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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 325 records · Page 18Linked to original sources
PubMed1987

Immature megakaryocytes in the mouse: synergistic response to megakaryocyte potentiator, thrombopoietic stimulatory factor with interleukin 3.

The in vitro biological activities of thrombopoietic stimulating factor, recombinant interleukin 3, and megakaryocyte potentiator from various sources were studied. Growth activities were assessed by the responsiveness of enriched populations of small, immature megakaryocytes to factor preparations by measuring increased numbers of acetylcholinesterase-positive cells and increased cell size as indices of megakaryocyte development. All factors stimulated optimum megakaryocyte growth at high concentrations. Immature megakaryocytes revealed the same responsiveness to titrated amounts of the various factors tested, with similar slopes to the dose-response curves. The activities of both thrombopoietic stimulating factor and megakaryocyte potentiator were additive when suboptimal doses were used. In contrast, low concentrations of recombinant interleukin 3 and thrombopoietic stimulating factor acted synergistically to stimulate an optimal response. The data indicate that at low and perhaps physiologically relevant concentrations, two classes of factors influence murine megakaryocyte development by different but related mechanisms.

Animals↗
PubMed1986

Treatment of chronic knee effusions with 90yttrium-correlation of in vitro radiation and chemical effects with clinical results at three and six months.

Twenty seven knees, mainly of rheumatoid patients, received intra-articular 90Y for chronic effusions; 24% were effusion-free at 6 months. In vitro chemical, radiation (32P-induced), and combined effects of cold (non-radioactive) yttrium and 32P on synovial fluid mononuclear cells, failed to show any significant correlation with subjective and/or objective clinical effects at 3 or 6 months. If 90Y exerts its therapeutic effect via these cells, it probably does so other than by a direct effect on mononuclear cell viability.

Chronic Disease↗
PubMed1986

Biochemical characterization of an in-vitro murine megakaryocyte growth activity: megakaryocyte potentiator.

The biochemical properties of an in-vitro megakaryocyte growth factor called megakaryocyte potentiator (Mk-POT) were investigated. P388D1 cell conditioned medium (P388D1 CM), was used as the source of Mk-POT. The potentiator activity had an apparent mol. wt of 21 kilodaltons (kd) by gel filtration and was eluted from DEAE-Sepharose pH 8.0 with 0.15 M NaCl. Chromatofocusing revealed three active species with apparent pIs of 4.0, 5.5 and above 6.0. Most Mk-POT activity does not bind to Concanavalin A-Sepharose. Mk-POT activity is sensitive to reduction by dithiothreitol and temperatures above 90 degrees C. Treatment with trypsin, alpha-chymotrypsin and pronase also reduced the Mk-POT activity, but it was not destroyed by RNase A or neuraminidase. It is precipitated in ammonium sulphate solutions of between 60 to 70% saturation, and by 80% ethanol. The Mk-POT activity is stable in solutions of pH 5.0-9.0. The data presented here suggest that megakaryocyte potentiator is either heterogeneous in its properties or more than one molecular species may express the in-vitro Mk-POT activity found in P388D1 CM.

Animals↗
PubMed1986

Octanol:water partition coefficients (P): measurement, estimation, and interpretation, particularly for chemicals with P greater than 10(5).

Methods for measurement and estimation of octanol:water partition coefficients are discussed with particular reference to high values (log P greater than 5). A novel experimental method for P measurement is described and preliminary results presented. The use of high performance liquid chromatography capacity factors for estimating P values has been investigated; better correlations between the two parameters have been found if HPLC results at different methanol:water liquid phases are extrapolated to pure water, but even this procedure does not always give reliable P values. The interpretation of high log P values in terms of fish bioconcentration is discussed and the correlations of molecular connectivity and molecular weight with fish bioconcentration are presented.

Animals↗
PubMed1986

Pel, the protein that permits lambda DNA penetration of Escherichia coli, is encoded by a gene in ptsM and is required for mannose utilization by the phosphotransferase system.

Mannose uptake and phosphorylation in Escherichia coli is catalyzed by the phosphoenolpyruvate:glycose phosphotransferase system (PTS). The mannose-specific complex of the PTS, designated IIMan, comprises lipid and two membrane proteins, II-AMan and II-BMan. The proteins are encoded by ptsM, located at approximately equal to 40 minutes on the E. coli chromosome. A different genetic marker, pel, maps with ptsM, and is required for lambda DNA penetration of the cytoplasmic membrane. Earlier studies suggested that both pel function and II-BMan are encoded by the same gene, while a different gene (also in ptsM) encodes II-AMan. In the present studies, a ptsM clone, pCS13, was isolated from an E. coli HindIII gene bank in pBR322 and restored both mannose termentation and pel+ function to ptsM mutants defective in II-BMan. Subclones of pCS13 show that two distinct genes, manY and manZ, encode the pel+ function and the II-BMan protein, respectively; each gene may have its own promoter; whereas the protein encoded by manY (Pel) alone seems sufficient for lambda sensitivity, all three gene products are required for mannose fermentation, transport of the mannose analogue 2-deoxyglucose, and phosphorylation of the latter by cytoplasmic membranes. Thus, Pel is required for function of the IIMan complex. The efficiency of the complex may depend on the ratio of Pel to IIMan.

Bacterial Proteins↗
PubMed1986

The pattern of HLA-DR and HLA-DQ antigen expression on clonable subpopulations of human myeloid progenitor cells.

Three subpopulations of human myeloid progenitor cells (CFU-GM) can be distinguished by differences in their kinetics of development; the liquid phase pre-CFU-GM, the day 14 CFU-GM, and the day 7 CFU-GM. The relative cell membrane densities of the HLA-DR and HLA-DQ antigens expressed by the three subpopulations was investigated by comparing the amount of antibody required to deplete bone marrow cell preparations of each cell type. Three separate approaches were used--complement (C') cytotoxicity, antiglobulin/C'-cytotoxicity and immune rosette depletion. Similar results were obtained for all three procedures, although the latter two gave a tenfold greater sensitivity over the standard C'-cytotoxicity method. At saturating anti-HLA-DR antibody concentrations, 85% to 95% of cells within the three myeloid subpopulations were found to express HLA-DR antigens. However, the relative amount of HLA-DR expressed by these subpopulations increased from the pre-CFU-GM to the day 7 CFU-GM. The expression of HLA-DQ antigens was considerably lower and could only be detected by using the more sensitive procedures. Only 50% of day 7 and 14 CFU-GM progenitor cells expressed detectable HLA-DQ antigens, whereas a greater proportion (80%) of the pre-CFU-GM were HLA-DQ positive. The pattern of HLA-DQ expression on these clonable precursors was quite distinct and opposite to the cell membrane density of the HLA-DR antigens. Because these three progenitor cell populations are thought to be linked in differentiation sequence, these results provide indirect support for the hypothesis that HLA class II antigens are implicated in regulatory mechanisms during normal myeloid cell differentiation.

Antibodies, Monoclonal↗
PubMed1985

Murine megakaryocyte colony stimulating factor: its relationship to interleukin 3.

A protocol for the partial purification of murine megakaryocyte colony stimulating factor from WEHI-3 cell conditioned medium is described. The procedure involving separation by anion exchange chromatography and molecular sieving on Sephadex G100, gave a 260-fold purification over starting material, as determined by in-vitro megakaryocyte colony formation. Fifty percent of maximum colony numbers were obtained at a dose of 1 microgram protein/ml. Electrophoretic analysis of the partially purified preparation followed by silver nitrate staining revealed four major protein bands with apparent molecular weights of 67 Kd, 43 Kd, 38 Kd and 28 Kd. All megakaryocyte colony stimulating activity and interleukin 3 activity was found in the 22-25 Kd fraction from a preparative SDS-polyacrylamide gel using non-reducing conditions, a molecular weight range that coincided with the 28-Kd molecule obtained when reducing conditions were employed.

Animals↗
PubMed1985

Dose rates from patients having nuclear medicine investigations.

Dose rates have been measured at 0.1 m, 0.5 m and 1.0 m from patients in a Nuclear Medicine Department. Data are presented for a variety of Nuclear Medicine procedures using doses of radiopharmaceuticals within the recommendations of the administration of Radioactive Substances Advisory Committee (ARSAC). The corresponding figures when the patient left the department, and the time average dose rate over the next 8 h were calculated. At 1.0 m the dose rates do not exceed 7.5 microSv h-1, and at 0.5 m the time average dose rate does not exceed 60 microSv h-1. Assuming that the nurse is as close to the patient as 0.1 m for 20 min in a working day, the accumulated dose over a working day would not exceed 60 microSv.

Hospital Departments↗
PubMed1985

In vitro inhibition of myelopoiesis by gold salts and D-penicillamine.

Leukopenia is one of the more serious side effects of gold and D-penicillamine therapy. We report that gold salts (gold thiomalate, gold chloride and gold thioglucose) and D-penicillamine suppressed the in vitro development of colonies of myeloid cells (macrophage, granulocyte and megakaryocyte) from progenitor cells in murine bone marrow; these drugs were also effective in inhibiting the development of macrophage and granulocytic colonies in human bone marrow. The drugs generally required concentrations of 10(-5) M in the murine system, whereas they were active at 10(-7)-10(-8) for the human progenitor cells. The disease suppressive activity of gold salts and D-penicillamine could result in part from the reduction of cell numbers in arthritic lesions; our findings would provide a mechanism for this possibility.

Animals↗