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Biomedical subjects

S Weiss

Publications and source records attributed to S Weiss.

At least 271 records · Page 15Linked to original sources

bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells.

In cultures of embryonic and adult mouse striatum, we previously demonstrated that EGF induces the proliferation of putative stem cells, which give rise to spheres of undifferentiated cells that can generate neurons and astrocytes. We report here that the spheres of undifferentiated cells contain mRNA and protein for the FGF receptor (FGFR1). Indirect immunocytochemistry demonstrated that many of the cells within the EGF-generated spheres were immunoreactive for FGFR1. Exogenous application of bFGF to the EGF-generated cells induced the proliferation of two progenitor cell types. The first, a bipotent progenitor cell, gave rise to cells with the antigenic and morphological properties of neurons and astrocytes; the other gave rise to cells with neuronal characteristics only. bFGF-generated cells with neuronal morphology exhibited electrophysiological properties indicative of immature central neurons. These results support the hypothesis that sequential actions of growth factors play a role in regulating the generation of neurons and astrocytes in the developing CNS.

Animals↗

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↗

Sedation of pediatric patients for nuclear medicine procedures.

Sedation of the pediatric patient for nuclear medicine imaging procedures requires careful planning, patient preparation, and monitoring to ensure patient safety. The American Academy of Pediatrics guidelines for the safe use of sedation recommend a systematic plan for the use of sedative agents. Elements of the plan include informed consent, a patient pre-sedation health evaluation, monitoring by a cardiopulmonary resuscitation-trained health-care practitioner, and recovery of the patient to the pre-sedation state before discharge. Other considerations include the formation of a sedation committee to monitor the sedation program, as well as provision of adequate space and equipment to monitor and care for patients appropriately. The choice of sedative to be used should be based on a predetermined sedation formulary and the assessment of the patient's physical status according to the American Society of Anesthesiologists' status classification system. Chloral hydrate used at a maximum dosage level of 100 mg/kg is a preferred sedative agent because it provides the widest margin of safety. Implementation of the guidelines provides a coordinated approach to the use of sedation for multiple procedures performed on the same day that require sedation, thus enhancing patient safety and successful completion of all procedures. Adequate resources, including personnel and equipment, are necessary for successful implementation of an adequate sedation program.

Child↗

Alcohol and the elderly: an overlooked phenomenon in the literature in developing countries-the Israeli case.

This paper provides a review and critique of research on Israeli older people's drinking. On the basis of a review of all published Israeli alcohol research, in Hebrew and English, it summarizes the findings concerned with alcohol and ageing in Israel. Research findings on this population are as inadequate in Israeli literature as is the case in other developing countries: this is a reflection of the common lack of interest in the problems of the elderly. In Israel and other developing countries, gerontologists are not interested in alcohol problems, alcohol researchers are not interested in the elderly, and alcohol abuse is not perceived as a problem of ageing. It is suggested that, with the increasing proportion of the population living past 65 years of age, the connections between ageing and alcohol abuse should be explored. Various directions for future research in Israel and other developing countries are suggested.

Journal Article↗

Anti-tumour activity of idiotype-specific, MHC-restricted Th1 and Th2 clones in vitro and in vivo.

Idiotypes (Id) can serve as individual markers on B cells; therefore, cytotoxic Id-specific T cells may play a significant role in immunological surveillance of Id+ B-cell tumours. We have investigated the anti-tumour activity of CD4+ BALB/c Th1 and Th2 clones which recognize a processed Id of the syngeneic lambda 2(315) L chain in the context of the class II MHC molecule I-Ed. Id-specific T cells and A20/46 B lymphoma cells transfected with the lambda 2(315) gene were injected s.c. into the same site of BALB/c mice (Winn assay). The results show that both Th1 and Th2 clones can protect against tumour development. The protection was Id-specific because T cells did not influence tumour development by an A20/46 B lymphoma cell line transfected with the pSV2neo expression vector alone. In vitro studies showed that the Th1 clones were cytotoxic to lambda 2(315)-transfected B lymphoma cells; by contrast, the Th2 clone was not cytotoxic in 51Cr-release assay even though the Th2 cells inhibited the growth of lambda 2(315) B lymphoma cells. The anti-lymphoma properties of both the Th1 and Th2 clones appear to involve as yet undefined cytotoxic and growth inhibiting molecules.

Animals↗

Frailty and injuries in later life: the FICSIT trials.

Physical frailty and fall-related injuries present two of the biggest threats to older people's functioning and quality of life. The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) trials represent a set of eight different clinical trials concerning physical frailty and injuries in later life. This report documents the history and organization of the trials and provides an overview of the measures being collected at multiple sites and the analytic strategies to be used for multi-site investigations.

Accidental Falls↗

Processing and presentation of idiotypes to MHC-restricted T cells.

Among the self antigens, immunoglobulins, and in particular idiotypes, are of special interest because of their extreme sequence heterogeneity and their postulated involvement in regulatory interactions in the immune system. We have therefore studied antigen processing and presentation of variable region peptides, processed idiotypes, to MHC class II molecule-restricted T cells. The immunoglobulin used has been the lambda 2(315) light chain produced by the BALB/c MOPC 315 plasmacytoma (alpha, lambda 2). The minimum length of a stimulatory synthetic idiotypic peptide comprises residues 91-101 of lambda 2(315) and is presented by the I-E(d) molecule to CD4+ T cells. T cell clones with specificity for the 91-101(lambda 2(315))/I-E(d) complex utilize a limited TCR repertoire and are of both Th1 and Th2 type. For presentation, extracellular lambda 2(315) requires endocytosis and processing, as previously described for conventional exogenous antigens. In addition, a B lymphoma cell can process and present its own endogenous lambda 2(315). This was shown by transfecting manipulated lambda 2(315) gene variants into B lymphoma cells, followed by evaluation of the APC function of the transfectants. These studies demonstrated that surface expression or secretion of lambda 2(315) is not necessary for presentation and suggested that the endoplasmic reticulum may be a processing compartment. To extend our findings to naive Id+ B cells and anti-Id T cells, we have generated lambda 2(315)-transgenic as well as TCR-transgenic mice. A model is presented for a T-B cell interaction based on presentation of processed idiotypes.

Amino Acid Sequence↗

Point of view: alcoholic physicians in Israel.

Data on alcohol drinking habits among medical students and levels of alcoholism in the general population imply that there are a significant number of alcoholic physicians in Israel. The tendency of the alcoholic doctor to conceal, the tendency of colleagues to deny and protect, and the inadequate education on the effects and consequences of alcohol dependence among physicians in Israel are presented as explanations for the absence of reporting of this phenomenon.

Alcoholism↗

[The effect of ethylenediaminetetramethylenephosphonate on the biodistribution of tumor-seeking radionuclides].

It is well known that after application of radioactive complexes for tumour diagnosis or therapy, such as 67Ga-citrate or radiolanthanide complexes (167Tm- or 169Yb-nitrilotriacetate, -citrate, -alpha-hydroxyisobutyrate, 90Y-citrate, etc.) activity is accumulated not only in the tumour but also in other organs, above all liver and bone. This is the main obstacle to their medical use. Recently published results encouraged us to use ethylenediaminetetramethylene phosphonate (EDTMP) for the reduction of extratumoural liver activity. The results show that even small amounts of EDTMP (1-2 mg/kg BW) reduce the activity deposition in the liver by about one order of magnitude. EDTMP provoked elimination of activity from tumour, skeleton and other tissues but not to the same extent as from the liver. Tumor/liver activity ratios > 5 are achievable in this manner.

Animals↗

[The effect of bone-seeking metal salts on the biodistribution of tumor-seeking heavy metal complexes].

This work attempted to overcome the problem of unwanted bone radioactivity after injection of tumour-affine heavy-metal compounds (prototype 169Yb-citrate) by pre-application of stable yttrium- and calcium-compounds into tumour-bearing mice in doses of 1 mg metal/kg body weight. The pre-application of stable yttrium and calcium resulted in a smaller bone radioactivity. The most favourable results were achieved by injecting the metal salts simultaneously at or within 5 h before the 169Yb-citrate. On the other hand a strong radioactivity increase in the RES (liver and spleen) by a factor of 2 to 4 was observed after yttrium-preapplication.

Animals↗

[Long term biokinetics of 169Yb following injection as citrate, hydroxyethylethylenediaminetetraacetate and nitrilotriacetate].

169Yb complexes with known biokinetics in tumour-bearing mice up to 48 h p.i. were injected into healthy mice to study the radionuclide biodistribution in various organs and tissues for 672 h after injection, in order to obtain reliable biokinetic data in an animal model, not affected by tumour-growth, as a basis for the calculation of biological half-life and dose distribution. The results demonstrated the existence of at least two components with different biological half-lives in the organs and tissues investigated. The effective half-lives of these components decreased with increasing stability of the complexes administered. The effective half-life of the fast component was a few hours and that of the slow one between about 200 and 800 h.

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↗