Allergic and related diseases will be studied by three approaches - serologic assessment of components of mediator systems, ultrastructural and phenotypic analysis of selected cells in situ in lesions, and characterization of isolated cells considered representative of the tissue process by biochemical and functional criteria. The cutaneous hypereosinophilic diseases identifed as fasciitis, cellulitis and angioedema will be analyzed for activity of the 5-lipoxygenase pathway of peripheral eosinophils and by in situ morphology. Necrotizing cutaneous venulitis, hypocomplementemic vs. normocomplementemic, will be defined in terms of expression of CR1/CR3 on neutrophils and activity of the 5-lipoxygenase pathway on isolated neutrophils and monocytes. Exercise-induced anaphylaxis will be addressed by a computer assisted survey and by experimentally-induced attenuated attacks to evaluate selected variables. Physical cutaneous allergy, both cold and cholinergic, and possibly exercise-induced anaphylaxis will be analyzed in situ for tissue mast cell character and by experimental elicitation of attacks for appearance of substance P, and for augmented expression of CR1/CR3 on neutrophils as evidence of elaboration of a chemotactic factor(s) of presumptive mast cell origin. Mast cells will be defined in situ in patients with systemic mastocytosis and chemically/immunochemically in biopsy tissues to seek differences which might be highlighted by a proliferative response from a limited number of progenitors and these patients will be studied neurophysiologically to clarify the perceived relationship to an affective disorder. Hepatic toxicity will be monitored in patients with inborn C1INH deficiency receiving attenuated androgens at the minimal effective dose, and nephrotoxicity will be assessed for cyclosporine immunosuppression in allograft recipients and medical patients by quantitation of renal glandular kallikrein. Patients with acquired C1INH deficiency will be studied for the mechanism by which idiotypic-anti-idiotypic complexes uniquely deplete C1 and C1INH and for the utilization profile of the contact activation-plasma kallikrein-kinin system. Patients with bronchial asthma will be evaluated for biosynthesis and metabolism of leukotrienes by alveolar lavage macrophages, for appearance of CR1/CR3 on neutrophils during experimentally induced compromised pulmonary function and for the effects of ingesting a diet enriched for fish oil fatty acids on the 5-lipoxygenation of arachidonic acid by selected cells and on the response of their airways to specific allergen and histamine.
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