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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 19 recordsLinked to original sources

Localization of the human B-type natriuretic peptide precursor (NPPB) gene to chromosome 1p36.

Cardiac myocytes synthesize and secrete a family of peptide hormones with potent natriuretic, diuretic, and vasodilatory properties. These peptides are derived from precursor molecules that are encoded by two different genes, the atrial natriuretic peptide precursor A (NPPA) and the B-type natriuretic peptide or natriuretic peptide precursor B (NPPB). A human genomic clone for the NPPB gene was used to determine the chromosomal location of the NPPB gene. Analysis of Southern blot hybridization to DNAs from various somatic cell hybrids and fluorescence in situ hybridization allowed assignment of the NPPB locus to human chromosome 1p36. This location coincided with that of the NPPA locus; pulsed-field gel electrophoresis placed NPPA and NPPB within 50 kb of each other. This close chromosomal linkage, together with the conserved primary sequences and structural organization of the two natriuretic peptide precursor genes, suggests that the natriuretic peptide loci may have evolved from a common ancestor gene.

Animals

[Do Israeli adolescents know what they are drinking?].

We assessed knowledge of the strength of 7 different types of alcoholic beverages among 1052 high school students from kibbutzim and development towns in eastern Upper Galilee and the northern Golan Heights (northeastern edge of Israel). Only 0.85% of subjects reported correct alcohol content of all 7 types. There was a trend toward more accurate estimates of the alcohol content of distilled spirits and less accurate estimates for light beer. The estimates of girls were less correct than those of boys, and youth from kibbutzim were more correct in their answers than those from development towns.

Adolescent

Listeriolysin generates a route for the presentation of exogenous antigens by major histocompatibility complex class I.

We have exploited the pore forming activity of listeriolysin, the hemolysin of Listeria monocytogenes, to activate CD8+ T cells with soluble proteins in vivo and in vitro. Immunization with soluble, hemolytically active listeriolysin induces both cytotoxic CD8+ T cells and CD4+ T cells, and the CD8+ T cells can be propagated with soluble listeriolysin in vitro. Moreover, conventional antigens like ovalbumin mixed together with listeriolysin are also efficiently introduced into the MHC class I pathway in vitro and in vivo. Hence, listeriolysin effectively directs itself and passenger molecules into the intracellular compartment that leads to the cytotoxic T cell response. In this way, we circumvent the bias of CD8+ T cells to recognize intracellular antigens presented by major histocompatibility complex class I molecules. As cytotoxic CD8+ T cells are of pivotal importance in eliminating viral and microbial pathogens, the findings reported here could prove to be useful in vaccine development.

Animals

Reasons for non-drinking among Israeli adolescents of four religions.

Adolescent abstainers have largely been ignored in the literature. This article describes the reasons for not drinking of 2366 Israeli Jewish, Moslem, Druze and Christian adolescents in the north of Israel in the winter of 1994. It analyzes the findings by religious group, religiosity (secular versus religious Jews), location and gender of Jews, and school grade of Jews and Moslems. Harmful health consequences of alcohol use and religious injunction are the most prevalent reasons for abstinence among Moslems and Druze. Jews abstain mainly because of disliking the taste and/or smell of alcohol and because they 'do not care for it'. Christians abstain mainly because of the harmful effects of alcohol on health and dislike of its taste and/or smell. The implications of the results for prevention are discussed.

Adolescent

Comparison of cardiac output measurements by thermodilution and thoracic electrical bioimpedance in critically ill versus non-critically ill patients.

Thoracic electrical bioimpedance (TEB) has been proposed as an alternative to thermodilution (TD) for the measurement of cardiac output in settings such as the Emergency Department where invasive monitoring is not available. Validation studies comparing TEB with TD suggest a wide range of variability in the agreement between the two methods. This prospective study tests the hypothesis that this variability may be related to the severity of patient illness. Fifteen non-critically ill patients undergoing cardiac catheterization and 13 critically ill patients who underwent Swan-Ganz catheterization in the medical intensive care unit (MICU) were enrolled. Fifty-one pairs of data from the catheterization laboratory and 49 pairs of data from the MICU were obtained. The patients were graded retrospectively according to the APACHE II scoring system. The mean difference (bias) between TEB and TD results was calculated for each patient using the method suggested by Bland and Altman. A pooled t-test was performed to determine whether there was any significant difference between the APACHE II scores or cardiac output measurements obtained by TEB and TD in the two groups. APACHE II scores were 4.7 +/- 1.2 for the catheterization laboratory and 14.2 +/- 5.0 for the intensive care unit patients (P < .001). The catheterization laboratory (cath lab) group bias was 0.23 +/- 2.19, whereas the MICU bias was .002 +/- 2.33. There was no significant difference in the bias between the two groups despite significant differences in the APACHE II scores. Standard deviations of the bias were less than 15% different from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE

Lithium and body weight gain.

Weight gain is an undesirable side-effect of long-term lithium administration which notably interferes with treatment compliance. The mechanisms of this weight gain remain unclear, making its management in patients difficult. In this paper, studies describing the features of this weight gain in patients and in rats treated with chronic lithium administration are reviewed. The effects of lithium on body weight differ between patients and rats in a number of ways, including the observation that excessive weight gain is observed in both male and female patients, but only in female rats. Nevertheless, an animal model of lithium-induced weight gain may be able to provide useful insights into some of the specific mechanisms involved, particularly those related to interactions with gonadal steroid function. We discuss the effects of lithium on the endocrine system, neurotransmitters, metabolism, electrolyte regulation, and feeding behavior, which might underlie lithium's effects on body weight. Finally, suggestions for the management of weight gain in the clinical setting are presented. These include, in the long term, dietary control and physical activity and, in the short term, choosing among several drugs that have been tested either in patients or in animal models of obesity. If weight gain still cannot be controlled and treatment compliance is at risk, the mood stabilizers carbamazepine or valproic acid might be substituted for lithium treatment.

Animals

Overexpression of active Syrian golden hamster prion protein PrPc as a glutathione S-transferase fusion in heterologous systems.

This article describes a procedure which permits for the first time the isolation of the prion protein PrPc from the Syrian golden hamster in heterologous systems. Using a glutathione S-transferase (GST) fusion approach, milligram amounts of stable, soluble, and homogeneous GST::PrPc protein were obtained in Escherichia coli and with baculovirus-infected insect cells. Authentic PrPc was released from the immobilized fusion protein by direct cleavage with thrombin. GST::PrPc expressed in these two expression systems and also authentic PrPc released by thrombin cleavage were recognized by a polyclonal antibody directed against amino acid 95 to 110 of the golden hamster PrPc protein. GST::PrPc was not detected by a monoclonal antibody recognizing the region encompassing amino acids 138 to 152 of the human prion protein. The fusion protein was sensitive to proteinase K digestion, demonstrating that the cellular rather than the proteinase K-resistant scrapie isoform was produced.

Animals

Sources of alcohol and drug information among Israeli urban adolescents.

This article describes a study which investigated sources of alcohol and drug information among Israeli urban adolescents in the north of Israel during the winter of 1993. Data were obtained from a sample of 1,346 students (50.9% males, 49.1% females), who were asked to indicate the amount of information (none, little, much) they had received from ten sources about eight categories of drugs. Among the findings: television is the primary source of information for all drugs, except inhalants, for which newspapers/magazines are the main source. Newspapers/magazines are of secondary importance for the rest of the seven categories of drugs. Teenagers are less likely to receive information from physicians/nurses and relatives than from other sources. Information based on personal experience is prominent concerning alcohol, cigarettes, inhalants and hashish/marijuana, and it prevails more among males than among females (p < .01). Females use school teachers as a source of information in all drug categories more than males (p < .01). There are differences in using various information sources among grades and types of places of living. Information based on personal experience with alcohol is notably correlated with that with cigarettes, whereas information based on personal experience with opiates is correlated with that with stimulants, hallucinogens and hashish/marijuana (p < .001). The mean number of sources of information used by the respondents is the highest concerning alcohol and the lowest concerning depressants. Implications for prevention are discussed.

Adolescent

BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors.

We have previously reported the isolation of an EGF-responsive precursor from the embryonic and adult mouse striatum. This precursor exhibits self renewal and the ability to produce a sphere of undifferentiated cells which can be induced to differentiate into neurons and glia. RT-PCR analysis of these spheres of undifferentiated cells revealed the expression of mRNA for the trkB neurotrophin receptor, both with and without the catalytic domain, and little or no expression of trkA or trkC. We examined the actions of BDNF on the fate of EGF-generated neural precursors. Ten days after a one-time exposure to BDNF, single EGF-generated spheres showed a twofold increase in neuron number and a marked enhancement in neurite outgrowth. Examination of neuronal nuclei with immunochemical probes for c-fos and bromodeoxyuridine revealed that the actions of BDNF were directly upon neuronal cells and did not involve division of neuronal precursors. The twofold increase in neuronal number due to BDNF, observed after 10 d in vitro, was significantly reduced after 21 d in vitro and was not apparent at 27 d in vitro. Quantitative analyses revealed that while repeated application of BDNF did not prevent the loss of neuron number over time, it did result in a significant increase in neurite numbers. Moreover, delayed addition of BDNF mimicked the increase in neuronal numbers seen when BDNF was present throughout. These BDNF actions did not appear to involve the enhancement of a novel neuronal phenotype, with all effects being due to increase in the numbers and neurite outgrowth of neurons that colocalize GABA and substance P. These findings suggest that BDNF markedly enhances the antigenic and morphologic differentiation of EGF-generated neuronal precursors. BDNF alone does not appear to act as a survival factor for neuronal precursors nor is it sufficient for preventing their death over time.

Animals

Mechanisms in adverse reactions to food. The joints and muscles.

There are several reasons for considering the hypothesis that food hypersensitivity might relate to rheumatic diseases. Food can evoke immune responses. Food can cause immunologically mediated symptoms. Immunological mechanisms are important in the pathogenesis of rheumatic diseases. Antigens triggering rheumatic responses are unknown. Rheumatic diseases have been associated with foods in many reports.

Food Hypersensitivity

T cell epitope analysis with peptides simultaneously synthesized on cellulose membranes: fine mapping of two DQ dependent epitopes.

Several MHC class II restricted, CD4+ human T cell clones from three donors were induced with soluble matrix protein of influenza virus. The epitopes recognized by these clones were mapped using a complete set of overlapping 15-mer peptides synthesized with the newly developed SPOT method which allows the simple simultaneous synthesis of numerous peptides on cellulose membranes. Fine analysis of two clones by truncation of the stimulatory peptide by single subsequent amino acids from either the NH2- or the COOH-terminus revealed the minimal stimulatory determinants of two DQ dependent T cell epitopes.

Amino Acid Sequence

Central nervous system growth and differentiation factors: clinical horizons--truth or dare?

Growth factors are potent and effective regulators of nerve-cell differentiation and survival. In the past year, several compelling studies have suggested that two proteins, glial derived neurotrophic factor and ciliary neurotrophic factor, may be useful in clinical approaches to treating injury or diseases of the nervous system. In addition, delivery of such factors to the central nervous system may be facilitated by a number of recently reported technologies: growth factor-antibody conjugates, polymer encapsulation and adenovirus vectors. These recent developments are part of new and innovative approaches towards brain repair.

Animals

Association of serum albumin with blood pressure in the normative aging study.

Little is known regarding serum albumin's epidemiologic relation to chronic disease. The relation of serum albumin to blood pressure was assessed in a longitudinal study of men who have been seen at 3- to 5-year intervals since the early 1960s. The authors analyzed data from over 20 years of observation using cross-sectional multiple regression models of blood pressure that allow for the correlation between repeated measures on the same individual (GLMIC models), longitudinal GLMIC models that incorporate terms for the interaction of time with serum albumin at baseline, and models of the slope of individuals' blood pressure over time. Serum albumin levels were found to have a consistently strong relation with both systolic blood pressure and diastolic blood pressure in the cross-sectional GLMIC models only. This relation did not change appreciably when covariates for age, body mass index, alcohol ingestion, smoking, serum calcium, hematocrit, heart rate, and antihypertensive medications were added. A rise in serum albumin of 1 g/dl was associated with 1.79-mmHg and 0.91-mmHg increases in systolic blood pressure and diastolic blood pressure, respectively. This phenomenon may be related to experimental studies linking tryptophan, the only amino acid to bind noncovalently to serum albumin, to a blood pressure-lowering effect mediated by promotion of 5-hydroxytryptamine synthesis in the brain.

Adult

Recombinant HIV-1 nucleocapsid protein p15 produced as a fusion protein with glutathione S-transferase in Escherichia coli mediates dimerization and enhances reverse transcription of retroviral RNA.

Human immunodeficiency virus 1 (HIV-1) nucleocapsid protein p15 was produced as a fusion protein with glutathione S-transferase (GST) in Escherichia coli. Rapid purification of GST::p15 in an active form by one-step glutathione-agarose chromatography was accomplished in the presence of an antioxidant. Recombinant p15 fused to GST was shown to stimulate the dimerization of viral RNA. HIV-1 reverse transcriptase-catalyzed in vitro synthesis of minus-strand cDNA from synthetic human tRNA(Lys3UUU) and natural bovine tRNA(Lys3SUU) primer molecules was enhanced by GST::p15. GST produced in E.coli revealed no effect with respect to RNA dimerization and cDNA synthesis, demonstrating that both activities reside in the p15 portion of the fusion protein.

Amino Acid Sequence

Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.

Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.

Animals

Synthetic human tRNA(UUULys3) and natural bovine tRNA(UUULys3) interact with HIV-1 reverse transcriptase and serve as specific primers for retroviral cDNA synthesis.

Full-length and 5'-truncated variants of human (h) tRNA(UUULys3) were synthesized by in vitro transcription using SP6 RNA polymerase. Bovine(b) tRNA(SUULys3) was purified from calf liver. Both full-length tRNA species were shown to be biologically active in an aminoacylation assay. Gel retardation assays revealed that both full-length tRNA species, as well as a 5'-truncated h-tRNA(UUULys3) molecule containing 24 nucleotides (nt) at the 3' end (Lys24), interact with human immunodeficiency virus (HIV)-1 reverse transcriptase (RT). Competition studies with these three tRNA species demonstrate that the 3' end of h-tRNA(UUULys3) contributes to the interaction with HIV-1 RT. Escherichia coli tRNA(UUULys) and tRNA(UUCGlu2) were also able to interact with the enzyme, whereas unrelated RNA molecules such as E. coli 5S rRNA did not bind to RT. Both b-tRNA(SUULys3) and h-tRNA(UUULys3) molecules, as well as the 5'-truncated variants, could be demonstrated to prime cDNA synthesis specifically using a HIV-1 RNA template, prepared by in vitro transcription, indicating that other viral or cellular proteins are not essential for this process. E. coli tRNA(UUULys) and tRNA(UUCGlu2), although able to interact with HIV-1 RT, failed to prime retroviral transcription. Products of cDNA synthesis were characterized by polymerase chain reaction, demonstrating that at least 18 nt at the 3' ends of h-tRNA(UUULys3) and b-tRNA(SUULys3) are still present in the cDNA product, whereas the 5' ends of both primer molecules were removed by the RNase H activity of HIV-1 RT.

Animals

Weak positive selection of transgenic T cell receptor-bearing thymocytes: importance of major histocompatibility complex class II, T cell receptor and CD4 surface molecule densities.

We have produced alpha beta T cell receptor (TcR)-transgenic mice and studied MHC-dependent positive selection of T cells bearing this receptor. The alpha and beta transgenes were isolated from an I-Ed-restricted, CD4+ BALB/c (H-2d/d) T cell clone specific for a peptide consisting of the 91-101 residues of the lambda 2 immunoglobulin light chain of MOPC315. Mice which carry the transgenes on a BALB/c background, but with H-2d/d, H-2b/d or H-2b/b major histocompatibility complex (MHC) haplotypes, were investigated for TcR expression in thymocytes and peripheral T cells. The thymocytes expressing the transgene-encoded alpha beta receptor are weakly positively selected when compared with previous findings in other TcR-transgenic mice models. Thus, alpha beta thymocytes vary in their efficacy of being positively selected by their restriction element. Furthermore, the density of TcR and CD4 on thymocytes, as well as the density of I-Ed molecules on thymic epithelial cells, appear critical for the extent of positive selection. A possible explanation is that the transgenic TcR has a marginal affinity for self-MHC molecules on thymic epithelium, and that this may be compensated for by an increase in the number of CD4/TcR/MHC ternary complexes forming between the maturing thymocyte and the cortical epithelial cells.

Animals