Search PubMed⌕ Search

Biomedical subjects

M Joseph

Publications and source records attributed to M Joseph.

At least 145 records · Page 8Linked to original sources
PubMed1986

A suppressive lymphokine of platelet cytotoxic functions.

The in vitro stimulation of mononuclear cells from human peripheral blood with mitogens is known to induce the release of factors (monokines and lymphokines) that possess distinct biologic activities. The present data describe the presence in Con A- and antigen-stimulated T cell supernatants (of man or rat) of a factor able to inhibit, in a dose-dependent manner, the platelet cytotoxicity toward the young larvae of Schistosoma mansoni. The production of oxygen metabolites by IgE-coated platelets, stimulated by anti-IgE or the specific antigen, was, likewise, strongly inhibited by this lymphokine. The producing T lymphocyte subpopulation was identified as OKT 8+. This suppressive lymphokine of platelet functions had an m.w. of 15,000 to 20,000 and a pI of 4.6. It was heat- and acid-stable and sensitive to trypsin and proteinase K, but neuraminidase had no effect on its activity. This platelet suppressive activity was specifically absorbed by platelet membrane, suggesting its action through the binding to a receptor.

Binding, Competitive↗
PubMed1986

Functional study of a monoclonal antibody to IgE Fc receptor (Fc epsilon R2) of eosinophils, platelets, and macrophages.

An IgM mAb (BB10) was produced by immunization of mice with human eosinophils purified according to their abnormal low density ("hypodense" cells), and previously shown to exhibit increased IgE-dependent antiparasite cytotoxicity. This BB10 antibody, selected for positive fluorescence staining of hypodense blood or lung eosinophils and low or negative staining of normodense eosinophils or neutrophils, could strongly inhibit IgE-dependent cytotoxicity of human eosinophils and platelets. The specificity for the IgE Fc receptor was suggested by the high levels of inhibition of IgE rosettes formed by eosinophils after incubation with the purified IgM fraction of BB10, whereas other receptors (Fc gamma R, CR1) were not affected. On the other hand, BB10, able to inhibit rat eosinophil Fc epsilon R, did not react with the IgE Fc receptor on mast cells or basophils. A technique using radioiodinated BB10 allowed us to quantify the specific binding of BB10 to human eosinophils and platelets. Competition experiments revealed a crossinhibition between the binding of BB10 and IgE, suggesting the specificity of BB10 for the IgE binding site of eosinophil, platelet, and monocyte Fc epsilon R. Three proteins having extrapolated Mr of 32,000, 43,000-45,000, and 97,000 were found in the platelet extract eluted from a BB10 or from an IgE immunosorbent column. These findings confirm the similarities between IgE Fc receptors on human eosinophils, platelets, and macrophages, already observed with polyclonal antibodies directed against the B lymphocyte Fc epsilon receptor. They suggest, moreover, that the mAb BB10 can represent a good reagent for further investigations on the structure and the functions of this IgE Fc receptor (Fc epsilon R2).

Animals↗
PubMed1986

Rat resistance to schistosomiasis: platelet-mediated cytotoxicity induced by C-reactive protein.

In rats infected with the parasite Schistosoma mansoni, the concentration of C-reactive protein in the serum increases after the lung stage of infection and is at its highest at the time of terminal worm rejection. The peak of platelet-mediated cytotoxicity induced by infected serum that has been heated (and is free of immunoglobulin E) as well as the time course for the development of platelet cytotoxic activity in infected rats was found to be correlated with the concentration of C-reactive protein. Rat and human platelets treated with homologous serum obtained during an acute phase of inflammation or with purified C-reactive protein were able to kill the immature forms of the worm in vitro. Platelets treated with C-reactive protein were furthermore capable of conferring significant protection against schistosomiasis in transfer experiments. Collectively these data indicate that a system that includes C-reactive protein and platelets participates in the natural resistance of the rat to schistosomal infection.

Animals↗
PubMed1986

The receptor for IgE on blood platelets.

Highly purified blood platelets from man and rat could be induced into cytotoxic effectors against schistosome larvae by an IgE-dependent mechanism. Such a process implied the existence of a receptor for the Fc part of IgE on the surface of these blood elements. Normal platelets, incubated in the serum of infected individuals as well as in the IgE-rich serum from asthmatic patients, showed similar capabilities. Flow cytofluorometric analysis evidenced that the platelets bearing IgE receptors represented a subpopulation (20%), the percentage of which was significantly increased (up to 50%) in rats or patients with high levels of circulating IgE. Radiolabeled IgE, whose binding was specifically inhibited by an excess of unlabeled IgE or by anti-Fc epsilon receptor antibody, allowed the demonstration that the receptor for this isotype on the platelet surface was saturable. The binding of increasing amounts of IgE followed a bimodal curve, with less than 1000 sites per platelet showing an affinity coefficient of 3.3 X 10(7) M-1 at low concentrations, and a Ka of 7.8 X 10(5) M-1 for higher concentrations. Beyond their interest in the demonstration of cytotoxic properties of thrombocytes, these observations place emphasis on the potential role of the platelets in immediate-type allergic reactions by their direct interaction with IgE antibody molecules, through a specific receptor.

Animals↗
PubMed1986

Protection tests against parasitic diseases.

The development of parasite immunology during the last decade has been highly beneficial to our understanding of immune processes against parasites, and recent research has been devoted to the target antigens of effector mechanisms, especially those localized on the surfaces of the pathogens. In this context, define antigenic structures have been identified, which induced significant degree of protection. In malaria, circumsporozoite and merozoite proteins, with large repetitive sequences, have been isolated from various species of Plasmodium and cloned. Monoclonal antibodies produced against these antigens inhibited the invasion of host cells by living parasites. Some results have also been obtained in protective immunity against Leishmania and Toxoplasma. In schistosomiasis, the main characteristic of defence processes is the narrow association between cellular and humoral immunity in antibody-dependent cell-mediated cytotoxic mechanisms. Eosinophils, macrophages, and platelets efficiently killed schistosome larvae when activated by specific antibody of anaphylactic classes, especially IgE. Some of the target antigens have been characterized and cloned. The transfer to normal animals of monoclonal antibodies, and, in one case, of an anti-idiotype antibody, has induced a significant protection against challenge infestations. Optimistic perspectives can therefore be opened concerning an efficacious immunoprophylaxis of an increasing number of parasitic diseases. An adequate conjunction between potentially protective antigens and selective immunomodulators and adjuvants should lead to vaccination. Such an aim nowadays appears as more than a hope.

Adjuvants, Immunologic↗
PubMed1986

A role for glycoprotein IIb-IIIa complex in the binding of IgE to human platelets and platelet IgE-dependent cytotoxic functions.

A possible relationship between binding sites for Immunoglobulin E (IgE) on human platelets, involved in IgE-dependent cytotoxic functions of platelets against helminth parasites, and well-characterized platelet constituents involved in haemostasis, was investigated. We first explored the interaction with IgE of platelets from patients with rare inherited deficiencies of defined platelet constituents and functions: Glanzmann's thrombasthenia, Bernard-Soulier and grey platelet syndromes. We report that only type I and II thrombasthenic platelets, which lack the membrane glycoproteins (GP) IIb and IIIa, failed to bind IgE and to exhibit IgE-dependent effector functions. Since thrombasthenic monocytes, however, showed normal interaction with IgE, this defect appeared restricted to platelets. Polyclonal and monoclonal antibodies directed against GP IIb-IIIa complex, but not monoclonal antibody directed against GP Ib, inhibited the binding of IgE to normal platelets, and their IgE-dependent cytotoxicity. Taken together, these findings indicate a relation between the GP IIb-IIIa complex and the expression of IgE binding sites and IgE-dependent effector functions in human platelets.

Blood Platelets↗
PubMed1986

Prevalence rates for alcoholism, associated depression and dementia on the Harlem Hospital Medicine and Surgery Services.

Current prevalence rates for alcoholism, and associated depression and dementia, were determined on random samples of approximately 200 patients admitted to the Medicine Service, and a similar sample to the Surgery Service, of the Harlem Hospital Center. The Medicine patients averaged 51 years of age, significantly older than the Surgery sample's average age of 44 years. Surgery patients also had a significantly greater proportion of patients (46.8 percent) who had achieved at least a high school education compared to Medicine (32.1 percent). The alcohol prevalence rate of 30.2 percent for Medicine was significantly greater than the 18.3 percent Surgery prevalence. Both Medicine and Surgery patients showed that a progressively serious pattern of drinking was associated with progressively serious depression. Progressive dementia was associated with progressive severity of drinking in the Medicine sample, but this finding was not demonstrated in the Surgery patients. Medicine and Surgery patients demonstrated dissimilar profiles of principal admitting diagnoses. Patient management is seriously handicapped by problems of alcoholism and associated problems of depression and dementia.

Adolescent↗
PubMed1986

Alveolar macrophage and its participation in the inflammatory processes of allergic asthma.

Purified alveolar macrophages (AM) obtained by bronchoalveolar lavage of allergic asthmatic patients are stimulated by incubation with anti IgE or the exposure to the related allergen. Confirming the demonstration of a receptor for the Fc fragment of IgE on the surface of macrophages, IgE was characterised on AMs by a rosette-assay, showing an increased percentage of cells forming rosettes with red blood cells coated with anti-IgE or the specific allergen. The IgE-dependent secretion of arachidonic acid metabolites, PAF-acether and chemotactic factors for neutrophils and eosinophils demonstrated in vitro, together with the in vivo demonstration of the activation of AMs by a local provocation test, suggest that besides mast cell, AM do participate in the inflammatory processes of allergic asthma.

Antibodies↗
PubMed1986

Nedocromil sodium inhibits IgE-dependent activation of rat macrophages and platelets as measured by schistosome killing, chemiluminescence and enzyme release.

The IgE-dependent activation of peritoneal macrophages and blood platelets can be measured by anti-parasite cytotoxicity, chemiluminescence and, in macrophages, lysosomal enzyme activity. Using these parameters, the present study demonstrates an inhibition by nedocromil sodium of the IgE-mediated stimulation of these non-mast cell inflammatory populations in the rat. These observations suggest that nedocromil sodium may be of value in the treatment of diseases of the lung where inflammatory mediator release is implicated.

Animals↗
PubMed1985

Defined antigens secreted by the larvae of schistosomes protect against schistosomiasis: induction of cytotoxic antibodies in the rat and the monkey.

The study of the immunology of schistosomiasis has allowed a clear understanding of the basic mechanisms of resistance, emphasizing the important role played by cellular and humoral factors. Whereas the production of polyclonal or monoclonal antibodies and the precise inventory of immune effector mechanisms in the rat and in man have led to the identification of potentially protective antigens, immunization with soluble schistosome components has not allowed a successful control of the destruction of schistosomula after infection. The experiments reported here show that schistosomulum-released products (SRP) were able to induce the production of antibodies, in the rat and the monkey, highly cytotoxic in antibody-dependent cellular cytotoxicity, using monocyte monolayers, platelets or eosinophils as effector cells. The immunization of rats with either total SRP or 25-30-kDa molecules purified from schistosomula conferred a significant protection towards a challenge infection by the parasite. IgE and to a lesser extent IgG antibodies represented the major humoral factors of cell activation leading to the schistosomulum killing when anti-SRP antisera, obtained after immunization of the monkey, were incubated with human effector cells.

Animals↗
PubMed1985

Regulatory role of a tripeptide (TKP) from the second constant domain of immunoglobulin G--I. Inhibition of rat and human macrophage activities.

We have previously shown that peptides released after the cleavage of IgG by parasite proteinases were strong inhibitors of the macrophage effector functions against schistosome larvae. The results presented here demonstrate that a single tripeptide set, Thr-Lys-Pro (TKP), inhibits various macrophage functions and can be considered as an immunologically active peptide. Indeed, not only IgE-dependent cytotoxicity but also beta-glucuronidase release, chemiluminescence and ILI production were reduced when rat macrophages were previously incubated with TKP or some analogues. Moreover, chemotaxis and IgE-specific receptor expression were inhibited in both rat and human macrophages after treatment with TKP, without affecting the cell viability. The substitution or acetylation of Thr diminished or suppressed the inhibitory effect of TKP.

Animals↗
PubMed1985

Regulatory role of a peptide from the second constant domain of immunoglobulin G--II. In vitro effect on granuloma formation around S. mansoni eggs.

Previous studies have shown that hydrolysis of IgG by proteases secreted by S. mansoni schistosomula release peptidic fragments which inhibit various macrophage functions. Several peptides from the second constant domain of IgG reduced granuloma formation in vitro with spleen cells from mice infected by S. mansoni eggs of the parasite. The maximal inhibitory effect was obtained by the tripeptide Thr-Lys-Pro (TKP). Inhibition occurred at the early stage of the granulomatous response. Among the cells involved only the adherent cell population was inhibited by the peptide. In addition, TKP-inhibited macrophage migration towards soluble egg antigens (SEA), suggesting that the reduced granuloma reaction by TKP is the result of the interaction between the peptide and macrophages. Injection of TKP into infected mice reduced the in vitro granulomatous response obtained using their spleen cells. This suggests an in vivo interaction between TKP and cells from the monocyte lineage. Moreover, the substitution of TKP on its NH2 or COOH terminal (Acetyl-TKP and TKP-amide) did not affect its in vitro activity. The latter result is of particular importance in the in vivo application of the peptide, at present under investigation.

Amino Acid Sequence↗
PubMed1985

Attempts to manipulate specific responses to induce resistance to Schistosoma mansoni in Kenyan baboons (Papio anubis).

Attempts were made to manipulate specific responses of baboons to protect them from infection with Schistosoma mansoni. In Experiment 1, eosinophilia was induced in naive baboons with Trichinella spiralis larvae given intravenously before intraperitoneal injection of globulin fractions from S. mansoni-infected baboon sera and subsequent percutaneous exposure to S. mansoni cercariae. In Experiment 2, baboons with 8- or 32-week-old primary S. mansoni infections received T. spiralis i.v. before an S. mansoni challenge. In experiments 3 to 5 respectively, naive baboons received intramuscularly before challenge: formalin-fixed S. mansoni schistosomula, with Bordetella pertussis as an adjuvant; a preparation of S. mansoni adult worm teguments; and a preparation of IgE-immune complexes obtained from S. mansoni-infected rat sera, with Freunds Complete Adjuvant. Minor, but statistically insignificant, protection was obtained in Experiments 2 (32-week infections) and 3, but was far less than that given by intact, irradiated living vaccines. There are signs on the horizon of non-living vaccines protecting rodents against S. mansoni infection and it would be prudent, as with drugs, to test these in primates before proceeding to man. The results of our experiments, though essentially negative, should help the design of any future vaccine trials in primates.

Animals↗
PubMed1985

Platelet mediated killing of larvae from different filarial species in the presence of Dipetalonema viteae stimulated IgE antibodies.

The platelets from normal rats interact with microfilariae of Dipetalonema viteae in vitro in the presence of antibodies leading to the killing of the parasite. The antibody involved in this reaction is identified as IgE because the absorption of immune rat serum on anti-rat IgE column or the pretreatment of platelets with anti-Fc epsilon receptor resulted in a significant reduction in the percentage of killing of microfilariae. This antibody, which mediates platelet activity towards microfilariae, appears early in the secondary infection and persists for a short period of time. This short-lasting IgE antibody is not apparently present in the form of large complexes since the supernatant but not the pellet after ultracentrifugation was able to mediate killing of microfilariae by platelets. IgE-dependent platelet-mediated parasite killing is neither stage- nor species-specific because the microfilariae (LI) of Brugia malayi or of Loa loa and infective larvae (L3) of D. viteae or of B. malayi were killed when they were incubated with the serum obtained from rats at day 8 after secondary infection with adult D. viteae worms. The results of the present study suggest that platelets can actively participate in the immunological killing of filarial larvae.

Animals↗
PubMed1985

New functions for platelets and their pathological implications.

We have recently demonstrated in Schistosoma mansoni infection that rat and human platelets could very efficiently kill parasite larvae, both in vivo and in vitro. The study of this IgE-dependent platelet effector function has led us to several subsequent findings. They concern: (1) the existence of a specific receptor for IgE on the platelet surface; (2) its close association with a platelet membrane glycoprotein of essential functional importance, the GPIIb-IIIa complex; (3) the observation, in extrinsic allergic asthma, of an allergen-specific IgE-dependent platelet activation; (4) the identification, in aspirin-sensitive asthma, of a similar, but non-IgE-dependent, platelet activation selectively induced by cyclo-oxygenase inhibitors, and prevented by salicylate. Beyond their implication in anti-parasite immunity, these findings provide a basis for new insights on the participation of platelets in disease.

Animals↗
PubMed1985

Aspirin-sensitive asthma: abnormal platelet response to drugs inducing asthmatic attacks. Diagnostic and physiopathological implications.

The pathogenesis of aspirin-sensitive asthma remains unknown. Using a new model of platelet activation, initially described as a response of platelets to IgE antibody-dependent stimuli, this study was designed to test the hypothesis of a possible involvement of platelets in aspirin-sensitive asthma. Washed platelets from 35 aspirin-sensitive asthmatics showed an abnormal in vitro response to cyclooxygenase inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs)--aspirin, indomethacin or flurbiprofen--characterized by the generation of a cytocidal supernatant and (14 patients explored) a burst of chemiluminescence; these drugs had no similar effect on platelets from 31 controls (p less than 0.0001). It was shown that the abnormal platelet response to NSAIDs was not mediated by IgE. In contrast to platelets, aspirin-sensitive asthmatic leukocytes generated neither cytocidal factors nor chemiluminescence in the presence of NSAIDs. Sodium salicylate and salicylamide, which, though structurally similar to aspirin, do not inhibit cyclooxygenase and are well tolerated by aspirin-sensitive asthmatics, did not activate their platelets to release cytocidal factors. Moreover, preincubation of platelets with sodium salicylate, salicylamide or prostaglandin endoperoxide PGH2, highly prevented their abnormal response to NSAIDs (greater than 80%; p less than 0.0001). Since several lipoxygenase inhibitors (NDGA, esculetin), including inhibitors of both cyclooxygenase and lipoxygenase (ETYA, BW755c), did not activate patient platelets and prevented the subsequent abnormal response to NSAIDs, it is suggested that the abnormal platelet activation by NSAIDs is not only the consequence of an inhibition of cyclooxygenase, but also involves generation of lipoxygenase metabolites of arachidonate. Besides, platelets from 4 aspirin-sensitive asthmatics undergoing aspirin desensitization were found to have completely lost their abnormal responsiveness to NSAIDs. These findings represent the first identification in aspirin-intolerant asthmatics of a specific abnormal cellular response to drugs inducing asthmatic attacks and open new perspectives into the pathogenesis, prevention and diagnosis of this disease. They also provide support to the concept of a role for platelets in asthma.

Adult↗