Biomedical subjects
S Shapira
Publications and source records attributed to S Shapira.
Suppression of NF-kappaB activation by infection with Toxoplasma gondii.
The interaction of host cells with microbial products or their invasion by pathogens frequently results in activation of the NF-kappaB family of transcription factors. The studies presented here reveal that in vivo, infection with Toxoplasma gondii results in the activation of NF-kappaB. To determine whether host cells could activate NF-kappaB in response to invasion by T. gondii, Western blots, immunofluorescence, and electrophoretic mobility shift assays were used to assess the response of host cells to infection. In these studies, infection of macrophages or fibroblasts with T. gondii did not result in the activation of NF-kappaB. In addition, the ability of lipopolysaccharide to activate NF-kappaB was impaired in cultures of macrophages infected with T. gondii. Together, these data demonstrate that invasion of cells by T. gondii does not lead to the activation of NF-kappaB and suggest that the parasite may actively interfere with the pathways that lead to NF-kappaB activation.
Interband scattering and the "Metallic Phase" of two-dimensional holes in GaAs /AlGaAs
The "metallic" characteristics of high density holes in GaAs/AlGaAs heterostructures are attributed to inelastic scattering between the two split heavy hole bands. Landau fan diagrams and weak field magnetoresistance are employed to measure the interband scattering rate. The inelastic rate is found to depend on temperature with an activation energy similar to that characterizing the longitudinal resistance. It is argued that acoustic plasmon mediated Coulomb scattering might be responsible for the Arrhenius dependence on temperature. The absence of standard Coulomb scattering characterized by a power-law dependence upon temperature is pointed out.
Anomalous behavior of superconducting-normal mesoscopic structures near T(c)
We observe a maximum in the conductance of Al/n-GaAs junctions at temperatures 20 mK lower than the superconducting transition temperature (T(c)). This is the first observation of a peak in the conductance near the superconducting transition in superconducting-normal (S/N) junctions. To accommodate this effect we calculate the full temperature dependence of the conductance of these structures, invoking quasiclassical Green's functions in the diffusive limit. In addition to the well-known low-temperature peak at temperatures on the order of the Thouless energy, we find a maximum near T(c). This peak has the same origin as the subgap conductance observed in S/N junctions at low temperatures.
The effect of storage on the expression of platelet membrane phosphatidylserine and the subsequent impacton the coagulant function of stored platelets.
BACKGROUND: Platelet concentrates (PCs) derived from whole blood and stored under standard blood bank conditions undergo changes that are referred to as the platelet storage lesion. This study assesses the effect of PC preparation and storage on the distribution of phosphatidylserine (PS) in the platelet membrane and the effect that this distribution may have on the thrombogenic potential of stored PCs. STUDY DESIGN AND METHODS: Fresh platelets and PCs donated by healthy donors were obtained. PCs derived from platelet-rich plasma were studied on Day 1, Day 3, and Day 6 of storage under blood bank conditions. RESULTS: Platelet aggregation after exposure to the platelet agonists ADP and epinephrine singly declined progressively, but, when ADP and epinephrine in combination and collagen and thrombin in combination were used as agonists, the decline in platelet aggregation was less marked. PS expression as measured by Annexin V binding (mean and SD) was 2.02 +/- 0.93 percent in fresh platelet samples and increased to 5.39 +/- 4.2 percent on Day 1, 22. 1 +/- 7.1 percent on Day 3, and 39.5 +/- 12.1 percent on Day 6. Platelet prothrombinase activity (mean +/- SD) as measured by thrombin generation increased from 1.49 +/- 0.7 micro per mL in fresh platelet samples to 3.68 +/- 1.1 micro per mL in Day 1 platelets (p<0.001), 5.15 +/- 2.5 micro per mL in Day 3 platelets (p<0.001), and 4.65 +/- 2.48 micro per mL in Day 6 platelets (p<0. 001). CONCLUSION: These results show that PS expression increases after preparation of PCs from platelet-rich plasma and rises progressively during platelet storage under blood bank conditions. Furthermore, the greater PS expression is associated with increased platelet- dependent thrombin-generating capacity.
Induced second trimester abortion by extra-amniotic prostaglandin infusion in patients with a cesarean scar: is it safe?
BACKGROUND: One result of the advancement in prenatal diagnosis is an increase in the need for second trimester pregnancy terminations. Extra-amniotic infusion of prostaglandins is a common technique used for such pregnancy termination. Since prostaglandins cause strong uterine contractions, many practitioners are hesitant to use this technique on women with a uterine scar. In this study we tried to evaluate the effectiveness and safety of the technique for women with a previous uterine scar. METHODS: This retrospective study included all women with a complete medical record who underwent a second trimester pregnancy termination at our institution by extra amniotic prostaglandin E2, during a 6 year period. The study group included all women with a previous uterine scar. The group of women without such a scar served as the control group. RESULTS: Three hundred and forty women had their pregnancy terminated, but only in 282 cases was the medical information complete (research population). The study group (35 women) characteristics were similar to those of the control group (247 women). We found no difference in the abortion interval, the need to use an additional method, the need for curettage and in bleeding complication between the two groups. There was no case of uterine rupture. The group of women with multiple uterine scars was too small for analysis. CONCLUSIONS: Our results suggest that extra amniotic prostaglandin infusion is an effective and safe technique in women with a uterine scar.
[Is it possible to predict and prevent primary biliary cirrhosis?].
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The role of uterine straightening by passive bladder distension before embryo transfer in IVF cycles.
PURPOSE: The present study investigated the effect of bladder distension on in vitro fertilization and embryo transfer (IVF-ET) results. METHODS: The study comprised 796 patients after successful transvaginal oocyte pickup and IVF, who, on the basis of bladder filling for ET, were divided into two groups. In group E, 385 patients underwent ET with an empty bladder, and in group F, 411 patients underwent ET with a full bladder. RESULTS: Sixty-four pregnancies were achieved in group E (16.6%), compared to 110 pregnancies in group F (26.8%, P = 0.006). A similar pregnancy loss rate was observed in both groups, 13 in group E (20.3%) and 29 in group F (26.4%; P = NS). CONCLUSIONS: A significantly higher pregnancy rate was achieved with routine bladder distension before ET, probably attributable to the smooth and easy insertion of the ET catheter.
Effect of epidural analgesia on duration and outcome of induced labor.
OBJECTIVE: To evaluate the effect of epidural block on the duration of labor and maternal and fetal outcome in induced-labor patients. METHOD: 210 women admitted for induction of labor at a level III university hospital, during the year 1991, were studied. Of these, 112 were given an epidural block and 98 served as controls. Outcome measures studied were: induction time and time in labor, c-section and instrumental delivery rates, intra-partum and post-partum complications, and Apgar scores at 1 and 5 min. RESULT: Multiple regression analysis revealed that epidural analgesia, before and after adjustment for confounding factors, significantly prolonged labor time (P < 0.0001) and was associated with an increase in instrumental delivery rates (P < 0.04). A significant reduction in intra-partum complication rate (FHR changes, meconium) was observed (OR = 0.32; P < 0.03), while c-section rate and Apgar scores were not found to be influenced by epidural analgesia. CONCLUSION: Epidural anesthesia, significantly prolongs labor time in induced patients. While instrumental delivery was more prevalent in these parturients, c-section rate was not increased and intra-partum complications were significantly reduced in these patients.
Thermodynamics of a Charged Fermion Layer at High rs Values.
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Sarin-induced neuropathology in rats.
Sarin, a highly toxic cholinesterase (ChE) inhibitor, administered at near 1 LD50 dose causes severe signs of toxic cholinergic hyperactivity in both the peripheral and central nervous systems (CNS). The present study evaluated acute and long-term neuropathology following exposure to a single LD50 dose of sarin and compared it to lesions caused by equipotent doses of soman described previously. Rats surviving 1 LD50 dose of sarin (95 micrograms/kg; IM), were sacrificed at different time intervals post exposure (4 h-90 days) and their brains were taken for histological and morphometric study. Lesions of varying degrees of severity were found in about 70% of the animals, mainly in the hippocampus, piriform cortex, and thalamus. The damage was exacerbated with time and at three months post exposure, it extended to regions which were not initially affected. Morphometric analysis revealed a significant decline in the area of CA1 and CA3 hippocampal cells as well as in the number of CA1 cells. The neuropathological findings, although generally similar to those described following 1 LD50 soman, differed in some features, unique to each compound, for example, frontal cortex damage was specific to soman poisoning. It is concluded that sarin has a potent acute and long-term central neurotoxicity, which must be considered in the design of therapeutic regimes.
Dose-dependent effect of nitric oxide synthase inhibition following transient forebrain ischemia in gerbils.
The extensive research concerning the interaction between nitric oxide (NO) and ischemic brain tissue has yielded contradictory results. The present study was designed to explore the effect of gradual inhibition of NO production on brain ischemia. Gerbils were administered (i.p.) either saline (control-ischemia), or 5, 10, 25 or 50 mg/kg of NG-nitro-L-arginine (NARG), a specific inhibitor of NO synthase (NOS), and 4 h later were subjected to 5 min of forebrain ischemia. A group receiving 50 mg/kg NARG with sham operation served as a second control (control-NARG) group. Body weights and spontaneous activity were monitored daily until day 6, when the gerbils were sacrificed and their brains processed for histologic-morphometric evaluation. All ischemia groups displayed significant decreases in body weights starting on day 1, as compared to control-NARG (non-ischemic) gerbils. At 24 h post-ischemia spontaneous activity was increased in all ischemia groups in a dose-dependent manner, reaching a peak at 25 mg/kg. Typical ischemia-induced neuronal cell degeneration was observed at the hippocampal CA1 layer in control-ischemia and in each of the dose-groups of 10 mg/kg NARG and above. The 5 mg/kg group displayed damage which was not different from control-NARG, and was milder (P < 0.01) than control-ischemia gerbils and each of the other dose-groups. It is suggested that during ischemia, NO activates a series of processes which are beneficial to brain tissue, whereas an excess amount of NO causes neurotoxic effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase diagram of the dilute Ising spin glass in general spatial dimension.
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NG-nitro-L-arginine enhances neuronal death following transient forebrain ischemia in gerbils.
Experiments were performed with Mongolian gerbils to study the effect of the specific nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) on ischemic brain damage induced by 5 min bilateral carotid occlusion. A single i.p. injection of L-NNA did not result in any neuronal loss in the central nervous system. In animals undergoing ischemia, a selective destruction of hippocampal CA1 cells was observed whereas pretreatment with 50 mg/kg L-NNA 4 h before administration of ischemia produced significantly more extensive cell damage in the hippocampus and other brain regions. These findings demonstrate that in this model inhibition of nitric oxide generation augments ischemia-induced neuronal cell injury in the brain.
Thickening of the adrenal zona glomerulosa in dogs induced by oxodipine, a calcium channel blocker.
Subchronic effects of oxodipine, a calcium channel blocker affecting the adrenal gland of the dog, are described. Thirteen wk of treatment at a high dose (24 mg/kg/day) of oxodipine resulted in drug-induced thickening of the zona glomerulosa and increased stimulation of its secretory activity. It is postulated that subchronic administration of oxodipine at this dosage resulted in a decrease in blood pressure, with uninterrupted stimulation of the adrenal zona glomerulosa to release aldosterone, causing an increase in the width of this portion of the gland involving cellular hyperplasia. Support for this indirect effect is found in the increased presence of renin granules in the juxtaglomerular apparatus.
Long-term study of brain lesions following soman, in comparison to DFP and metrazol poisoning.
The long-term histopathological effects of acute lethal (95 micrograms kg-1) and sublethal (56 micrograms kg-1) doses of soman were studied in rats and were compared to lesions caused by equipotent doses of either another cholinesterase (ChE) inhibitor, DFP (1.8 mg kg-1), or a non-organophosphorus convulsant, metrazol (100 mg kg-1). Severe toxic signs were noted following one LD50 dose administration of all the compounds, yet only soman induced brain lesions. Moreover, even when administered at a sublethal dose (0.5 LD50), soman induced some histological changes without any clinical signs of intoxication. Soman-induced brain lesions were assessed quantitatively using a computerized image analyser. The analysis was carried out for up to 3 months following administration, and a dynamic pattern of pathology was shown. The cortical thickness and area of CA1 and CA3 cells declined significantly as early as 1 week post-exposure. No pathological findings were detected following DFP and metrazol administration. It is therefore suggested that brain lesions are not common for all ChE inhibitors and that convulsions per se are not the only factor leading to brain damage following the administration of soman. The degenerative process (found also with the sublethal dose of soman) might be due to a secondary effect, unrelated to soman's clinical toxicity, but leading to long-term brain injuries.
Butyrylcholinesterase and acetylcholinesterase prophylaxis against soman poisoning in mice.
Human butyrylcholinesterase (BChE, EC 3.1.1.8) or acetylcholinesterase (AChE, EC 3.1.1.7) from fetal bovine serum (FBS), administered i.v. in mice, sequestered at approximately 1:1 stoichiometry the highly toxic anti-ChE organophosphate, 1,2,2-trimethylpropyl methyl-fluorophosphonate (soman). A quantitative linear correlation was demonstrated between blood-ChE levels and the protection conferred by exogeneously administered ChE. Results presented here demonstrate that either human BChE or FBS-AChE is an effective prophylactic measure sufficient to protect mice from multiple LD50S of soman without the administration of post-treatment supportive drugs.
A goldfish model for evaluation of the neurotoxicity of omega-conotoxin GVI A and screening of monoclonal antibodies.
The neurotoxicity of omega-conotoxin (omega-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. omega-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. omega-CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antibodies was investigated in vivo by either (1) preincubation of the antibody with omega-CgTx at 4 degrees C overnight, or (2) pretreatment with antibody, 30 min before omega-CgTx injection in a 10:1 antibody/omega-CgTx molar ratio. The LD50 dose of omega-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with omega-CgTx (5 nmol/kg ip) significantly (p less than 0.05) reduced mortality, ASB, and toxicity time. The antitoxin activity of the monoclonal antibodies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by omega-CgTx (0.03 nmol/rat icv) were significantly (p less than 0.02 and p less than 0.01, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple, accurate, and inexpensive in vivo model for the study of the toxicity of omega-CgTx.