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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 361 records · Page 20Linked to original sources
PubMed1982

Immunoenhancing activity of NPT 15392: a potential immune response modifier.

NPT 15392, a new immunomodulating compound related to inosine in structure and isoprinosine in action, enhances T-cell dependent immune responses. Antibody responses to sheep red blood cells are augmented two to threefold in mice receiving NPT 15392 while T-cell independent antibody responses to TNP-LPS are unaffected. NPT 15392 does not enhance or alter the number of clonable B cells. This drug also increases cytotoxic T-lymphocyte responses to allogeneic tumor cells but does not alter the number of cytotoxic precursor cells. Immature hematopoietic cell classes (clonable progenitor cells) were also monitored and found not to be influenced by NPT 15392.

Adjuvants, Immunologic↗
PubMed1982

The effect of acute opioid administration on the phosphorylation of rat striatal synaptic membrane proteins.

The acute administration of morphine, methadone, etorphine, methionine-enkephalin, leucine-enkephalin and some related pharmacologically active peptides to rats produces biphasic effects on the degree of phosphorylation of striatal synaptic plasma membrane (SPM) proteins by endogenous protein kinases in the membranes. At 1 to 5 min after opioid administration, the phosphorylation of several SPM proteins is enhanced, followed at 10 to 20 min by a severe reduction in the rate of phosphorylation of the same proteins. Multiphasic responses follow the initial biphasic response after the injection of some opioids. Naloxone is able to block the agonist effects. The injection of saline or an inactive narcotic isomer has no effect on the phosphorylation of striatal SPM proteins. The administration of other psychoactive drugs such as clonidine or haloperidol also produces changes in phosphorylation, although the patterns of change are distinctly different from those produced by opioids. The proteins affected by opioid administration resemble those susceptible to stimulation of phosphorylation in the presence of Ca++/calmodulin. The role of Ca++/calmodulin-regulated reactions in the mechanisms of action of opioids has been evaluated by the addition of these modulators to the assays of preparation from opioid-treated rats. Neither modulators, added separately or together to the assay, was able to restore a depressed phosphorylation to normal levels, although each modulator was effective in stimulating the phosphorylation of many SPM proteins.

Animals↗
PubMed1982

Immature megakaryocytes in the mouse: physical characteristics, cell cycle status, and in vitro responsiveness to thrombopoietic stimulatory factor.

The heterogeneity among immature megakaryocytes has been examined by physical properties, cell cycle status, and responsiveness to thrombopoietic stimulatory factor. Three types of immature megakaryocytes exist that can be recognized by acetylcholinesterase staining, nuclear shape, high nucleus/cytoplasm ratio, and small size (8--18 mu) with respect to mature megakaryocytes (greater than 18 mu). These three acetylcholinesterase-containing cell types are distinguished by their nuclear configuration: a round, indented, and lobed nucleus. The lobed cell type was found to overlap with and enhance detection of megakaryoblasts (stage I megakaryocytes). These cells had a sedimentation velocity range of 3.5--19.0 mm hr-1 and a density range of 1.072--1.095 g cm-3. Separation of these three classes of immature megakaryocytes was achieved by equilibrium density centrifugation with modal buoyant densities of 1.079 g cm-3 (round), 1.084 g cm-3 (indented), and 1.089 g cm-3 (lobed). In the presence of thrombopoietic stimulatory factor, the round nucleated cells, but not the indented or lobed nuclei morphology, were observed to develop into large mature megakaryocytes in 60-hr semisolid cell cultures. Development of two cell groups, or colonies of megakaryocytes, was not observed during this in vitro incubation period. In vivo treatment with hydroxyurea indicated that 57.5% +/- 19% of the round nucleus form were actively synthesizing DNA. No reduction in the numbers of indented or lobed nucleus forms were observed following hydroxyurea treatment. The data in this report strongly support the concept that these three types of immature megakaryocytes reflect the early maturation stages occurring in megakaryocyte differentiation.

Acetylcholinesterase↗
PubMed1981

Immature Megakaryocytes in the Mouse: Morphology and quantitation by acetylcholinesterase staining.

Three types of immature megakaryocytes, detected by their morphological properties, have been characterized in bone marrow of normal C57BL/6 mice. Morphological classification of these cells was carried out by determining (1) presence and relative amount of acetylcholinesterase, (2) cell size, (3) nuclear/cytoplasm ratio, and (4) nuclear shape. The immature megakaryocytes were classified as: (A) cells distinguished by a round nucleus (10.6 +/- 1.1 mu diameter; mean +/- SEM), which had the highest nucleus / cytoplasm ratio and lowest content of acetylcholinesterase; (B) cells with an indented nucleus (13.0 +/- 1.9 mu diameter), which had increased acetylcholinesterase content and reduced nucleus/cytoplasm ratio compared to the round-nucleus cell type; and (C) lobed-nucleus cells (14.5 +/- 2.9 mu diameter), which showed further increase in acetylcholinesterase content and reduction in nucleus/cytoplasm ratio. Increased numbers of immature megakaryocytes were detected, indicating that a proportion of these cells are undetected using conventional staining techniques. Based on the observed alterations in size, acetylcholinesterase content, and nuclear complexity, it was concluded that these cells constitute part of a progressive maturation sequence intermediate between the progenitor cell (CFU-Mk) and mature easily recognizable megakaryocytes.

Acetylcholinesterase↗
PubMed1981

Cell interactions influencing murine marrow megakaryocytes: nature of the potentiator cell in bone marrow.

Auxiliary bone marrow cells are required for optimal murine megakaryocyte colony formation in addition to progenitor cells and a colony stimulating activity (CSA) present in WEHI-3 cell conditioned medium. These auxiliary cells are adherent, with a sedimentation rate of 5.8 mm hr-1 and buoyant density of 1.065-1.078 gcm-3. The activity from bone marrow cells is loss at irradiation doses above 900 rad. Bone marrow cells with these characteristics, and supernatants from lung, bone shafts, and peritoneal exudate cells were all active in enhancing megakaryocyte colony incidences in mouse bone marrow cultures above those stimulated by an obligatory activity in WEHI-3 cell conditioned medium. Certain macrophage cell lines (J774, P388D1) could elaborate the activity. This study confirms that a potentiation activity enhances CSA stimulation of megakaryocyte colony formation. The potentiator is elaborated by bone marrow cells in limiting amounts requiring either high cell concentrations or an exogenous source of the activity for optimal colony growth.

Animals↗
PubMed1981

Abrogation of the non-specific toxicity of abrin conjugated to anti-lymphocyte globulin.

A covalent conjugate of abrin and anti-human lymphocyte globulin (AHLG) was prepared in an endeavour to create a cytotoxic agent with specificity for human lymphoid cells. The AHLG--abrin conjugate was found to be around 10-fold better able to inhibit 3H-leucine uptake by the human lymphoblastoid cell line, Daudi, in tissue culture than was the control conjugate comprising abrin and normal IgG (nIgG). Both materials were less potent than native abrin. Galactose, which is known competitively to antagonize the binding of abrin to cells, strongly inhibited the toxicities of abrin and the nIgG--abrin conjugate whereas that of ALG--abrin was unimpaired. Thus, at least for Daudi cells in tissue culture, abrin can be made selectively toxic, by linkage to AHLG, towards cells bearing antigens to which the antibody moiety of the conjugate can attach.

Abrin↗
PubMed1980

The maturation state of three types of granulocyte/macrophage progenitor cells from mouse bone marrow.

The progenitor cells of neutrophil granulocytes and macrophages which are able to proliferate and differentiate in vitro (CFU-c) form a heterogeneous population. By the use of specific colony stimulating activities and cell separation by equilibrium density centrifugation, three subpopulations of CFU-c can be detected. These three CFU-c are characterized by buoyant densities of 1.070, 1.075 and 1.080 g.cm-3 and by their proliferative response to 18 h postendotoxin serum, colony stimulating factor from extracts of mouse embryos and uteri (CSF-pmue) and erythrocyte lysate, respectively. The three CFU-c are compared with respect to their differentiation potential, the maturation rate of their progeny cells and their proliferation capacity. It is shown that with increasing density of the CFU-c the maturation rate increases (sequential maturation of colonies derived from CFU-c with densities of 1.080, 1.075, 1.070 g.cm-3) and the proliferation capacity decreases (colony size decreases in the sequence of CFU-c with densities 1.070, 1.075, 1.080 g.cm-3). Concerning the differentiation potential it is shown that all three CFU-c detected have the capacity to form granulocytes as well as macrophages. On the basis of these results it is concluded that the CFU-c with densities of 1.070, 1.075 and 1.080 g.cm-3 represent a maturation sequence.

Animals↗
PubMed1980

The effect of mouse lung granulocyte-macrophage colony-stimulating factor and other colony-stimulating activities on the proliferation and differentiation of murine bone marrow cells in long-term cultures.

The roles of colony-stimulating factors in long-term bone marrow cultures were studied and compared. After single additions of high concentrations of unpurified colony-stimulating activities to the cultures, rapid deterioration of the cultures was observed. This appears to result from contaminants in the stimulatory preparations. Cultures to which one purified colony-stimulating factor (csf) from endotoxin mouse lung-conditioned medium was added did not run down ten weeks after addition and were found to be the same as the controls. The deterioration of the cultures to which unpurified stimulators were added could not be accounted for by accelerated granulopoiesis leading to subsequent exhaustion of the cultures. The inability of purified CSF to affect the cellularity of the suspension cells did not result from instability or masking of the activity in the cultures, nor did CSF preferentially stimulate the cells within the adherent layer. The suspension cells responded to purified CSF after separation from the adherent cells. The data suggest that if CSFs are marrow stimulators, their effects in turn may be stringently regulated within the marrow.

Animals↗
PubMed1980

Limitation of macrophage production in long-term marrow cultures containing prostaglandin E.

Addition of prostaglandin E2 (PGE2) significantly altered the cellular composition of murine long-term bone marrow cultures. After 4--5 weeks of culture, increased cellularity in the suspension phase was observed in all cultures containing prostaglandin. These suspension cells contained markedly higher proportions of differentiated neutrophils than did cells cultured in the absence of PGE2. Granulocyte-macrophage progenitor cell levels in the suspension layer were increased 3--20 fold after five weeks in prostaglandin-containing cultures compared with control cultures. Fewer cells comprised the adherent layer in cultures containing prostaglandin. The number of macrophages in this layer was reduced 3--8 fold in these cultures compared with control cultures, while the number of granulocytes was increased 2--3 fold. The progenitor cells biased toward macrophage development were selectively inhibited in the cultures with PGE2. There was no significant effect of PGE2 on pluripotent stem cell levels or on the longevity of the cultures. It is concluded that excessive monopoiesis in bone marrow may be limited by PGE2 without influencing either stem cell maintenance or the development of other marrow-derived cell types.

Animals↗
PubMed1979

Human megakaryocytes. I. Characterization of the membrane and cytoplasmic components of isolated marrow megakaryocytes.

Human marrow megakaryocytes have been isolated with high purity and yield by processing marrow cells sequentially through density centrifugation and velocity sedimentation. Analysis of the isolated cells for various platelet-associated components by immunofluorescence demonstrated that fibrinogen, plasma factor VIII antigen (factor VIII:AGN) platelet myosin, platelet glycoproteins I and III are present on the membrane and in the cytoplasm of over 90% of marrow megakaryocytes. Parallel studies of human and mouse megakaryocytes and platelets for IgG receptor (FcR), complement receptor type one (CR1) (C3b receptor), complement receptor type two (CR2) (C3d receptor), and Ia antigen by fluorescence and (or) rosette formation methods were performed. FcR were present on most human megakaryocytes and platelets. The Ia antigen was detected on a proportion (10-15%) of human megakaryocytes but it was undetectable on human platelets. CR1 was found on 20-40% of mouse megakaryocytes and also on a proportion of mouse platelets. These differentiation markers may be of use in monitoring megakaryocyte maturation.

Animals↗