Biomedical subjects
Publications and source records attributed to M Joseph.
This is the first report of a case of malignant hyperthermia (MH) from Saudi Arabia. MH was probably triggered by response to Halothane. The diagnosis was suspected by the clinical signs of tachycardia, severe rigidity, cyanosis and rising temperature. The case was successfully managed by vigorous cooling, dantrolene sodium and diuresis.
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Aspirin-sensitive asthma is a common and severe disorder characterized by asthmatic attacks after oral ingestion of cyclooxygenase inhibiting drugs. Yet its pathophysiology remains unknown, and no specific in vitro abnormality, neither humoral nor cellular, has been detected in these patients. We have recently described a new model of platelet activation--IgE-dependent platelet activation--expressed by the release of cytocidal mediators and oxygen metabolites. We have now investigated whether cyclooxygenase inhibitors induce a similar response in platelets from aspirin-sensitive asthmatics in vitro. Aspirin or indomethacin strikingly activated platelets from 12 aspirin-sensitive asthmatics to the same extent as IgE-dependent stimuli, but had no effect on platelets from 18 controls (p less than 0.0001). Sodium salicylate, which does not inhibit cyclooxygenase, did not trigger platelets from aspirin-sensitive asthmatics. Preincubation with sodium salicylate or prostaglandin endoperoxides (PGH2), selectively prevented further platelet activation by aspirin or indomethacin (90% inhibition), suggesting that this abnormal platelet activation is the consequence of cyclooxygenase inhibition. This represents the first identification of a specific abnormal cellular response in aspirin-sensitive asthma, provides the basis for an in vitro diagnostic test of the disease, and for new insights on its pathogenesis and its prevention.
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The immunogenicity of molecules shed by schistosomula into culture medium (antigens present in schistosomula-released products, SRP-A) has been studied. The results obtained show that SRP-A preferentially induce an IgE response when injected into rats, without the need for adjuvants. Moreover, anti-SRP-A IgE is cytotoxic in vitro for the larvae in the presence of macrophages, eosinophils or platelets, which have previously been demonstrated as being the three efficient killer cells for schistosomula in the presence of specific IgE. Immunofluorescence analysis locates the target antigens at the schistosomulum surface. Among the antigens recognized by anti-SRP-A IgE, two molecules of 26 and 22 kDa have been identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by western blotting.
The studies presented in this article demonstrate the release of an IgE-dependent chemotactic factor for polymorphonuclear neutrophils (PMN) and eosinophils by alveolar macrophages (AMs) from normal subjects (n = 15) and allergic asthmatic patients (n = 15). A 60-minute incubation of normal AMs previously sensitized by 20% nonheated allergic sera with anti-human IgE antibody or the related allergen induced the release of a chemotactic activity (CA) for PMN and eosinophils in culture supernatants. When AMs were obtained from asthmatic patients, direct incubation with anti-IgE or the related allergen induced the same CA, whereas incubation with an unrelated allergen failed to produce CA (neutrophil CA after addition of anti-IgE, 22.5 +/- 3.5 cells per high power field; with related allergen, 15.8 +/- 3.6; with unrelated allergen, 0.7 +/- 1.8; p less than 0.0001). A partial characterization of the neutrophil chemotactic factor was carried out. Enzymatic treatment by trypsin or carboxypeptidase or by heating (56 degrees C for 3 hr) failed to abolish the neutrophil CA. After gel filtration the greater part of the neutrophil CA (80%) was recovered among low-molecular-weight components (300 to 1300 daltons). A preliminary deactivation of PMN by leukotriene B4 suppressed the CA of AM supernatants. These results indicate that IgE-dependent stimulation of AMs produces a neutrophil and eosinophil CA, present in a low-molecular-weight fraction possibly related to leukotrienes, and emphasizes the role of AMs in inflammatory lung processes during allergic asthma.
Lingual tonsillectomy is a surgical treatment that is seldom performed because lingual tonsillitis is infrequently diagnosed. We have reviewed a group of patients with lingual tonsillitis or lingual tonsil hyperplasia who were treated with lingual tonsillectomy. Lingual tonsil lesions, the anatomy and histology of the lingual tonsil, and surgical approaches to lingual tonsillectomy are discussed.
Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases).
Human blood platelets, incubated with the serum from patients with schistosomiasis or allergic asthma, became cytotoxic for schistosome larvae, in an allergen-specific mechanism linked to surface bound IgE on platelets. Cytotoxic factors, among which oxygen metabolites might be involved, were able to kill schistosomula through platelet-retaining filters. Flow cytometry showed that platelets bearing IgE receptors represented a subpopulation, the percentage of which significantly increased in patients with high levels of circulating IgE.
Several killing mechanisms against schistosomes have been described in vitro, involving cellular and humoral factors. Neutrophils, eosinophils--with an accessory role for mast cells--monocytes and macrophages have been shown to exhibit cytotoxic properties against Schistosoma mansoni larvae, in association with antibodies of various isotypes or with complement (reviewed in ref. 1). Lymphocyte participation in effector functions is mediated mainly through lymphokines inducing cytotoxic macrophages, and, in certain cases, directly by T cells. The experiments reported here show that platelets, taken from rats after specific periods of infection with S. mansoni, were able to kill schistosomula, and that normal human or rat platelets acquired toxic properties towards the same target in the presence of serum from infected individuals. The humoral factor involved in this process was shown to be IgE, and evidence was obtained of a Fc receptor for IgE on human and rat platelets. The passive transfer of immune platelets to normal rats conferred a high degree of protection towards a challenge infection by the parasite.
Dermatophagoîdes pteronyssinus allergen was instilled into the alveolar space of 7 allergic asthmatic patients during bronchoalveolar lavage. beta-glucuronidase concentration in the bronchoalveolar fluid from the challenged lung became significantly higher than that in the opposite control lung (3.90 +/- 1.88 nmol/h versus 0.86 +/- 0.55). The intracellular level of beta-glucuronidase in the alveolar macrophages in the challenged lung was 40.3% lower than that in the control lung. In 3 controls intracellular concentrations of beta-glucuronidase were similar before and after allergenic challenge and no enzyme activity could be detected in bronchoalveolar lavage fluid. These results suggest that alveolar instillation of an allergen in asthmatic patients rapidly stimulates alveolar macrophages, which may be involved in immediate hypersensitivity reactions in asthma.
We have shown that IgG hydrolysed by Schistosoma mansoni schistosomula inhibited various macrophage functions, especially phagocytosis and anti-schistosome cytotoxicity. Here we show that a tripeptide, Thr289-Lys-Pro291, of the second constant domain of human immunoglobulin G (peptide 286-292) reproduced the inhibitory effect of a total hydrolysate. Indeed the beta-glucuronidase release from IgE-anti-IgE-stimulated rat and human macrophages decreased and its intracellular level did not rise after a prior incubation of the cells with Thr-Lys-Pro (500 nmol/ml). Moreover, the cell migration as well as the superoxide anion O2 generation were 50-80% reduced by the tripeptide. These results suggest that a single peptide set may be responsible for the decrease of the macrophage functions at the early stage of the parasite infection in the mammalian host. The pharmacologic properties of this tripeptide are under investigation.
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Alveolar macrophages from nonatopic donors were passively sensitized with allergen-specific IgE antibody from the serum of asthmatic patients. A selective release of 4-8% of the lysosomal beta-glucuronidase of these cells occurred within 30 min of contact with the related allergen or with anti-human IgE antibody, in the absence of any mast or basophil cells. The cell reactivity was dependent on the interaction of macrophages with IgE, as shown by the disappearance of the allergen-induced enzyme release after heating or IgE-immune adsorption of the sensitizing serum, but not after IgG-adsorption. Alveolar macrophages from asthmatic patients behaved similarly to passively sensitized normal macrophages. Contact with the related allergen or with anti-IgE antibody induced the same percentage of enzyme release, demonstrating that these cells possess allergen-specific IgE bound on their surface. 18% of them formed rosettes with anti-IgE-coated sheep erythrocytes, and 15-22% with allergen-coated erythrocytes, but lost this property after preincubation with the specific allergen. The presence of IgE-specific receptors on the macrophage surface was demonstrated both at the ultrastructural level with immunoperoxidase labeling, and at low magnification by the formation of 15-18% rosettes with human IgE-coated erythrocytes. The formation of such rosettes was inhibited after incubation of alveolar phagocytes with aggregated myeloma IgE. On the basis of these observations, the participation of the alveolar macrophages in IgE-mediated pulmonary hypersensitivity must be considered. Its precise involvement requires, however, further investigations.
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Explore the source record for details and available documents.