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Biomedical subjects

M M Friedman

Publications and source records attributed to M M Friedman.

At least 19 recordsLinked to original sources
PubMed1990

Sequential appearance of basophils and mast cells from human bone marrow in long-term suspension culture.

Human bone marrow cells grown in liquid culture in the presence of conditioned medium from concanavalin A stimulated peripheral blood mononuclear cells, from mixed lymphocyte reactions, or from an osteogenic sarcoma tumor line gave rise to basophils which were maximal in number at 1-3 weeks. Basophils had a multilobed nucleus, contained large cytoplasmic granules of variable size which stained metachromatically with acid, but not neutral toluidine blue, were negative for chloroacetate esterase, and did not contain human mast cell tryptase. In long-term cultures, mast cells were detected after 5-6 weeks. Mast cells had cytoplasmic granules that stained with acid and neutral toluidine blue, were positive for chloroacetate esterase, and contained human mast cell tryptase. It, therefore, appears that in liquid cultures even in the absence of feeder layers, human bone marrow cell cultures can give rise initially to basophils, and then to mast cells.

Animals↗
PubMed1990

Transcultural family nursing: application to Latino and black families.

The thesis of this article is that for family nursing to be effectively provided, a transcultural perspective must be incorporated. The underlying rationale for the integration of transcultural knowledge and values is presented, as well as an approach for integrating cultural aspects into family assessment and intervention. Black and Latino families are discussed in terms of their culturally-derived familial patterns.

Black or African American↗
PubMed1988

A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders.

It has been suggested that patients who present with episodes of unexplained anaphylaxis (UEA) or unexplained flushing (UEF) have systemic mastocytosis (SM), a proposal believed to be supported by the presence of excess mast cell (MC) numbers in the skin of these individuals. To examine this hypothesis, we determined the number and distribution of MCs in the skin of nine normal subjects, nine patients with UEA/UEF, six patients with urticaria pigmentosa (UP), and 14 patients with SM. Skin biopsy specimens of normal subjects contained 38.4 +/- 4 (mean +/- SEM) MCs per square millimeter. Biopsy specimens of patients with UEA/UEF contained 71.8 +/- 13 MCs per square millimeter. Although the numbers were significantly different from numbers in skin of normal subjects (p less than 0.05), similar modest increases in MC numbers are observed in a number of skin conditions. In marked contrast, lesional biopsy specimens of patients with UP contained 596.5 +/- 278 MCs per square millimeter (p less than 0.05, n = 6, compared to MC numbers in the skin of normal subjects), and patients with SM had 720.6 +/- 176 MCs per square millimeter in lesional skin (p less than 0.01, n = 12, compared to normal skin). Patients with UP or SM also had increased MC numbers in nonlesional skin compared to normal skin (168.0 MCs per square millimeter, p less than 0.05, n = 5, and 184.4 MCs per square millimeter, p less than 0.01, n = 10, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine↗
PubMed1988

Ultrastructural changes in human skin mast cells during antigen-induced degranulation in vivo.

Human skin mast cells were degranulated in vivo by intradermal injection of antigen. Biopsy specimens of control and stimulated skin were obtained at 5 minutes, again at 10 to 15 minutes, and analyzed by electron microscopy. Degranulation, defined as dissolution of granule contents and swelling in at least 20% of secretory granules of mast cells was observed in one third of mast cells at 5 minutes and in nearly two thirds of mast cells at 10 to 15 minutes, but was absent in biopsy specimens of control subjects. Anaphylactic degranulation was characterized by extensive fusion of granules to form degranulation channels, fusion of channels with the cell membrane to form large pores, and exocytosis of amorphous or fibrillar granule matrix into the connective tissue. Extruded secretory granules of skin mast cells persist for at least 15 minutes in the connective tissues, in apparent contrast to the process of in vivo degranulation in nasal and lung mast cells.

Allergens↗
PubMed1988

Characterization of basophil-like cells derived from nonhuman primate bone marrow.

In order to determine whether mast cells or basophils could be derived from nonhuman primate bone marrow, cells from bone marrow aspirates were cultured in the presence of concanavalin A-stimulated nonhuman primate spleen cell supernatants (CAS). Culture conditions were identical to those used for culturing mucosal-like mast cells from mouse bone marrow. In this situation, basophil-like cells (BLC) could be identified in liquid cultures and averaged 14-19 microM in size, were round or oval in appearance, had lobulated nuclei, and contained less than 100 metachromatically staining granules per cell. By electron microscopy, granules had dense oval or semilunar cores with surrounding fibrous whorls. BLC were peroxidase positive, chloroacetate esterase negative, stained positively with acid toluidine blue, and contained 0.1-0.3 pg histamine per cell. BLC expressed IgE receptors and were Leu 5b and Leu 16 negative. IgE-sensitized BLC released histamine after stimulation with antihuman IgE or the calcium ionophore A23187. [35S]-labeled proteoglycans were degraded with chondroitinase ABC but not with heparinase, indicating the absence of heparin in BLC. Thus, culture conditions that include the use of CAS and lead to the growth of mast cells from rodent bone marrow result in the growth of BLC from nonhuman primate bone marrow. These observations suggest that fundamental differences exist in the type of histamine containing cells that arise from rodent and primate bone marrow when such bone marrow cells are cultured under identical conditions.

Animals↗
PubMed1987

Separation and function of neutrophil karyogranuloplasts and comparison with cytoplasts and intact cells.

Since neutrophil cytoplasts lacking nucleus and granules were first prepared by centrifuging neutrophils over a discontinuous Ficoll gradient containing cytochalasin B, several functional deficits have been reported in these cytoplasts. Although these functional deficits have been considered to originate from the absence of organelles, cell damage during preparation could not be excluded. Therefore, in the following experiments the Ficoll gradient was modified to isolate both cytoplasts and karyogranuloplasts, which have a nucleus and granules and represent the cell after loss of the cytoplast. Electron microscopy and analysis of marker proteins and cell volume showed that karyogranuloplasts were distinct from neutrophils. The phorbol myristate acetate (PMA) or N-formylmethionylleucylphenylalanine (FMLP)-induced O2- release, corrected by surface area, was in the following order: neutrophils greater than cytoplasts greater than karyogranuloplasts. Both aggregation and membrane potential depolarization were maximal in neutrophils, intermediate in karyogranuloplasts, and lowest in cytoplasts when either PMA or FMLP was used as a stimulant. Extracellular release of the granule contents (degranulation) was triggered by FMLP in both neutrophils and karyogranuloplasts. Cytochalasin B pretreatment greatly enhanced FMLP-induced O2- release, degranulation, aggregation, and depolarization of membrane potential in neutrophils and karyogranuloplasts, but not in cytoplasts. The ability of cytochalasin B to potentiate FMLP-triggered cell function probably depends on granules or cell organelles which are depleted in cytoplasts. Chemokinesis and chemotaxis were impaired in both karyogranuloplasts and cytoplasts. Specific FML[3H]P binding was greater in karyogranuloplasts than in cytoplasts. Cellular actin content, measured by the DNase I inhibition assay, was abundant in cytoplasts and was extremely low in karyogranuloplasts. Karyogranuloplasts retain various neutrophil functions, except for chemotaxis, and provide an important control when studying the role of cell organelles in cytoplast function.

Cell Aggregation↗
PubMed1987

Receptor-mediated clearance of Aspergillus galactomannan.

The fate of radiolabeled Aspergillus fumigatus galactomannan was studied after intravenous injection into rabbits and rats. At 1 hr, the liver contained 35% of the injected dose in rabbits and 30% in rats. Excretion of galactomannan into the urine, measured in rabbits, was another major catabolic route and accounted for 35% of the dose by 24 hr. Immunization of rabbits increased hepatic uptake and decreased urinary excretion. Hepatic uptake in unimmunized rats could be decreased by Saccharomyces cerevisiae mannan, alpha-methyl mannoside, and N-acetylglucosamine, known inhibitors of the macrophage mannose receptor. Autoradiography showed hepatic radiolabeled galactomannan to be concentrated in Kupffer cells, which express the mannosyl receptor for glycoproteins. Macrophage mannosyl receptors may constitute a general mechanism for clearing fungal mannans from the bloodstream.

Acetylglucosamine↗
PubMed1986

Using humor in evaluating student performance.

This article describes an investigation of the effects of deliberate teacher humor as an evaluative strategy on anxiety and performance levels of beginning associate degree nursing students in a stress-producing simulated laboratory setting. While quantitative findings did not show that deliberate teacher humor reduced anxiety, and only partially demonstrated that humor improved performance, qualitative findings indicate that humor influenced both anxiety and performance. The authors suggest that this additional evaluative strategy may enhance the nurse educator's effectiveness in carrying out stress-producing evaluations.

Adult↗
PubMed1985

Mediator release in local heat urticaria: protection with combined H1 and H2 antagonists.

Two patients with local heat urticaria were examined for evidence of histamine release and for changes in mast cell morphology after local heat challenge. Both patients demonstrated significant release of histamine into the draining venous blood in the challenged arm. Biopsy specimens revealed mucosal edema after 30 min, followed by a mononuclear, perivascular infiltrate by 6 hr, and increasing in intensity by 24 hr. Degranulated mast cells were observed by electron microscopy. Heat challenge was repeated after treatment with hydroxyzine, cimetidine, or a combination of both drugs. Neither hydroxyzine nor cimetidine alone affected the clinical response to challenge, but both drugs together completely abolished the clinical response. In addition, the combination of both drugs taken regularly completely prevented symptoms. This observation suggests that histamine is one of the major mediators of this disorder and that both H1 and H2 receptors are operative.

Adult↗
PubMed1985

In situ degranulation of human nasal mucosal mast cells: ultrastructural features and cell-cell associations.

Mucosal mast cells in human nasal turbinates obtained at surgery were studied by electron microscopy before and after exposure en bloc to a degranulating stimulus. Mast cells occurred as solitary cells and in islets typically containing one mast cell and one to three mononuclear cells. All islets and most solitary mast cells were associated with thin cytoplasmic processes of distinctive, branched stromal cells that also phagocytosed debris from pyknotic mast cells. Mast cells were grouped into three categories based largely on published ultrastructural criteria. Resting (nondegranulating) mast cells possessed secretory granules that typically packed the cytoplasm and contained a densely stained amorphous material and scroll-like crystalline profiles. Granules in some resting cells were larger, more polymorphic, and appeared nearly homogeneous. Secretory granules of degranulating mast cells possessed crystalline, scroll-like, or reticular constituents predominantly with interspersed amorphous material. Granules were fewer in number and were often concentrated in the peripheral cytoplasm. Few degranulating mast cells exhibited labyrinth formation or exocytosis of granule contents. Largely degranulated mast cells had few if any typical granules but possessed small vacuoles containing recognizable granule remnants. Resting and degranulating mast cells possessed very long cell surface projections that, in places, interdigitated to form stacks of parallel folds above the plasmalemma, resulting in a threefold increase in cell-surface area. The surface membrane of the folds appeared to be continuous with that lining intracytoplasmic channels extending from the cell surface to the Golgi zone.

Cell Membrane↗
PubMed1985

Interactions between mast cells, fibroblasts and connective tissue components.

It has long been recognized that mast cells occur throughout connective tissues. Histologic studies have revealed that such cells release their granules into the surrounding environment upon exposure to both immunologic and nonimmunologic stimuli. By microscopy these extracellular granules appeared to be phagocytosed by fibroblasts and by blood-borne phagocytic cells as they entered the site of mast cell degranulation. Such in vivo observations led to the suggestion that mast cells both altered connective tissue components and influenced fibroblast function through these discharged granules. Recent in vitro studies using cultured fibroblasts and isolated mast cells and mast cell granules have confirmed both these hypotheses. In addition, such studies have also documented that fibroblasts degrade ingested mast cell granules. Such studies document that a number of critical interactions may occur between mast cells and connective tissue components.

Animals↗
PubMed1985

Biochemical and microscopic evidence for the internalization and degradation of heparin-containing mast cell granules by bovine endothelial cells.

Incubation of [35S]heparin-containing mast cell granules with cultured bovine endothelial cells was followed by the appearance of 35S-granule-associated radioactivity within the endothelial cells and a decrease in radioactivity in the extracellular fluid. These changes occurred during the first 24 hours of incubation and suggested ingestion of the mast cell granules by the endothelial cells. Periodic electron microscopic examination of the monolayers confirmed this hypothesis by demonstrating apposition of the granules to the plasmalemma of endothelial cells, which was followed by the engulfment of the granules by cytoplasmic projections. Under light microscopic examination, mast cell granules within endothelial cells then appeared to undergo degradation. The degradation of [35S]heparin in mast cell granules was demonstrated by a decrease in the amount of intracellular [35S]heparin proteoglycan after 24 hours and the appearance of free [35S]sulfate in the extracellular compartment. Intact endothelial cells were more efficient at degrading [35S]heparin than were cell lysates or cell supernatants. These data provide evidence of the ability of endothelial cells to ingest mast cell granules and degrade native heparin that is presented as a part of the mast cell granule.

Animals↗
PubMed1984

Auranofin affects early events in human polymorphonuclear neutrophil activation by receptor-mediated stimuli.

Auranofin, a new oral antirheumatic gold compound, in concentrations achieved therapeutically, inhibits neutrophil phagocytosis, chemotaxis, chemiluminescence, reduction of cytochrome c, and release of lysosomal enzymes. To further characterize the mechanism by which auranofin affects neutrophils, we studied the effects of auranofin on unstimulated properties and functions of neutrophils as well as on rapidly stimulated functions. When examined by electron microscopy, 4 micrograms/ml of auranofin significantly decreased the number of visualized centriole-associated microtubules in resting cells. Furthermore, auranofin inhibited neutrophil spreading on glass and caused a decrease in negative surface charge (electrophoretic mobility). In addition, auranofin inhibited several fmet-leu-phe-stimulated responses such as shape change, increases in centriole-associated microtubules, decreases in surface charge, and elicited membrane potential changes (di-O-C5(3) dye response). Auranofin (1 micrograms/ml) inhibited fmet-leu-phe-stimulated superoxide and hydrogen peroxide production by 80% (p less than 0.05), and also increased the affinity of receptors for fmet-leu-phe (from Ka 0.035 to Ka 0.48, p less than 0.001). Auranofin also affected neutrophil responses to phorbol myristic acetate (PMA). The total amount of PMA-stimulated superoxide production was suppressed by as little as 0.4 micrograms/ml of auranofin, but the lag time for activation was shortened by low concentrations of auranofin (0.5 to 1 microgram/ml). Four micrograms per milliliter of auranofin suppressed the decrease in surface charge induced by PMA. However, auranofin did not influence superoxide production elicited by the ionophore A23187. The results indicate that auranofin affects the earliest detected responses in neutrophil activation by certain receptor-mediated stimuli.

Anti-Inflammatory Agents↗
PubMed1984

Organelle-depleted human neutrophil cytoplasts used to study fmet-leu-phe receptor modulation and cell function.

Organelle-depleted human neutrophil cytoplasts were used to study N-formylmethionylleucylphenylalanine (fmet-leu-phe) receptor regulation and adaptation, aggregation, chemotaxis, and chemoattractant-elicited changes in shape, volume, and surface charge. Cytoplasts aggregated in response to the chemoattractant fmet-leu-phe, but the magnitude of the response was less than that in neutrophils. Unlike neutrophils, cytoplasts did not exhibit a second wave of aggregation with the addition of cytochalasin B and also failed to disaggregate. In chemotactic assays, cytoplasts migrated poorly into cellulose nitrate filters, and compared with intact neutrophils required a 100-fold greater concentration of fmet-leu-phe to elicit shape change. In contrast to neutrophils, cytoplasts did not decrease their surface charge in response to fmet-leu-phe and did not exhibit an increase in the binding of fmet-leu-[3H]phe after stimulation with phorbol myristate acetate. However, receptor adaptation and induced changes in membrane potential, as measured by using the membrane probe di-O-C5(3), were similar in cytoplasts and in neutrophils. The data suggest that the presence of functional intracellular organelles is required for normal aggregation and disaggregation, chemotaxis, and shape change induced by fmet-leu-phe, and also peptide receptor upregulation in response to secretagogues. The data show that peptide receptor adaptation occurs in the absence of secretory granules and is independent of receptor upregulation .

Carbocyanines↗
PubMed1983

Ultrastructural, biochemical, and functional characteristics of histamine-containing cells cloned from mouse bone marrow: tentative identification as mucosal mast cells.

Two histamine-containing granulated cell lines were cloned from mouse bone marrow by using sequential soft agar and limiting dilution techniques. Concanavalin A-stimulated mouse spleen cell supernatants were required for cell proliferation. Cloned cell lines were Lyt-1.2, Lyt-2.2, Thy-1.2, surface Ig negative, I-A positive, and failed to ingest latex particles. Cells expressed 6.4 to 9.0 X 10(4) IgE high affinity receptors and contained approximately 1 to 2 pg of histamine per cell. Electron microscopy revealed granule and surface membrane features characteristic of mast cells. The cloned histamine-containing granulated cell lines synthesized a proteoglycan containing glycosaminoglycan side chains with an estimated average m.w. of 40,000. The glycosaminoglycan side chains consisted only of chondroitin sulfates identified by charge characteristics and through the use of selective polysaccharidases. These cells degranulated to immunologic stimuli and the calcium ionophore A23187 but not to compound 48/80. Taken together, the above findings suggest that these histamine-containing granulated cell lines that are cloned from bone marrow are mucosal (atypical) mast cells.

Animals↗
PubMed1982

Effects of taxol on human neutrophils.

Taxol, a plant alkaloid, promotes and stabilizes microtubule assembly in cells and cellfree systems. In the present study, the effects of taxol on various functional, morphologic, and biochemical phenomena in human peripheral blood PMN (Hypaque-Ficoll) were examined. Taxol (10(-7) M) inhibited PMN chemotaxis stimulated by N-formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe) or endotoxin-activated serum by more than 60%. The inhibition was not readily reversed by washing, and taxol itself was not a chemoattractant, nor is it a secretagogue. Spontaneous nondirected migration, cell spreading on a glass surface, and orientation of cell organelles in response to a chemoattractant gradient were also inhibited by taxol. Taxol (10(-5) M) decreased killing of Staphylococcus aureus, but did not alter phagocytosis of heat-killed Candida or hexose monophosphate shunt activity in resting or stimulated PMN. Ultrastructural studies showed that PMN incubated in f-met-leu-phe, taxol, or both had increased (p less than 0.001) numbers of centrosome-associated microtubules, and the microtubules of cells incubated in taxol with or without f-met-leu-phe were organized into bundles. Taxol (10(-5) M) markedly inhibited post-translational tyrosinolation of alpha-chains of tubulin in both resting and f-met-leu-phe-stimulated PMN. The data indicate that taxol inhibits PMN locomotion and bacterial killing, supporting a role for microtubules in these processes. The ultrastructural and biochemical data also support the view that taxol mediates its effects on PMN by its effect on microtubules.

Alkaloids↗