Biomedical subjects

D B Cines

Publications and source records attributed to D B Cines.

101 records · Page 6Linked to original sources

PubMed1980

Heparin-associated thrombocytopenia.

We studied the mechanism of platelet injury in 20 patients receiving heparin, three of whom became thrombocytopenic. Platelets from these three patients had increased levels of IgG and C3, which correlated with the presence of thrombocytopenia; their plasma caused the release of serotonin from normal platelets at concentrations of heparin within the usual therapeutic range. This reaction required IgG and an intact classic complement pathway. The 17 patients receiving heparin in whom thrombocytopenia did not develop had normal levels of platelet-associated IgG and C3. Plasma from 14 of these patients caused the release of serotonin, but only at heparin concentrations above the therapeutic range, in a reaction that also required IgG and complement. The addition of heparin to 15 normal plasma samples did not cause platelet injury in vitro. These studies indicate that heparin administration can be associated with complement-mediated platlet injury. The dose-dependent nature of this process may account for the occurrence of thrombocytopenia in some of these patients.

Aged↗

PubMed1980

Immunologic infertility: identification of patients with antisperm antibody.

Immunologic causes of infertility have been postulated for many years, but a precise means for identification of men or women with antibodies against sperm has not been available. We studied 614 patients, including 257 couples, with unexplained in fertility, to detect the presence of circulating antisperm antibody. Using a specific radiolabeled-antiglobulin test, we identified a subset of patients (10 per cent) with IgG antisperm antibody; this antibody was present in 13 per cent of the women and 7 per cent of the men. We followed the course of six infertile couples in whom one partner had sperm antibody. In four couples, pregnancy was achieved; pregnancy correlated with resolution of antibody activity. In two of these four couples the partner (one man and one woman) with antisperm activity had been pretreated with corticosteroids. We conclude that this objective test may be used to identify and then to help manage infertility in patients with suspected antibody-mediated infertility.

Adult↗

PubMed1979

Immune thrombocytopenia. Use of a Coombs antiglobulin test to detect IgG and C3 on platelets.

We applied a radiolabeled Coombs antiglobulin test to the diagnosis and management of immune thrombocytopenia in adults and children. This assay substantiated that the majority of patients with idiopathic thrombocytopenic purpura have increased levels of IgG on their platelets. Platelet-associated C3 was elevated in a subset of these patients, some of whom had normal levels oet-associated IgG, thus suggesting a role for C3 in the pathogenesis of the thrombocytopenia. The assay enabled us to anticipate a change in clinical status, establish the presence of immunologic remission after splenectomy and propose several mechanisms by which corticosteroids act. Platelets from a patient with the post-transfusion-purpura syndrome also carried increased IgG, indicating a role for IgG antibody or IgG-containing immune complexes in the destruction of host platelets in this disease. The radiolabeled Coombs test provides a general means to help diagnose, manage and study immune platelet disorders.

Adolescent↗

PubMed1979

Effect of anti-P1A1 antibody on human platelets. II. Mechanism of the complement-dependent release reaction.

We studied the mechanism by which complement activated by anti-P1A1 antibody elicits the platelet release reaction. Anti-P1A1 antibody mediates its action through the classic complement pathway, and its effect depends on the concentration of IgG antibody on the platelet surface. At relatively high concentrations of anti-P1A1 antibody the release reaction was mediated by a mechanism in part independent of extracellular ADP and metabolic energy and inhibited by only high concentrations of PGE1. However, at lower concentrations of anti-P1A1 antibody the release reaction was dependent on metabolic energy and ADP, and the concentration of PGE1 required to inhibit platelet release was similar to that required to inhibit ADP-induced release. The cyclooxygenase inhibitor acetylsalicylic acid inhibited the release reaction at all nonlytic antibody levels studied. None of the agents studied inhibited the induction of platelet lysis by very high concentrations of anti-P1A1 antibody, and no effect of antibody on platelet 14C-serotonin uptake was observed at antibody concentrations that did not mediate direct in vitro alteration. These studies suggest the possible use of pharmacologic agents in modifying some complement-mediated platelet alterations.

Adenosine Diphosphate↗

PubMed1979

Effect of anti-P1A1 antibody on human platelets. I. The role of complement.

We studied the interaction of complement with human platelets. Complement was activated by IgG anti-P1A1 antibody obtained from 3 patients with the post-transfusion purpura syndrome. We used a heparin-plasma buffer system that permits complement activation and also preserves platelet function. With this system complement activation was efficient, and platelet immune alteration was extensive. Anti-P1A1 antibody was effective only in the presence of complement, in which case both platelet lysis and serotonin release (release reaction) in the absence of lysis were observed. Platelet lysis, as assessed by 51Cr loss, required 10-fold more antibody than was necessary to induce platelet aggregation and release of 14C-serotonin. This platelet release reaction required an intact classic complement sequence through C6. The extent of platelet serotonin release parallelled the depletion of C1 and C4 from platelet-rich plasma. Concentrations of antibody insufficient to induce platelet aggregation and serotonin release could still activate C1 and deposit increased C3 on the platelet surface. These studies demonstrated that complement activation by anti-P1A1 antibody can alter human platelets in a nonlytic system. Several phases of complement-mediated human platelet alteration are possible, depending on the concentration of anti-P1A1 antibody.

Animals↗

PubMed1978

Increased fluidity of human platelet membranes during complement-mediated immune platelet injury.

Complement appears to be involved in the destruction of platelets in certain clinical disorders, such as quinidine purpura and post-transfusion purpura. In both disorders, the classical complement sequence is activated by antigen-antibody complexes. It has been suggested that the terminal components of the complement sequence insert into the hydrophobic core of cell surface membranes and that this process leads to cell lysis. Fluidity is a fundamental property of lipids within the membrane's hydrophobic core. To examine the interaction of complement with membranes, we investigated the effect of complement activation on the fluidity of human platelet membranes. Complement was fixed to platelets using a post-transfusion purpura antibody, and membrane lipid fluidity was assessed in terms of fluorescence anisotropy using two fluorescent probes, 1,6-diphenyl-1,3,5-hexatriene and 9-(12-anthroyl) stearic acid. Microviscosity, expressed in poise, was derived from the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene.Post-transfusion purpura antibody plus complement made platelet membranes more fluid as evidenced by a 21% decrease in anisotropy and a 35% decrease in microviscosity of platelets at 37 degrees C, and this was associated with platelet lysis ((51)Cr release). Complement damage to platelets was accompanied by a 10-15% increase in DeltaE, the fusion activation energy for microviscosity, indicating that complement not only decreased membrane microviscosity but also made membrane lipids less ordered. These changes were consistent and rapid, with platelet lysis and the reduction in microviscosity being half-maximal by 6 min. They were prevented by inactivation of complement with heat or with EDTA, and they were not observed when C5-deficient plasma was used as the complement source. Qualitatively similar changes in platelet membrane fluidity were observed when complement was fixed to platelets by a quinidine-dependent anti-platelet antibody rather than by post-transfusion purpura antibody. Post-transfusion purpura antibody plus complement also decreased the microviscosity of isolated platelet membranes. Moreover, the lipids extracted from platelets lysed by complement had a 22% decrease in microviscosity (P < 0.01), with no associated changes in the amount of cholesterol relative to phospholipid or in the amounts of the various phospholipids. These studies demonstrate that lipids within the hydrophobic core of platelet membranes damaged by complement become more fluid, and this is associated with platelet lysis. These findings are consistent with the concept that the insertion of the terminal complement components into the platelet membrane bilayer perturbs lipid-lipid interactions within the membrane's hydrophobic core.

Antibodies↗

PubMedDate not supplied

Catheter-delivered ultrasound potentiates in vitro thrombolysis.

PURPOSE: To develop a catheter-directed method to enhance urokinase- mediated thrombolysis with use of ultrasound. MATERIALS AND METHODS: A prototype catheter was constructed by using a 9-F piezoelectric crystal capable of producing 640-kHz pulsed ultrasound energy. Clots formed in vitro from whole blood were trace-labeled with iodine-125 fibrinogen, and the release of radiolabeled fibrin degradation products was measured in the presence of urokinase, ultrasound, or a combination of urokinase and ultrasound. RESULTS: By 30 minutes, clot lysis was more complete with urokinase plus ultrasound (78.7% +/- 5.3 [mean +/- SD]) than with ultrasound alone (19.3% +/- 10.0) or urokinase alone (47.9% +/- 10.0) (P < .001 for ultrasound and urokinase vs either alone). The time to 50% clot lysis was shortened by 46% on average with the application of urokinase and ultrasound compared with urokinase alone (P < .03). CONCLUSIONS: Catheter-based ultrasound enhances enzymatic thrombolysis in vitro and may be a practical means to reduce the dose of enzyme and the time needed to achieve clot lysis in vivo.

Adult↗

PubMedDate not supplied

Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells.

Receptors for the Fc portion of immunoglobulins or for the third component of complement (C3) are present on a variety of circulating and fixed tissue cells including granulocytes, monocytes, lymphocytes and glomerular epithelial cells. Cells which lack Fc receptors may express them after infection by herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus or varicella zoster virus. We recently reported that infection by HSV-1 induces both Fc and C3 receptors on human endothelial cells. Glycoprotein E of HSV-1 has been shown to function as an Fc receptor. We now demonstrate that glycoprotein C (gC) of HSV-1 functions as a C3b receptor. This receptor appears following HSV-1, but not HSV-2, infection. Detection of the C3b receptor is blocked by monoclonal antibodies to glycoprotein C (gC) of HSV-1, but not by monoclonal antibodies to other HSV-1 glycoproteins. In addition, the MP mutant of HSV-1, which lacks gC, fails to express a C3b receptor. These results assign a new function of gC of HSV-1 and demonstrate potentially important differences between HSV-1 and HSV-2 glycoproteins.

Complement C3b↗

PubMedDate not supplied

Heterogeneity of human red cell autoantibodies assessed by isoelectric focusing.

Human red cell (RBC) autoantibodies may be the products of a single lymphocyte clone or of a restricted number of clones. For insight into the clonal distribution of human RBC autoantibodies, serum fractions from 28 individuals with various forms of autoimmune hemolytic anemia (AHA) and two nonanemic individuals with positive direct antiglobulin tests were separated by isoelectric focusing (IEF), and RBC binding in each fraction was quantitated with a solid-phase radioimmunoassay. IEF fractions of serum from normal volunteers and patients with nonimmune hemolytic anemia served as controls. These studies indicate that RBC antibodies are found in a restricted number of IEF fractions in sera from some patients with immune hemolytic anemia. IEF fractions containing RBC-binding activity vary among patients with idiopathic AHA, and distinct patterns of binding activity are found in serum from some patients with AHA associated with alphamethyldopa and procainamide or with B-cell immunoproliferative diseases. These findings suggest that the mechanism leading to autoantibody production may differ among patients with the various forms of immune hemolytic anemia.

Anemia, Hemolytic, Autoimmune↗

PubMedDate not supplied

Disorders associated with antibodies to endothelial cells.

Antibodies that bind to endothelial cells have been identified in patients with diverse forms of vasculitis and thrombosis. Sera from patients with systemic lupus erythematosus contain both complement-fixing antibodies and immune complexes that bind to cultured endothelial cells. Sera from patients with heparin-associated thrombocytopenia and thrombosis contain antibodies that react with heparin bound to the endothelium and cross-react with heparan sulfate synthesized by endothelial cells. Children with Kawasaki syndrome may develop cytolytic IgM antibodies that recognize surface antigens induced on endothelial cells by interferon-gamma, interleukin 1, and tumor necrosis factor. The presence of alloantibodies to tissue-restricted polymorphic antigens expressed by endothelial cells is frequently associated with thrombotic microvascular injury and hyperacute allograft rejection. Binding of antibodies and immune complexes to endothelial cells in vitro initiates platelet adherence, production of tissue factor, and secretion of plasminogen activator inhibitor. Antibody-mediated endothelial cell injury may play a role in other vascular disorders of unknown cause.

Autoantibodies↗

PubMedDate not supplied

BRa (HPA-5b) incompatibility may cause thrombocytopenia in neonates of mothers with immune thrombocytopenic purpura.

PURPOSE: The association of anti-Br(a) immunoglobulin G (IgG) platelet alloantibodies with the development of thrombocytopenia in neonates of mothers with autoimmune thrombocytopenic purpura (ITP) is reported. METHODS: Between March 1994 and July 1997, 28 consecutive pregnant women with ITP seen at New York Hospital were screened for platelet-reactive antiglycoprotein (glycoprotein [GP] IIb/IIIa, Ib/IX, and Ia/IIa) antibodies. RESULTS: The sera from 6 of these 28 women contained IgG alloantibodies to GP Ia/IIa directed against the Br(a) (HPA-5b) antigen. Only three families each had at least one Br(a)+ and at least one Br(a)- infant. Platelet typing in these families revealed that the mothers were Br(b/b) (Br(a)-) and the fathers were Br(a/b) (Br(a)+). Platelet counts < 100,000/microl occurred only in 2 of the 3 infants who were Br(a)+. The platelet counts were significantly lower in the three Bra+ infants compared to the five Br(a)- infants (p = 0.038). CONCLUSION: Platelet alloimmunization with anti-Br(a) can cause neonatal thrombocytopenia in infants of mothers with ITP. Platelet antibody testing in the pregnant women with ITP is recommended.

Antigens, Human Platelet↗