Search PubMed⌕ Search

Biomedical subjects

Y Barak

Publications and source records attributed to Y Barak.

At least 109 records · Page 6Linked to original sources
PubMed1995

A functional p53-responsive intronic promoter is contained within the human mdm2 gene.

The mdm2 gene is a target for transcriptional activation by the p53 tumor suppressor gene product. Previous work has revealed that the mouse mdm2 gene contains two promoters: one is located upstream to the gene and is active in the absence of p53, the other resides within the first intron and requires p53 for transcriptional activity. To determine whether this unique promoter activation pattern is biologically important, we investigated the structure and function of the corresponding region of the human mdm2 (hmdm2) gene. We report here that the hmdm2 gene also contains an intronic, p53-dependent promoter. The structural features of this promoter are highly conserved between mouse and man, as opposed to the lack of conservation of the first exon. This promoter is triggered in vivo in the presence of activated wild type p53, leading to the production of novel mRNA species. The intronic hmdm2 promoter contains two tandem p53 binding elements. Deletion analysis suggests that optimal promoter activity requires the simultaneous binding of p53 to both elements; this may serve to prevent premature triggering of the promoter by p53.

Animals↗
PubMed1995

Molecular basis of late infantile metachromatic leukodystrophy in the Habbanite Jews.

Late infantile metachromatic leukodystrophy (MLD) is a neurodegenerative disease, most commonly caused by the deficiency of the lysosomal enzyme arylsulfatase A (ARSA). Late infantile MLD is frequent (1/75 live birth) in a small Jewish community which lived in Habban, isolated from the other Jewish populations. The gene coding for ARSA was sequenced in one of the Habbanite patients, who was found to be homozygous for an allele having three mutations. Two mutations are A to G transitions in the ARSA gene at positions 1788 and 2723, causing the loss of an N-glycosylation site and a polyadenylation signal, respectively. These mutations are characteristics for the ARSA pseudodeficiency (PD) allele, which in homozygozity is associated with low enzymatic activity, but does not cause disease. The third mutation, which occurred on the background of the PD allele, is a C to T transition at position 2119, predicting a substitution of proline-377 by leucine (P377L). Biosynthesis studies performed with cells expressing the ARSA cDNA into which this mutation was introduced demonstrated a severely reduced half-life of the mutant enzyme. Five of 10 patients from the Habbanite community could be studied and were homozygous for the P377L allele. These observations confirm the genealogical data which pointed to a common ancestor for all the carriers of MLD among the Habbanite Jews. In addition, the same mutation was demonstrated to be relatively frequent among the Yemenite Jews. The origin and the means by which the mutation spread between the two communities remain unknown.

Alleles↗
PubMed1995

Maintaining schizophrenic patients on benzodiazepines.

The role of benzodiazepines (BZDs) in the treatment of schizophrenia is widely researched since the sixties. Nevertheless the role of BZD's as sole agents for the maintainance phase in pharmacotherapy of schizophrenic patients received little attention. We have conducted a retrospective review of all medical records of ambulatory schizophrenic patients in an out-patient setting receiving only BZD maintainance treatment. Three factors characterized these patients: long duration of illness, few hospitalizations and a relatively low dose response to BZD's.

Adult↗
PubMed1995

Ultrastructural changes in sperm with improved fertilizability after treatment with egg yolk.

OBJECTIVES: To determine the existence of differences in the ultrastructural parameters between the medium-washed sperm samples of the affected and nonaffected egg yolk (EY) groups and to verify whether ultrastructural changes occur in the EY-affected spermatozoa after EY preincubation. SETTING: The study was performed in the Laboratory of the IVF Unit, Serlin Maternity Hospital, and the Laboratory of Male Fertility, Bar-Ilan University, Ramat Gan, Israel. PATIENTS: The positive group included 12 males who underwent 1.9 IVF cycles with 0% fertilization rate that increased to 68% after EY treatment. The negative group included 11 males with 1.2% fertilization rate in 1.1 IVF cycles with no improvement after preincubation of spermatozoa in EY. RESULTS: Compared with the laboratory standard, patients of both groups exhibited a lower normalcy of the head sperm cell subcellular organelles. With EY treatment, the positive group exhibited a decrease in the frequency of some sperm head organelle specific malformations. CONCLUSIONS: Fertilization capacity of mature spermatozoa might be reduced because of an excess of acrosome malformations, postacrosomal lamina, and chromatin caused by in vitro sperm manipulations. The manipulation effect may be avoided by EY treatment.

Acrosome↗
PubMed1995

Transfer of six or more embryos improves success rates in patients with repeated in vitro fertilization failures.

OBJECTIVE: To examine the results of six or more embryos transferred to patients whose IVF-ET cycles repeatedly met with failure. DESIGN: Prospective clinical evaluation of pregnancy rates and pregnancy outcome. SETTING: IVF-ET Unit. PATIENTS: Seventy-two IVF patients who had failed at least four previous IVF cycles. INTERVENTIONS: Forty-one patients (group A) received six or more embryos, and 31 patients (group B) chose to receive five embryos. MAIN OUTCOME MEASURES: Per embryo implantation rate, pregnancy rate, multiple pregnancies, and outcome were evaluated. RESULTS: With the transfer of six or more embryos, the pregnancy rate was significantly higher than with the transfer of five embryos (56% versus 29%, respectively). This was associated with a slight, but insignificant, increase in multiple gestations. No difference in pregnancy outcome was noted among the groups. CONCLUSIONS: Patients who have had repeated IVF failures may have higher pregnancy rates if six or more embryos are transferred in subsequent cycles.

Adult↗
PubMed1995

Resting energy expenditure in patients with thalassemia major.

The effect of non-iron-deficiency anemia was studied in seven patients with thalassemia major (beta thalassemia) ages 22-30 y. Each patient was studied before and 3 days after blood transfusion. Hemoglobin concentrations increased significantly after blood transfusion (111-153 vs 81-102 g/L, P < 0.02). Heart rate decreased from 96 +/- 12 to 81 +/- 7 beats/min (mean +/- SD; P < 0.05). No significant difference was found in venous blood pH, bicarbonate concentrations, or lactic acid concentrations before and after blood transfusion. Resting energy expenditure (REE) was greater before blood transfusion in absolute numbers and as a percentage of the predicted value, and returned to normal range thereafter (6138 +/- 112 vs 5678 +/- 738 kJ.kg-1.d-1 and 111.7 +/- 11.3% vs 103.2 +/- 7.8%, respectively). Protein contribution to REE was low before blood transfusion (9.7 +/- 4.2%) and returned to normal range thereafter (15.3 +/- 5.2%) (P < 0.09). This finding may indicate that increased protein turnover as well as increased cardiac work contribute to the observed increase in REE.

Adult↗
PubMed1995

Pyoderma gangrenosum and sterile multifocal osteomyelitis preceding the appearance of Takayasu arteritis.

A 9-month-old infant had pyoderma gangrenosum (PG) and sterile osteomyelitis. Three years later the patient developed Takayasu arteritis (TA). Sterile osteomyelitis was reported in approximately 30 patients with different skin lesions, but never together with pyoderma gangrenosum. The association of PG and TA has been reported rarely, and then mainly in adults or in children over age 9 years. This rare association should alert physicians with a case of infantile PG of unknown etiology to consider the possible diagnosis of TA.

Dose-Response Relationship, Drug↗
PubMed1995

Double-blind, controlled trial of inositol treatment of depression.

OBJECTIVE: CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial. METHOD: Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks. RESULTS: The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function. CONCLUSIONS: This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.

Adult↗
PubMed1995

Season of birth and autistic disorder in Israel.

OBJECTIVE: Variations in month of birth were examined in patients with infantile autism to test the hypothesis that birth in a particular month may be a risk factor for this disorder. METHOD: Data for autistic patients registered with the National League for Autism in Israel (N = 188) during the years 1964-1986 were compared with data on monthly distribution of live births in Israel for the corresponding period. RESULTS: After risk ratio estimates were computed for children born with infantile autism for each month, a significant increase was observed for children born in March and August. This association was true for each year throughout the study. An additional finding was a significantly higher rate of birth of autistic children in the years 1970-1976. CONCLUSIONS: This study, although made in a different climatic area than three earlier studies, further emphasizes the earlier findings that March and August births are a risk factor for development of autistic disorder.

Autistic Disorder↗
PubMed1995

Changes in interleukin-1 beta and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients.

Some evidence points towards a possible autoimmune role in the aetiology of schizophrenia. Experimental findings provide contradictory results regarding abnormalities in cytokine production in this disorder. In the present study we tested the production of cytokines in CSF and serum in 16 schizophrenic patients and 10 healthy controls (tumor necrosis factor alpha - TNF alpha; interleukins IL-1 beta, IL-2, IL-6, soluble IL-2 receptor). Cytokine levels were evaluated by radioactively-labeled antibodies (IL-1 beta, IL-2, IL-6), by enzyme-linked immunoassay (TNF) and by a sandwich enzyme immunoassay (soluble IL-2 receptor). No significant differences were found in either CSF fluid or serum levels of TNF and IL-2 or IL-6. Interleukin-1 beta was significantly decreased in patients' CSF and serum as compared to controls. Soluble interleukin-2 receptor levels were decreased in CSF of patients, but highly increased in their serum in comparison with controls. Changes in various cytokine levels in CSF fluid and serum of schizophrenic patients probably reflect interrelated process of growth, degeneration or neuroimmunological abnormalities, which may all play a role in the pathophysiology of schizophrenia. The present study supports evidence for change in immune activation, probably of peripheral origin, in schizophrenic patients.

Adult↗
PubMed1995

Disabling compulsions in 11 mentally retarded adults: an open trial of clomipramine SR.

BACKGROUND: Clinicians and researchers who work with mentally retarded subjects have reported on the frequent exhibition of mental disorders and behavioral problems in this population. Rituals are often among the disturbances described. We decided to treat disabling cleaning and collecting compulsions in mentally retarded adults with clomipramine 75 mg/day, sustained release (SR) preparation. METHOD: The 8-week trial included 11 subjects, mean age of 24.1 years (range, 21-27) with a mean +/- SD I.Q. of 65.0 +/- 11.0. The majority of subjects (N = 9) were occupied with washing rituals that took hours to complete. Subjects were started on a schedule of 32.5 mg of clomipramine SR once daily for 1 week, then received 75 mg SR once daily for an additional 7 weeks. RESULTS: Improvement was assessed by using the National Institute of Mental Health Global Obsessive Compulsive Scale and the Global Improvement score of the Yale-Brown Obsessive Compulsive Scale. Statistically significant reduction in severity of rituals (p < .05) was found at the trial's completion. CONCLUSION: Once-daily clomipramine SR 75 mg is effective in treating adults with mental retardation and disabling rituals.

Adult↗
PubMed1995

Follow-up and relapse analysis of an inositol study of depression.

A recent controlled double-blind study of 28 patients treated with 12 gm daily of inositol or placebo revealed significant antidepressant effect for this second messenger precursor. Patients were followed-up by interview and Hamilton Depression Scale 10-12 months after the end of the study. Half of the patients who had responded well to inositol relapsed rapidly after inositol discontinuation whereas none of those who responded to placebo relapsed rapidly after placebo cessation. Klein suggested that true drug responders to tricyclic antidepressants respond slowly and gradually whereas placebo responders improve early in an abrupt fashion. However, in the recent study both inositol and placebo responders improved at similar rates. Hamilton Depression Scale Scores 10-12 months after completion of the study were not significantly different between those who had responded and those who had not responded to inositol or to placebo.

Adult↗
PubMed1995

Fluoxetine induced weight loss: a pilot study in postpartum women.

Twelve women who developed an average postpartum weight gain of 18.3kgs (SD +/- 6.09) entered an open trial, for three months, of fluoxetine 20 mg daily. The weight gain during their pregnancies was nearly twice that recommended by the treating gynecologists. Seventy-five percent success rate was achieved -8/12 were +/- 5% of their pre-pregnancy weights upon completion of the trial. Mean weight upon entering the trial was 82.25kgs (SD +/- 13.39), and at termination, 65.75kgs (SD +/- 8.59), P < 0.001. Anorexia and weight loss (more than 5% of body weight) have been reported in the literature in 9% and 13%, respectively, of depressed patients treated with fluoxetine. The use of this drug to promote weight loss is here reported in a selected population of women without signs or symptoms of depression, whose weight gain during pregnancy was excessive.

Adult↗
PubMed1995

Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous leukemia. World statistical analysis.

BACKGROUND AND DESIGN: The concurrent finding of neurofibromatosis type 1 (NF), juvenile chronic myelogenous leukemia (JCML), and juvenile xanthogranuloma (JXG) has been repeatedly reported. Juvenile chronic myelogenous leukemia has been found more frequently in patients with NF and may present with various cutaneous manifestations, including JXG. To our knowledge, the relationship among these three entities has never been explored. The purpose of the present study is to explore this relationship by using a systematic review of the literature. We present five demonstrative cases of various associations among NF, JCML, and JXG. RESULTS: A family history of NF was found in 85% to 95% of children with NF and JCML (with or without JXG), as compared with that found in 47% of children with NF and JXG. The observed frequency of the triple association is 30-fold to 40-fold higher than that expected. It is estimated that children with NF and JXG have a 20-fold to 32-fold higher risk for JCML than do patients with NF who do not have JXG. CONCLUSIONS: A concomitant finding of JCML and JXG in children with NF represents a true association, rather than a coincidence. A finding of JXG in an infant with NF should alert a physician to a possible development of JCML.

Child, Preschool↗
PubMed1995

MELAS syndrome: peripheral neuropathy and cytochrome C-oxidase deficiency: a case report and review of the literature.

A 4-year-old boy presented with developmental delay, aggressive behavior, and incoordination. His EEG showed a diffuse encephalopathy. At age 10 he developed convulsions and severe migraine-like headaches. Muscle wasting, arreflexia, and lactic acidemia following exercise were noted. Electromyography was myopathic and nerve conduction studies revealed a peripheral neuropathy. Muscle biopsy demonstrated variation in fiber size and an excess of lipid droplets. He than had several stroke-like episodes and periods of unconsciousness, associated with severe metabolic acidosis. Muscle cytochrome C oxidase was abnormally low. This boy displayed the classical clinical and biochemical features of MELAS syndrome, namely Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes. Treatment included carnitine, vitamin C, vitamin K, riboflavin, coenzyme Q10, and corticosteroids. He died at the age of 14 years following an episode of seizures, coma, and gastrointestinal hemorrhage. This is the first reported case of MELAS syndrome in Israel.

Child, Preschool↗
PubMed1994

Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential.

The mdm2 proto-oncogene product binds to the p53 tumor suppressor protein and inhibits its ability to trans-activate target genes. One such target gene is mdm2 itself, which is therefore considered a component of a p53 negative feedback loop. Two tandem p53-binding motifs residing within the first intron of the murine mdm2 gene confer upon it p53-mediated activation. We now report that in murine cells p53 activates an internal mdm2 promoter (P2) located near the 3' end of intron 1, resulting in mRNA whose transcription starts within exon 2. P2 is activated by p53 within artificial constructs, as well as within the context of the chromosomal mdm2 gene. Activation follows either the introduction of overexpressed wild-type p53 into cells or the induction of endogenous wild-type p53 by ionizing radiation. The upstream, constitutive (P1) mdm2 promoter is only mildly affected by p53, if at all. The p53-derived mdm2 transcripts lack exon 1 and a few nucleotides from exon 2. As the first in-frame AUG of mdm2 is located within exon 3, the two types of mdm2 transcripts should possess similar coding potentials. Nevertheless, in vitro conditions, where each of these transcripts yields a distinct translation profile, reflect the differential usage of translation initiation codons. Initiation of translation at internal AUG codons, which occurs also in vivo, gives rise to MDM2 polypeptides incapable of binding to p53. In vitro translation profiles of the various mdm2 transcripts could be manipulated by changing the amounts of input RNA. Thus, p53 can modulate both the amount and the nature of MDM2 polypeptides through activation of the internal P2 promoter.

3T3 Cells↗
PubMed1994

[Interferon for hemangiomas of infancy].

Hemangioma, the most common tumor of infancy, is usually harmless. It frequently appears soon after birth, proliferates for 8-18 months, and then slowly regresses over the next 5-8 years, leaving the skin normal or only slightly blemished. However, hemangiomas sometimes cause devastating tissue damage and may be associated with thrombocytopenia and life-threatening hazards. About a third of these cases respond to corticosteroid therapy, but often with rapid rebound following its discontinuation. Successful treatment of large and life-threatening hemangiomas with interferon alpha-2a has recently been reported. We found it effective in a 3.5-month-old male with a large symptomatic hemangioma. After 6 months of daily interferon alpha-2a (Referon, Hoffman-LaRoche), 3 million units/m2/day, all symptoms disappeared and the lesion was halved in size. There were no significant side-effects. This treatment is effective and safe and should be considered in infants with large, symptomatic hemangiomas.

Head and Neck Neoplasms↗