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Biomedical subjects

A Shalev

Publications and source records attributed to A Shalev.

At least 37 records · Page 2Linked to original sources
PubMed1996

The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily implicated in adipocyte differentiation. The observations that PPAR alpha is a regulator of hepatic lipid metabolism and that the insulin-sensitizing thiazolidinediones are ligands for PPAR gamma suggest that cross-talk might exist between insulin signaling and PPAR activity, possibly through insulin-induced PPAR phosphorylation. Immunoprecipitation of endogenous PPAR alpha from primary rat adipocytes prelabeled with [32P]-orthophosphate and pretreated for 2 h with vanadate and okadaic acid demonstrated for the first time that PPAR alpha is a phosphoprotein in vivo. Treatment with insulin induced a time-dependent increase in PPAR phosphorylation showing a 3-fold increase after 30 min. Insulin also increased the phosphorylation of human PPAR alpha expressed in CV-1 cells. These changes in phosphorylation were paralleled by enhanced transcriptional activity of PPAR alpha and gamma. Transfection studies in CV-1 cells and HepG2 cells revealed a nearly 2-fold increase of PPAR activity in the presence of insulin. In contrast, insulin had no effect on the transcriptional activity of transfected thyroid hormone receptor in CV-1 cells, suggesting a PPAR-specific effect. Thus, insulin stimulates PPAR alpha phosphorylation and enhances the transcriptional activity of PPAR, suggesting that the transcriptional activity of this nuclear hormone receptor might be modulated by insulin-mediated phosphorylation.

Animals↗
PubMed1994

Chlorpromazine prophylaxis of steroid-induced psychosis.

We report a case of successful prophylactic treatment for psychiatric side effects of megadose glucocorticoid therapy by the administration of chlorpromazine. We review currently used prophylactic treatment strategies and discuss the rationale for adding neuroleptic treatment as an alternative to these strategies.

Adult↗
PubMed1993

The relationship between short-term antibiotic treatments and fatigue in healthy individuals.

Antibiotic treatment tends sometimes to result in sensations of fatigue and decreased physical performance. The effects of antibiotics were therefore studied in 50 healthy, male trainees, aged 18-25 years, assigned in a random, double-blind fashion to one of the following treatments: tetracycline, ampicillin, trimethoprim/sulphamethoxazole, placebo I and placebo II. Duration of treatment was five times the half-life of each agent and the placebo was matched accordingly. Muscle enzyme activity (serum glutamine oxaloacetate transaminase, lactate dehydrogenase, creatine phosphokinase), maximal aerobic capacity (VO2max), muscle strength (MS), and rating of subjective sensation of fatigue were assessed prior to and upon conclusion of treatment. Compared to pretreatment values, plasma enzymes activity was elevated in all five groups (P < 0.005). No differences in VO2max or in MS were found among the subjects treated with either one of the antibiotics or those given a placebo. A significant difference in VO2max was found between the groups treated for 1 day (antibiotic and placebo) and the groups treated for 3 days (antibiotic and placebo) (P < 0.0001). The rating of subjective sensation was not affected by any of the agents. We concluded that in healthy individuals, a short-term antibiotic treatment had no deleterious effect on aerobic capacity or on muscle strength and was not associated with subjective side effects. The time interval between the two maximal tests could, however, have affected the aerobic capacity. Physiological disturbances associated with a sensation of fatigue following a longer period of antibiotics cannot be excluded.

Adolescent↗
PubMed1993

Poor neuroleptic response in acutely exacerbated schizophrenic patients.

Poor neuroleptic response is a major unresolved clinical problem. Precise data concerning the frequency of poor neuroleptic response are not available. The implementation of treatment modalities that are specifically recommended for non-responders (such as clozapine) increases the desirability of such data. This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol, chlorpromazine and perphenazine, in randomly determined order. The overall improvement rate was 95%. The frequency of good responses to the first, second and third drug were 67%, 55%, and 67% respectively. Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug.

Adolescent↗
PubMed1993

The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin.

The levels and expression of the proteins CD63 and granulophysin in platelets from control and from a Hermansky-Pudlak syndrome subject (a condition characterized by dense granule and lysosomal deficiencies and the accumulation of ceroid-like material in reticuloendothelial cells) were examined. Immunofluorescence studies indicated that anti-CD63 and anti-granulophysin antibodies recognized similar numbers of granules; coapplication of antibodies did not identify more granules than the individual antibodies. Significantly fewer granules were recognized in Hermansky-Pudlak syndrome platelets than in control using either antibody. Immunoblotting studies demonstrated that anti-CD63 and anti-granulophysin antibodies apparently recognize the same protein, which was deficient in Hermansky-Pudlak platelets. Analysis by fluorescence-activated cell sorter (FACS) showed biphasic expression of CD63 and granulophysin after thrombin stimulation of control but not Hermansky-Pudlak platelets. Anti-CD63 effectively blocked detection of the protein by anti-granulophysin using immunofluorescence, ELISA, immunoblotting, and FACS analysis. Amino-terminal sequencing over the first 37 amino acids revealed that granulophysin was homologous to CD63, melanoma antigen ME491, and pltgp40. These results suggest that granulophysin and CD63 are possibly identical proteins. This is the first report of a protein present in platelet dense granules, lysosomes, and melanocytes, but deficient in a patient with Hermansky-Pudlak syndrome.

Adult↗
PubMed1993

Wide distribution of granulophysin epitopes in granules of human tissues.

BACKGROUND: The identification and characterization of granule membrane proteins are becoming increasingly important in understanding the packaging and secretory function of granules and characterizing diseases involving granules. A granule membrane protein, granulophysin, has recently been identified in the membranes of platelet dense granules, organelles that contain stored ADP, ATP, serotonin, and calcium. Antibodies that recognize granulophysin also stain granules of monocytes, neutrophils, and lymphokine activated killer cells. EXPERIMENTAL DESIGN: In the present study, the distribution of epitopes recognized by antigranulophysin monoclonal antibodies in human tissues was investigated using immunohistochemistry on paraffin sections. Quantitation of the protein was also performed by enzyme-linked immunosorbent assay. The protein was also analyzed in various tissues using Western blotting. RESULTS: Granulophysin was localized to the granules of skin melanocytes, neurons, endocrine gland cells, exocrine glands (except mucin producing cells), and surface lining cells. Analysis by Western blots revealed a typical staining pattern for granulophysin in lung, adrenal gland, liver, brain, prostate, and pituitary. Atypical bands were present in the pancreas head (47 kDa) and skeletal muscle (34 kDa). A clear distinction was demonstrated between granulophysin and synaptophysin through both immunochemistry and blotting, despite the known cross-reactivity of these two proteins. CONCLUSIONS: The findings demonstrate that granulophysin is a widely distributed protein that is frequently associated with granules. We speculate that it may be critical in granule function.

Antibodies, Monoclonal↗
PubMed1992

Quantification of a novel dense granule protein (granulophysin) in platelets of patients with dense granule storage pool deficiency.

An antigen-capture sandwich enzyme-linked immunosorbent assay (ELISA) was developed for a novel protein granulophysin, a constituent of the platelet dense granule (DG) membrane and used to characterize patients with dense granule storage pool deficiency (delta-SPD). The assay uses two monoclonal antibodies against the protein, one of which is conjugated to peroxidase. Purified DGs, an enriched source of the protein, were used for the standard curve. Granulophysin levels were only low in forms of delta-SPD associated with albinism. Granulophysin levels in platelet homogenates of 30 patients with the Hermansky-Pudlak syndrome form of delta-SPD were 1/4 to 1/5 of levels in controls or obligate heterozygotes. Two patients with the Chediak-Higashi form of delta-SPD syndrome also had markedly reduced levels of granulophysin. Patients with other forms of delta-SPD had normal levels of granulophysin. Two sisters with delta-SPD in one family had normal granulophysin present in empty dense granule membrane vesicles. Three members of another family with delta-SPD had low DG counts but normal granulophysin levels, indicating that in this group the level of granulophysin was maintained despite the reduction in granule formation. Thus, granulophysin quantitation facilitates characterization of delta-SPD patients and may provide clues to the nature of defective granules in delta-SPD subtypes.

Adult↗
PubMed1992

Sharing of antigenic epitopes between synaptophysin and granulophysin.

The immunological crossreactivity between the two granule-specific membrane glycoproteins, synaptophysin and granulophysin, was studied using a series of site-specific monoclonal and polyclonal antibodies. The epitope relatedness of six monoclonal antibodies against granulophysin was examined by competitive ELISA. The antibodies are shown to recognize distinct, but overlapping epitopes within a compact region that is constructed by the three-dimensional configuration of the molecule. All these antibody clones also recognize rat neuronal synaptophysin. Two monoclonal antibodies against synaptophysin, of which one is the well-characterized SY38 antibody, directed against the carboxy terminal of the molecule, are also shown to react with granulophysin. Characterized polyclonal antibodies against different peptide antigens of synaptophysin failed to recognize granulophysin. Synaptophysin and granulophysin are distinctly recognized in brain cell (white matter) and the pituitary both qualitatively and quantitatively. Based on these and other observations, it is suggested that the repeat motif in the cytoplasmic tail of synaptophysin represents an immunodominant construct that is the target for the observed crossreactive antibodies and that a similar tertiary construct has been preserved in granulophysin and in other transmembrane proteins.

Animals↗
PubMed1992

[Lithium augmentation for mianserin-resistant depression in the elderly].

Depression in the elderly is characterized by a prolonged course and resistance to pharmacological treatment. Moreover, in old age sensitivity to the anticholinergic and cardiac side-effects of tricyclic antidepressants (TCA) increases. Recently new antidepressants with fewer side-effects have been developed. Of these, trazodone and mianserin have been particularly recommended for the treatment of depression in older patients. However, the effects of these new compounds on depression are similar to those of the older TCA's, leaving a substantial number of elderly patients with resistant depression. While there are many publications on the potentiation of the effect of TCA's by lithium carbonate, there is little data on the potentiation of the effects of trazodone and of mianserin by lithium, and no reports of their combined use in elderly patients. Birkhimer et al. reported a case of successful treatment of refractory depression with trazodone and lithium in a 45-year-old man. Heninger et al. successfully treated 2 treatment-refractory patients (aged 52 and 58 years, respectively) with a combination of mianserin and lithium. Price et al. reported that 85% of 12 drug-resistant patients improved when treated with lithium and mianserin, but only 22% of 9 patients treated with lithium and trazodone. We report a 73-year-old man with resistant depression whose physical condition contraindicated tricyclic antidepressants, in whom the combination of mianserin and lithium was both safe and effective.

Aged↗
PubMed1990

Posttraumatic stress disorder: somatic comorbidity and effort tolerance.

To explore psychological and somatic distress following trauma, the authors compared 50 combat veterans with chronic posttraumatic stress disorder (PTSD) with 48 age-matched combat veterans without PTSD. Both groups were evaluated on symptom reports, physical examination findings, and laboratory tests. Subjects with PTSD reported significantly more symptoms, but they did not differ from controls on their physical examination and laboratory test findings. Adverse health practices (smoking, alcohol use, and deregulation of food intake) were significantly more frequent in the PTSD group. Low effort tolerance, as has been reported in panic disorder patients, was observed in the PTSD group.

Adult↗
PubMed1989

Delayed onset PTSD among Israeli veterans of the 1982 Lebanon War.

This is an exploratory study of the nature, course and rates of delayed post-traumatic stress disorder (PTSD). We reviewed 150 medical files of Israeli soldiers who sought help between 6 months and 5 years after the 1982 Lebanon War. Results indicated that only 10% of the cases were truly examples of delayed PTSD; in a large proportion of the cases, help-seeking rather than onset was delayed.

Adult↗
PubMed1989

Mortality from neuroleptic malignant syndrome.

The authors assess the mortality from the neuroleptic malignant syndrome (NMS) based on an exhaustive review of 202 published case reports, including a differential assessment of risk factors and protective factors. The results indicate a significant (p less than .05) decrease in mortality since 1984 (11.6% vs. 25% before 1984), which occurs independently of the therapeutic use of dopamine agonists and dantrolene. A significantly (p less than .001) lower rate of mortality from haloperidol-induced NMS (7%) and a high rate of mortality (38.5%) among patients with organic brain syndrome were also found. Myoglobinemia and renal failure are strong predictors of mortality, representing a mortality risk of approximately 50%. The authors discuss the implications of these findings.

Adolescent↗
PubMed1989

Multiple exostosis, brain ventricular enlargement and schizophrenia.

Case histories of two family members with multiple exostosis and schizophrenia are presented. There are no previous reports of such an association. The computerized axial tomography scan revealed signs of hydrocephalus in one patient and substantial enlargement of lateral brain ventricles in the other. The mutual occurrence of all three clinical findings (multiple exostosis, ventricular brain enlargement and psychosis) in two family members may suggest a subgroup of patients who manifest schizophrenic symptomatology.

Adult↗
PubMed1989

Chlorprothixene-induced hypouricemia: a biologic indicator of drug compliance.

Chlorprothixene is a neuroleptic as well as a potent uricosuric drug that consistently lowers the levels of plasma uric acid (PUA). The usefulness of this relative hypouricemia as an indicator of compliance with treatment was evaluated in 17 outpatients treated from 120 to 600 days. Plasma uric acid values were substantially reduced in all patients with all doses within the therapeutic range. Low levels of PUA remained stable as long as the patients were treated and returned to normal within 7 days after treatment was terminated. The authors discuss the advantages and the limitations of PUA as an indicator of chlorprothixene treatment compliance.

Adult↗
PubMed1988

Audiological evaluation of nonalcoholic, drug-free posttraumatic stress disorder patients.

Auditory functions of 32 Israeli soldiers with posttraumatic stress disorder (PTSD) were evaluated and compared with those of 32 matched controls without PTSD. The evaluation included peripheral auditory functions, tolerance to noise, and central auditory informational functions. Tolerance of intense auditory stimuli by PTSD patients was similar to that of controls. Significant differences were found between left and right ear central auditory functions in a subgroup of 13 PTSD subjects, but neither in other PTSD patients nor in controls. These findings are discussed in the light of previous research concerning abnormal responses to auditory stimulus in PTSD, hemispheric disconnection, alexithymia, and psychosomatic disorders.

Adult↗
PubMed1988

Khat-induced hypnagogic hallucinations.

Khat is a plant whose leaves are chewed for their stimulating effect. This effect is attributed to cathinone, an alkaloid identical to dextroamphetamine. Khat chewing is widespread among eastern African and Yemenite populations and is believed to be innocuous. Our experience shows, however, that a substantial number of chronic khat chewers experience persistent hypnagogic hallucinations - a symptom that has not yet been described. Three vignettes illustrates this phenomena, which often interferes with psychiatric diagnosis. Different explanatory models are discussed, among them chronic suppression of REM sleep.

Adjustment Disorders↗