 0.0001 versus baseline, for both groups). The change in BMI (delta BMI) was similar in both groups (P < 0.9). We conclude that the increase in body weight caused by long-term (> 6 months) clozapine treatment is comparable to that obtained following long-term classical antipsychotic agents treatment.

Adult↗