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Biomedical subjects

M A Moore

Publications and source records attributed to M A Moore.

At least 379 records · Page 21Linked to original sources
PubMed1982

IgA nephropathy associated with seronegative spondylarthropathies.

Three patients with a seronegative spondylarthropathy were found to have IgA nephropathy. Two patients had ankylosing spondylitis (one with psoriasis), and one had incomplete Reiter's syndrome. All three had a focal proliferative glomerulonephritis with IgA-dominant mesangial immune deposits. One patient had a leukocytoclastic vasculitis. This association of IgA nephropathy with seronegative spondylarthropathies raises the possibility of a common or related pathogenesis. There is evidence to suggest that both diseases are mediated by genetically controlled immune responses to mucosal contact with etiologic antigens.

Adult↗
PubMed1982

G-CSF: its relationship to leukemia differentiation-inducing activity and other hemopoietic regulators.

The murine myelomonocytic leukemia WEHI-3B exists as differentiation-inducible (D+) and noninducible (D-) cell lines. Both lines produce a CSF species that stimulates exclusively the formation of neutrophil granulocyte colonies. This G-CSF copurifies with a mast cell growth factor but can be separated from M- and GM-CSF. NZB bone marrow is unresponsive to G-CSF stimulation. WEHI-3B D+ cells can induced to terminal granulocyte differentiation by a factor present in murine and human postendotoxin serum that is different from G-CSF present in WEHI-3B D+ or D- CM since the latter has little or no leukemia differentiation-inducing activity. Endotoxin treatment of C. parvum primed mice leads to simultaneous induction of serum activities with selective action on myeloid leukemic cells, a serum differentiation inducing activity and a leukemic colony inhibitory activity. These factors act synergistically to block leukemic stem cell self-renewal. The results suggest that a variety of inducible factors may have potent and selective antileukemic activity.

Animals↗
PubMed1982

Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver.

The livers from a total of 51 Sprague-Dawley rats treated with different doses of N-nitrosomorpholine (80-120 mg/l in the drinking water) for up to 14 weeks together with the livers of 28 control animals were histochemically investigated at the cessation of carcinogenic insult and at varying periods thereafter for their glycogen content, basophilia and activities of various enzymes of carbohydrate metabolism: glycogen synthetase, glycogen phosphorylase, glucose-6-phosphatase, glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. The enzymatic patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and compared with reference to the morphologically defined stages of tumor development in the liver. The early appearing glycogen storing areas, localized in the peripheral and intermediate lobular regions, did not show significant changes in the histochemically demonstrable activities of the enzymes tested. After cessation of the carcinogen treatment the more pronounced glycogen storage foci which developed within the aforementioned regions of the liver acinus usually showed a reduction in the activities of phosphorylase and glucose-6-phosphatase while the activity of glucose-6-phosphate dehydrogenase, a key enzyme for the pentose phosphate pathway, was increased. The mixed cell foci, neoplastic nodules and tumors which emerged at later stages were characterized by a progressive shift away from glycogen metabolism towards glycolysis and the pentose phosphate pathway, as indicated by an increase in glyceraldehyde-3-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase activities. These changes in enzyme pattern are supportive of a developmental sequence leading from glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas.

Animals↗
PubMed1982

The dose dependence and sequential appearance of putative preneoplastic populations induced in the rat liver by stop experiments with N-nitrosomorpholine.

Different doses of N-nitrosomorpholine (NNM) (80, 120, 160, 200 mg/l drinking water) were administered for various periods of time (1, 4, 7, 14, 20 weeks) to male Sprague-Dawley rats in order to investigate the dose dependence and sequential appearance of preneoplastic and neoplastic lesions in the liver. With all dose levels studied a sequence was established leading from clear cell and acidophilic cell glycogen storage foci through mixed cell foci and neoplastic nodules to hepatocellular carcinomas. The first appearance and frequency of the different lesions investigated proved dependent on dose of carcinogen administered. Morphometric analysis demonstrated that the rare small clear cell foci apparent after 7 weeks treatment with NNM increase in number and size with progression through the sequence to carcinomas without further administration of carcinogen. No evidence was found to suggest that pronounced focal populations were reversible upon cessation of NNM-treatment under the present experimental conditions.

Animals↗
PubMed1982

Ultrastructural analysis of pancreatic carcinogenesis. V. Changes in differentiation of acinar cells during chronic treatment with N-nitrosobis(2-hydroxypropyl)amine.

An electron microscope study was carried out on changes in the pancreatic acinar tissues of male Syrian hamsters during the course of induction of pancreatic neoplasia by lifetime weekly injections of N-nitroso-bis(2-hydroxypropyl)amine (BHP). The dominant process observed was a loss of differentiation of the acinar cells, leading to the development of a new population of cells that closely resemble centro-acinar or ductular cells. During this process, the original centro-acinar and ductular cells appear to be relatively unaffected by exposure to BHP. Thus, acinar cell de-differentiation appears, in this experimental model, to be an important preliminary stage in neoplastic development. It is argued that these findings may have implications for the histogenesis of human pancreatic adenocarcinoma, considered hitherto to be ductal in origin.

Adenocarcinoma↗
PubMed1982

Ultrastructural analysis of pancreatic carcinogenesis. VI. Early changes in hamster acinar cells induced by N-nitroso-bis(2-hydroxypropyl)amine.

Male Syrian golden hamsters were given weekly s.c. injections of 250 mg/kg body weight of N-nitroso-bis(2-hydroxypropyl)amine (BHP) for up to 15 weeks. Electron microscope studies were carried out on early changes in the exocrine pancreas of these hamsters for 2 weeks to 15 weeks. The majority of observed alterations occurred in the acinar cells and included the appearance of "dark" and "light" cells, the former showing nuclear shrinkage and irregularity but maintaining a normal rough endoplasmic reticulum (ER) and zymogen content. The "light" cells exhibited a variety of early fine structural alterations including conformational changes in their rough ER, together with a reduction in zymogen granules, increased autophagic vacuoles and Golgi hypertrophy. Ducts and ductules were relatively unaffected. The observations indicate that the acinar cells were most affected, morphologically, by BHP and are consistent with the view that these cells are the primary target for BHP.

Animals↗
PubMed1982

Immuno-electron microscopic tracing of lactoferrin, a regulator of myelopoiesis, into a subpopulation of human peripheral blood monocytes.

Lactoferrin (LF), an iron binding glycoprotein present in the specific granules of mature granulocytes, is capable of suppressing the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) by monocytes and macrophages in vitro and rebound myelopoiesis in vivo. By an immuno-electron microscopic technique (peroxidase-antiperoxidase procedure) in combination with a three-step fixation and detergent treatment of mononuclear blood cells pulsed with LF, intracellular localization of LF in a sub-population of human monocytes with a well-preserved subcellular morphology was demonstrated. LF was found in the monocytes after a 30 min pulse with concentrations of LF as low as 10(-14) M. Under the electron microscope, deposits of approximately 110 nm diameter appeared scattered in the area of the endoplasmic reticulum. Large numbers of smaller deposits (20-70 nm) were found in the euchromatin. The heterochromatin and other cytoplasmic organelles were free of LF. These results suggest that the euchromatin might be the functional site for LF inhibition of the production of GM-CSF by a subpopulation of human monocytes.

Cytoplasmic Granules↗
PubMed1982

Production of presumptive humoral haematopoietic regulators in canine cyclic haematopoiesis.

Conditioned media (CM) were prepared according to previously published techniques from the bone marrow of dogs with cyclic haematopoiesis (CH). CM prepared from day 9 marrows inhibited mouse bone marrow CFU-s proliferation rate while CM from day 10 marrows were stimulatory and also contained an erythroid stimulating factor which appeared to be erythropoietin. In addition a highly significant trend from CM containing CFU-s inhibitory materials to media with CFU-s stimulatory activity was observed through cycles day 1 to 8. These studies further support the concept that CH is due to a defect in factors controlling stem cell proliferation and suggest that a major event occurs in CH dog marrow on days 9 and/or 10 of the cycle.

Animals↗
PubMed1982

Expression of Ia-antigens on normal and chronic myeloid leukemic human granulocyte-macrophage colony-forming cells (CFU-GM) is associated with the regulation of cell proliferation by prostaglandin E.

The presence of la-antigens and their relationship to the inhibitory effect of prostaglandin E on the proliferation of human CFU-GM was studied in animals and patients with chronic myeloid leukemia. Consistent reduction of normal colony formation to approximately 50% of baseline levels was observed using a monoclonal anti-human la antibody in a complement-dependent cytotoxicity assay titrated over serial dilutions. ELimination of the la-antigen-bearing CFU-GM population was associated with virtually a complete loss of responsiveness to the inhibitory effects of prostaglandin E. Maintenance of bone marrow cells in short-term suspension culture at 37 degrees C prior to agar culture resulted in the loss of detectable la-antigen on the CFU-GM and, similarly, loss of response to prostaglandin. In contrast, most patients with chronic myeloid leukemia showed greatly reduced levels of la-antigens on their CFU-GM in fresh marrow together with lack of prostaglandin sensitivity, suggesting a correlation with the abnormal growth regulation observed in these patients. In two chronic myeloid leukemia patients, levels of la-antigen higher than that observed in the majority of patients could be detected and correlated with a residual response to prostaglandin E. These results suggest a relationship in normals between the expression of la-antigens on CFU-GM and the physiologic response to regulation by prostaglandin E, and a possible mechanism for the aberrant regulatory response in patients with chronic myeloid leukemia.

Adolescent↗
PubMed1982

Pathophysiological mechanisms operating in the development of myelofibrosis: role of megakaryocytes.

In this article current concepts on the regulation of bone marrow collagen are reviewed and a hypothesis regarding the mechanisms leading to marrow fibrosis associated with Primary Myelofibrosis (PMF) is presented. Type I and type III collagen, products of marrow fibroblasts, are the main constituents of myelofibrotic tissue and megakaryocytes are the predominant cells proliferating in PMF. There is evidence for the clonal nature of the hematopoietic cell proliferation and the secondary origin of myelofibrosis. Also, evidence exists indicating that defective megakaryocyte maturation, i.e. ineffective megakaryocytopoiesis occurs in patients with PMF. It is postulated that ineffective megakaryocytopoiesis leads to an excessive concentration of megakaryocyte components in the marrow intercellular space and that the development of marrow fibrosis involves mainly 2 megakaryocytic products: growth factor and factor 4. The growth factor stimulates fibroblast proliferation and collagen secretion. Factor 4 inhibits the activity of the enzyme collagenase. Thus, the imbalance between increased collagen production and decreased collagen degradation leads to an excessive deposition of collagens in bone marrow matrix.

Bone Marrow↗
PubMed1982

Long-term in vitro culture of murine mast cells. III. Discrimination of mast cells growth factor and granulocyte-CSF.

Long-term in vitro growth of murine mast cells was dependent on the presence of a mast cell growth factor (MCGF) present in media conditioned by mitogen-activated splenic leukocytes or by various murine leukemic cell lines. MCGF shared a number of properties with granulocyte colony-stimulating factor (G-CSF). Both factors were present in media conditioned by the myelomonocytic leukemic WEHI-3 and the T cell lymphoma, LBRM-33 cell lines. They were relatively sensitive to trypsin treatment, and were resistant to boiling temperature. NZB mice that failed to respond to WEHI-3-derived G-CSF also failed to respond to MCGF. MCGF differed from G-CSF, however, in sensitivity to neuraminidase and lactoferrin, an inhibitor of macrophage CSF production, suppressed G-CSF production by WEHI-3 cells without affecting MCGF production. Furthermore, peritoneal cells produced G-CSF but not MCGF when stimulated with lipopolysaccharide. In vitro production of MCGF by normal spleen cells required the presence of T lymphocytes and is relatively macrophage-independent. The role of T cells in the maturation and growth of mast cells and the physiologic function of MCGF are discussed.

Animals↗
PubMed1982

Characteristics of bone marrow fibroblast colony-forming cells (CFU-F) and their progeny in patients with myeloproliferative disorders.

Chronic myeloproliferative disorders (MPD) are clonal diseases of the pluripotent hematopoietic stem cell frequently associated with myelofibrosis (MF). There is only indirect evidence indicating that the increased deposition of collagen in bone marrow matrix is a secondary phenomenon. A liquid culture system for cloning and growing bone marrow fibroblasts has permitted us to approach more directly the understanding of the pathogenesis of myelofibrosis by comparing the biophysical, growth, and functional characteristics of fibroblasts from normals, MPD patients without MF, and those with MF. In patients with MF, marrow fibroblast colony (CFU-F) formation could not be studied; fibroblasts were grown from marrow explants. CFU-E from normals and MPD patients exhibited similar cell density distribution and similar cell sedimentation rates. These similarities contrasted sharply with the differences seen when the erythroid and granulocyte-macrophage progenitors were studied by the same methods. There was a marked light density shift and a rapidly sedimenting shift of MPD hematopoietic colony-forming cells. Marrow fibroblasts from MPD patients with and without MF displayed the same in vitro growth characteristics as fibroblasts from normals. Both types of fibroblasts exhibited anchorage and serum dependence, and contact inhibition of growth. Marrow fibroblasts were also characterized for the presence and distribution of fibronectin and collagen types by immunofluorescent staining using monospecific antibodies. Extracellular matrix, membrane-, and cytoplasm-associated fibronectin, type I, type III, and type V collagen showed a similar staining pattern in both normal and myelofibrotic marrow fibroblasts. Plasminogen-dependent fibrinolytic activity elicited from normal and myelofibrotic marrow fibroblasts were equivalent. Chromosomal analysis of hematopoietic cells and marrow fibroblasts from Philadelphia chromosome positive chronic myelocytic leukemia patients with and without MF showed that the Philadelphia chromosome was present only in hematopoietic cells. The results of these studies taken together demonstrate that bone marrow collagen-producing cells from MPD patients with and without MF behave in vitro as do those from normals. These findings support the hypothesis that that the marrow fibrosis observed in patients with MPD results from a reactive process rather than from a primary disorder affecting the marrow collagen-producing cells.

Adult↗
PubMed1981

Methods and clinical relevance of terminal deoxynucleotidyl transferase determination in leukemic cells.

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase which is only found in immature cells of lymphoid lineage (pre-T/pre-B). Because of this restricted distribution of TdT, biochemical and immunofluorescence techniques have been employed to determine the distribution of TdT phenotypes in human leukemias and lymphomas, showing high levels of TdT in approximately 95% of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), approximately 50% of patients with acute undifferentiated leukemia (AUL), approximately 10 of patients with acute nonlymphoblastic leukemia (ANLL), and approximately 30% of patients with chronic myeloid leukemia (CML) and other myeloproliferative (MPS) or myelodysplastic (MDS) syndromes in blast crisis. High levels of TdT activity are associated with a clinical response to remission inducing therapy with vincristine and prednisone in a high proportion of patients (50%-90%), irrespective of clinical and morphologic diagnosis. Preliminary studies furthermore suggest that TdT might serve as a sensitive indicator of subclinical disease in ALL in complete remission.

DNA-Directed DNA Polymerase↗
PubMed1981

T-cell growth factor (interleukin 2) and terminal transferase activity in human leukemias and lymphoblastic cell lines.

Mononuclear blood cells from patients with different types of leukemia, and from controls as well as cells from established lymphoblastic cell lines were analyzed with respect to terminal transferase (TdT) activity and T-cell growth factor (TCGF; Interleukin 2, IL-2), to determine the significance of TCGF production and response as functional markers for human leukemias. The data obtained so far suggest that the aberrant proliferation and lack of maturation observed in these leukemias may be associated with or be the result of a break-down in cellular-mediated control of proliferation.

Acute Disease↗