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Biomedical subjects

Y Barak

Publications and source records attributed to Y Barak.

At least 91 records · Page 5Linked to original sources
PubMed1996

Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes.

The human erythropoietin receptor (EpoR) gene has been cloned and characterized. Very few EpoR genetic abnormalities have been reported so far. Polycythemia vera (PV) is characterized by low/normal serum erythropoietin (Epo) levels with proposed Epo hypersensitivity. Myelodysplastic syndromes (MDS) are characterized by refractory anemia with variable serum Epo levels. Several reports have suggested EpoR abnormalities in both types of stem cell disorders. We analyzed DNA obtained from peripheral blood mononuclear cells of seven healthy controls, 20 patients with myeloproliferative disorders (MPD, 11 patients with PV, five agnogenic myeloid metaplasia with myelofibrosis, four essential thrombocytosis) and eight patients with refractory anemia with ringed sideroblasts (RARS), an MDS variant. The DNA was digested with four restriction enzymes (BamHI, Bgl II, Sacl and HindIII), followed by Southern blot, using a 32P radiolabeled probe, containing 1.5 kb of the human EpoR cDNA. All 20 MPD patients and seven out of the eight MDS patients demonstrated a restriction pattern which was identical to the seven normal controls, as well as to the erythroid cell line K562, and also consistent with the expected restriction map, for all four enzymes tested. One RARS patient had a normal pattern with three enzymes but a different one with HindIII. The HindIII 12 kb large band was replaced by a faint 12 kb band and a new (about 9 kb) band appeared. The EpoR restriction map and the normal pattern obtained with the other three enzymes suggest that this patient has a 3 kb upstream deletion in one allelic EpoR gene. The same molecular pattern was detected in the patient's sister, who suffers from anemia with mild bone marrow (BM) dyserythropoiesis and plasmacytosis. Northern blot analysis showed that the patient's BM RNA carried normal EpoR message. This familial pattern may represent polymorphism. However, the patient's very high serum Epo level, her resistance to treatment with recombinant Epo, and the abnormally low growth rate of in vitro erythroid cultures, suggesting poor response to Epo in this MDS patient as well as the hematological abnormalities in her sister, support the speculation that the different EpoR gene might serve as a genetic predisposing marker and potentially could be involved (probably via post-transcriptional mechanisms and by an interaction with other factors or cytokines) in the pathogenesis. Our data suggest that the EpoR is intact in MPD and in most patients with RARS. One RARS patient had a familial different genetic structure, which could represent polymorphism. However, we can speculate also that it might be involved in the pathogenesis of the disease.

Aged↗
PubMed1996

Inositol treatment of Alzheimer's disease: a double blind, cross-over placebo controlled trial.

1. A double-blind controlled crossover trial of 6 gm of inositol daily vs glucose for one month each was carried out in 11 Alzheimer patients. 2. Overall CAMCOG scores showed a trend for greater improvement with inositol that was not significant. 3. Language and orientation improved significantly more on inositol than on placebo. There were no serious side effects. 4. Higher doses of inositol should be studied in Alzheimer's Disease for longer periods.

Aged↗
PubMed1996

Is the heart a source for elevated circulating endothelin levels during aorta-coronary artery bypass grafting surgery in human beings?

Reports have shown increased systemic levels of endothelins during coronary artery bypass grafting in human beings. It was not known whether increased endothelin levels during coronary artery bypass grafting reflect a general systemic response to the surgical procedure or increased myocardial production of endothelins in response to ischemia and reperfusion. We therefore measured endothelin levels in the right atrium and proximal aorta of 15 patients undergoing coronary artery bypass grafting for anginal syndrome immediately before aortic crossclamping and again after cessation of cardiopulmonary bypass. In five patients, we also measured coronary sinus levels of endothelins during cardiopulmonary bypass circulation. We found that endothelin levels were elevated throughout the surgical procedure. Right atrial endothelin levels were significantly elevated after cessation of cardiopulmonary bypass circulation with respect to values immediately before aortic crossclamping (11.1 +/- 3.1 vs 14.2 +/- 3.7 pg/ml, p = 0.008), whereas endothelin levels in the proximal aorta did not rise significantly (10.5 +/- 2.3 vs 11.6 +/- 2.4 pg/ml, p > 0.5). Coronary sinus endothelin levels tended to decline temporarily during cardiopulmonary bypass circulation (11.1 +/- 2.1 pg/ml before aortic crossclamping, 7.9 +/- 1.9 1 minute after release of aortic crossclamp, and 9.9 +/- 2.1 pg/ml after release of partial aortic crossclamping, p = 0.06). We conclude that the rise in right atrial endothelin levels during coronary artery bypass grafting reflects systemic production and secretion of endothelins, probably by vasculature or organs distal to the proximal aorta, and is not the result of increased myocardial production and secretion of endothelins.

Aged↗
PubMed1996

An outbreak of antibiotic multiresistant Klebsiella at the Neonatal Intensive Care Unit, Kaplan Hospital, Rehovot, Israel, November 1991 to April 1992.

From November 1991 through April 1992, 8 infants developed systemic infections due to antibiotic multiple resistant Klebsiellaa (MRK). All were premature and 6 of the 8 weighed less than 1100 g; 7 of the 8 had received previous antibiotic therapy. Five infections occurred during the first week of life. MRK were isolated from blood (8 cases), tracheal secretions (TS-6), stool (3), and CSF (1). All Klebsiella blood isolates were resistant to ampicillin, mezlocillin, and cefotaxime, 7 of 8 to ceftazidime and amikacin, and 4 of 7 to aztreonam; all isolates were sensitive to quinolones and imipenem. Four infants died. In all 4 of the isolates, they were sensitive only to quinolones and imipenem, and the empiric therapy used for suspected sepsis proved to be inappropriate. The outbreak was terminated by temporary closure of NICU in May 1992. Strict hand washing practices were reemphasized, and the previous empiric antibiotic protocol used for suspected sepsis (mezlocillin plus amikacin, and lately ceftazidime plus amikacin) was changed to imipenem and amikacin in the risk population. At closure, 5 additional infants had MRK in stools and/or tracheal suction specimens. Development of MRK organisms should dictate a rational use of empiric antibiotics for neonatal infections in NICU.

Anti-Bacterial Agents↗
PubMed1996

The effect of chlorpromazine and haloperidol on DNA transcription.

The ability of human cells to repair DNA damage can be indirectly assessed by measuring transcriptional activity relating to active genes, a process referred to as RNA synthesis. This study was carried out to investigate the effects of chlorpromazine and haloperidol on the transcriptional activity of actively transcribed genes as an expression of DNA damage and repair. Three cultured human fibroblast lines were used: two were "normal" in previous RNA recovery testings and one was abnormally sensitive to UV irradiation. In the "normal" line, recovery of RNA synthesis occurred within 1 hour of UV after exposure to three concentrations of chlorpromazine (125, 250 and 500 ng/ml) and haloperidol (5, 10 and 20 ng/ml). Following treatment with the same concentrations of chlorpromazine and haloperidol, the UV-sensitive cell line showed markedly depressed recovery of RNA synthesis at 1 and 4 hours. Complete recovery was not reached even after 24 hours. Our results suggest that neuroleptics widely used in clinical practice adversely affect cell lines that are sensitive to DNA-damaging agents.

Antipsychotic Agents↗
PubMed1996

Influence of Volatile Fatty Acids on Nitrite Accumulation by a Pseudomonas stutzeri Strain Isolated from a Denitrifying Fluidized Bed Reactor.

Intermediate nitrite accumulation during denitrification by Pseudomonas stutzeri isolated from a denitrifying fluidized bed reactor was examined in the presence of different volatile fatty acids. Nitrite accumulated when acetate or propionate served as the carbon and electron source but did not accumulate in the presence of butyrate, valerate, or caproate. Nitrite accumulation in the presence of acetate was caused by differences in the rates of nitrate and nitrite reduction and, in addition, by competition between nitrate and nitrite reduction pathways for electrons. Incubation of the cells with butyrate resulted in a slower nitrate reduction rate and a faster nitrite reduction rate than incubation with acetate. Whereas nitrate inhibited the nitrite reduction rate in the presence of acetate, no such inhibition was found in butyrate-supplemented cells. Cytochromes b and c were found to mediate electron transport during nitrate reduction by the cells. Cytochrome c was reduced via a different pathway when nitrite-reducing cells were incubated with acetate than when they were incubated with butyrate. Furthermore, addition of antimycin A to nitrite-reducing cells resulted in partial inhibition of electron transport to cytochrome c in acetate-supplemented cells but not in butyrate-supplemented cells. On the basis of these findings, we propose that differences in intermediate nitrite accumulation are caused by differences in electron flow to nitrate and nitrite reductases during oxidation of either acetate or butyrate.

Journal Article↗
PubMed1996

Brainstem auditory evoked potentials of panic disorder patients.

Panic attacks are subjectively reported by patients as a cluster of autonomic nervous symptoms. Taken together with the evidence from pharmacological studies focusing on the locus ceruleus and the dorsal raphe nuclei, the hypothesis of brainstem involvement in panic attacks is of major interest. Functional evaluation of the brainstem is carried out using electrophysiological recordings, such as the brainstem evoked potentials. We have investigated the pathophysiology of these parameters in 16 patients fulfilling the DSM III-R criteria for panic disorder (8 females and 8 males) in comparison to a group of 10 normal controls. The patients were found to have two electrophysiological variables significantly different from controls: (a) N3 latency tme was reduced (p < 0.05) and (b) the N3-5 interval was prolonged (p < 0.05). The N3 latency period significantly correlated with the Hamilton Anxiety Scale scores (p < 0.005). N3 is a peak reflecting pontine activation, where the locus ceruleus is located. The N3-5 interval reflects evoked potential passage from the pons to the midbrain. In conclusion, our results support previous studies indicating a dysfunction of the locus ceruleus possibly causing disruption of pons-midbrain transmission in patients suffering from panic disorder.

Adult↗
PubMed1996

Defective in vitro granulopoiesis in patients with anorexia nervosa.

Patients with anorexia nervosa (AN) frequently suffer from a mild degree of anemia and from moderate leukopenia on top of their undernourished state and metabolic disarrangements. To evaluate in vitro granulopoiesis and its relationship to cytokine production and undernutrition, we have studied 10 adolescent girls with moderate AN (age range, 13.5-18.0). Study methods included assessment of peripheral blood (PB) granulocyte-macrophage colony-forming cells (GM-CFC) of the patients and age-matched controls, and determination of plasma and conditioned medium (CM) of mononuclear cells levels of IL-1, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF), all of which may play a role in GM-CFC growth regulation. GM-CFC numbers were significantly lower in AN patients compared with the normal controls (13.09 +/- 11.15 versus 39.33 +/- 26.61 colonies/5 x 10(5) cells, p < 0.01). No inhibitory effect was found in either plasma or CM of patients with AN. However, when CM were applied to non-recombinant human GM-CSF-stimulated normal bone marrow GM-CFC targets, the number of colonies stimulated by the CM of patients with AN was significantly lower than those stimulated by the CM of the controls (73.5 +/- 20.1 versus 113.0 +/- 11.6, p < 0.025). GM-CSF concentrations in CM were significantly lower in patients with AN compared with normal controls, but no such differences were found in IL-1, IL-3, IL-6, or TNF concentrations. These results indicate defective in vitro granulopoiesis in AN patients, manifested by a reduction of both GM-CFC and GM-CSF. It has to be determined whether these changes are the result of the basic disease process or are they due to malnutrition.

Adolescent↗
PubMed1996

Sweet syndrome associated with G-CSF treatment in a child with glycogen storage disease type Ib.

Acute febrile neutrophilic dermatosis (Sweet syndrome) is rare in children and is regularly associated with underlying malignancies or inflammtory diseases. A 5-year-old girl with glycogen storage disease type Ib, neutropenia, and recurrent infections developed characteristic skin eruption of Sweet syndrome after 2 years of granulocyte colony-stimulating factor (G-CSF) therapy. This association points to a possible role of G-CSF-induced granulopoiesis and granulodyte activation in the pathogenesis of Sweet syndrome.

Biopsy↗
PubMed1996

Intravenous immune globulin in multiple sclerosis: clinical and neuroradiological results and implications for possible mechanisms of action.

Extensive evidence exists indicating that immunoregulatory mechanisms are involved in the pathogenesis of Multiple Sclerosis (MS). Several possible mechanisms by which intravenous immune globulin (IVIG) modulates the course of the disease are related to limiting the inflammatory process and repairing the damage by enhancing remyelination. Presently, the evidence for the effect of IVIG in MS is based on the results of small open trials, some of which have been encouraging. In the current study, the positive impact of IVIG treatment on arresting disease progression was evident by decreased brain Magnetic Resonance Imaging (MRI) scores of the lesion area. In an effort to extend these findings, the authors initiated a multicentre, prospective, randomized, double-blind, placebo-controlled study. The trial was designed to compare the efficacy of IVIG treatment with placebo in relapsing-remitting patients (ages 20-55 years) with definite MS, disease duration of 2-10 years and frequency of exacerbations 1-3/year during the 2 years prior to the study. Patients were examined monthly and brain MRI studies scheduled at entry, and after the first and second years of the trial. The primary endpoints included the number of acute exacerbations and neurological disability. The secondary endpoints included change in the MRI lesion burden, evaluated by the number and area of lesions. The trial ended in June 1995.

Adult↗
PubMed1996

Circannual pattern of autistic births: reanalysis in three ethnic groups.

Seasonal variations in births of autistic subjects have been reported for the United States, Canada, Sweden, Japan, and Israel. Here, data from England, Japan, and Israel are reanalyzed using spectral analysis for the cosine function. A sample of 583 autistic births occurring over 40 years (1947-1989) is meta-analyzed, focusing on rhythmicity. Major periodicities of 17.6, 18.6, and 21.8 years, on which minor periodicities ranging from 2.2 to 4.1 years were superimposed, yielded the best-fitting cosine function to significantly explain variance of autistic birth patterns. It is interesting that the function composed of a major period with several minor periods is remarkably similar in each of the three ethnic groups. In all three countries the acrophases (calculated function) aggregate in the period 1963-1970. In light of this apparent universality of rhythms in autistic births across continents, we call for further investigations into the role of environmental factors, possibly viral pandemics, in the etiology of autism.

Autistic Disorder↗
PubMed1996

Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates.

The purpose of this study was to examine the sexual complaints and severity of sexual dysfunction in relapsing-remitting multiple sclerosis patients and to correlate them with psychological, neurological, and radiological variables. Frequency and characteristics of sexual disturbances were reported by 41 multiple sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical neurologic variables tested were disease duration, exacerbation rate, and disability; psychological variables tested were anxiety and depression. All patients underwent a brain magnetic resonance imaging (MRI) scan at the time of this study. The sexual dysfunction questionnaire included items based on the 3 phases of human sexual response: loss of libido, excitement (arousal difficulties, impotence, premature ejaculation), and anorgasmia. Five males (55.5%) and 16 females (50.0%) reported at least 1 sexual disturbance. The most frequent dysfunctions were loss of libido (26.8%) and arousal difficulties (19.5%). Females rated their difficulties as more severe. Sexual dysfunctions correlated with depression, (r = 0.68, P = 0.001). No correlation between MRI score and depression was found. Anorgasmia correlated with brain stem and pyramidal abnormalities (r = 0.56, P = 0.011; r = 0.56, P = 0.012, respectively). The total area of lesions (plaques) on the brain MRI scan also correlated with anorgasmia (r = 0.41, P = 0.02). Sexual dysfunctions in multiple sclerosis patients are frequent, are mild to moderate in severity, correlate with depression and in some cases central nervous system (CNS) demyelinating process, and thus may be related either to the psychological impact of this disease or to specific organic lesions in the brain.

Adult↗
PubMed1995

Deamination of cytosine-containing pyrimidine photodimers in UV-irradiated DNA. Significance for UV light mutagenesis.

The realization that cytosine in cyclobutyl pyrimidine dimers rapidly deaminates to uracil raised the possibility that this chemical transformation, rather than an enzymatic polymerase error, is the major mutagenic step in UV mutagenesis. We have established a sensitive bioassay system that enabled us to determine the rate of deamination of cytosine in cyclobutyl pyrimidine dimers in plasmid DNA. This was done by in vitro UV irradiation and deamination of a plasmid carrying the cro gene, followed by photoreactivation, and assaying uracils in DNA by their ability to cause Cro- mutations in an indicator strain that was deficient in uracil DNA N-glycosylase. DNA sequence analysis revealed that 27 out of 29 Cro- mutants carried GC --> AT transitions, as expected from deamination of cytosine. Deamination of cytosines in the cro gene in UV-irradiated plasmid pOC2 proceeded at 37 degrees C with first-order kinetics, at a rate of (3.9 +/- 0.6) x 10(-5) s-1, corresponding to a half-life of 5 h. Physiological salt conditions increased the half-life to 12 h, whereas decreasing the pH increased deamination. The temperature dependence of the rate constant yielded an activation energy of 13.6 +/- 3.3 kcal/mol. These kinetics data suggest that deamination of cytosine-containing dimers is too slow to play an important role in UV mutagenesis in Escherichia coli. However, it is likely to play an important role in mammalian cells, where the mutagenic process is slower.

Base Composition↗
PubMed1995

Intracranial meningiomas: correlation of peritumoral edema and psychiatric disturbances.

Patients with proven intracranial meningioma were reexamined for psychiatric morbidity. Distribution according to type of meningioma was as follows: 72% convexity meningiomas and 28% base-of-skull meningiomas. No psychiatric disorders were diagnosed in the nonconvexity group in contrast to 44% in the convexity meningiomas. Among the convexity meningiomas, no difference between right- and left-hemispheric locations was found. Psychiatric comorbidity in the right-hemisphere group was found only in patients with frontal lobe meningiomas. Edema width was measured on all computed tomographic scan slices on which it appeared, and the average of all the slices was calculated. No correlation was found between neurological symptoms and edema severity. A statistically significant correlation was found between edema volume and the presence of coexisting psychiatric disorders, but not between the tumor's mass volume and the psychiatric symptoms.

Adult↗