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Biomedical subjects

M M Glovsky

Publications and source records attributed to M M Glovsky.

At least 19 recordsLinked to original sources
PubMed1992

Effect of adenylate cyclase activators on C5a-induced human neutrophil aggregation, enzyme release and superoxide production.

The effect of adenylate cyclase activators on C5a- and f-Met-Leu-Phe-induced human neutrophil aggregation, enzyme release and superoxide production was investigated. C5a-stimulated superoxide production was markedly inhibited by adenylate cyclase activators, and the order of potency was PGE1 greater than isoproterenol greater than epinephrine greater than PGF2 alpha, which correlated with intracellular cAMP levels. However, neutrophil aggregation was inhibited by PGE1, PGE2, isoproterenol and epinephrine only at concentrations greater than 10(-6) M. Lysozyme release was inhibited only via PGEs in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine. These results suggest that in the human neutrophil: (1) C5a-induced superoxide production is more sensitive to regulation by cAMP than neutrophil aggregation or enzyme release, and (2) the type of receptor occupied as well as the threshold level of cAMP are important in the regulation of neutrophil aggregation and enzyme release stimulated by C5a.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury.

Complement activity was studied in patients with spinal cord transection. In some sera acute phase reactants: haptoglobin, C-reactive proteins, ceruloplasmin, as well as fibrinogen and fibrin degradation products, and immune complexes were monitored. Complement and acute phase reactants are increased in a majority of patients. Continuing inflammation and release of inflammatory mediators could be responsible for poor healing that commonly occurs in spinal cord injury. Urinary tract and other infections are associated with some but not all of the protein abnormalities. These proinflammatory proteins may contribute to the lack of healing of spinal transection.

Acute-Phase Proteins↗
PubMed1991

Effect of maternal immunotherapy on immediate skin test reactivity, specific rye I IgG and IgE antibody, and total IgE of the children.

The effect of specific immunotherapy during pregnancy was studied in 14 children, 3 to 12 years after delivery. Fourteen additional children from the same allergic mothers, in whom immunotherapy was not given during the pregnancy, served as controls. The immediate skin test response to grass allergens of the children of mothers given immunotherapy. Levels of rye I IgG and total IgE were lower in the sera of children born to mothers who received immunotherapy (not statistically significant) than their control cohorts. Paired cord blood and maternal blood samples drawn at delivery showed similar levels of rye I IgG, indicating that blocking antibody freely crosses the placenta. This evidence indicates that immunotherapy during pregnancy may have an inhibitory effect on immediate skin reactivity to grass allergens in some of the offspring. Whether tolerance to other allergens can be induced in children by maternal immunotherapy remains to be determined.

Adolescent↗
PubMed1990

C3a57-77, a C-terminal peptide, causes thromboxane-dependent pulmonary vascular constriction in isolated perfused rat lungs.

Pulmonary hypertension occurs after the intravascular activation of complement. However, it is unclear which activated complement fragments are responsible for the pulmonary vascular constriction. We investigated the 21-carboxy-terminal peptide of C3a (C3a57-77) to see if it would cause pulmonary vascular constriction when infused into isolated buffer-perfused rat lungs. Injection of C3a57-77 (225 to 450 micrograms) caused mean pulmonary arterial pressure (Ppa) to rapidly increase. However, the response was transient, with Ppa returning to baseline within 10 min of its administration. C3a57-77 also resulted in an increase in lung effluent thromboxane B2 (TXB2), concomitant with the peak increase in Ppa. C3a57-77 did not affect the amount of 6-keto-PGF1 alpha in the same effluent samples. Indomethacin inhibited the C3a57-77-induced pulmonary artery pressor response and the associated TXB2 production. Indomethacin also decreased lung effluent 6-keto-PGF1 alpha. The thromboxane synthetase inhibitors CGS 13080 and U63,357 inhibited the C3a57-77-induced pulmonary artery pressor response and TXB2 production without affecting 6-keto-PGF1 alpha. These inhibitors did not inhibit pulmonary artery pressor responses to angiotensin II. Tachyphylaxis to C3a57-77 occurred because a second dose of C3a57-77 administered to the same lung failed to cause a pulmonary artery pressor response or TXB2 production. The loss of the pressor response was not due to a C3a57-77-induced decrease in pulmonary vascular responsiveness because pressor responses elicited by angiotensin II were not altered by lung contact with C3a57-77. Thus, C3a57-77 caused thromboxane-dependent pulmonary vascular constriction in isolated buffer perfused rat lungs.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Blocking of passive sensitization of human mast cells and basophil granulocytes with IgE antibodies by a recombinant human epsilon-chain fragment of 76 amino acids.

The recombinant peptide corresponding to residues 301-376 at the junction of constant regions 2 and 3 of the human IgE epsilon chain blocked the in vivo passive sensitization of human skin mast cells and in vitro sensitization of human basophil granulocytes with human IgE antibodies. An injection of the recombinant peptide or E myeloma protein into normal skin sites 1 hr before sensitization with an allergic serum blocked passive sensitization. In this system, approximately 10-fold higher molar concentration of the recombinant peptide than E myeloma protein was required for 50% inhibition of Prausnitz-Küstner reactions. When the mononuclear cells of two normal individuals were preincubated with the recombinant peptide or E myeloma protein for 15 min before passive sensitization with the same allergic serum and the cells were challenged with an optimal concentration of an antigen, approximately 11- to 13-fold higher concentration of the recombinant peptide than E myeloma protein was required for 50% inhibition of antigen-induced histamine release. Further studies with several recombinant peptides indicated that amino acid resides 363-376 in the Fc epsilon-chain fragment are not essential for binding of the peptide to Fc epsilon-chain receptor I.

Base Sequence↗
PubMed1989

Effect of monoclonal antihuman IgE on recombinant IgE(301-376) inhibition of specific IgE histamine release.

To explore the binding domains of rCIgE(301-376) necessary for inhibition of passive transfer of rye grass and Chinese elm IgE to human basophils, we employed monoclonal antibodies known to bind to IgE(301-336), M-272, and to IgE(367-376), M-27. By preincubating M-272, but not M-27, with rCIgE(301-376), passive transfer of specific IgE to basophils was partially inhibited. This implies that M-272 recognizes a binding site on rCIgE(301-376) or sterically interferes with the rCIgE(301-376) high-affinity binding domains on human basophils.

Allergens↗
PubMed1989

Inverse correlation of expiratory lung flows and sputum eosinophils in status asthmaticus.

Seventy-six consecutive patients admitted to Los Angeles County General Hospital with acute asthma were studied. Blood and sputum smears for cell counts were obtained on all patients within 12 hours of admission. Fifty-one (67%) patients were able or willing to perform spirometry and flow/volume curves in the first 24 hours of hospitalization. The severity of airway obstruction as assessed by forced expiratory volume in one second (FEV1), maximum mid-expiratory flow rate (MMFR), and forced vital capacity (FVC) was compared with blood and sputum eosinophil counts. Although there was no relation between the blood eosinophilia and airway obstruction, an inverse relationship between the number of eosinophils in the sputum and airway flow rates was observed. Higher percentages of sputum eosinophils were associated with diminished flow rates. We believe that sputum eosinophils may be helpful in the initial assessment of severe bronchial asthma.

Adolescent↗
PubMed1988

Anaphylatoxin C3a peptide contracts human pulmonary vasculature.

Complement anaphylatoxin C3a C-terminus octapeptide Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg (C3apep) contracted both pulmonary artery (PA) and pulmonary vein (PV) in a dose-dependent manner over the concentration range of 0.1 micrograms/ml to 100 micrograms/ml with the latter having maximal contractile activity. Removal of the terminal arginine caused complete loss of activity of C3apep. Contractions consisted of an early and a sustained component with the latter component being much greater in PV than PA. The early component was inhibited by pretreatment of tissues with the cyclooxygenase inhibitor indomethacin, or the thromboxane synthase inhibitors dazoxiben or U63,557A. The sustained contractile component was inhibited by the leukotriene antagonist FPL55712 or the 5-lipoxygenase inhibitors U60,257 (Piriprost) or nordihydroguaiiararetic (NDGA). C3apep challenge of both PA and PV resulted in the generation of leukotriene C4. These results suggest that C3apep causes contraction of human pulmonary arteries and veins by the production of thromboxane A2 and leukotrienes.

Amino Acid Sequence↗
PubMed1987

Activation of human serum complement with allergens. I. Generation of C3a, C4a, and C5a and induction of human neutrophil aggregation.

To understand the relevance of allergens in generation of C3a, C4a, and C5a in normal human serum, we studied extracts of several allergens (house dust, house dust mite, Aspergillus fumigatus, and perennial ryegrass). Known complement activators zymosan and endotoxin were used as controls. Generation of C3a, C4a, and C5a (determined by radioimmunoassays) occurred with extracts of house dust and Aspergillus more than with house dust mite and ryegrass. Anaphylatoxins were produced both in dose and time-dependent fashions. Serum activated with house dust and Aspergillus extracts induced neutrophil aggregation when this serum was added to neutrophil suspensions. Less aggregation occurred when house dust mite and perennial ryegrass extract-activated sera were added to human neutrophils. We propose that some allergens may induce biologic responses by activation of sera and generation of anaphylatoxins as well as by IgE-mediated responses.

Adult↗
PubMed1987

Anaphylatoxin-induced neutrophil chemotaxis and aggregation. Limited aggregation and specific desensitization induced by human C3a and synthetic C3a octapeptides.

Human neutrophil aggregation was induced by highly purified human C3a and chemically synthetic COOH-terminal peptides of C3a (C3a-8R; Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg) in a dose-dependent manner and was 40% of human C5a-induced aggregation at each optimal concentration. In contrast to C5a and formyl-Met-Leu-Phe (f-MLP), C3a and C3a-8R showed little chemotactic activity. Specific desensitization of neutrophil aggregation was observed with C3a, C3a-8R, C5a and f-MLP, but not with C3a-des-Arg-7R, indicating that the human neutrophil has C3a-specific binding sites which are different from C5a and f-MLP receptors. An additive effect on aggregation was observed at suboptimal concentrations of C5a (1 X 10(-8) M) and C3a (1 X 10(-6) M) or C3a-8R (1 X 10(-5) M). These studies suggest that a subpopulation of human neutrophils have specific binding sites for C3a and C3a may work cooperatively with C5a during the process of neutrophil activation by increasing aggregation and lysosomal enzyme release.

Anaphylatoxins↗
PubMed1985

Regulation of human neutrophil guanylate cyclase by metal ions, free radicals and the muscarinic cholinergic receptor.

We have examined the properties of soluble guanylate cyclase activity in the human neutrophil. The enzyme showed complex regulation by metal ions. A 10-fold higher activity was observed in the presence of Mn2+ than Mg2+, while Ca2+ caused an increase in activity only in the presence of Mg2+ ion. Sodium nitroprusside (SNP), azide and hydrogen peroxide were activators of the enzyme. Dithiothreitol blocked the activation by SNP, suggesting the involvement of thiol groups in the activation process. Carbachol acting through the muscarinic cholinergic receptor caused a dose-dependent activation, which was blocked by atropine. Higher concns of carbachol were required to activate guanylate cyclase than were required for the modulation of enzyme release elicited by N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Nordihydroguaracetic acid inhibited carbachol stimulation of guanylate cyclase. By contrast, trifluoperazine (TFP), a calmodulin antagonist, caused a biphasic modulation of basal activity in the presence or absence of carbachol. Our results indicate that: allosteric interactions of metal ions are important to the regulation of the enzyme, the free radical nitroxide as well as hydrogen peroxide enhances enzyme activity, agonist occupancy of the muscarinic cholinergic receptor activates neutrophil guanylate cyclase probably through a mechanism involving calcium influx and the activation of the lipoxygenase pathway, and a TFP-sensitive site (possibly calmodulin) is involved in the selective regulation of basal enzyme activity.

Azides↗
PubMed1979

Anaphylatoxin-induced histamine release with human leukocytes: studies of C3a leukocyte binding and histamine release.

Purified human C3a and synthetic COOH-terminal peptides of C3a, i.e., a pentapeptide, Leu-Gly-Leu-Ala-Arg (5R), and an octapeptide, Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg (8R) induced histamine release from human basophil granulocytes. On a molar basis, 5R was one-tenth and 8R was one-fifth as active as C3a in causing histamine release. It was found that 125I-C3a binds to whole leukocytes, interacting with both mononuclear cells and neutrophils and the binding was inhibited by preincubation of cells with unlabeled C3a, but not by C5a. 5R and 8R also inhibited the binding of 125I-C3a to the cells. However, on a molar basis, 2,000 times more 8R or 6,000 times more 5R is required for 50% inhibition of 125I-C3a binding as compared with native C3a. Autoradiography of cells using 125I-C3a and 125I-C5a showed preferential binding of 125I-C3a to eosinophils and basophils, whereas 125I-C5a binds primarily to neutrophils and eosinophils and to a lesser extent to basophils. The preferential binding of C3a and C5a to different cell types may herald significance related to their physiological functions.

Anaphylatoxins↗
PubMed1978

Autoreactivity between lymphocytes and thymus cells in myasthenia gravis.

Thymus cell preparations from four of five myasthenia gravis patients with thymic hyperplasia and from one additional patient with thymic involution stimulated autologous peripheral blood lymphocytes. No autostimulation was observed in two patients with thymoma. Autostimulation as associated with an increase in the fraction of B lymphocytes in the thymus.

Adult↗
PubMed1977

Quantitative requirements for C3 to induce Forssman systemic shock and cutaneous hemorrhagic vasculitis in guinea pigs.

The requirements of complement (C) to induce systemic and cutaneous Forssman reactions were studied in inbred DHC-BA and Hartley strain guinea pigs. After intravenous injection of Forssman antibody, fatal systemic shock was associated with a marked drop in CH50, C4, and C3 and a lesser decrease in C5 hemolytic activity. Platelet counts and leukocyte counts dropped as well. With the use of the purified low molecular weight factor from cobra venom (CVF) to deplete C3, guinea pigs with less than 1% intravascular C3 were protected from lethal shock. Approximately 1% to 3% C3 activity is required for Forssman cutaneous vasculitis. These results confirm earlier studies that classical complement pathway activation occurs in Forssman shock and demonstrate the exquisite biologic efficiency of C3 in provoking the shock syndrome.

Anaphylatoxins↗
PubMed1977

Gamma A myeloma with hyperviscosity and obstructive uropathy.

A patient with gamma A myeloma, hyperviscosity and an obstructive uropathy is described. Operation revealed a proteinaceous mass obstructing the right renal pelvis. Immunoprecipitin and immunofluorescent analysis of this mass and concentrated urine demonstrated the presence of gamma A myeloma protein, kappa light chains and albumin. This is the first description of an obstructive uropathy in multiple myeloma owing to a proteinaceous matrix containing paraprotein.

Blood Viscosity↗
PubMed1977

Reiter's syndrome in childhood.

Seven boys with Reiter's syndrome are described. Three had diarrhea and 2 had venereal contact as antecedent events. All developed the complete triad of symptoms in a 5- to 24-day period. Joint involvement of the lower extremities was seen in each boy. HLA-B27 typing was positive in 6 of 7 (86%). Serum and synovial fluid levels of CH50 and C3 were elevated in 5 boys and confirm similar findings in adults. Two boys recovered spontaneously without therapy and 3 boys received aspirin with a rapid and complete resolution of symptoms. The two oldest boys had the most severe joint involvement and were receiving phenylbutazone with continuing active arthritis when they were lost to followup. Reiter's syndrome in children may be infrequently reported because its antecedents and the triad symptoms are common occurrences in pediatric practice.

Adolescent↗