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M S Klempner

Publications and source records attributed to M S Klempner.

82 records · Page 5Linked to original sources
PubMed1979

Stimulation of neutrophil oxygen-dependent metabolism by human leukocytic pyrogen.

The ability of highly purified human leukocytic pyrogen (LP) to stimulate neutrophil oxygen-dependent metabolism was studied. Human peripheral blood neutrophils exposed to leukocytic pyrogen in vitro demonstrated an increase in the percentage of neutrophils reducing nitroblue tetrazolium (NBT) dye and a marked stimulation of superoxide dismutase inhibitable reduction of ferricytochrome c. LP stimulation of neutrophil oxygen-dependent metabolism was dose and time dependent. Procedures that destroyed the pyrogenicity of LP also abolished the effects on neutrophil metabolism. Neutrophil hexose monophosphate shunt activity was also stimulated by LP. In a rabbit model, the effect of in vivo LP on neutrophil superoxide generation was also studied. There was a consistent increase in the percent and absolute number of NBT positive neutrophils. Peak stimulation of neutrophil metabolism occurred after defervescence suggesting several possible mechanisms. The observations reported here may, in part, explain the nonspecificity of the NBT test in febrile, noninfected patients and provide further understanding of neutrophil physiology during acute inflammation.

Adult↗
PubMed1978

Human leukocytic pyrogen induces release of specific granule contents from human neutrophils.

The ability of highly purified human leukocytic pyrogen (LP) to induce neutrophil lysosomal protein release is described. Human peripheral blood neutrophils isolated by Ficoll-Hypaque and dextran sedimentation were exposed to purified human LP. The specific granule-associated proteins, lysozyme and lactoferrin were selectively released, whereas primary granule (beta-glucuronidase) and cytoplasmic (lactic dehydrogenase) enzyme markers were not. Optimum release was observed after 45 min in the presence of Ca++ and Mg++. Cytochalasin B (5 microgram/ml) had no effect on LP-induced lysosomal enzyme release. Since the pyrogenicity of LP is dependent on prostaglandin synthesis, the effect of two potent inhibitors of prostaglandin synthesis on lysozyme release was studied. Both indomethacin and naproxen failed to inhibit specific granule protein release. These observations suggest that the concommitance of fever, elevated serum or urine lysozyme and hypoferremia may, in part, be explained by the interaction of LP and peripheral blood neutrophils.

Cations, Divalent↗
PubMed1978

Separation and functional characterization of human neutrophil subpopulations.

Human neutrophils have been considered to be a functionally homogeneous population of cells. We have developed a density sedimentation technique for separation of neutrophils into two populations based on their ability to form rosettes with IgG-coated human erythrocytes (7SEA). Under the experimental conditions 80% +/- 4.3% of normal human peripheral blood neutrophilis form rosettes. Functionally rosette-forming neutrophils are more adherent to nylon wool, able to phagocytize more 14C-labeled Staphylococcus aureus, more efficient in killing S. aureus, and more responsive to endotoxin-activated human serum in a 51-cr chemotaxis assay that the non-rosette forming neutrophils. However, there is no difference among neutrophil subpopulations' ability to phagocytize latex particles. Paired samples of exudate neutrophils from cutaneous abscess fluid and peripheral neutrophils from three patients were investigated for their ability to form 7SEA rosettes. In each case exudate neutrophils contained greater than 96% rosette-forming neutrophils, whereas peripheral blood contained the normal 80% ( less than 0.01). Thus we show that peripheral blood contains at least two distinct populations of neutrophils. However, an essentially homogeneous neutrophil population is present in cutaneous exudate fluid.

Animals↗
PubMed1978

Inhibition of neutrophil Fc receptor function by cotricosteroids.

The ability of hydrocortisone sodium succinate to inhibit the adherence of IgG-sensitized erythrocytes (EA) to human peripheral blood neutrophil monolayers is described. The steroid inhibitory effect was dose-dependent with a 32.4+/-2.4% decrease in EA binding at 2 X 10(-4)M. There was no difference between the addition of hydrocortisone prior to or at the same time as EA and steroid interference with EA binding was completely reversible. In addition, hydrocortisone was unable to displace bound EA. These findings suggest that hydrocortisone interferes with the availability of the neutrophil Fc receptor for binding and provides further insight into the host factors which are compromised during corticosteroid administration.

Cell Adhesion↗
PubMed1975

Central nervous system disease in systemic lupus erythematosus. Therapy and prognosis.

The effect of corticosteroid therapy in 28 patients with 52 episodes of neuropyciatric disease in systemic lupus erythematosus (SLE) was elevated. Categories of organic central nervous system disease were seizures (eight patients), organic brain syndromes (nine patients), aseptic meningitis (four patients) and a variety of focal neurologic findings (seven patinets). Fourteen pateints had 15 episodes of functional psychosis without other evidence of neurologic disease. Although there was a general correlation between clinical and serologic evidnce of active SLE and the development of organic neurolgic disease, there was no evidence that therapy with very large doses of corticosteroids was beneficial. Of the deaths in this series, two were due to probable active SLE involving the central nervous system wheras five were attributable to complications of therapy. The long-term morbidity, likewise, was high in the patients who recieved large doses of corticosteroids. In all, 12 patients had major complications of corticosteroid therapy. Functional psychosis was usually preciptated by corticsoteroid therapy and respond to a reduction in steroid dosage and administration of psychotropic drugs.

Adolescent↗
PubMedDate not supplied

Probing the phagolysosomal environment of human macrophages with a Ca2+-responsive operon fusion in Yersinia pestis.

Several microorganisms, including Yersinia sp., Salmonella sp., Brucella sp., Mycobacterium sp. and Leishmania sp., have successfully adapted to grow within macrophage phagolysosomes. Infections caused by these intracellular pathogens are among the most difficult to treat. As part of an antimicrobial strategy directed at modifying the phagolysosomal environment to the disadvantage of these important pathogens, we are defining the ambient conditions within the organism-containing phagolysosome. To probe this environment, we have used Yersinia pestis, whose expression of several virulence attributes is highly dependent on the Ca2+ concentration in its growth environment. We first genetically engineered a strain of Y. pestis which responds to a low-calcium environment by transcription of inserted structural genes of the Escherichia coli lac operon. Using this mutant organism as a relevant biological probe, we demonstrate here that the calcium concentration in Y. pestis-containing phagolysosomes is sufficiently low to permit virulence gene expression; this resolves the question of where Y. pestis might express its Ca2+-regulated genes in vivo.

Antigens, Bacterial↗
PubMedDate not supplied

Interactions of polymorphonuclear leukocytes with anaerobic bacteria.

The interactions of anaerobic bacteria with polymorphonuclear leukocytes (PMNs) are reviewed. Anaerobes, including species of Propionibacterium, Fusobacterium, and Bacteroides, produce serum-independent chemotactic factors capable of attracting PMNs. In addition, these bacteria produce chemoattractants by complement activation and possibly by interaction with host lipids. Bacteroides species are optimally phagocytosed by PMNs when opsonized by both immunoglobulin and complement although the latter appears to provide the critical opsonin. As is the case with several aerobic bacteria, the polysaccharide capsule of Bacteroides fragilis interferes with PMN phagocytosis and antibody to the capsule partially overcomes this virulence property. The presence of Bacteroides species may also inhibit PMN phagocytosis and killing of aerobic gramnegative bacteria either by competing for limited opsonins or by decreasing intracellular killing. Bactericidal activity of PMNs against anaerobes appears to proceed primarily through oxygen-independent mechanisms, although the relevant microbicidal components have not been identified. Some antibiotics with activity against anaerobic bacteria penetrate PMNs, and antibiotic pretreatment of B. fragilis, with levels below the minimal inhibitory concentration, facilitates PMN phagocytosis of these organisms.

Anti-Bacterial Agents↗
PubMedDate not supplied

Comparison of granulocyte-macrophage colony stimulating factor and interleukin-1 production from human peripheral blood mononuclear cells as measured by specific radioimmunoassays.

Attention has focused on cytokine networks in which gene and protein expression of some cytokines is under the influence of other cytokines. In the present studies, we addressed the relationship between the synthesis of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-1 (IL-1) in human peripheral blood mononuclear cells (PBMC) stimulated with mitogens. Since bioassays for cytokines are sensitive to more than one of these factors, it was necessary to measure the amounts of IL-1 and GM-CSF independent of bioassays. A specific and sensitive (40 pg/ml) radioimmunoassay (RIA) was developed for human GM-CSF. The sensitivity of the RIA was greater when lysine residues were iodinated with Bolton-Hunter reagent than tyrosine residues using chloramine T. After stimulating PBMC with concanavalin A (Con A), the biological activity of GM-CSF was determined in bone marrow cultures and compared to immunoreactive GM-CSF; GM-CSF levels detected by bioassays and RIAs were highly correlated in two separate sets of experiments (r2 = 0.95 and 0.43). Incubation with Con A for 48 h induced more GM-CSF than stimulation by phytohemagglutinin (PHA) despite the fact that PHA stimulates large amounts of IL-1 alpha; indomethacin had no effect on Con A stimulated synthesis of GM-CSF or IL-1 alpha. In two separate studies, PBMC from 14 donors and a second group of 12 donors were incubated with Con A for 48 h and the total amount of immunoreactive IL-1 alpha and GM-CSF was determined in the same cell cultures. There was no correlation of the amount of either cytokines in these cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗