Joseph W. Shands

Pyoderma gangrenosum in a kindred: Precipitation by surgery or mild physical trauma

Five cases of pyoderma gangrenosum occurring in a kindred are presented. Three of the cases occurred after abdominal surgery and tended to be confused with postoperative wound infections. Two cases occurred after superficial injury to the leg and were also thought to represent a peculiar form of cellulitis. None of the patients are known to have any of the underlying diseases usually associated with pyoderma gangrenosum. The cases are presented to alert the physician to this entity and to document the unusual familial occurrence. (J Am Acad Dermatol 1987;16:931-4.)

Selective effects of mitogens on subpopulations of mouse lymphoid cells

Abstract The mitogenic effects of phytohemagglutinin (PHA), pokeweed mitogen (PWM), staphylococcal enterotoxin B (SEB) and endotoxins upon mouse spleen cells and various subpopulations were examined. The differential responses to these mitogens by cells of varying density indicate that LPS stimulates a different subpopulation from that of PHA and SEB. The subpopulation containing cells responsive to PWM seemed to differ from both of these patterns. In contrast to the effect of PHA, PWM, and SEB, thymus cells were not stimulated by LPS. LPS- and PWM-stimulated cells taken from both neonatally thymectomized and adult-thymectomized, irradiated, and bone-marrow-reconstituted animals: SEB and PHA failed to do this. It is concluded that the subpopulation responding to SEB, like that to PHA, is thymus dependent but that the two are probably not completely overlapping. That containing PWM responsive cells involves both thymus-independent and thymus-dependent cell components. The subpopulation stimulated by LPS is contained in a low density sub-population, which appears to be completely T independent.

The hypoglycemic activity of endotoxin. I. Occurrence in animals hyperreactive to endotoxin.

Summary Mice were made hyperreactive to endotoxin by BCG infection, zymosan injections, and by adrenalectomy, and the effect of endotoxin on the blood sugar concentration of these animals was determined. All of the mice developed hypoglycemia after small doses of endotoxin and in the BCG mice and in the zymosan-treated mice the hypoglycemia was often of sufficient magnitude to cause death. Efforts to save endointoxicated BCG mice by intermittent glucose administration were unsuccessful, and experiments with diabetic mice showed that the hypoglycemic and lethal effects of endotoxin were not necessarily associated with one another.

Lymphocyte collaboration is not required for the induction of murine macrophage procoagulant by endotoxin

The putative requirement for lymphocytes as instructor cells in the induction of macrophage procoagulant (PCA) by endotoxin (LPS) was tested on elicited mouse peritoneal macrophages and on bone marrow-derived macrophages. Percoll purification of thioglycollate macrophages to at least 99.8 percent failed to diminish PCA induction by LPS. Bone marrow macrophages synthesized most PCA in response to LPS when they constituted more than 95 percent of the cells. In addition, PCA synthesis by these cells was not enhanced by the addition of splenic lymphocytes in a ratio of four to one. Exudate macrophages from endotoxin unresponsive C3H/HeJ mice failed to increase PCA synthesis in the presence of LPS. The addition of responsive C3H/HeN splenic lymphocytes to non-responsive HeJ macrophages did not permit LPS to induce the synthesis of PCA, suggesting the absence of unidirectional lymphocyte-instructed pathway. These data provide no evidence for lymphocyte collaboration in the LPS induction of murine macrophage PCA. LPS appears to induce PCA by acting directly on the macrophage.

Endotoxin-induced insulin sensitivity in BCG infected mice.

Summary The administration of endotoxin to BCG-infected mice induces a marked sensitivity to insulin. When insulin is administered after endotoxin, a profound hypoglycemia ensues. The stimulation of endogenous insulin secretion in endotoxin-poisoned BCG-infected mice by glucose administration may also lead to a reactive hypoglycemia from which the mice do not recover. These observations illustrate the loss of homeostatic control caused by endotoxin and are consistent with previous observations that endotoxin impairs gluconeogenesis.

Endotoxin induced metabolic alterations in BCG infected (hyperreactive) mice.

Summary The cause of hypoglycemia induced by endotoxin in BCG infected mice was investigated. The major abnormality, known to be defective gluconeogenesis, was studied to determine whether a specific point in the gluconeogenic pathway is involved or whether the derangement is more general. The inability of endotoxin poisoned mice to synthesize glucose from glycerol and fructose in addition to pyruvate indicated that the entire pathway was in disarray. The in vivo oxidation of glucose, glycerol and palmitate to CO2 was reduced, indicating that enhanced aerobic oxidation was not responsible for the hypoglycemia. This decrease in substrate oxidation also suggests that impaired gluconeogenesis may be due to decreased energy available to maintain the gluconeogenic pathway. Pharmacologic doses of glucocorticoids were protective in endotoxin poisoned BCG infected mice. The rate of development of hypoglycemia was rapidly lessened, and mortality reduced. The data suggest that steroids confer protection by preventing or interfering with some of the toxic effects of endotoxin or perhaps by activating glyconeogenic enzymes. It is unlikely that glucocorticoid mediated enzyme induction plays an anti-endotoxin role in this model.

Endotoxin-stimulated spleen cells: dissociation between DNA synthesis and IgM production at the cellular level.

Summary LPS stimulation of mouse spleen cells in the presence of Hu resulted in almost total suppression of [3H]thymidine incorporation without affecting the percentage of cells induced to produce IgM. Utilizing a method which permitted the simultaneous measurement of IgM production and [3H]thymidine incorporation in individual cells, it was demonstrated directly that LPS stimulation of IgM production can occur in the absence of DNA synthesis.

Biological Effects of Poly rI:rC and Endotoxin in Mice Infected with Mycobacterium BCG: Interferon Induction and Toxicity

Summary Infection of mice with BCG failed to enhance sensitivity to poly rI:rC, as assayed by the amount of polymer required for interferon induction or for lethal toxicity. The amount of interferon induced in normal mice reached a plateau at a poly rI:rC dose of 200 μg per mouse. In contrast, the amount of interferon elaborated by BCG-infected mice following poly rI:rC doses of ≥200 μg per mouse was greater than that of normal mice, and increased with increasing amounts of inducer. Complete hyporeactivity to interferon induction by endotoxin was observed in normal mice pretreated with poly rI:rC, even when the dose of poly rI:rC elicited only a minimal interferon response, whereas a poly rI:rC dose-related hyporeactivity was observed in BCG-infected mice. The research for this paper was supported by National Institute of Health Grants 5TI AI0128-12 and AI07257-06.