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Biomedical subjects

R I Walker

Publications and source records attributed to R I Walker.

At least 91 records · Page 5Linked to original sources
PubMed1981

Indomethacin improves survival in gram-negative sepsis.

A clinically relevant rat model of peritoneal sepsis was developed through the use of (a) intraperitoneal insertion of rat fecal pellets or (b) live E. coli intraperitoneal injections. Therapy with indomethacin and lidocaine were evaluated in this model. Indomethacin alone, or in combination with appropriate antibiotics, significantly improved survival. Lidocaine did not show an increase in survival. These findings suggest that indomethacin may be beneficial in treatment of human sepsis.

Animals↗
PubMed1981

Campylobacter fetus ss. Jejuni, a newly recognized enteric pathogen: morphology and intestinal colonization.

Campylobacter fetus ss. jejuni has recently been recognized as a frequent enteric pathogen of man. Although long known as a significant pathogen of domestic animals, little is known regarding mechanisms of colonization and pathogenesis. In an effort to study the colonization and morphology of this organism, we used scanning electron microscopy to examine ilea and colons from mice in which a human isolate of C. fetus ss. jejuni had been inoculated. When inoculated into the ileum of the mice, a transient colonization was observed by 24 hours and had disappeared by 48 hours. Colonization of the colon first appeared at 48 hours and persisted at least three weeks. When inoculated directly into the colon, colonization appeared within 24 hours in the colon and persisted at least 16 days. Severe colonic necrosis and mucosal degeneration were observed in colons only in those mice which were inoculated via the colon. In the infected colons, the C. fetus ss. jejuni organisms were enmeshed in a fibrous network which may play a role in the attachment of bacteria to the mucosal surface. Differences between the morphology of C. fetus ss. jejuni in the mouse model and that found in pure culture were observed and may represent distinct tissue and culture phases of growth.

Animals↗
PubMed1980

Clearance of inflammatory cells from the microcirculation of endotoxin-resistant C3H/HeJ mice.

We studied the deposition of platelets and leukocytes in resistant (C3H/HeJ) and sensitive (C3Heb/FeJ) strains of mice challenged intraperitoneally with 1 mg of Salmonella typhi endotoxin, a dose lethal only for the sensitive strain. Comparable degrees of leukopenia and thrombocytopenia were evident at all time periods observed, but in contrast to sensitive mice, leukocytes and platelets were quickly cleared from the pulmonary microcirculation of resistant mice.

Animals↗
PubMed1980

Evidence that antibodies to polysaccharide alter platelet responses to endotoxin in tolerant rabbits.

When rabbits are made resistant (tolerant) to Salmonella typhi endotoxin by administration of five intraperitoneal injections of small amounts of endotoxin on consecutive days, a plasma factor appears which accelerates the in vitro aggregation response of platelets to endotoxin. Furthermore, in contrast with the reaction in normal animals, this aggregation is often quickly reversible. The present study was undertaken to determine some characteristics of this plasma factor. The humoral factor responsible for altering the platelet aggregation-disaggregation response to endotoxin is apparently antibody against polysaccharide antigen rather than an endotoxin degrading substance because (1) appearance of the factor correlated with presence of antibodies to polysaccharide, (2) the factor was stable at 56 degrees C for 1 h, (3) its effect only took a few seconds to occur, and (4) plasma from tolerant animals reacted only with complete endotoxin, obtained from smooth bacteria, but not lipid A. In fact, lipid A did not induce platelet aggregation unless its specific antibody was also present.

Animals↗
PubMed1980

Protection of dogs from lethal consequences of endotoxemia with plasma or leukocyte transfusions.

The contribution of cellular and humoral factors of normal blood to resistance to endotoxin was evaluated by selectively transfusing them into beagle dogs prior to IV challenge with a lethal (2.75 mg/kg) dose of Salmonella typhi endotoxin. Supplementation of normal host defenses with 250 ml of plasma containing a heatlabile (56 degrees C for one hour) factor protected the dogs from lethal effects of the toxin. A similar volume of heparinized saline or a lesser volume of plasma (100 ml) was ineffective. The presence of 1 X 10(9) platelets and 7 X 10(10) leukocytes from leukapheresed foxhounds in some transfusion preparations did not affect survival. Protection by treatment with plasma was accompanied by severe tissue injury and loss of circulating platelets and leukocytes. Granulocyte concentrates also afforded protection and decreased tissue injury, as indicated by SGPT and taurine levels. Survivor and nonsurvivor animals experienced an early hyperglycemia as well as elevation of serum glutamic pyruvic transaminase and taurine levels. Thrombocytopenia was great in all experimental groups but was less marked in dogs transfused with cells. Leukopenia was comparable in all groups until six hours after challenge, at which time numbers of circulating leukocytes began a significant return toward normal levels in the cell-transfused group. Impairment of macrophage function was indicated by the depression of the release of colony-stimulating factor in survivor and nonsurvivor animals. Thus, normal plasma alone can protect dogs from endotoxin, but not without a significant amount of injury to the host.

Animals↗
PubMed1979

Isolation and characterization of granulocyte lysosomal proteins and study of their effects on the clotting system.

Lysosomes (granules) of rabbit PMN leukocytes were extracted with either HCl or H2SO4, and the extracts were chromatographed over Sephadex to separate protein constituents. Some of the low molecular weight cationic proteins homogeneous on SDS PAGE (8% and 12.5% gels) were characterized by electrophoretic mobility in acid gels and by amino acid analysis. A 3,700 dalton polypeptide, rich in arginine and cysteine, prolonged the partial thromboplastin time of normal plasma. In low concentration, this protein shortened the clotting time of pure fibrinogen by thrombin. In high concentration this lysosomal cationic protein precipitated fibrinogen from solution; no fibrinopeptides were released to suggest cleavage of fibrinogen. Fibrinolytic protease activity was detected in crude H2SO4 extracts but not in crude HCl extracts. Two separate plasminogen activators, differing from kallikrein or prekallikrein, were isolated from the H2SO4 lysosomal extract and were partially characterized; neither exhibited proteolytic activity on fibrinogen free of plasminogen.

Amino Acids↗