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Biomedical subjects

E W Ferguson

Publications and source records attributed to E W Ferguson.

At least 37 records · Page 2Linked to original sources
PubMed1981

Pharmacologic characterization of immune complex induced bronchoconstriction in guinea pigs.

Intravenous injections of soluble immune complexes to anesthetized guinea pigs resulted in bronchoconstriction that was inhibited by FPL 55712, indomethacin, oxarbazole, soybean trypsin inhibitor, and cobra venom factor. Immune complex induced bronchoconstriction was not inhibited by atropine, imidazole, mepyramine, ketotifen, methysergide, and the anti-anaphylactic compound DPP (Diethyl [2-(4-pyridyl)-4-pyrimidinyl]aminoethylene malonate). Immune complex induced bronchoconstriction in guinea pigs appears to involve activation of complement and formation of anaphylatoxins. In addition, products of cyclo-oxygenase metabolism of arachidonic acid and kinins may be involved.

Airway Resistance↗
PubMed1981

Fibrinolytic activity without fibrinogenolysis during long-distance racing in horses.

Fourteen horses were studied during a 157-km endurance ride. Two humans who ran the 157 km were also evaluated at the finish. Fibrin monomer samples were examined by two-dimensional gel electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Two major species of horse Beta-chain with higher molecular weights and different isoelectric mobilities than human beta-chain were observed. Horse alpha-chains had higher molecular weights than human alpha-chains but similar alpha-chain heterogeneities. Mean euglobulin lysis time (ELT) in the horses was accelerated to similar levels throughout the ride (52% of control at 44 km, P less than 0.01), but mean plasma clot lysis time (PCLT) decreased progressively during the ride (30% of control at finish, P less than 0.005). Similar values for ELTs and PCLTs were noted in the runners and horses at the finish. Although fibrinolytic activity was accelerated for an extended period by the strenuous activity of this long-distance race, no evidence of increased carboxyl terminal degradation of the A alpha-chain was observed. This study suggests that prolonged physiological stimulation of the fibrinolytic enzyme (plasmin) system is not responsible for fibrinogen A alpha-chain heterogeneities observed in horses and humans. It further demonstrates the usefulness of horses as models for the study of exercise-induced fibrinolysis.

Animals↗
PubMed1981

Erythrocyte alterations endurance exercise in horses.

The erythrocytes of 14 conditioned horses participating in a 157-km endurance ride (requiring 14-21 h) were examined before the ride, immediately upon entering the 44-91-, and 130-km rest stops, and at the finish. At the first rest stop (44 km), the mean erythrocyte count increased 41% (P less than 0.001), the mean hematocrit (Hct) increased 30% (P less than 0.001) and the mean hemoglobin (Hb) increased 33% ( P less than 0.001). Although subsequent mean erythrocyte counts, Hct, and Hb values remained significantly elevated above controls, the values decreased 9-9% from the 4-km values later in the ride. These changes suggest a lost of red cells mass during the prolonged exercise. Spiculated red blood cells that increased markedly in number during exercise were also observed in these conditioned horses. The appearance of an increased number of spiculated red cells with exercise was associated with corresponding changes in red cell indices.

Animals↗
PubMed1979

Fibrinogenolysis and fibrinolysis with strenuous exercise.

Twenty healthy young men were exercised on a treadmill according to the protocol of Balke and Ware. Mean duration of exercise was 24.9 +/- 5.7 min and mean maximum heart rate was 195 +/- 9. Fibrinolytic activity was markedly accelerated with euglobulin lysis times decreasing to 36% of control values and fibrinogen-fibrin degradation products increasing 109% after exercise. Assays for fibrin monomer were negative in all samples. In vivo fibrinogen A alpha-chin degradation was assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis of reduced samples of fibrin monomer isolated by clotting plasma samples in the presence of 0.1 M epsilon-aminocaproic acid and 1% disodium ethylenediaminetetraacetate. The A alpha-chain, the fibrinogen chain most susceptible to plasmin degeneration, showed no evidence of increased degeneration after exercise. Gel scans showed no decrease in the ratio of total alpha-chain to beta- and gamma-chains after exercise. The ratio of intact alpha 1 chain (alpha 1, 67,000 mol wt) to total alpha-chain was 0.66 +/- 0.13 before exercise, 0.64 +/- 0.14 immediately after exercise, and 0.65 +/- 0.13 1 h after exercise. The rate and extent of crosslinking of the alpha-chain of fibrin formed by clotting plasma samples was unaltered by exericse. These data suggest that physiologically significant fibrinogenolysis does not occur with strenuous exercise, even when fibrinolytic activity is markedly accelerated.

Adult↗
PubMed1978

Localization of the alpha-chain cross-link acceptor sites of human fibrin.

The potential cross-link acceptor sites of fibrin were specifically labeled with the fluorescent, substitute cross-link donor monodansyl cadaverine (MDC). Several fluorescent alpha-chain peptides generated from enzymatic and cyanogen bromide (CNBr) cleavage of the labeled fibrin were identified by sodium dodecyl sulfate disc gel electrophoresis; they were isolated and then characterized by amino acid analysis, NH2-terminal sequence analysis, and chromatographic and electrophoretic analyses of their digestion products. Ancrod cleavage of MDC-labeled fibrin produced a series of six alpha-chain peptides of molecular weights 34,000 to 12,000, each of which contained an MDC-labeled acceptor site, and an NH2-terminal alpha-chain derivative of molecular weight 37,500. The latter remains disulfide bound in the residual fibrin and has two MDC-labeled sit-s which are separable by CNBr cleavage. Mild plasmin digestion of MDC-labeled fibrin generated fluorescent alpha-chain peptides of molecular weights 45,000, 42,000, 35,000, 23,000, 21,000, and 2,500 in the supernatant and a nonfluorescent NH2-terminal alpha-chain derivative of molecular weight 25,000 which remained in the insoluble residual fibrin. The alignment of these plasmic supernatant peptides was determined from NH2-terminal sequence analyses which indicated that an MDC acceptor site was located at approximately residue 255 of the Aalpha-chain. Cleavage of the MDC-labeled alpha-chain by CNBr, however, localized most of its fluorescence (approximately 80%) to a fragment of molecular weight 29,000 which had the same NH2-terminal sequence as the labeled plasmic peptide of molecular weight 21,000. Both peptides were cleaved by ancrod into two acceptor site-containing peptides of approximately equal fluorescence. The preliminary NH2-terminal sequence analyses of these peptides, when combined with the above findings, indicated that these two other cross-link acceptor sites are in a peptide segment which comprises the middle 17% of the Aalpha-chain.

Amino Acids↗
PubMed1975

A re-examination of the cleavage of fibrinogen and fibrin by plasmin.

Three Fragment D species (D1, D2, D3) were isolated with time from a plasmin digest of fibrinogen and had molecular weights of 92,999, 86,000 and 82,000 by summation of subunit molecular weights from sodium dodecyl sulfate polyacrylamide gel electrophoresis. Their molecular weights by sedimentation equilibrium ultracentrifugation were 94,000 t87,000, 88,000 to 82, 000, and 76,000 to 70,000 depending on the values calculated for the partial specific volumes. Each of the Fragment D species contained three disulfide-linked subunits derived from the Aalpha, Bbeta, and gamma chains of fibrinogen and differed only in the extent of COOH-terminal degradation of their gamma chain derivatives. Plasmin cleaved Fragment D1 to release the cross-link sites from its gamma' subunit of 38,000 molecular weight; however, the beta'' subunit of 42,000 molecular weight and the alpha'' subunit of 12,000 molecular weight were resistant to further digestion by plasmin. Fragment D isolated from highly cross-linked fibrin had a dimeric structure due to cross-link formation between the gamma' subunits of two fibrinogen Fragment D species. The molecular weight of fibrin Fragment D was 184,000 by summation of subunit molecular weights and 190,000 to 175,000 by sedimentation equilibrium. Cross-linking the gamma chain, as well as incorporating the site-specific fluorescent label monodansyl cadaverine into the gamma chain cross-link acceptor site, prevented its COOH-terminal degradation by plasmin. Therefore, only one species of fibrin Fragment D, as well as only one species of monodansyl cadaverine-labeled fibrin Fragment D monomer, was generated during plasmin digestion. These results show unequivocally that each fibrinogen Fragment D contains only three subunit chains and therefore the digestion of fibrinogen by plasmin must result in the production of two Fragment D molecules from each fibrinogen molecule. The recently proposed model of fibrinogen cleavage that postulates the generation of a single Fragment D with three pairs of subunit chains from each fibrinogen molecule is incorrect. Incorporation of monodansyl cadaverine into the cross-link acceptor sites of the alpha chain did not alter its cleavage by plasmin detectably. A series of monodansyl cadaverine-labeled peptides, which ranged in molecular weight from 40,000 to 23,000, were cleaved from the alpha chain of monodansyl cadaverine-labeled fibrin monomer during the early stages of plasmin digestion. These peptides were degraded progressively to a brightly fluorescent plasmin-resistant peptide of 21,000 molecular weight and a weakly fluorescent peptide of 2,500 molecular weight. Thus both alpha chain cross-link acceptor sites are contained within a peptide segment of 23,000 molecular weight.

Amino Acids↗