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Biomedical subjects

M Joseph

Publications and source records attributed to M Joseph.

At least 127 records · Page 7Linked to original sources

IgE-dependent killing of Brugia malayi microfilariae by human platelets and its modulation by T cell products.

Platelets isolated from patients infected with filariasis were cytotoxic for microfilariae in vitro. Moreover, platelets from normal donors acquired killing properties in the presence of serum from infected individuals. The humoral factor involved in this cytotoxic process was shown to be IgE. This IgE-dependent cytotoxicity of platelets was strongly inhibited by antigen-stimulated T lymphocyte supernatants from filarial patients.

Animals↗

IgE-dependent killing of Schistosoma mansoni schistosomula by human platelets: modulation by T cell products.

The in vitro stimulation of T lymphocytes is known to induce the release of factors that possess distinct biological activities. In the present report, we describe the presence, in supernatants of Schistosoma mansoni antigen stimulated T cells from S. mansoni infected patients, of a factor able to inhibit the IgE-dependent platelet cytotoxicity of the same individuals toward the young larvae of S. mansoni.

Animals↗

Management of complicated retinal detachment by vitrectomy and silicone oil injection.

One hundred eyes of 95 patients were operated with vitrectomy and silicone oil injection. The patients were divided into 3 groups: Penetrating trauma (PT)-22 eyes, proliferative diabetic retinopathy (PDR)-14 eyes, and proliferative vitreoretinopathy (PVR)-64 eyes. All of the eyes had retinal detachment including the macula. Final attachment of the retina was achieved in 40% of PT, 50% of PDR, and 60% of PVR. Improvement of visual acuity following the operation was noted in 54% of PT, 43% of PDR, and 67% of PDR. Postoperative complications included band keratopathy, elevation of IOP, hypotony, and cataract. Neovascularization of the iris, either preoperative or postoperative, is associated with very poor prognosis.

Adolescent↗

[Coronary angioplasty in the elderly patient. Immediate results and mid-term outcome].

Between April 1980 and July 1986, 50 patients over 65 (32 men and 18 women; mean age: 72 years) were treated by transluminal coronary angioplasty. Before the dilatation, 58 p. cent of the patients presented a severe angor (class III or IV) and 44 p. cent were multi-truncular. The dilatation was successful in 39 patients (78%) and 13 patients developed a recurrent stenosis successfully treated in 9 instances by re-dilatation. Among the complications, there were 2 deaths (4%), 3 infarctions (6%) and 3 emergency coronary bypass operations (6%). With a mean 28 months follow-up, the overall survival is 92 p. cent. After a successful dilatation, 49 p. cent of the patients are completely asymptomatic and the subsequent cardiological hospitalizations are rare (11%). These results show that coronary dilatation represents an interesting therapeutic option in elderly coronary patients.

Aged↗

Lymphocyte-mediated regulation of platelet activation during desensitization in patients with hymenoptera venom hypersensitivity.

T cells from peripheral blood of hymenoptera sensitive patients were studied before and after venom desensitization. Before treatment, T cells showed a variable but higher proliferative response to allergen than T cells of treated patients or controls. While before desensitization, T cell products, specifically released after in vitro allergen stimulation, were able to amplify the IgE-dependent platelet activity, we showed that after treatment of the same patients, T cell products strongly reduced platelet activation. Considering the modifications in platelet activation previously observed in patients treated by specific immunotherapy, the present results suggest that, through a modification of T cell reactivity to allergen, T cell functions are modulated by desensitization, and emphasize the involvement of T cell products in the desensitization mechanisms.

Adolescent↗

Decrease of IgE-dependent platelet activation in Hymenoptera hypersensitivity after specific rush desensitization.

A receptor for the Fc fragment of IgE on human platelets has been recently described, which mediated an IgE-dependent activation in the presence of specific allergen. We investigated the allergen-induced activation of platelets from patients with Hymenoptera hypersensitivity before and after specific rush desensitization. Nineteen patients with a history of anaphylactic reactions were included (15 sensitive to yellow-jacket and four to honey-bee venom), fourteen/nineteen having experienced severe life-threatening systemic reactions and 5/19 large local reactions. All showed positive skin tests and high values of specific IgE. By comparison to the baseline results obtained before desensitization, a significant decrease of platelet activation (76.8% inhibition) after rush desensitization was observed. In the case of two polysensitized patients, after Hymenoptera venom desensitization alone, platelets not only lost their reactivity to venom but also towards the other allergen. This modulation of the IgE-dependent platelet reactivity during desensitization offers therefore a new approach for the study of allergen-induced desensitization.

Adolescent↗

Perturbation of the lipid bilayer of model membranes by synthetic signal peptides.

The interaction of synthetic peptides corresponding to the signal sequences of Escherichia coli alkaline phosphatase: Lys-Gln-Ser-Thr-Ile-Ala-Leu-Ala-Leu-Leu-Pro-Leu-Leu-Phe-Thr-Pro-Val-Thr- Lys-Ala - OCH3, chicken lysozyme: Met-Lys-Ser-Leu-Leu-Ile-Leu-Val-Leu-Cys(Bzl)-Phe-Leu-Pro-Leu- Ala-Ala-Leu-Gly-OCH2-C6H5 and variant of the chicken lysozyme signal sequence with a charged residue in the hydrophobic region: Lys-Leu-Leu-Ile-Ala-Leu-Val-Leu-Lys-Phe-Leu-Pro-Leu-Ala-Ala- Leu-Gly-OCH3 with model membranes of brain phosphatidylserine (PS) and egg phosphatidylcholine (PC) have been investigated by 90 degrees light scattering and fluorescence spectroscopy. Our results indicate that the association of signal peptides with model membranes results in extensive perturbation of the lipid bilayer so as to cause fusion of PS vesicles and aggregation of PC vesicles. The vesicles are also rendered permeable to hydrophilic molecules like carboxyfluorescein. The variant peptide with the lysine residue in the hydrophobic region also has the ability to perturb lipid bilayers of model membranes.

Alkaline Phosphatase↗

Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated cytotoxicity against schistosomes.

The participation of complement receptor type 3 (CR3) in antibody-dependent effector function of human eosinophils against parasites was studied by using monoclonal antibodies directed against various surface molecules. Both adherence and cytotoxicity of hypodense eosinophils to IgE-coated schistosomula of Schistosoma mansoni were strongly inhibited by anti-CR3 antibodies (OKM1 or Mo1). The specificity of the inhibitory effect for the alpha-chain of CR3 was shown by the lack of inhibition of anti-beta-chain or anti-LFA1 alpha-chain monoclonal antibodies, although these antigens were expressed on human eosinophils. These results associated to previous works on IgE receptors demonstrate that both receptor for Fc fragments of IgE and CR3 are essential in IgE-dependent cytotoxicity of human eosinophils. Flow microfluorometry analysis revealed that hypodense eosinophils were more intensively stained by OKM1 antibodies than the normodense populations. In the case of IgG-mediated cytotoxicity by normodense eosinophils, only the enhancement of cytotoxicity due to monokine activation was inhibited by anti-CR3 alpha-chain antibodies. These findings suggest an increased expression of CR3 on eosinophils after activation either in vivo or in vitro. The participation of CR3 in IgE-mediated cytotoxicity against schistosomes was also required in the case of blood monocytes but not for platelet-mediated killing, which does not require prior adherence. The biologic role of CR3 is therefore extended to effector mechanisms involving eosinophils and two different isotypes of antibodies and possibly implied in immunity against schistosomes.

Antibodies, Monoclonal↗

Purification and characterization of trichosanthin. Homology to the ricin A chain and implications as to mechanism of abortifacient activity.

Trichosanthin, a protein from the Chinese medicinal herb Trichosanthes kirilowii, was purified in two essentially quantitative steps involving CM-Sephadex chromatography and reverse-phase high performance liquid chromatography. The protein was found to have a molecular mass of 25-26 kDa, to contain no cysteine, and to contain no glycosidic linkages. Pure trichosanthin was found to have potent abortifacient activity in pregnant mice. In order to understand the molecular basis of this unique biological activity, we have examined the amino acid sequence of the protein. As purified, trichosanthin was found to contain two amino-terminal sequences which differed only in the absence or presence of a tyrosine at residue 1. Sequence analysis of trichosanthin has allowed for determination of the NH2-terminal 38-amino acid residues. Comparison of this sequence to those present in a data base revealed homology with the ricin A-chain. Consistent with this structural homology, we have found that trichosanthin is a potent inhibitor of protein synthesis in a reticulocyte lysate system.

Abortifacient Agents↗

Functional properties of a rat monoclonal IgE antibody specific for Schistosoma mansoni.

A rat monoclonal antibody of IgE isotype (B48-14) raised against Schistosoma mansoni has been generated by the fusion of mesenteric lymph node cells from LOU/M rats immunized with a preparation of adult schistosome worms and IR973F nonsecreting rat myeloma cells. Investigation of the in vitro effector functions of this IgE antibody showed a high level of cytotoxicity against S. mansoni schistosomula in the presence of eosinophils, macrophages, and platelets. A significant level of protection (40 to 60%) against a challenge infection with S. mansoni cercariae was achieved by passive transfer experiment of B48-14 IgE to naive recipient rats. By immunoprecipitation, B48-14 IgE antibodies were shown to react with an antigen of 26 kDa present in excretion-secretion products of schistosomula, previously described as a potential immunogen eliciting a protective IgE response against schistosomiasis.

Animals↗

Induction of platelet cytotoxic functions by lymphokines: role of interferon-gamma.

Antigen- or mitogen-stimulated CD4+/CD- lymphocytes produced factors able to induce normal human platelets into cytotoxic effectors toward the young larvae of Schistosoma mansoni. The neutralization by monoclonal anti-IFN-gamma antibody of the induction of the platelet killer effect, the presence of IFN-gamma in the CD4+/CD8- lymphocyte supernatant, and, finally, the direct inducer effect of recombinant IFN-gamma clearly demonstrated that IFN-gamma was one of the factors responsible for the induction of platelet cytotoxic functions.

Adult↗

A solid-phase radioimmunoassay using digitonin-permeabilized cells to screen surface or intracellular membrane-bound antigens.

Membrane-bound receptor or enzyme distribution between cell surface and cell interior can be determined using the non-ionic detergent digitonin. A solid-phase radioimmunoassay using myocardial cells from newborn rats was performed to screen hybridoma culture supernatants and the cells were rendered permeable with increasing concentrations of digitonin (0-0.1%). This was achieved in 5 min at 37 degrees C and did not require the continuous presence of detergent. A characteristic amount of cytoplasmic protein (approximately equal to 45%) was released with subunit molecular weights of up to 200,000. This allowed exogenous molecules such as immunoglobulin G to gain access to the intracellular targets. The binding to rat myocardial cells of 36 monoclonal antibodies was examined by this procedure. The binding assays were carried out for 30 min at 37 degrees C using cells previously treated for 10 min with 0.05% of digitonin. This appears to be a simple and rapid method of screening and selecting the hybridoma culture supernatants.

Animals↗

Circular dichroism studies on a synthetic peptide corresponding to the membrane-spanning region of vesicular stomatitis virus G protein and its fatty acyl derivative.

The conformations of synthetic peptides Lys-Phe-Phe-Phe-Ile-Ile-Gly-Leu-Ile-Ile-Gly-Leu-Phe-OCH3 and Lys(epsilon-palmitoyl)-Phe-Phe-Phe-Ile-Ile-Gly-Leu-Ile-Ile-Gly-Leu-Phe-O CH3, which constitute a part of the membrane-spanning region of the vesicular stomatitis virus G protein, have been studied by circular dichroism (CD) spectroscopy. Secondary structural features are observed for both peptides in trifluoroethanol, methanol, aqueous mixtures of trifluoroethanol and methanol and in a micellar environment. In trifluoroethanol, the CD spectra indicate the presence of a helical conformation, whereas in aqueous mixtures of organic solvents, both helical and beta-conformations are observed. While fatty acid acylation does not directly modulate peptide conformation, it promotes self-association of the acylated peptide and association with micelles. In a micellar environment, the acylated peptide adopts an alpha-helical conformation.

Circular Dichroism↗

Platelets as effectors in immune and hypersensitivity reactions.

IgE receptors have been recently characterized on human blood platelets. These receptors share common properties within the Fc epsilon R2 previously described on macrophages and eosinophils with a Ka of 3 X 10(7) M-1 and a mean number of 600-1,000 binding sites for IgE per platelet. The production of an anti-Fc epsilon R2 monoclonal antibody has allowed the identification on platelet membrane preparations of two major bands of 43-45 and 31 kD. In parasitic infections (schistosomiasis, filariasis) IgE-dependent killing by platelets has been demonstrated. In allergic asthma and in Hymenoptera venom sensitivity patients, IgE-dependent activation of platelets expressed by the release of cytocidal mediators and oxidative burst can be specifically triggered by the corresponding allergen. In aspirin-sensitive asthma, a direct, non-IgE-dependent platelet activation by nonsteroidal anti-inflammatory drugs has been demonstrated. The platelet abnormality apparently involved a defect of the prostaglandin H2 binding to its specific receptor and a possible imbalance in the regulatory functions of the lipoxygenase metabolites. Platelet effector functions have been recently shown to be regulated by T cell factors. A novel suppressive lymphokine (PASL) produced by OKT8 T cell subset inhibits platelet activation and killing whereas IFN-gamma has been identified among T cell factors produced by OKT4+ cells able to trigger platelet activation. These observations open original perspectives into the pathogenesis, the diagnosis and the prevention of allergic and pseudoallergic disorders, and they provide support to the concept of a role for platelets in various immune and hypersensitivity reactions.

Animals↗

[Blood platelets and asthma caused by aspirin].

Platelets isolated from patients with aspirin-induced asthma (ASA patients) react abnormally in vitro to aspirin and to non-steroid anti-inflammatory drugs (NSAID), by generating cytocidal molecules, that can kill parasitic larvae and to oxygen-dependent free radicles, which may be detected by chemiluminescence, although these drugs do not have a similar effect on platelets from normal donors or allergic asthmatics. The abnormality appears to be associated with the inhibiting properties of NSAID and aspirin on the cyclo-oxygenase pathway, that leads to a defect of the binding of prostaglandin endoperoxide PGH2 to its receptors on the platelet membrane. In addition, another metabolite from the lipoxygenase pathway which is at present poorly defined seems to participate in the anomaly. Sodium salicylate, a naturally produced catabolite of aspirin, that is well-tolerated by ASA patients, inhibits the abnormal response of the platelets and this opens new perspectives in the management of aspirin-sensitive intolerance.

Aspirin↗