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N Dainiak

Publications and source records attributed to N Dainiak.

At least 37 records · Page 2Linked to original sources
PubMed1992

Capnocytophaga bacteremia in a patient with Hodgkin's disease following bone marrow transplantation: case report and review.

Capnocytophaga is a gram-negative, capnophilic, facultatively anaerobic bacillus that normally inhabits the oral cavity. We report the case of a patient who developed capnocytophaga bacteremia following autologous bone marrow transplantation for Hodgkin's disease, and we review other reported cases of capnocytophaga bacteremia in immunocompromised patients. In our case infection followed pretransplantation conditioning and was associated with severe oral mucositis and neutropenia. Antibiotic therapy resulted in clinical resolution of infection. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients (e.g., those undergoing bone marrow transplantation) especially in the presence of mucositis and gingival bleeding.

Adult↗
PubMed1991

Surface membrane-associated regulation of cell assembly, differentiation, and growth.

The role of the surface membrane in regulating proliferation and differentiation of eukaryotic cells is highly complex. Proximal cell-cell interactions are involved, including physical contact via junctional complexes, exfoliation of surface membrane vesicles, proteolytic cleavage of membrane-bound precursors, and exocytosis of soluble proteins (see Fig 5). At another level, the surface expresses receptors and other proteins that mediate cell-cell adhesion, a multistep event that may be sufficient to activate some growth-associated genes and alter cell shape. The evidence indicates that together with secreted growth factors, surface membrane-associated molecules play a dynamic role in regulating multicellular assembly and cell differentiation and growth.

Animals↗
PubMed1991

A cryoglobulin with cold agglutinin and erythroid stem cell suppressant properties.

A 93-year-old woman presented with profound anemia (hematocrit 23% [0.23]); there was clumping of her red cells in test tubes and on peripheral blood smears. There was also a marked decrease in erythroid precursors in the bone marrow and reticulocytopenia in the peripheral blood. An IgM kappa monoclonal gammopathy was found in low concentration (approximately 1%) in her serum, and the cold agglutinins had a titer of 2560. However, the cold agglutinin titer of the supernatant after cryoglobulin precipitation was 40. Redissolving the cryoglobulin in the supernatant resulted in a cold agglutinin titer of 1280. Moreover, the addition of the patient's whole serum inhibited erythroid colony formation in culture. The inhibition was removed by cryoprecipitation of the cryoglobulin. The patient was given steroid therapy, to which she responded with reticulocytosis and an elevation of hematocrit. By 3 months, the cold agglutinin titer had fallen to 10. She remained well 4 years later. Whereas reports of cryoprecipitable cold agglutinins are rare, this case is unique because there have been no previous reports that these cold active proteins also have erythroid stem cell-suppressant properties.

Aged↗
PubMed1991

Expression of a negative regulator of human erythropoiesis by fluidized lymphocyte plasma membranes.

Regulation of hematopoiesis by paracrine molecules occurs in vitro. In some cases, hematopoietic paracrine factors have been localized to the plasma membrane of accessory cells. We have purified a unique integral membrane glycoprotein from normal human B cells that functions in vitro as a paracrine factor whose activity is directed toward erythroid progenitor cells. This factor is also spontaneously exfoliated from the cell surface as a component of extracellular vesicles. Analysis of the lipid and protein compositions and membrane lipid order of these extracellular vesicles reveals them to be biochemically distinct and more fluid than their parent membranes. Evidence in nonhematopoietic culture systems indicates that cell membrane function may be altered by modifying membrane fluidity. In an effort to accelerate growth factor release, plasma membranes of B cells were fluidized by incubation with an emulsion of Liposin II, phosphatidylcholine, and phosphatidylethanolamine. Fluidity assessed by steady-state fluorescence polarization was reduced in lipid-treated cells. Exfoliation was 3-4-fold higher from lipid-treated cells relative to untreated cells. Unexpectedly, a negative signal for burst-forming unit-erythroid (BFU-E) proliferation was expressed in membranes, in shed extracellular vesicles, and in supernatants of medium conditioned by the fluidized cells. Purification of the inhibitor is under way. The data are consistent with the hypothesis that accessory cell plasma membranes may positively or negatively regulate erythroid differentiation, depending upon the exchange of cholesterol and phospholipids between plasma membrane and ambient lipid pools.

B-Lymphocytes↗
PubMed1991

Inhibition of major histocompatibility complex class I antigen shedding up-regulates the surface expression of class I antigens on the lymphocyte cell surface.

Interferon-gamma induces the expression of major histocompatibility complex class I and class II gene products. Moreover, the density of MHC antigens present on the lymphocyte surface is regulated by exfoliation of the plasma membrane. To probe the cellular mechanisms involved in IFN-gamma-induced alteration of MHC antigen expression, we measured the effects of IFN-gamma on the rate of MHC antigen shedding and the biosynthesis of H-2Dd. Balb/c splenic lymphocytes were surface-iodinated with 125I and incubated in the presence and absence of up to 1000 U/ml IFN-gamma, or they were metabolically labeled with [35S]methionine with or without 500 U/ml IFN-gamma. Radioiodinated or 35S-labeled H-2Dd was quantified by immunoprecipitation of H-2Dd from detergent lysates of radiolabeled cells that were incubated with the appropriate antibody for 4-20 h at 37 degrees C. Monoclonal antibody 34-5-8 was employed as a specific probe for H-2Dd. Loss of radioiodinated H-2Dd from the cell surface was diminished by 75-90% at 12 h in tests of lymphocytes continuously cultured with IFN-gamma (compared to control, p less than 0.05). In contrast, the biosynthetic rate was unaffected during the initial 10 h of incubation. The net result of these changes was the early appearance of an increase in H-2Dd on the cell surface. This result was in accordance with data obtained by phenotyping the untreated and treated cells using double-antibody staining methods and fluorescence-activated cell sorter analysis. Our results suggest that IFN-gamma induces MHC expression by initially retarding the exfoliation of MHC antigens from the lymphocyte surface. Delayed effects on MHC expression may be, on the other hand, mediated by increased antigen biosynthesis.

Animals↗
PubMed1991

Intracellular regulation of the production and release of human erythroid-directed lymphokines.

Erythroid burst-promoting activity (BPA) is released from B lymphocytes in soluble (sBPA) and membrane-bound (mBPA) forms. To study intracellular processes involved in production of these physically separable factors, we measured their time course release into serum-free medium from B cells that were pulse-exposed for 5-240 min to nonmitogenic base medium or inhibitors of energy-dependent metabolism (2,4-dinitrophenol, sodium azide, and 2-deoxy-D-glucose), transcription and translation (actinomycin D and cycloheximide), replicative DNA synthesis (cytosine arabinoside), or posttranslational processing (monensin). mBPA and sBPA were initially detectable after 1 and 2 h, respectively. Maximum cumulative levels of 8 +/- 0.6 and 9 +/- 1.0 U/ml, respectively, were reached after 8 h. In contrast, cumulative mBPA and sBPA levels in medium prepared from cells treated with metabolic inhibitors were reduced by up to 90%. Both surface exfoliation and mBPA expression by intact plasma membranes were diminished. Whereas pulse-exposure to cytosine arabinoside had no effect, treatment with actinomycin D or cycloheximide abolished BPA expression. Exposure to monensin reduced mBPA and sBPA levels to zero in a concentration-and time-dependent fashion. We conclude that production and release of BPA is an energy-dependent process, requiring mRNA synthesis and translation and posttranslational remodeling of the protein but not replicative DNA synthesis.

2,4-Dinitrophenol↗
PubMed1991

Induction of circulating neonatal stem cell populations.

Hematopoietic cell differentiation and growth are regulated by paracrine molecules that include insulin and insulin-like growth factors (IGFs). IGF-I and -II stimulation of erythropoiesis in cultures of adult bone marrow and peripheral blood cells and murine fetal liver cells has been previously reported. In order to investigate whether these paracrines also influence differentiation and proliferation of human neonatal progenitor cells, we assessed their effects in cultures of umbilical cord blood and adult blood and marrow cells, using a serum-substituted system. IGF-I stimulated colony-forming unit-erythroid (CFU-E)-derived colony formation by adult cells by up to 265%, while IGF-II augmented colony formation by up to 100% in the presence of erythropoietin. Stimulation occurred in a saturable fashion over concentrations of 0 to 200 ng/ml. Similar results were obtained in subcultures of adult-circulating progenitors. Moreover, a subpopulation of erythropoietin-independent adult CFU-E was stimulated to proliferate by IGF-I but not by IGF-II. In contrast to these effects in adult marrow culture, IGF-II exerted a greater stimulatory effect on neonatal CFU-E proliferation than did IGF-I in erythropoietin-containing cultures. Additionally, IGF-II stimulated proliferation of erythropoietin-independent neonatal CFU-Es in a concentration-dependent fashion. Together, the data are consistent with the hypothesis that somatomedins are involved in developmental regulation of erythropoiesis.

Adult↗
PubMed1990

Characterization of biologically active, platelet-derived growth factor-like molecules produced by murine erythroid cells in vitro and in vivo.

Platelet-derived growth factor (PDGF) is an important serum regulator of erythropoiesis in vitro. We have now obtained evidence suggesting that PDGF-like molecules may also modulate erythropoiesis in vivo. Western blot analysis of cytoplasmic extracts from Rauscher murine erythroleukemia cells and phenylhydrazine-treated mouse splenic erythroid cells revealed the presence of several PDGF-like proteins. The presence of PDGF-like proteins in the cytoplasm of these two erythroid cell types was confirmed by immunohistochemical staining. Using a serum-free biologic assay, PDGF-like biological activity was found in cell lysates and conditioned medium of both Rauscher cells and phenylhydrazine-treated mouse erythroid cells. Subcellular localization experiments revealed the biological activity to be concentrated in the cytosolic fraction. Using a series of antibodies to hematopoietic growth factors we demonstrated that PDGF-like biological activity was specifically immunoprecipitated by both monoclonal and polyclonal anti-human PDGF antibodies but not by antibodies to burst-promoting activity, granulocyte-macrophage colony-stimulating factor, IL-3, or erythropoietin. Taken together, the data are consistent with the hypothesis that PDGF-like molecules play a role in the regulation of mammalian erythropoiesis in vivo.

Animals↗
PubMed1990

Cell membrane family of growth regulatory factors.

Both negative and positive regulators of cell growth and differentiation have been found in association with the surface of a variety of cell types, including fibroblasts, lymphocytes, undifferentiated components of the slug, neuronal cells, monocytes and mesenchymal cells (see Table 3). These molecules have been implicated in mediating contact inhibition, suppression of lymphopoiesis, inhibition of DNA synthesis in erythroid progenitors, induction of differentiation in Dictyostelium, stimulation of Schwann cell proliferation, and stimulation of the proliferation of a variety of hematopoietic cells, including myeloid (Price et al, 1975), erythroid and macrophage progenitor cells. In some cases, families of membrane bound growth factors have been described or are currently being appreciated. The importance of cell surface-associated regulators in mediating close cell-cell interactions in vitro and in vivo as well is under active investigation.

Axons↗
PubMed1989

B-lymphocyte-derived erythroid burst-promoting activity is distinct from other known lymphokines.

Previously we have demonstrated that, in contrast to various panspecific or multilineage hematopoietic growth factors, lymphocyte-derived erythroid burst-promoting activity (BPA) is lineage specific, stimulating BFU-E proliferation in serum-free culture by up to 600% of control values while failing to enhance nonerythroid colony formation. To further determine the cellular source(s) of this important erythropoietic growth regulator, we have separated normal nonadherent peripheral blood and splenic lymphocytes by nylon wool fractionation, SRBC rosetting, and panning with monoclonal antibodies (MoAbs). These unstimulated T- and B-lymphocyte-enriched populations were used as cell sources to produce conditioned media (CM) and to prepare plasma membranes (PM). When CM fractions or purified PM were assayed in serum-free human bone marrow culture, BPA was localized entirely to the B-lymphocyte-derived fractions. While CM or PM from unstimulated T lymphocytes failed to stimulate BFU-E proliferation, activation of T cells by either phytohemagglutinin-M (1%) or concanavalin A (Con A; 5 micrograms/mL) induced the expression of a factor on the PM and in the resultant CM that stimulated the formation of erythroid bursts. In addition to enhancing BFU-E proliferation, this T-cell factor stimulated the proliferation of CFU-GM and CFU-GEMM in serum-free culture. When compared biochemically (in terms of temperature stability, localization by ammonium sulfate fractionation, and sensitivity to dithiothreitol) or immunochemically (using antibodies specific for lymphocyte-derived BPA, GM-CSF, or interleukin-3 [IL-3]), as well as by lineage specificity, B- and activated T-lymphocyte-derived growth factors appeared to be distinct. The burst stimulatory activities expressed by recombinant human GM-CSF and IL-3 were immunologically distinct from that associated with octylglucoside extracts of plasma membranes from resting B lymphocytes. Our results suggest that the BFU-E-directed growth-promoting activity released from activated T lymphocytes is apparently due to GM-CSF, while both resting and mitogen-stimulated normal B lymphocytes express erythroid-specific BPA and neither GM-CSF nor IL-3.

B-Lymphocytes↗
PubMed1989

DNA topoisomerase inhibitors block erythropoiesis and delay hemoglobinization in vitro.

To examine the importance of topological constraints on DNA during erythroid development, we measured the effects of camptothecin and teniposide, two tumoricidal agents which are also specific inhibitors of type I and type II topoisomerases respectively, on the formation of hematopoietic colonies by cultured human bone marrow cells. When added to bone marrow culture, each inhibitor alone impairs the formation of early BFU-E-derived colonies, late CFU-E-derived colonies and mixed hematopoietic (CFU-GEMM-derived) colonies by up to 100%. Inhibition of colony formation is directly related to the time of inhibitor addition and the inhibitor concentration tested. Although either inhibitor alone reduces colony formation by 90%, when added together at a submaximal concentration, camptothecin and teniposide exert a synergistic suppressive effect. Furthermore, addition of topoisomerase inhibitors to culture impairs hemoglobinization of colony erythroblasts in a time-dependent fashion. In contrast to the effects of topoisomerase inhibitors, the antiproliferative agent aphidicolin reduces erythroid colony number and size without altering hemoglobinization of colony erythroblasts. Since neither topoisomerase inhibitor alters the morphology of cultured cells, the capacity of cells to exclude trypan blue or the potential to form erythroid colonies through the interval required for the first progenitor cell division, it is unlikely that camptothecin or teniposide are cytotoxic to hematopoietic cells. Human mononuclear cells enriched in bone marrow lymphocytes and nucleated erythroblasts from both human and mouse sources release DNA into the detergent soluble fraction. Release requires functional topoisomerases and is altered by acute exposure to topoisomerase inhibitors. Our results suggest that topoisomerases are critical not only to proliferation but also to differentiation of human marrow erythroid progenitor cells and stem cells in culture.

Aphidicolin↗