Rappaport Faculty of Medicine

About: Rappaport Faculty of Medicine is a based out in . It is known for research contribution in the topics: Population & Heparanase. The organization has 3205 authors who have published 3915 publications receiving 114533 citations.

Induction of apoptosis by adenovirus E4orf4 protein.

Abstract: Adenovirus E4orf4 protein is a multifunctional viral regulator that induces p53-independent apoptosis in transformed cells, but not in normal cells. E4orf4-induced apoptosis can occur without activation of known caspases, although E4orf4 induces caspase activity in some cell lines. The interaction of E4orf4 with a specific subpopulation of protein phosphatase 2A (PP2A) molecules that contain B subunits, but not with those that contain B′ subunits, is required for induction of apoptosis. This review suggests the potential use of E4orf4 in cancer therapy, and discusses whether E4orf4-induced apoptosis plays a role in the viral life cycle. Future research directions are also highlighted.

Pregnenolone treatment reduces severity of negative symptoms in recent‐onset schizophrenia: An 8‐week, double‐blind, randomized add‐on two‐center trial

Abstract: Aims Management of recent-onset schizophrenia (SZ) and schizoaffective disorder (SA) is challenging owing to frequent insufficient response to antipsychotic agents This study aimed to test the efficacy and safety of the neurosteroid pregnenolone in patients with recent-onset SZ/SA Methods Sixty out- and inpatients who met DSM-IV criteria for SZ/SA, with suboptimal response to antipsychotics were recruited for an 8-week, double-blind, randomized, placebo-controlled, two-center add-on trial, that was conducted between 2008 and 2011 Participants were randomized to receive either pregnenolone (50 mg/day) or placebo added on to antipsychotic medications The primary outcome measures were the Positive and Negative Symptoms Scale and the Assessment of Negative Symptoms scores Secondary outcomes included assessments of functioning, and side-effects Results Analysis was by linear mixed model Fifty-two participants (867%) completed the trial Compared to placebo, adjunctive pregnenolone significantly reduced Positive and Negative Symptoms Scale negative symptom scores with moderate effect sizes (d = 079) Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0010) Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 057), especially on blunted affect, avolition and anhedonia domain scores Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation Pregnenolone was well tolerated Conclusions Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers Further studies are warranted

The Clinical Spectrum of Leukocyte Adhesion Deficiency (LAD) III due to Defective CalDAG-GEF1

Abstract: Leukocyte adhesion deficiency (LAD) type III is a rare syndrome characterized by severe recurrent infections, leukocytosis, and increased bleeding tendency. All integrins are normally expressed yet a defect in their activation leads to the observed clinical manifestations. Less than 20 patients have been reported world wide and the primary genetic defect was identified in some of them. Here we describe the clinical features of patients in whom a mutation in the calcium and diacylglycerol-regulated guanine nucleotide exchange factor 1 (CalDAG GEF1) was found and compare them to other cases of LAD III and to animal models harboring a mutation in the CalDAG GEF1 gene. The hallmarks of the syndrome are recurrent infections accompanied by severe bleeding episodes distinguished by osteopetrosis like bone abnormalities and neurodevelopmental defects.

Growth hormone involvement in the regulation of tartrate-resistant acid phosphatase-positive cells that are active in cartilage and bone resorption

Abstract: Young male Sprague-Dawley rats (5–7 weeks old, 80–120 g) were hypophysectomized (HX) and maintained on thyroxin and dexamethasone replacement therapies. Ten days after surgery, some HX rats received a single injection of human growth hormone (hGH), and others five daily injections of hGH. Tartrate-resistant acid phosphatase (TRAP) histochemistry was employed in order to evaluate the number of cells of resorptive potential in the metaphyseal bone of the proximal tibiae of HX rats and was compared with normal rats and HX rats that further received hGH replacement therapy. In normal rats, two populations of TRAP-positive cells were identified: multinuclear cells, which showed histological characteristics of osteoclasts, and small mononuclear cells, the number of which was overwhelming when compared with the number of TRAP-positive multinuclear cells. Both populations were reduced in the HX rat, but more so the mononuclear cells, which were assumed to represent the precursor pool of mature osteoclasts and chondroclasts (P<0.005). Five daily injections of hGH to HX rats brought about a significant increase in the number of TRAP-positive multinuclear cells, the number of nuclei of these cells, and the number of mononuclear TRAP-positive cells, throughout the metaphyseal bone (P<0.05). A single injection of hGH increased only the number of TRAP-positive multinuclear cells in the trabecula/bone marrow interface (P<0.05), indicating a very rapid fusion of precursor cells into mature osteoclasts in that particular location. It was concluded that GH depletion caused a major reduction in the number of cells presenting resorption capacity and that a short hGH replacement regimen resulted in a gradual restoration of these cells n the metaphyseal bone of the proximal tibia of the HX rat.

The effects of proteasomal inhibition on synaptic proteostasis.

Abstract: Synaptic function crucially depends on uninterrupted synthesis and degradation of synaptic proteins. While much has been learned on synaptic protein synthesis, little is known on the routes by which synaptic proteins are degraded. Here we systematically studied how inhibition of the ubiquitin‐proteasome system (UPS) affects the degradation rates of thousands of neuronal and synaptic proteins. We identified a group of proteins, including several proteins related to glutamate receptor trafficking, whose degradation rates were significantly slowed by UPS inhibition. Unexpectedly, however, degradation rates of most synaptic proteins were not significantly affected. Interestingly, many of the differential effects of UPS inhibition were readily explained by a quantitative framework that considered known metabolic turnover rates for the same proteins. In contrast to the limited effects on protein degradation, UPS inhibition profoundly and preferentially suppressed the synthesis of a large number of synaptic proteins. Our findings point to the importance of the UPS in the degradation of certain synaptic proteins, yet indicate that under basal conditions most synaptic proteins might be degraded through alternative pathways.