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Biomedical subjects

I Stein

Publications and source records attributed to I Stein.

At least 19 recordsLinked to original sources
PubMed1995

Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes.

Expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a potent angiogenic factor, is upregulated in response to a hypoxic or hypoglycemic stress. Here we show that the increase in steady-state levels of VEGF mRNA is partly due to transcriptional activation but mostly due to increase in mRNA stability. Both oxygen and glucose deficiencies result in extension of the VEGF mRNA half-life in a protein synthesis-dependent manner. Viewing VEGF as a stress-induced gene, we compared its mode of regulation with that of other stress-induced genes. Results showed that under nonstressed conditions, VEGF shares with the glucose transporter GLUT-1 a relatively short half-life (0.64 and 0.52 h, respectively), which is extended fourfold and more than eightfold, respectively, when cells are deprived of either oxygen or glucose. In contrast, the mRNAs of another hypoxia-inducible and hypoglycemia-inducible gene, grp78, as well as that of HSP70, were not stabilized by these metabolic insults. To show that VEGF and GLUT-1 are coinduced in differentially stressed microenvironments, multicell spheroids representing a clonal population of glioma cells in which each cell layer is differentially stressed were analyzed by in situ hybridization. Cellular microenvironments conducive to induction of VEGF and GLUT-1 were completely coincidental. These findings show that two different consequences of tissue ischemia, namely, hypoxia and glucose deprivation, induce VEGF and GLUT-1 expression by similar mechanisms. These proteins function, in turn, to satisfy the tissue needs through expanding its vasculature and improving its glucose utilization, respectively.

Animals↗
PubMed1994

The single translation product of the FUM1 gene (fumarase) is processed in mitochondria before being distributed between the cytosol and mitochondria in Saccharomyces cerevisiae.

The yeast mitochondrial and cytosolic isoenzymes of fumarase, which are encoded by a single nuclear gene (FUM1), follow a unique mechanism of protein subcellular localization and distribution. Translation of all FUM1 messages initiates only from the 5'-proximal AUG codon and results in a single translation product that contains the targeting sequence located within the first 32 amino acids of the precursor. All fumarase molecules synthesized in the cell are processed by the mitochondrial matrix signal peptidase; nevertheless, most of the enzyme (80 to 90%) ends up in the cytosol. The translocation and processing of fumarase are cotranslational. We suggest that in Saccharomyces cerevisiae, the single type of initial translation product of the FUM1 gene is first partially translocated, and then a subset of these molecules continues to be fully translocated into the organelle, whereas the rest are folded into an import-incompetent state and are released by the retrograde movement of fumarase into the cytosol.

Animals↗
PubMed1992

The central New Jersey neonatal brain haemorrhage study: design of the study and reliability of ultrasound diagnosis.

Over a 34-month period, 1105 newborns weighing between 501 and 2000 g at birth were enrolled in a prospective study of the aetiology and consequences of neonatal brain haemorrhage. The three participating hospitals care for approximately 85% of births in the study weight range in Middlesex, Monmouth and Ocean counties, New Jersey. Cranial ultrasonographic imaging through the anterior fontanelle was carried out a mean age of 4.9 +/- 2.2 hours, 25.5 +/- 4.8 hours and 7.2 +/- 0.8 days to detect haemorrhage and other brain lesions. In 93.2% of study infants, scans were read by two independent expert readers (blind to the clinical status of the child) with submission of the scan to a third reader in cases of disagreement. Confirmation of both presence or absence and, when present, scan of first diagnosis of germinal matrix and/or intraventricular haemorrhage (GM/IVH) by two independent readers was achieved in 76.3% of study infants. The first two readers agreed as to presence or absence of GM/IVH in 82.4% of infants (Kappa = 0.56). Interobserver agreement was affected by the reported scan quality and by the number of scans available, but not by the hospital of origin, race or birthweight of the infant.

Birth Weight↗
PubMed1992

Sensitization to the toxic effects of cocaine in mice is associated with the regulation of N-methyl-D-aspartate receptors in the cortex.

Repeated exposure to cocaine results in sensitization to many of the behavioral effects of the drug. The present study was undertaken to examine the role of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in the development of sensitization to the convulsive and lethal effects of cocaine in Swiss Webster mice. Repeated administration of subconvulsant doses of cocaine (45 mg/kg for 7 days) produced a progressive increase in the convulsive responsiveness to the drug. This phenomenon was accompanied by an increase in lethality rate after the 5th day of the treatment. Pretreatment with the noncompetitive NMDA receptor antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10-imine) abolished completely the development of sensitization to cocaine-induced seizures and lethality. In addition, MK-801 attenuated cocaine-induced loss in animals body weight after 7 days of drug treatment. The lethal effects of acute administration of increasing doses of cocaine were also reduced by pretreatment with MK-801. In vitro receptor binding experiments demonstrated an increase (139% of control) in the number of NMDA receptors, labeled with the competitive NMDA receptor antagonist [3H]CGP 39653 ([3H]-2-amino-4-propyl-5-phosphono-3-pentenoic acid), in cortical membranes derived from the mice treated for 7 days with cocaine (45 mk/kg). In agreement with the latter finding, binding of [3H]MK-801 to the phencyclidine/NMDA site in cortical membranes of cocaine-treated mice was more sensitive to the stimulatory effect of glutamate compared to control (saline treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Regulation of sigma receptors and responsiveness to guanine nucleotides following repeated exposure of rats to haloperidol: further evidence for multiple sigma binding sites.

The sigma binding sites are postulated to be involved in various central nervous system (CNS) disorders. The neuroleptic drug, haloperidol, displays high affinity for these receptor sites in the CNS. In the present study the effect of repeated exposure of rats to haloperidol (4 mg/kg/day for 14 days) on sigma binding sites labeled with (+)-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine [+)-3-PPP) and 1,3-di-o-tolyl-guanidine (DTG) was investigated. In addition, the regulatory effect of guanine nucleotides on the binding of these two ligands to brain membranes derived from saline and haloperidol-treated rats was examined. Repeated administration of haloperidol induced down-regulation of (+)[3H]-3-PPP binding sites (75% decrease in the number of binding sites compared to control) which persisted for at least 7 days after termination of the haloperidol-treatment. The down-regulation of (+)-3-PPP binding sites was accompanied by reduced responsiveness to guanine nucleotides (i.e. 5-guanylylimidodiphosphate (Gpp(NH)p) compared to the sensitivity of (+)-3-PPP binding sites to the nucleotides tested in control membranes. However, at the 28th day after termination of the haloperidol-treatment, a complete recovery in the total number of (+)[3H]-3-PPP binding sites was observed, and the sensitivity to guanine nucleotides was regained. These findings suggest a marked plasticity in (+)-3-PPP/sigma receptor binding activity. In contrast, [3H]DTG binding sites expressed neither sensitivity to the repeated exposure to haloperidol nor to guanine nucleotides, suggesting a distinction between DTG and (+)-3-PPP binding sites in rat brain.

Adenosine Triphosphate↗
PubMed1991

Effect of fat pre-feeding on bile flow and composition in the rat.

Studies were conducted in rats to determine if the increase in lymph triacylglycerol output on pre-feeding a 20% glyceryltrioleate diet (Mansbach, C.M., II and Arnold, A. (1986) Am. J. Physiol. 251, G263-269) was due to an increase in phosphatidylcholine output into bile. Rats who were fed chow or pre-fed the 20% fat diet were equipped with biliary and duodenal cannulas and infused with glucose-saline while bile was collected hourly. The next day a taurocholate-glyceryltrioleate infusion was given and bile collected for 5 h. Bile flow, bile acid, phosphatidylcholine and cholesterol output were greater in the chow fed group than controls during the 6 h of the glucose saline period. Outputs were low overnight. During the taurocholate-glyceryltrioleate infusion, bile flow, bile acid, phosphatidylcholine and cholesterol output were all greater in the fat pre-fed group than the chow fed controls. We conclude that fat pre-feeding profoundly influences biliary composition and flow. The 2-fold increase in biliary phosphatidylcholine output during duodenal lipid infusion offers a potential explanation for the increased delivery of triacylglycerol into the lymph in rats on a similar fat pre-feeding program.

Animals↗
PubMed1991

Thymocyte maturation following interaction with thymus-derived macrophages.

Murine C57BL/6 thymocytes were cultivated together with syngeneic thymus-derived macrophages (TDM phi) for up to 96 hr to determine whether TDM phi participate in thymocyte maturation. The expression level of H-2b and Thy-1.2 antigens served as thymocyte differentiation surface markers as analyzed by flow cytometry. Indirect immunofluorescent staining profiles of the thymocytes demonstrate a dramatic increase in H-2b expression and a profound decrease in Thy-1.2 expression during cultivation with TDM phi. A similar phenomenon was observed when enriched populations of immature thymocytes were cocultivated with TDM phi. These changes were not observed when thymocytes were cultivated alone or with trypsin-treated TDM phi; neither were they observed when cortisone-resistant thymocytes manifesting mature characteristics were cultivated together with TDM phi. These findings suggest that interaction of thymocytes with TDM phi, involving binding and engulfment, results in the appearance of mature thymocyte subsets.

Animals↗
PubMed1991

Characterization of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) binding sites in C57BL/6 mouse brain: mutual effects of monoamine oxidase inhibitors and sigma ligands on MPTP and sigma binding sites.

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson-like symptoms in humans, nonhuman primates, and mice. Several studies suggest that MPTP is metabolized by monoamine oxidase (MAO) type B to yield N-methyl-4-phenyl-pyridinium (MPP+), which is responsible for the neurotoxic effects of the drug. In the present study, the pharmacological properties of [3H]MPTP binding sites in C57BL/6 mouse brain membranes were investigated, and a possible relationship to the sigma binding sites was examined. Both equilibrium binding experiments and kinetic assays indicate that [3H]MPTP labels two distinct binding sites in C57BL/6 mouse brain. The high affinity [3H]MPTP binding sites (Kd = 13 nM) are selectively blocked by the MAO type A inhibitor clorgyline, and the residual low affinity [3H]MPTP sites (Kd = 1100 nM) display the pharmacological specificity of MAO-B binding sites. In contrast, the low affinity [3H]MPTP binding sites are blocked by the selective MAO-B inhibitor (-)-deprenyl, and the drug-specificity profile of the remaining high affinity sites is consistent with the properties of MAO-A binding sites. The affinities of several MAO inhibitors tested and of MPTP for the high affinity MPTP/MAO-A binding sites correlate well (r = 0.96) with their affinities for the sigma binding sites labeled with [(+)-[3H]-3-PPP]. The sigma receptor ligand (+)-3-PPP displays moderately high affinity for the MPTP/MAO-A binding sites but negligible affinity for MPTP/MAO-B sites. Moreover, (+)-3-PPP alters the dissociation kinetics of MPTP from the high affinity MPTP/MAO-A sites. The finding that [3H]MPTP labels MAO-B sites supports the hypothesis that the drug is a substrate for these enzyme binding sites. However, the finding that the high affinity sites, labeled by [3H] MPTP, are particularly sensitive to MAO-A inhibitors, which also display high affinity for the sigma binding sites, may suggest a possible relationship between MAO-A and sigma binding sites. In turn, the kinetic experiments imply that sigma ligands [i.e., (+)-3-PPP] may allosterically modulate the binding to MAO-A binding sites.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Binding of sigma-ligands to C57BL/6 mouse brain membranes: effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of sigma-receptor subtypes.

Our preliminary studies indicated that certain monoamine oxidase (MAO) inhibitors display high affinity for the sigma-binding sites labeled with (+)[3H]-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine [(+)[3H]-3-PPP] in C57BL/6 mouse brain (Itzhak, Y., and Kassim, C. D.: Eur. J. Pharmacol. 176: 107-108, 1990). In the present study, the drug specificity and the subcellular distribution of (+)[3H]-3-PPP, (+)[3H]-N-allylnormetazocine [(+)[3H]SKF 10047] and [3H]1,3-di-o-tolyl-guanidine ([3H]DTG) binding sites in C57BL/6 mouse brain were investigated, and the properties of clorgyline interaction with the (+)-3-PPP/sigma-binding site(s) were examined. (+)[3H]-3-PPP binding, but not [3H]DTG binding, is inhibited by low concentrations (nM) of the dextrorotatory (+)-isomers of SKF 10047, 3-PPP and deprenyl and the type A MAO inhibitor, clorgyline. The haloperidol-sensitive/(+)[3H]SKF 10047 binding sites display virtually identical sensitivity towards the MAO inhibitors as (+)-3-PPP binding sites. These observations suggest a distinction between [3H]DTG and (+)[3H]-3-PPP/(+)[3H]SKF 10047 binding sites in the mouse brain. Clorgyline interaction with (+)-3-PPP/sigma-sites is competitive and reversible unlike the interaction of clorgyline with MAO-A. The sigma-ligands tested do not inhibit MAO activity and bind to sites that are apparently distinct from the MAO binding sites labeled with [3H]-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. However, the mitochondrial fraction of the mouse brain that expresses MAO activity and high density of [3H]-N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine binding sites also comprises high density of (+)-3-PPP/(+)SKF 10047 binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Sigma binding sites in the brain; an emerging concept for multiple sites and their relevance for psychiatric disorders.

An increasing amount of evidence suggests the existence of specific binding sites for psychotomimetic drugs from the opiate-benzomorphan and arylcyclohexylamine series. The sigma binding sites have preferential affinity for the dextrorotatory isomers of certain opiate benzomorphans, such as (+)SKF 10047, (+)cyclazocine and (+)pentazocine and also for some neuroleptics (e.g., haloperidol). The PCP receptor has preferential affinity for phencyclidine (PCP) analogs and other non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists. The physiological significance of the PCP receptor is associated with the blockade of the NMDA type of the glutamate receptor, implying a neuroprotective role of the PCP receptor. However, the significance of the sigma binding sites is less conspicuous. It is not only that drugs from distinct pharmacological classes display a certain degree of affinity for the "sigma/haloperidol" binding sites, but also that drugs which do not induce or block psychotomimetic activity, i.e., (+)3-(3-hydroxyphenyl)-N-(1-propyl) piperidine [(+)3-PPP] and 1,3-di-o-tolyl-guanidine (DTG), display relatively high affinity for the sigma binding sites. The diversity of the compounds which are proposed to interact with the sigma receptors and the variety of the responses elicited by these drugs suggest the existence of sigma receptor subtypes. The finding that the type A of monoamine oxidase (MAO) inhibitors, which are used in treatment of affective disorders, display high affinity for the sigma binding sites suggests their involvement in affective or schizoaffective disorders. Revealing the existence of sigma receptor subtypes may help to elucidate their association with various psychiatric disorders.

Animals↗
PubMed1990

A group of indole-negative bovine strains with high deoxyribonucleic acid homology to Pasteurella multocida.

A group of nine bovine Pasteurella strains not producing indole were investigated for their taxonomic relationships with Pasteurella multocida, Pasteurella haemolytica and Pasteurella canis. For all strains, DNA-DNA hybridization has revealed a high genetic relatedness at the species level to P. multocida and significantly lower homologies of only 18-41% towards P. haemolytica and 11-15% towards P. canis. Guanine plus cytosine values of 38.0 to 42.1 mol% and several phenotypic characters have been found to be different from the established pattern for P. multocida subspecies. It is suggested that the strains represent a new taxon, possibly another P. multocida subspecies.

Animals↗
PubMed1990

[Typing and virulence testing of Pasteurella haemolytica field strains].

The greater part of 145 typed Pasteurella haemolytica strains from calf could be attributed to Type A 1. Hence, in the context of virulence testing, this is the most important type at present for calf. Clearly manifest pneumonia was caused in calf by other strains of Types A 2, A 6, A 12, and T 10 which were also tested for their virulence parameters. The same applied to a number of strains which had so far been characterised merely as T or A/T strains.

Animals↗
PubMed1988

Interobserver variability in neonatal cranial ultrasonography.

The reliability of cranial ultrasound diagnosis in the premature neonate was examined using data from an ongoing multicentre study of the epidemiology and long-term consequences of neonatal brain haemorrhage. First week ultrasound films (obtained at 4 hours, 24 hours and 7 days) from 60 study subjects were randomly selected for independent review by two groups of experienced interpreters, and results were recorded separately for observations (i.e. presence or absence of an abnormal echodense area on a film) and interpretations (i.e. presence or absence of haemorrhage or ventricular dilatation) in each hemisphere. Because of deaths in the first week of life, the total number of films examined was 138. Concordance on the presence or absence of an abnormal echodensity was examined for each individual film for three areas of interest: the germinal matrix, the ventricles and the parenchyma. Concordance on the presence or absence of haemorrhage or ventricular dilatation was examined only for the seventh-day film, or the final film prior to death. Finally, concordance was analysed with the diagnostic interpretations grouped into categories thought to differ prognostically for long-term outcome. In general, concordance was poorest for germinal matrix lesions and best for parenchymal lesions. Concordance was lower for observations made on each individual film than it was for interpretation of the final film in each case. Fifty-five of 60 cases (92%) were assigned to the same major prognostic category by both readers. Ultrasound review conferences were held periodically and there was evidence that concordance in ultrasound reading and interpretation improved during the course of the study.

Cerebral Hemorrhage↗
PubMed1987

Body surfing as a cause of luxatio erecta: report of four cases.

True inferior dislocation of the shoulder (luxatio erecta) is a rare type of shoulder dislocation. It is caused by hyperabduction of the arm while in the overhead position. We report four recent cases, all of which occurred while body surfing. All of the individuals in this report were struck by a wave with their arms in the overhead position and their arms were forced into the sand.

Adult↗