The major emphasis of the program carried out in relation to the Asthma and Allergic Diseases Center continues to be on the chemical mediators of immediate hypersensitivity, including histamine, slow reacting substance of anaphylaxis (SRS-A), and the eosinophil chemotactic factor of anaphylaxis; the interrelationships and control of the Hageman factor dependent sequences, namely bradykinin generation, fibrinolysis, and coagulation; the analysis of the classical and alternative complement sequences and their control; the recognition and measurement of new factors which modulate polymorphonuclear leukocyte function such as kallikrein and the high molecular weight neutrophil chemotactic factor (HMW-NCF), which may be of significance in subacute or immune complex hypersensitivity; and the study of urinary proteins such as urokallikrein. There have been meaningful methodologic advances in our capacity to understand and measure each of these systems in terms of human plasma proteins, cells, or tissues, and thus, in our ability to relate or possibly exclude a particular effector system of inflammation as playing a role in a particular disease state. Clinical studies will be furthered by the application of the newly developed methodologies for the assessment of previously recognized and more recently recognized effector substances and by the introduction of new patient groups or the expansion of existing groups. Simultaneously, the search for additional factors involved in tissue injury and most especially the clinical measurement of effector pathways and substances which cannot now be fully assessed will be continued. Although the principal motivation is to determine the contribution along or in combination of these various effector systems to hypersensitivity states, the possible use of such information to direct physiologic studies and to assess therapeutic maneuvers serves as an important additional stimulus.
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