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Biomedical subjects

R I Walker

Publications and source records attributed to R I Walker.

At least 127 records · Page 7Linked to original sources
PubMed1976

Contribution of granulocytopenia to endotoxin sensitivity of mice irradiated or undergoing graft-versus-host reaction.

Animals compromised by irradiation or graft-versus-host reaction (GVHR) are highly sensitive to endotoxin (ET). In order to determine the causes of the increased sensitivity of compromised mice, we studied alterations of hepatic (central) and bloodborne (peripheral) ET clearance processes. We observed that increased sensitivity to ET, as determined by mortality, occurred shortly after irradiation and correlated with granulocytopenia nd thrombocytopenia rather than with impairment of liver function. The involvement of granulocytes in ET clearance was indicated by injection of 51Cr-ET suspended in whole blood. By comparison with clearance of ET injected with saline or plasma, greater amounts of 51Cr-ET were sequestered in peripheral organs than in the liver. Similar results were obtained when Cr-ET in whole blood was perfused through a rat liver. ET clearance was enhanced 50% over that seen in M-199, plasma, or platelet-rich plasma. It was also found that intestinal ET contributes to mortality of granulocytopenic-thrombocytopenic mice. This was supported by the observation that bacteriologically decontaminated, irradiated animals were eight times more resistant to challenge with ET than were conventional animals. Thus, an important aspect of increased sensitivity to ET, in comprised mice, is defective peripheral clearance.

Agranulocytosis↗
PubMed1975

Klebsiella pneumoniae and Staphylococcus aureus infection in mice: difference in uremia and ammoniagenesis.

Lethal infections by Staphylococcus aureus and Klebsiella pneumoniae were compared for kidney-related effects in mice. K. pneumoniae caused uremia and an increase in blood ammonia that could reach 2.5 times normal. These events did not occur in mice inoculated with S. aureus. Use of germfree animals indicated that most of the increase in ammonia arose from the gut, presumably due to greater availability of urea and ureolysis. Injected ornithine restored blood ammonia to nearly normal levels and extended survival.

Ammonia↗
PubMed1975

Evaluation of biologic activity of ferric chloride-treated endotoxin in mice.

Endotoxin (lipopolysaccharide, LPS) treated with ferric chloride was tested for its potential as a non-toxic agent for enhancement of non-specific host resistance. A 1 mg dose of untreated endotoxin, injected i.p. into mice, resulted in 100 per cent mortality, whereas the same amount of chemically-treated endotoxin resulted in less than 35 per cent lethality. The radio-protective potential of the treated endotoxin was similar to that of untreated endotoxin, as 70 per cent of each group of mice tested with either substance survived a dose of 850 rad x-ray. Irradiated mice, challenged 8 days after 850 rad x-irradiation, died when injected with 25 mug of either untreated or treated endotoxin. Antibiotic decontamination of the intestinal tract of host animals reduced the possibility of toxicity from endogenous endotoxin after challenge. This treatment resulted in 100 per cent survival from a 25 mug challenge at 8 days post-irradiation. The ferric chloride-treated proved to be a more effective B-lymphocyte mitogen. At a dose of 100 mug, treated endotoxin resulted in a 50 per cent greater mitogenic stimulation of B-lymphocytes as compared with that found after exposure to untreated endotoxin. Several lines of evidence support the contention that tolerance to untreated endotoxin was induced by repeated injections of either endotoxin preparation 1) 100 per cent of all endotoxin-tolerant mice survived a 1 mg challenge dose of untreated endotoxin, 2) there was a reduced mitotic response of splenic B-lymphocytes after re-exposure with untreated endotoxin as compared with that observed for cells derived from saline-treated mice, and 3) all antibiotic decontaminated mice engrafted with spleen cells from mice made tolerant to either endotoxin preparation survive graft-versus-host disease. In conclusion, based on survival data from normal mice, ferric chloride-treated endotoxin is safer to use than normal endotoxin. Also, treated endotoxin can elicit biologic responses similar in magnitude to those found after injection of mice with untreated endotoxin.

Animals↗