PubMed Health⌕ Search

Biomedical subjects

M A Moore

Publications and source records attributed to M A Moore.

At least 433 records · Page 24Linked to original sources

Dissociation of the diurnal variation of aldosterone and cortisol in anephric subjects.

Diurnal variation of plasma aldosterone and cortisol concentration in man was studied in 13 anephric subjects and 7 normal subjects. All subjects were ambulatory and active throughout the study except during an 8-hour sleep period. Six anephric subjects received Kayexalate (sodium polystyrene sulfonate) during the studies to prevent potassium accumulation and increase in plasma potassium concentration. Diurnal variation of plasma aldosterone concentration with peak and nadir concentrations at 12:00 noon and 12:00 midnight respectively was demonstrated in the studies on normal subjects. Changes in plasma aldosterone concentration were not significantly correlated with changes in plasma concentration but were highly correlated with changes in PRA (P less than 0.001). There was a highly significant correlation between plasma aldosterone and potassium concentration in the anephric subjects studied without Kayexalate administration (P less than 0.001). In the anephric subjects who received Kayexalate, plasma aldosterone and potassium concentration remained stable, and no correlation could be demonstrated. No diurnal variation of plasma aldosterone concentration could be demonstrated in either group of anephric subjects, whereas plasma cortisol concentration varied as in the studies on normal subjects. Conclusion. Diurnal variation of plasma aldosterone concentration is dependent on continued stimulation by the renin-angiotensin system. Loss of this stimulation has no demonstrable effect on the diurnal variation of plasma cortisol concentration.

Adult↗

Induction of prostaglandin E synthesis in normal and neoplastic macrophages: role for colony-stimulating factor(s) distinct from effects on myeloid progenitor cell proliferation.

The biosynthesis of prostaglandin E (PGE) by normal and neoplastic macrophages is intrinsically linked to their synthesis of, and exposure to, myeloid colony-stimulating factors (CS-factors). The defect in responsiveness to endotoxin lipopolysaccharide (LPS) by macrophages from C3H/HeJ mice extends equally to the synthesis of CS-factor and PGE. However, C3H/HeJ macrophages can be stimulated to synthesize PGE by treatment with agents other than LPS [zymosan, tuberculin purified protein derivative, concanavalin A, poly(I).poly(C)], which also stimulate CS-factor production, or by the addition of various preparations of soluble CS-factor. In peritoneal wash preparations, constitutive PGE synthesis occurred in rapidly sedimenting macrophage cells, whereas constitutive CS-factor production and inducible PGE synthesis occurred in slower sedimenting adherent cells. A similar functional heterogeneity in CS-factor and PGE production was found in neoplastic macrophagae cell lines. The association of elevated CS-factor levels and PGE synthesis by macrophages suggests a role for CS-factor in many of the physiological responses heretofore associated with elevated tissue levels of the E type prostaglandins.

Animals↗

Abnormalities in clonable B lymphocytes and myeloid progenitors in autoimmune NZB mice.

Cloning procedures were used to study B lymphocytes and progenitors of granulocytes and macrophages in NZB mice. Numbers of B cells that were detected in sheep erythrocyte-containing semisolid cultures were only slightly elevated in NZB tissues, and these were normally sensitive to inhibition by anti-mu or anti-delta antibodies or prostaglandin E. However, NZB mice rapidly developed large numbers of B cells that could be cloned in the presence of lipopolysaccharide, and these included unusual anti-mu resistant cells. Numbers of myeloid precursors in NZB bone marrow that were responsive to colony-stimulating activity in L-cell conditioned medium or endotoxin serum were at least normal, but at all ages granulocyte-macrophage precursors were poor responders in cultures stimulated by WEHI-3 cell conditioned medium. Almost no colonies were elicited in NZB cultures with a colony-stimulating activity moiety from WEHI-3 cells. Prostaglandin sensitivity of myeloid precursors from NZB and CBA mice was also different. Codominant genetic control of these abnormalities was suggested by their partial expression in F1 hybrid NZB X CBA and NZB X NZW mice. NZB mice expressed an unexpected IgD allotype allele.

Animals↗

Colony-forming units in diffusion chambers (CFU-d) and colony-forming units in agar culture (CFU-c) obtained from normal human bone marrow: a possible parent-progeny relationship.

An series of experiments was performed to elucidate the relationship between cells that form granulocytic colonies in fibrin clot diffusion chambers implanted into the peritoneum (i.p.) of irradiated mice (CFU-d) and day 7 and day 14 CFU-U which give rise to colonies after 7 and 14 days in agar cultures in vitro, respectively. Normal human bone marrow cells were cultured in suspension in vitro or in diffusion chambers implanted into irradiated or non-irradiated mice. During these culture conditions there was an initial decrease in the number of CFU-c per culture. This was followed by an increase between day 2 and day 7 of culture. No similar increase of neutrophilic CFU-d was observed. When CFU-d, day 14 and day 7 CFU-c in normal marrow were separated by velocity sedimentation and cultured in suspension culture or in diffusion chambers for 7 days, the maximum increase of day 7 and day 14 CFU-c was observed in slowly sedimenting cell fractions which contained the majority of CFU-d. After 3 days in suspension culture, the maximum increase of day 14 CFU-c was found in fractions which also gave rise to maximum numbers of CFU-c after 7 days. However, day 7 CFU-c were found in fractions which initially contained the majority of day 14 CFU-c. No increase in CFU-d was found in fractions initially containing peak numbers of CFU-c. Between 53 and 71% of CFU-c harvested from diffusion chambers in irradiated mice or from suspension cultures were sensitive to pulse incubation with tritiated thymidine, suggesting that the cells were proliferating during these culture conditions. In diffusion chambers implanted into non-irradiated mice, however, CFU-c were found to be relatively resistant to this treatment (3-11% sensitive to tritiated thymidine). Thus marked increases in CFU-c were also observed during experimental conditions, where no significant DNA synthesis was detected. A reproducible time sequence of increase in CFU-c populations in culture was observed. Day 14 CFU-c and cells that gave rise to clusters on day 7 in agar increased between day 2 and day 4, whereas day 7 CFU-c increased between day 4 and day 7. The results suggested that CFU-d gave rise to CFU-c in culture and that day 14 CFU-c were precursors of day 7 CFU-c.

Animals↗

Practical management of chronic renal failure.

Initial evaluation of patients with chronic renal failure demands a careful search to exclude reversible causes such as dehydration, obstruction and nephrotoxins. Subsequently, strict management of sodium and fluid intake is necessary to avoid either dehydration or congestive heart failure. As renal failure advances, restriction of dietary protein and potassium and binding of phosphate are indicated. Referral to an end-stage renal disease center should be accomplished early, before and appearance of uremic symptoms, to facilitate a smooth transfer to the next phase of rehabilitative therapy.

Anemia↗

Prolonged hematopoiesis in a primate bone marrow culture system: characteristics of stem cell production and the hematopoietic microenvironment.

Maintenance of myelopoiesis and pluripotential stem cell production for prolonged periods in vitro hitherto has been limited to mouse bone marrow culture. In an effort to adapt the system for use in higher species, particularly in human and non-human primates, studies were undertaken using the prosimian species, Tupaia glis (tree shrew). In a number of experiments the duration of sustained normal hematopoiesis observed in cultures of this species, following a single inoculum of 5 X 10(6)--10(7) bone marrow cells, with or without addition of fresh allogeneic bone marrow exceeded 1 yr. Analysis of suspension cells obtained by weekly demidepopulation of such cultures revealed production of CFU-C, differentiating neutrophils, and basophils at high levels. Direct comparison with murine cultures indicated that in both species a complex series of cellular interactions takes place within an adherent environment of marrow-derived endothelial cells, macrophages, and fat-containing cells. Certain functional and ultrastructural features served to distinguish murine from Tupaia marrow cultures, and the prolonged duration of in vitro hematopoiesis in the latter species could be attributed to a regenerative capacity possessed by its adherent hematopoietic microenvironment. The availability of this primate marrow culture system should facilitate studies of hematopoiesis, viral leukemogenesis, and transplantation biology, which have more direct relevance to man than that provided by the existing murine system.

Animals↗

Communication between white cells and the abnormalities of this in leukemia.

The production of white blood cells is mediated by cellular communication. Proliferation and differentiation of granulocytic and monocytic progenitor and immature cells have been studied in detail and are regulated by stimulatory and inhibitory molecules produced and released from the progeny of the progenitor cells. The resultant interactions between cells and cell-derived molecules suggest operable positive and negative feed-back mechanisms during normal hematopoiesis, and what one sees in the end is the net result of these interactions. The complexities of cellular regulation are partially unravelled by physical separation of the different populations and biochemical analysis of the regulatory molecules. Subpopulations of granulocyte-monocyte progenitors (CFU-c) exist and evidence suggests that they vary in responsiveness to different molecules. Stimulatory molecules are themselves chemically and physically heterogenous and, until recently, believed to have similar biological actions, but this concept must be re-evaluated. Different molecules may activate different subsets of progenitor cells, and there is now a role for substances which enhance the stimulatory interactions. Many studies on normal and leukemic cell responsiveness to stimulation must be re-examined in light of this recent information. Several inhibitory substances operate during normal hematopoiesis. Mature granulocytes, progeny of CFU-c, appear to elaborate at least two inhibitory activities. One activity influences immature, recognizable granulocytes and the other indirectly reduces progenitor cell proliferation by decreasing the production and release of molecules which stimulate CFU-c. In addition, mononuclear phagocytes produce and release E-type prostaglandins in direct response to elevated levels of the stimulatory molecules and E-type prostaglandins counteract increased stimulatory levels by decreasing the sensitivity of CFU-c to stimulators. Much of our present level of sophistication derives from in vitro experimentation and it is apparent that we are only beginning to understand these inter-relationships and their relevance to the in vivo situation. However, these in vitro studies have shed light on the interactions occurring during leukemia. Leukemic cells retain the capacity to respond to normal regulators and must therefore be considered dependent rather than autonomous neoplasms. Abnormalities do exist in leukemic cell interactions: the progenitor cells themselves may be defective and leukemic cells may respond to molecules which normal cells do not. The degree of sensitivity to stimulators and inhibitors will have to be carefully investigated to determine if and what differences may exist between normal and leukemic cells. Normal mature granulocyte derived inhibitory activity is quantitatively deficient in leukemic cells but another inhibitory activity which appears to be specifically present in cells from patients with leukemia and some cases of myelodysplasia is present...

Animals↗

Inhibition of human erythropoietic colony formation in culture by treatment with Ia antisera.

Incubation with Ia antiserum, followed by complement, markedly inhibited erythroid colonies arising from hematopoietic cells present in the nonadherent low density fractions of normal bone marrow. Both erythropoietin-dependent colonies and bursts were eliminated at dilutions of antiserum equivalent to, or greater than the dilutions required to abolish the granulocyte-macrophage colony formation. The inhibitory effect of the Ia antiserum was abolished by absorption with B but not T cells from lymphoid lines. Available evidence suggested that Ia determinants are expressed on the erythropoietin-sensitive progenitors of the erythroid series in precise analogy to their sequence of expression on the granulocyte lineage. In both lineages, as shown previously, the Ia determinants become undetectable during subsequent stages of differentiation.

Antigen-Antibody Reactions↗

Isolation of a granulocyte colony inhibitory factor derived from human polymorphonuclear neutrophils.

An inhibitory factor obtained from mature human granulocytes which suppresses granulocyte and monocyte-macrophage colony formation by an action on the endogenous colony stimulating factor-producing cells has been partially purified and characterized. The methods for purification consisted of a combination of ultracentrifugation, DEAE-Sephadex chromatography, SDS polyacrylamide gel electrophoresis and isoelectric focusing. The material had a molecular weight range of 102--128 000 and an isoelectric point between pH 6.2 and 6.4. The inhibitory factor was found to be heat stable and glycoprotein in nature.

Cell Differentiation↗