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Biomedical subjects

Y Barak

Publications and source records attributed to Y Barak.

At least 127 records · Page 7Linked to original sources

Ro 5-4864 has a negative inotropic effect on human atrial muscle strips that is not antagonized by PK 11195.

The effects of Ro 5-4864, a peripheral benzodiazepine receptor agonist (9 x 10(-6) M and 9 x 10(-5) M) and of PK 11195, a peripheral benzodiazepine receptor antagonist (3 x 10(-6) M and 3 x 10(-5) M), alone or together, on contraction parameters of human atrial muscle strips were studied. Atrial muscle strips were obtained from patients undergoing cardiac surgery. The strips were suspended in Krebs-Henseleit solution at 36.8 +/- 0.2 degrees C, connected to an isometric force transducer and then stimulated at 15 V above threshold and paced at 1.5 Hz. Ro 5-4864 at its higher concentration, alone or mixed with PK 11195 at both concentrations, depressed the contraction amplitude to 80% of the control value (P < 0.05). In conclusion, Ro 5-4864 had a small but significant depressant effect on the contraction amplitude of human atrial strips. Surprisingly, this effect was not reversed by the peripheral benzodiazepine receptor antagonist PK 11195.

Adult↗

Use of lasers in assisted fertilization and hatching.

The erbium-yttrium-aluminium-garnet (Er:YAG) laser has been applied to micromanipulation in humans. It was used in the fertilization process for both subzonal insemination (SUZI) and for partial zona dissection (PZD). Laser-assisted micromanipulation achieved significantly higher fertilization rates (34.8%) when compared to mechanical SUZI (16.1%), but use of the laser did not improve the PZD results (laser 14.8% versus mechanical 14%). The Er:YAG laser was used to assist hatching. In the mouse it significantly improved the hatching rate (80 versus 29.3%) 110 h after administration of human chorionic gonadotrophin. This technique was applied in two different centres to patients with previous in vitro fertilization (IVF) failures. the implantation rate per embryo (14.4% laser-assisted hatching versus 6% control group) and the pregnancy rate per transfer (40 versus 16.2%) were improved.

Adult↗

Tourette's disorder.

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Diagnosis, Differential↗

Body esteem in Israeli university students.

Body-esteem is an important dimension in the general concept of body-image. The Body Esteem Scale (BES) was developed and tested in the USA. We tested young men and women in Israel all of whom were university students after their army service. Our results show that Israeli men score lower (feel more negative) on the virility reflecting subscale while Israeli women score higher (feel more positive) in the weight concern subscale--compared to their American counterparts. We discuss the possible explanations of this difference, focusing mainly on the impact of army discharge and the move to the academic field.

Adolescent↗

[Assisted hatching and micro-fertilization].

Erbium-YAG laser has been applied for micromanipulation in human beings. In a first series of attempts it was used in the fertilization process for subzonal insemination (SUZI): laser assisted micromanipulation achieved significant higher fertilization rates (34.8%) when compared to mechanical SUZI (16.1%), and for partial zona dissection (PZD): in this case laser did not improve the results (laser 14.8% vs mechanical 14%). Erbium-YAG laser was used to assist hatching. In the mouse it significantly improved the hatching rate (80% vs 29.3%) 110 hours post hCG. This technique was applied in two different centres to patients with previous IVF failures. The implantation rate per embryo (14.4% laser assisted hatching vs 6% control group) and the pregnancy rate per transfer (40% vs 16.2%) were improved.

Animals↗

Differential responses of fetal, neonatal, and adult myelopoietic progenitors to interferon and tumor necrosis factor.

Human fetal liver (FL) and neonatal cord blood (CB) granulocyte-monocyte colony-forming progenitor cells (GM-CFC) are unique in their physiological environment and in certain proliferative and differentiative capacities. Tumor necrosis factor (TNF) and interferon (IFN) may inhibit or stimulate the growth of human bone marrow GM-CFC in vitro. The effects of recombinant human (rh) TNF-alpha, rhIFN-alpha, and rhIFN-tau on recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)-stimulated clonogenic cultures of day 7 GM-CFC from FL and umbilical CB were compared with rhGM-CSF-stimulated GM-CFC from normal human bone marrow (BM). We demonstrate that, in comparison to BM progenitor cells, GM-CFC from both FL and CB were highly resistant to growth inhibition by all three cytokines. Furthermore, clonogenic growth of progenitors from FL and CB was markedly potentiated by IFN-tau in GM-CSF-stimulated cultures and was stimulated by IFN-tau in the absence of GM-CSF. Depletion of potential accessory cells resulted in a marked stimulatory response of CB cells to TNF-alpha, in the presence of GM-CSF, while it did not alter the responses to IFN. The stimulatory effects of IFN-tau and TNF-alpha may be indirectly mediated, at least in part, through induction of increased GM-CSF production and increased GM-CSF receptor expression by fetal cells. Divergent responses of myelopoietic cells, derived from various hematopoietic compartments, to regulatory actions of cytokines may provide a basis for further understanding the role of the environment in maturation and differentiation of granulocytes and monocytes.

Adult↗

mdm2 expression is induced by wild type p53 activity.

We have recently characterized a 95 kDa protein, p95, which exhibits enhanced binding to temperature-sensitive p53 (ts-p53) when cells are shifted down to 32.5 degrees C, a temperature at which ts-p53 possesses wild-type (wt)-like activities. In the present study we show that p95 is a product of the mdm2 putative proto-oncogene. The enhanced complex formation of mdm2 with ts-p53 in cells maintained at 32.5 degrees C is due to an elevation in total mdm2 protein levels following the temperature shift. We further demonstrate that the induction of mdm2 expression by t p53 activity is at the mRNA level. The induction occurs with very rapid kinetics and does not require de novo protein synthesis, suggesting a direct involvement of p53 in the process. Based on these data and on recent findings implicating p53 as a transcription factor, we suggest that the mdm2 gene is a target for activation by wt p53. In view of the ability of mdm2 to act as a specific antagonist of p53 activity, this induction process may serve to tightly autoregulate p53 activity in living cells.

Animals↗

Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53 - MDM2 complexes.

An immune selection procedure was employed in order to isolate p53 binding sites from mouse genomic DNA. Two DNA clones capable of tight specific interaction with wild type p53 were subjected to further characterization. In both cases, the p53 binding regions displayed a high degree of sequence homology with the consensus binding site defined for human genomic DNA. One of the clones was found to be derived from the LTR of a retrovirus-like element (a member of the GLN family). The region encompassing the GLN LTR p53 binding site could confer p53 responsiveness upon a heterologous promoter. Furthermore, the expression of the endogenous, chromosomally integrated GLN elements was significantly induced upon activation of wild type p53 in cells harboring a temperature sensitive p53 mutant. Finally, it was demonstrated that p53 - MDM2 complexes fail to bind tightly to such a p53 binding site. This may contribute to the inhibition by MDM2 of p53-mediated transcriptional activation.

Animals↗

Congenital juvenile chronic myelogenous leukemia: therapeutic trial with interferon alpha-2.

A newborn with congenital juvenile chronic myelogenous leukemia (JCML) is described. The diagnosis was suggested by the characteristic clinical and hematologic presentation, and was confirmed by the results of in-vitro cultures of the hematopoietic progenitors, which showed excessive proliferation of monocytic colonies, with and without the addition of exogenous granulocyte-macrophage colony stimulating factor (GM-CSF). Based on published in-vitro response of JCML cells to alpha interferon-2 (alpha IFN 2), we treated this child for 17 weeks with subcutaneous alpha interferon, 1,000,000 units per day. In contrast to previous in vitro results, treatment of this patient affected neither the clinical course of the disease, nor the in vitro growth of the peripheral blood-derived monocytic colonies.

Colony-Forming Units Assay↗

Increased anti-Sm antibodies in schizophrenic patients and their families.

1. Autoantibodies in the Sm complex have become a useful serologic aid in the diagnosis of systemic lupus erythematosus (SLE) and have rarely been observed in other diseases. 2. A subset of SLE patients have a variety of psychiatric abnormalities, including schizophrenia. 3. The authors have recently observed that schizophrenic patients have a high incidence of autoantibodies suggesting that autoimmune phenomena may play a role in the pathogenesis of this disease. 4. In the present study the authors investigated multicase families with schizophrenia for the presence of anti-Sm antibodies and showed that these autoantibodies are elevated both in patients and in their healthy relatives. 5. An autoimmune process may be involved in the pathology of schizophrenia.

Adolescent↗

When multiple gestational sacs are seen on ultrasound, 'take-home baby' rate improves with in-vitro fertilization.

During a 5.5 year period, 309 clinical pregnancies were recorded in our in-vitro fertilization (IVF) unit. A single gestational sac was identified by early ultrasonography in 233 patients, while in 76 others, multiple gestational sacs were noted. 'Take-home baby' rate, in patients in whom multiple sacs were observed, was higher than that in patients with a single sac. Delivery of at least one live newborn occurred in only 73.8% of patients with a single sac, compared with 93.3% and 91.7% in patients with two and three gestational sacs, respectively. Conversely, the early and late abortion rates were decreased in patients with multiple sacs. Embryonic implantation rate, defined as the ratio of gestational sacs observed to the number of embryos transferred, was found to be a valuable prognostic factor for a live delivery, and can serve as a tool in assaying the prognosis of pregnancy detected by early sonography. The observation of a higher 'take-home baby' rate in cases with multiple sacs identified by ultrasound and with higher embryonic implantation rate, might be the result of a better embryo quality and/or improved uterine receptivity, promoted by a favourable hormonal milieu or by as yet unknown endometrial factors.

Abortion, Spontaneous↗

Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene.

The p53 tumor suppressor gene product can complex with polypeptides encoded by the mdm2 putative protoncogene. In addition, mdm2 mRNA levels have been shown to increase following the activation of wild type (wt) p53. To determine the basis for the effect of wt p53 on mdm2 mRNA, we studied the interaction of the mdm2 gene with p53. We report that wt p53 can bind sequence-specifically to a DNA region residing downstream to exon 1 of the mdm2 gene. This is correlated with a pronounced p53-dependent transcriptional activation. Efficient p53-dependent transactivation can be obtained with an mdm2 genomic DNA fragment lacking the putative mdm2 promoter. These findings suggest that p53 can induce transcription from an internal promoter located within the mdm2 gene. These findings raise the possibility that, in addition to increasing the overall levels of mdm2 mRNA, wt p53 may also modulate the repertoire of mdm2 transcripts present within the cell.

Animals↗

Organic delusional syndrome associated with tamoxifen treatment.

The authors describe two cases of tamoxifen-induced organic delusional syndrome that resulted from administration of 40 mg daily for the adjuvant treatment of breast carcinoma. After discontinuation of the tamoxifen therapy, the psychiatric episode resolved within 2 to 4 weeks. Because tamoxifen might cause delusional syndrome, the authors recommend full psychiatric evaluation in appropriate cases.

Adenocarcinoma↗

Enhanced binding of a 95 kDa protein to p53 in cells undergoing p53-mediated growth arrest.

To explore the biochemical functions of p53, we have initiated a search for cellular p53-binding proteins. Coprecipitation of three polypeptides was observed when cell lines overexpressing a temperature-sensitive (ts) p53 mutant were maintained at 32.5 degrees C (wild-type p53 activity, leading to growth arrest) but not at 37.5 degrees C (mutant p53 activity). One of these three proteins, designated p95 on the basis of its apparent molecular mass, was highly abundant in p53 immune complexes. We demonstrate herein that p95 is a p53-binding protein, which exhibits poor p53-binding in cells overproducing several distinct mutant p53 proteins. Yet, p95 associates equally well with both the wild-type (wt) and the mutant conformations of the ts p53 in transformed cells growth-arrested at 32.5 degrees C. On the basis of our findings we suggest that wt p53 activity increases p53-p95 complex formation and that such interaction may play a central role in p53 mediated tumour suppression.

Animals↗

High initial values of beta-subunits of human chorionic gonadotropin in ovum donation pregnancies indicate better implantation.

Fifty-five patients were treated by ovum donation, and a control group of 165 patients underwent IVF. The number of pregnancies obtained were 28 and 25, respectively. The initial beta-hCG values, as well as the PRs and implantation rates, in the ovum donation series were significantly higher than those of the IVF series. The clinical significance and potential application of these observations are discussed.

Chorionic Gonadotropin↗