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D E Chenoweth

Publications and source records attributed to D E Chenoweth.

76 records · Page 5Linked to original sources
PubMed1978

Demonstration of specific C5a receptor on intact human polymorphonuclear leukocytes.

Human C5a, a complement-derived anaphylatoxin, is a potent mediator of human leukocyte chemotaxis. Using a homogeneous preparation of C5a that was 125I-labeled, we have demonstrated the presence of a specific cellular receptor for this glycoprotein on intact human polymorphonuclear leukocytes. Cellular uptake of the radiolabeled ligand occurred rapidly and the rate of dissociation was extremely slow. Cellular binding was saturable with respect to 125I-labeled C5a, and half-saturation occurred at a concentration of 3-7 X 10(-9) M. The number of C5a binding sites per cell was estimated as 1-3 X 10(5). The ligand (C5a) displays specific structural features that are required for binding because analogs of C5a such as C5ades Arg or a yeast carboxypeptidase-digested C5a derivative C5a-(I-69) inhibited the binding but C3a anaphylatoxin, which resembles C5a chemically, did not. Both C5a-mediated leukocyte chemotaxis and C5a-induced lysosomal enzyme release from cytochalasin B-treated cells closely paralleled uptake of the ligand, clearly indicating that it is a receptor-C5a interaction that leads to stimulation of these cellular responses.

Binding Sites↗
PubMedDate not supplied

The biocompatibility of artificial organs.

Thromboembolic events in very short-term ventricular assistance have been uncommon. However, patients who are bridged or have long-term artificial heart implantations have almost uniformly experienced serious thromboembolic sequelae. Anticoagulation regimens for this form of circulatory assistance have varied but results are inconclusive. Intravenous heparin is commonly used, while low molecular weight Dextran, aspirin, and other antithrombotic agents are occasionally used. Mechanical cardiac valve failures requiring reoperation are due primarily to thrombosis, tissue overgrowth, and structural failure. Reoperations of tissue valves indicate sterile degeneration, usually related to calcification and tears, as the principal cause of failure. Despite improvements in biomaterials and an appreciation of the influence of disordered flow on graft patency, antithrombotic therapy represents the most clinically relevant approach to prevention of occlusion of vascular prostheses. The location of neointimal hyperplasia in vascular prostheses is different from that in vein grafts, the effect concentrating at the anastomosis. No clear rationale exists for antithrombotic therapy for hyperplasia in this instance. However, a rationale does exist for early antithrombotic therapy to reduce surface thrombogenicity. The lessons learned from clinical trials of antithrombotic therapy in the case of vein grafts might be profitably studied with regard to synthetic grafts and other artificial organs. Early low-dose aspirin and, possibly, dextran-40 treatment are justified in this case. However, continuation of these therapies past the early healing phase does not appear warranted. Clinical and experimental studies with hemodialysis and other membranes suggest complement activation through the alternate pathway is commonly observed; the biologic responses are consistent with the known properties of C5a. Factors governing anaphylatoxin exposure can be ascribed to the nucleophilicity and number of surface reactive groups. Elimination of surface reactive groups, or binding of bystander plasma proteins such as albumin, may be expected to limit complement activation.

Artificial Organs↗