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Biomedical subjects

S Schrader

Publications and source records attributed to S Schrader.

33 records · Page 2Linked to original sources
PubMed1999

An open-label trial of stavudine, lamivudine and efavirenz in the treatment of HIV-positive, treatment-naive patients, and implications for clinical practice.

A phase II, open-label study of stavudine, lamivudine and efavirenz resulted in significant reductions in plasma HIV-1 RNA over a 24 week period in human immunodeficiency virus (HIV)-infected individuals. The trial currently has 68 patients, and this presentation covers data on the first 42 patients enrolled for 24 weeks. The mean plasma HIV-1 RNA on entry was 75858 HIV RNA copies/ml, and the mean CD4 count was 380 cells/mm3. After 24 weeks, the CD4 count increased by 169 cells/mm3 above baseline. plasma HIV-1 RNA was markedly reduced: at 24 weeks, more than 97% of patients had <50 HIV RNA copies/ml based on observed data, and 89% of patients had <50 copies/ml based on strict intent-to-treat analysis (non-completer=failure). The favourable interactions of these agents resulted in no discontinuations owing to adverse effects. This regimen provides an important first-line treatment for antiretroviral-naive patients.

Adult↗
PubMed1992

The carboxy-terminal extension of the D1-precursor protein is dispensable for a functional photosystem II complex in Chlamydomonas reinhardtii.

The D1-precursor protein of the photosystem II reaction centre contains a carboxy-terminal extension whose proteolytic removal is necessary for oxygen-evolving activity. To address the question of the role of the carboxy-terminal extension in the green alga Chlamydomonas reinhardtii, we truncated D1 by converting codon Ser345 of the psbA gene into a stop codon. Particle gun transformation of an in vitro modified psbA gene fragment also carrying mutations conferring herbicide resistance yielded a homoplasmic transformant containing the stop codon. Since oxygen evolution capacity is not affected in this mutant as compared with herbicide-resistant control cells, the carboxy-terminal extension is dispensable for a functional photosystem II complex under normal growth conditions.

Amino Acid Sequence↗
PubMed1992

Methods for assessing rat sperm motility.

Computer-assisted sperm analysis (CASA) systems are becoming more widely used. With this spread of technology come more data from toxicology studies, designed to determine if treatment with putative toxicants affects sperm motion parameters. While these CASA methods provide us with more ways to evaluate toxicity and thus perhaps increase our chances of successfully protecting human health, there is also a greater likelihood that different laboratories will use different methods of collecting data on sperm motility. Different systems used with different methods in different laboratories will inevitably generate data that are difficult to compare. In a prospective attempt to address this issue of comparability and limit the problems, a group of individuals using CASA systems to analyze rat sperm motility convened to discuss methodologic issues, share data, and try to reach a consensus about methods for performing these studies. This article shares those meetings and data in the hope that common methods will enhance interlaboratory comparisons.

Animals↗
PubMed1991

Indirect fertility analysis in painters exposed to ethylene glycol ethers: sensitivity and specificity.

Semen analysis has proven useful in the clinical diagnosis of infertility and is the most widely used method of monitoring the effects of occupational exposure on male fertility. Collection and analysis of semen samples in a field setting, however, require a highly motivated population and excellent technical resources, limiting the widespread application of the method. Techniques of monitoring male worker fertility using questionnaires to avoid some of the difficulties of semen analysis have been developed. These methods compare the rate of observed births for wives of workers with expected birth rates derived either from U.S. fertility tables or from unexposed workers. The present study compares the sensitivity of this questionnaire method with that of semen analysis in an evaluation of reproductive function in men exposed to ethylene glycol ethers. The reproductive function of 74 married painters exposed to ethylene glycol ethers was compared with that of 51 married controls employed at a shipyard. The groups differed in sperm count, but the questionnaire method showed no effect of exposure on fertility. This analysis suggests that the questionnaire assessment of fertility is less sensitive than semen analysis as a screening tool for male reproductive function.

Adult↗
PubMed1991

[Therapy of banal HSV lesions: molecular mechanisms of the antiviral activity of zinc sulfate].

Preparations of heparin in combination with the physiologically harmless and even beneficial zinc sulphate are available for the topical treatment of superficial mucocutaneous lesions caused by HSV (herpes simplex virus). We study the molecular mechanism of the antiviral effects of zinc ions. A concentration of 100 mumol/l Zn2+ in the culture medium reduces the virus yield in a HSV infected AGMK cell line to less than 1/1000 of the control. At this concentration zinc sulphate does not exert any major cytotoxic effects, nor does it block the synthesis of viral or cellular DNA. Free virus, however, is inactivated by 8 orders of magnitude by 15 mmol/l zinc sulphate within a few hours. The inactivated virus is limited in the glycoprotein-dependent functions adsorption and penetration. Electron micrographs show massive deposition of zinc onto virion components. The dramatic antiviral effect in vivo is therefore explained by an inhibition of virion glycoprotein functions after accumulation of zinc in the virion, presumably by binding to sulphhydryl groups of glycoprotein B.

DNA, Viral↗
PubMed1990

The mechanism of the antiherpetic activity of zinc sulphate.

The molecular mechanism of the effects of zinc ions against herpes simplex virus (HSV) infection was investigated. Zinc sulphate (100 microM) in the culture medium of an HSV-infected African green monkey kidney cell line did not block viral DNA synthesis and, at this concentration, only moderate cytotoxic effects were observed in uninfected cells. Nevertheless, virus yields were reduced to less than 1% of the control. Thus the long standing hypothesis that zinc might block multiplication of HSV by selective intranuclear inhibition of the viral DNA polymerase apparently has lost its validity. Inhibition of virus growth in the absence of severe cytotoxicity must therefore result from other effects of ZnSO4. Free virus is inactivated by 15 mM-ZnSO4 within a few hours of its addition. The inactivated virus is defective in the glycoprotein-dependent functions of penetration and, to some extent, adsorption. Electron micrographs show massive deposition of zinc onto virion components. In a virion, transmembrane transport of zinc ions is not expected and the established antiviral effect is therefore explained by an inhibition of virion glycoprotein function after non-specific accumulation of zinc into many virion membrane components.

Adsorption↗
PubMed1987

Autostimulatory mechanisms in myeloid leukemogenesis.

WEHI-274 is a monocytic leukemia that arose in a BALB/c mouse infected with Abelson murine leukemia virus. A series of subclones were derived from early passages of this tumor. Three subsets of these leukemogenic subclones were identified. Two subsets demonstrated autostimulatory patterns of growth. This was due to the ectopic production of the T-cell lymphokine the panspecific hemopoietin IL-3 in one case and of the T-cell lymphokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in the other. The third type of subclone did not secrete any autostimulatory growth factor. In the subclone producing IL-3, one copy of IL-3 gene was rearranged and abnormal IL-3 RNA transcripts were present in the nucleus. Subclones producing GM-CSF also contained abnormal GM-CSF RNA transcripts, although no rearrangement of the GM-CSF gene was detected. All three sets of subclones shared a common rearrangement of one c-myb oncogene, suggesting that they share a common ancestor. These results suggest that initiation or progression of leukemogenic behavior in this abnormal clone occurred in three different ways, two of which involved autostimulation by the ectopic activation of T-cell lymphokine genes.

Animals↗
PubMed1987

Murine c-myc retroviruses alter the growth requirements of myeloid cell lines.

Recombinant retroviruses encoding a murine c-myc gene were utilised to explore the consequences of constitutive c-myc expression for interleukin 3-dependent murine myeloid cell lines. The c-myc virus-infected cells exhibited a diminished requirement for growth factor and serum when grown in soft agar, but no factor-independent cells could be isolated and the cells were not tumorigenic. Thus deregulated expression of a c-myc gene at physiological levels apparently renders myeloid cells more responsive to growth factors but cannot abrogate this requirement or render the cells malignant.

Animals↗
PubMed1984

In vitro approaches to lymphopoiesis, hemopoiesis, and oncogenesis.

Lymphopoiesis still remains a black box. Much remains to be learned about the identification of the cellular stages and the factors that regulate the rate of production of lymphocytes. Modifications of the Dexter system should assist with answers to these questions. Our work on PSF and that of other groups who have studied what is almost certainly the same factor under names such as hemopoietic growth factor, IL-3, BPA or multi-CSF suggests that this factor may provide an alternative means of generating cells for transplantation and replacement therapy. At present the only established sources of PSF are the activated T cell or tumors in which we think the gene has been anomalously activated, such as WEHI-3B; the long-term bone marrow culture system, however, seems to be defining a factor or influence that may be identical with, or is able to replace, the T cell factor. Finally, our experiments with the heterogeneous P cell lines and the initiation of oncogenesis by activation of the PSF gene raise some caveats about the use of cultured cells for human therapy. In the mouse system the production of immortalized factor-dependent lines appears to be more frequent in cells taken from long-term bone marrow cultures rather than normal bone marrow. Obviously, further information on the mechanism of immortalization and on the frequency and mechanism of activation of PSF genes in such lines will be of great importance in guiding the practical use of in vitro-derived cells and in the understanding of leukemogenesis.

Animals↗
PubMed1979

In vitro studies on lymphocyte differentiation. II. Generation of terminal deoxynucleotidyl transferase-positive cells in long-term cultures of mouse bone marrow.

The enzyme TdT is the earliest known marker of lymphocytic differentiation in rodents. Cells containing this enzyme were demonstrated in suspension cultures of mouse bone marrow cells that had been maintained in vitro for periods of 7 to 45 days. The cells were detected by immunofluorescence using purified antibodies to homogeneous TdT. Between 0.04 and 2.0% of cultured bone marrow cells from a variety of mouse strains were positive. More than 40% of the TdT-positive cells incorporated 3H-thymidine during a 20-min pulse. Surface Ig and Thy-1 antigens were not detected on the TdT-positive cells. The prevalence of TdT-positive cells was decreased 10-fold in cultures that had been treated with 10(-6) M hydrocortisone 24 hr before harvesting. The results indicate that lymphoid progenitor cells can be generated in vitro.

Animals↗
PubMed1978

In vitro studies on lymphocyte differentiation. I. Long term in vitro culture of cells giving rise to functional lymphocytes in irradiated mice.

In vitro cultures of mouse bone marrow cells, maintained for periods up to 7 wk, were shown to contain cells able to repopulate irradiated hosts with T and B lymphocytes. The lymphocytes were fully functional and there did not appear to be any gross restriction of their receptor repertoire. The cultured cells reconstituted irradiated semiallogenic hosts without evidence of graft-versus-host disease, suggesting that culture of donor marrow might be a useful preliminary to transplantation when tissue matching is incomplete.

Antibody Formation↗
PubMed1978

Immunologic functions and in vitro activation of cultured macrophage tumor lines.

Five murine monocyte of macrophage tumor lines adapted to culture were characterized for differentiated properties. They ingested zymosan and latex beads, bore receptors for immunoglobulin and complement, synthesized lysozyme (most of which was secreted), and produced granulocyte colony-stimulating activity, either spontaneously or inducibly. Some of the lines also mediated phagocytosis and exocytosis of red blood cells (RBC) and lysis of tumor targets, dependent on the presence of specific antitarget sera. All the lines were growth inhibited by zymosan and Mycobacterium bovis BCG, but not by latex beads. Other macrophage-activating agents, dextran sulfate and lipopolysaccharide (LPS), as well as tuberculin purified protein derivative (PPD), inhibited most of the lines. Except for Fc and C receptors, most of the above properties were not found with other types of hematopoietic tumors in culture. In attempts to activate the macrophage lines in vitro to the "angry" state, we found that preincubation with concentrations of LPS and PPD cytostatic to the cells stimulated antibody-dependent RBC lysis, but not antibody-independent or tumor cytolysis. A classification of monocyte-related tumors and normal cells is proposed based on functional activities and differential sensitivity to immunostimulating agents.

Animals↗
PubMedDate not supplied

Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. ILSI Risk Science Institute Expert Working Group on Sperm Evaluation.

Reproductive toxicity studies are increasingly including assessments of sperm parameters including motility, morphology, and counts. While these assessments can provide valuable information for the determination of potential reproductive toxicity, the methods for conducting the assessments have not been well developed in all laboratories and are continually evolving. The use of different methods in different laboratories makes comparison of data among laboratories difficult. To address the differences in methods, a working group was convened to discuss methods currently in use, share data, and try to reach consensus about optimal methods for assessing sperm parameters in rats, rabbits, and dogs. This article presents the consensus report, as well as future research needs, with the hope that optimized common methods will aid in the detection of reproductive effects and enhance interlaboratory comparisons.

Animals↗