Search PubMed⌕ Search

Biomedical subjects

Moshe Kotler

Publications and source records attributed to Moshe Kotler.

At least 73 records · Page 4Linked to original sources

The Vif protein of human immunodeficiency virus type 1 (HIV-1): enigmas and solutions.

HIV-1 and other complex retroviruses express six auxiliary genes in addition to the canonical retroviral genes, gag, pol and env. Vif (virion infectivity factor) protein is absolutely essential for productive HIV-1 infection of peripheral blood lymphocytes and macrophages, the two major HIV-1 target cells in vivo. However, Vif is not required for production of infectious particles in several human cell lines. In spite of the prominent phenotype of Vif mutations, the mechanism of its action remains unknown. During the last decade several models were suggested to explain the mechanism of Vif activity. One view holds that Vif is active in virions after budding or after entry into target cells during the early stages of HIV-1 replications. The second view places the action of Vif at the late stage of HIV-1 replication in virus producing cells, which affects the production of infectious virus. According to this view, Vif either compensates the cell factor required for production of infectious virus, or alternatively, it neutralizes a cell factor, which prevents the production of infectious particles in these cells. This review is addressed to summarize the models envisioned to explain Vif activities. The findings described here, that Vif interacts with viral and cellular components, elaborates the importance of Vif as a novel target for developing anti HIV-1 drugs.

Gene Products, vif↗

Renal insufficiency in long-term lithium treatment.

OBJECTIVE: To compare long-term lithium patients who developed renal insufficiency (RI) with those who did not, and to examine what characterized these groups. METHOD: One hundred fourteen subjects with DSM-IV bipolar, major depressive, or schizoaffective disorder who had been taking lithium for 4 to 30 years from 1968 to 2000 were studied retrospectively. Subjects with blood creatinine levels > or = 1.5 mg/dL were defined as RI patients, and creatinine levels < 1.5 mg/dL indicated no renal insufficiency (NRI). Ninety-four unmedicated subjects, matched for sex and age, served as a comparison group and had 2 measures of creatinine with a mean interval of 11.88 years. RESULTS: Twenty-four (21%) of the lithium-treated patients were defined as RI patients. These subjects exhibited the "creeping creatinine" phenomenon as their creatinine levels increased progressively. The NRI subjects showed no increase of creatinine levels in up to 30 years and remained comparable to the comparison group. RI was associated with episodes of lithium intoxication and diseases or medicines that could affect glomerular function, but not with sex, psychiatric diagnosis, age at onset of diagnosed disorder, duration of lithium therapy, serum lithium concentration, and cumulative lithium dose. CONCLUSIONS: Long-term lithium therapy did not influence glomerular function in an overwhelming majority of patients. However, about 20% of long-term lithium patients exhibited "creeping creatinine" and developed renal insufficiency.

Adolescent↗

[Comorbid psychiatric symptoms in pathological gamblers: anxiety, depression and substance abuse].

Over the centuries, gambling behaviour has been well known and characterized by the combination of pleasure, luck and competition. Our study explored the relationship between pathological gambling, depression and anxiety. We also explored demographic findings and behavioural patterns of the pathological gamblers. Fourty-seven patients were included in this study and they anonymously completed questionnaires which included demographic findings, the Hamilton depression rating scale and the Hamilton anxiety rating scale. The study results demonstrated a strong correlation between depression, anxiety, substance abuse, and pathological gambling. It also presented lower income and higher anxiety levels associated with a higher tendency for gambling. The subjects suffering from depression and anxiety also showed higher levels of suicidality and other abuse dependencies. In order to confirm these preliminary results larger studies are needed in this field.

Anxiety Disorders↗

DSM-IV self-report and subjective evaluation by psychiatrists in Israel.

BACKGROUND: Psychiatric disorder, with the range of both subsyndromal and syndromal manifestation, is an important, yet often unrecognized and unacknowledged, problem among physicians. It is a subject that remains understudied, particularly among psychiatrists. The purpose of this study was to explore the subjective perception of mental illness among members of the psychiatric profession. METHOD: Psychiatrists attending an educational symposium completed, anonymously, a self-evaluation questionnaire in which they were asked to self-diagnose the presence of DSM-IV disorders. RESULTS: 110 responses were received (response rate: 52.1%); 90% of respondents indicated the presence of at least one syndrome or trait. The most common disorders on axis I and axis II were "mood disorder" and "narcissistic traits" respectively, with the least common being "psychotic disorder" and "schizotypal traits." Female psychiatrists reported more impairment, particularly among axis I disorders. The reported number of axis I and II conditions decreased with subjects' age. CONCLUSIONS: Manifestations of psychiatric conditions including the range of subthreshold phenomena, as self-diagnosed according to DSM-IV criteria, appear to be prominently reported, albeit with low severity, in a subjective manner by psychiatrists. Our findings may be of importance in encouraging the implementation of special programs in training and ongoing occupational support.

Adult↗

Efficient vaccine against the virus causing a lethal disease in cultured Cyprinus carpio.

We have isolated a virus, which causes a mortal disease in cultured ornamental Koi and Common carps (Cyprinus carpio) in many countries worldwide. This unclassified virus, which causes nephritis and gill necrosis, and so has been given the name carp nephritis and gill necrosis virus (CNGV), has a morphology resembling the herpes virus, but bears a genomic DNA of ca 250-300 kbp. So far, both others and we have been unable to find CNGV-DNA sequences possessing a significant similarity to known DNA viruses. The virus induces a lethal disease when water temperature ranges between 18 and 25 degrees C (permissive temperature). In this report, we demonstrate that carps, exposed to the virus at 23 degrees C for 3-5 days and then transferred to the non-permissive temperature of 30 degrees C, became resistant to a challenged infection and their sera demonstrated a high level of virus-specific antibodies. We have isolated attenuated non-pathogenic viruses that render virus-vaccinated carps resistant to the disease. Furthermore, vaccinated fish developed high levels of antibodies against the virus. We suggest, therefore, that this attenuated virus could be used as a live vaccine for the eradication of the mortal disease afflicting Common and ornamental carp fisheries in many countries.

Animals↗

Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia.

CONTEXT: Negative symptoms of schizophrenia are a prominent feature of the illness, and frequently remain refractory to treatment. Dehydroepiandrosterone (DHEA), along with its sulfated form, DHEA-S, is an important circulating neurosteroid with several vital neurophysiological functions, including the regulation of neuronal excitability and function. OBJECTIVE: Since the administration of DHEA has demonstrated improvement in mood, sense of well-being, interest, activity, and energy in several subpopulations, we investigate the efficacy of DHEA in the management of the negative symptoms of schizophrenia. DESIGN: Thirty DSM-IV-diagnosed schizophrenic patients with prominent negative symptoms (inpatients in a large referral state hospital) were randomized to receive either DHEA or placebo in double-blind fashion, in addition to regular antipsychotic medication, dose-stabilized prior to study entry. The DHEA was titrated up to a dose of 100 mg in divided doses during 6 weeks. RESULTS: Results indicated significant improvement in negative symptoms (P<.001), as well as in depressive (P<.05) and anxiety (P<.001) symptoms in individuals receiving DHEA. This effect was especially noted in women. The improvement in negative symptoms was independent of improvement in depression. No differences were noted on the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) or on the total PANSS score as compared with placebo. Subjects receiving DHEA demonstrated a significant increase in DHEA (P<.05) and DHEA-S (P<.01) plasma levels, without changes in cortisol levels. Increases in DHEA and plasma DHEA-S levels were correlated with improvement in negative symptoms (P<.05), but not with improvement in depressive and anxiety symptoms. No obvious adverse effects were experienced by participating subjects. CONCLUSIONS: Our preliminary observations report for the first time in double-blind fashion the efficacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. The findings from this study raise important issues regarding the role of neurosteroids in general, and DHEA in particular, in the ongoing symptomatology and pharmacotherapy of schizophrenia.

Adult↗

Impaired heart rate variability in euthymic bipolar patients.

BACKGROUND: Power spectral analysis of heart rate variability (HRV) has recently been shown to be a reliable non-invasive test for quantitative assessment of the central sympathovagal interaction that modulates cardiovascular autonomic function. METHODS: We studied 39 euthymic bipolar patients and 39 controls, matched for age and sex. A high-resolution electrocardiogram was obtained during complete rest. Spectral analysis of R-R intervals was performed by the fast Fourier transform algorithm. RESULTS: Euthymic bipolar patients at rest are characterized by markedly low HRV, independent of specific drug treatments. CONCLUSION: While these results of autonomic stability in euthymic bipolar patients are counter-intuitive, the findings may be important in understanding pathophysiology of bipolar affective illness.

Adolescent↗

Amantadine as augmentation therapy in the management of treatment-resistant depression.

Treatment-resistant depression is an important clinical problem presenting a major challenge to clinical psychiatry. While several strategies have been attempted, including medication switch, antidepressant polypharmacy and various augmentative regimens, success remains limited. Amantadine (AMN), an agent traditionally used in the treatment and prophylaxis of influenza, is now known to exhibit prominent effects at the level of dopaminergic, monoamine oxidase and N-methyl-D-aspartate systems. The present reports on the efficacy of AMN as augmentation to standard antidepressant treatment in patients with treatment-resistant depression. Eight patients with treatment-resistant depression consented to receive AMN, titrated up to a dose of 300 mg, over a period of 4 weeks in a non-blinded fashion. Improvement in both depression and anxiety scores were observed from week 1, with patients exhibiting improvement of depressive scores of up to 49% by study completion. Females appeared to exhibit a stronger response, and within a shorter period of time. Side-effects reported included dry mouth and sedation. AMN appears to demonstrate efficacy as a safe and effective augmentative agent in treatment-resistant depression. Further studies are clearly mandated to test these preliminary observations in a double-blinded manner.

Adult↗

[Compulsory treatment of nondelinquent drug-alcohol abusers in Israel: the present situation and feasible solutions].

The number of persons affected by alcoholism and/or substance abuse is constantly increasing in Israel as well the number of those suffering from severe addictions. The Israel Law for the Treatment of the Mentally Ill, 1991, does not allow the compulsory treatment of nondelinquent alcoholics and/or drug abusers who refuse treatment and who are not in a psychotic condition which includes severe and immediate danger to themselves or others. This paper analyzes and discusses the possibilities of assisting this group of patients within the framework of the present Israel legislation, other than the Law for the Treatment of the Mentally Ill of 1991, as well as focusing on modifications of this law that would be necessary to facilitate the implementation of urgent therapeutic interventions.

Alcoholism↗

[Vitamin B6 add-on therapy in treatment of schizophrenic patients with psychotic symptoms and movement disorders].

INTRODUCTION: Although there is great progress in the treatment of positive symptoms in schizophrenic patients and movement disorders induced by neuroleptics, it is still a problem for clinicians. In this study vitamin B6 treatment was provided to 15 patients who suffered from schizophrenia and schizoaffective disorder with positive psychotic symptoms and tardive dyskinesia. METHODS: This study was a double-blind crossover controlled during 9 weeks. Each patient was treated with up to 400 mg/day vitamin B6 versus placebo. Every week the patients' conditions were evaluated with Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Symptoms Rating Scale (ESRS) and a blood sample of level pyridoxal was taken. RESULTS: The results did not show any therapeutic effect of psychotic symptoms from vitamin B6 added to antipsychotic agents, which patients received on a constant base. On the other hand, there was significant improvement in tardive dyskinesia and parkinsonian symptoms. There was no direct correlation between pathological symptoms and the serum baseline level of vitamin B6 nor its level during the treatment. CONCLUSION: The authors suggest that vitamin B6 may be efficient as the treatment for tardive dyskinesia and parkinsonism induced by neuroleptic agents. There is a need for further studies with larger samples and higher doses of vitamin B6 in order to examine the possibility of a positive therapeutic effect as an augmentation agent for the treatment of psychotic symptoms.

Adolescent↗

The structural reform of mental health services.

During past decades many countries have initiated extensive mental health care system reforms, and the main goal of these reforms has been the transfer of treatment of the mentally ill from psychiatric hospitals to the community. For example, assessment of the results of these reforms in Italy and Austria demonstrates considerable reduction in the number of psychiatric beds, higher quality and more available community services, and increased total expenditure for mental health services. However, because sufficient data is not yet available, many questions regarding how these reforms impact improvement in patient clinical parameters remain unanswered. Some of the answers to these questions can be gleaned from the results of research carried out in the United States and Canada in the 1980s. This research evaluated transfer of psychiatric treatment from a hospital setting to a community service setting. The results demonstrated that community treatment models were more effective than a hospital treatment model in reducing the number of hospitalizations and shortening length of stay. Patient monitoring also demonstrated good integration into the community. However, alongside the research supporting these reforms, there is some research that demonstrates a number of possible disadvantages: an increase in the number of homeless and in the mortality rate among psychiatric patients, and an increase in rehospitalization rates of chronically ill patients," referred to as the "Revolving Door Syndrome." To avoid the disadvantages that could possibly accompany the reform, particular attention needs to be given to planning and funding, so that development of community services and reduction in psychiatric hospital system correspond. Care must be taken to ensure that the number and the geographic location of these services meets the need of the population at risk, and that staff is available and well trained. A monitoring system should be set in place to monitor the patients according to the clinical standards agreed upon, and at the same time guidelines should be set up to evaluate the functioning of community services. The structural reform is progressing and should be completed at the end of 2005. However, development of community services is not progressing at the desired rate. In January 2003, the Israeli government made a decision to transfer the responsibility for medical insurance for the mentally ill from the government to the Sick Funds. However, an agreement between the Ministry of Health, the Ministry of the Treasury and the Sick Funds has yet to be signed and the government's decision has yet to be realized. This has caused development of community services to come to a halt, and neither the government nor the Sick Funds are investing in community development. We can only hope that the transfer of responsibility for health insurance for the mentally ill from the State to the Sick Funds will be completed soon and that development of community service for the mentally ill will then move forward quickly.

Health Care Reform↗

Sodium dodecyl sulphate-treated proteins as ligands in ELISA.

Insoluble proteins generally do not adsorb to microtitre wells and, therefore, cannot be used as antigens in enzyme-linked immunosorbent assay (ELISA). However, denaturation and solubilization with 2% sodium dodecyl sulphate (SDS) renders these proteins suitable ligands for ELISA. In quantitative ELISA using polyclonal antibodies as primary antibody, comparable results were obtained with native and SDS-denatured protein ligands. The binding of the antibodies to the SDS-treated ligands was completely inhibited by premixing the primary antibody with the corresponding native antigen. Nonspecific binding of primary and secondary antibodies to SDS-treated ligands was not observed. SDS-treated proteins are able to attach to ELISA microwells, retain their antigenic epitopes and do not engender an elevated background. The concentration of SDS-treated proteins required for coating is the same as that of the native proteins.

Enzyme-Linked Immunosorbent Assay↗

A highly significant association between a COMT haplotype and schizophrenia.

Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size-to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P=9.5x10-8). The approach presented can be widely implemented for the genetic dissection of other common diseases.

Case-Control Studies↗

HIV-1 Vif-derived peptide inhibits drug-resistant HIV proteases.

Vif, one of the six accessory genes expressed by HIV-1, is essential for the productive infection of natural target cells. Previously we suggested that Vif acts as a regulator of the viral protease (PR): It prevents the autoprocessing of Gag and Gag-Pol precursors until virus assembly, and it may control the PR activity in the preintegration complex at the early stage of infection. It was demonstrated before that Vif, and specifically the 98 amino acid stretch residing at the N'-terminal part of Vif (N'-Vif), inhibits both the autoprocessing of truncated Gag-Pol polyproteins in bacterial cells and the hydrolysis of synthetic peptides by PR in cell-free systems. Linear synthetic peptides derived from N'-Vif specifically inhibit and bind HIV-1 PR in vitro, and arrest virus production in tissue culture. Peptide mapping of N'-Vif revealed that Vif88-98 is the most potent PR inhibitor. Here we report that this peptide inhibits both HIV-1 and HIV-2, but not ASLV proteases in vitro. Vif88-98 retains its inhibitory effect against drug-resistant HIV-1 PR variants, isolated from patients undergoing long-term treatment with anti-PR drugs. Variants of HIV protease bearing the mutation G48V are resistant to inhibition by this Vif-derived peptide, as shown by in vitro assays. In agreement with the in vitro experiments, Vif88-98 has no effect on the production of infectious particles in cells infected with a G48V mutated virus.

Amino Acid Substitution↗

Effect of intraperitoneal mRNA antisense-oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats: association with pre-experimental stress.

RATIONALE: Cholecystokinin and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. Cholecystokinin receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. We demonstrated that intracerebroventricular administration of Cholecystokinin-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. OBJECTIVE: This study was designed to examine the effects of peripheral (intraperitoneal) administration of Cholecystokinin-ASODN on anxiety-like and learning behaviors in rats, in general and in a pre-experiment stress paradigm. METHODS: In the first study Cholecystokinin-ASODN was injected intraperitoneally to rats five times at 24-h intervals. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On the sixth day, the rats were assessed in the elevated plus-maze paradigm and in the Morris water maze. In the second study, rats were pre-exposed to a cat for 10 min as a model for psychological stress, and then treated with intraperitoneal Cholecystokinin-ASODN and tested in both paradigms. RESULTS: The results show that for intact rats, intraperitoneal Cholecystokinin-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups. In stressed rats, Cholecystokinin-ASODN reduced anxiety-like behaviors in the plus-maze and improved performance in the water maze compared with controls. CONCLUSIONS: These results indicate that the anxiolytic effect of intraperitoneal Cholecystokinin-ASODN may be dependent on the baseline endogenous level of stress (i.e., on the Cholecystokinin levels). Basal endogenous levels of Cholecystokinin, as well as exogenous dosage of Cholecystokinin agonists and/or anxiolytic agents, appear to play an important role in the expression and/or control of anxiety-related behaviors in rats.

Animals↗

Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder.

The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of "much" or "very much" improved. The baseline CAPS-2 total severity score was 94.3 +/- 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 +/- 0.3 for sertraline and 3.4 +/- 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (chi2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (>or=30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (chi2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.

Adult↗