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Biomedical subjects

S Sinclair

Publications and source records attributed to S Sinclair.

At least 37 records · Page 2Linked to original sources
PubMed1993

Intensive care.

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Critical Care↗
PubMed1991

Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro.

The cellular basis for the variation in induction of monocyte procoagulant activity (PCA) by murine hepatitis virus strain 3 (MHV-3) was examined using a set of recombinant inbred strains of mice derived from the resistant (A/J) and susceptible C57B1/6J (B) progenitors. Induction of PCA by MHV-3 required live virus and host protein and RNA synthesis. Absolute restriction for induction of PCA was observed at the level of the macrophage. Peritoneal macrophages from resistant parental A/J and RI strains (AXB5) could not be induced to express PCA when stimulated by MHV-3 alone or in the presence of lymphocytes from susceptible and H-2 compatible RI mice (AXB3) although they did respond to endotoxin (LPS). In contrast, macrophages from both susceptible (AXB3) and semisusceptible (AXB1) RI strains of mice expressed a similar increase in PCA after stimulation with MHV-3 in the absence of lymphocytes. The levels of PCA expressed by macrophages in the presence of Thy-1.2+ lymphocytes correlated with susceptibility to disease. Thy-1.2+ lymphocytes from susceptible RI AXB3 mice could induce levels of PCA in macrophages from semisusceptible RI AXB1 mice equivalent to that seen in cultures of macrophages and lymphocytes from susceptible mice. Further subfractionation of Thy-1.2+ cells demonstrated that L3T4+ cells instructed macrophages to produce PCA. Thy-1.2+ cells from MHV-3 immunized resistant AXB5 mice, but not from non-immunized mice, were able to suppress induction of PCA. This suppressor cell activity could be detected 4 days after immunization, reaching maximal activity at day 7 with significant suppression even at 28 days. The PCA was shown to have direct prothrombin cleaving activity (prothrombinase) by ELISA and immunofluorescence staining using the mAb 3D4.3. These results demonstrate that induction of a unique PCA (prothrombinase) is restricted at the level of the macrophage and define a regulatory role for T lymphocytes in its induction.

Animals↗
PubMed1990

Fulminant hepatitis.

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Blood Coagulation Disorders↗
PubMed1990

Eicosanoids and the liver.

Prostaglandins and leukotrienes are ubiquitous mediators of a wide variety of physiologic and immunologic effects in liver function and disease. Although the biochemical, synthetic and catabolic pathways of these compounds from arachidonic acid are well known, their cellular mechanisms of action are less well understood. Numerous studies have demonstrated the role for leukotrienes in the pathogenesis and the protective action of PG in experimental animal models of liver injury. These have included models of liver cell damage due to ischemia, galactosamine, carbon tetrachloride, and lipopolysaccharide. More importantly, the results of these studies have led to the demonstration of protective properties of 16, 16 dimethyl PGE2 (dm PGE2) in a mouse model of viral hepatitis. These results have led to the use of IV PGE1 in the treatment of patients with fulminant viral hepatitis, where 71% overall survival was observed as well as in the setting of primary non function and recurrent hepatitis B following liver transplantation. While the mechanisms of prostaglandin hepatic protection are not well understood, it has been demonstrated that dm PGE2 abrogates the induction of tumour necrosis factor, leukotriene B4 (LTB4) and procoagulant activity by macrophages as well as attenuating the expression of major histocompatibility class antigens on the surface of hepatocytes, and may inhibit viral replication. Finally, prostaglandins are known to play a role in the renal dysfunction associated with cirrhosis and fulminant hepatic failure, and therefore further studies of these agents in the pathophysiology and treatment of liver diseases and their complications are warranted.

Animals↗
PubMed1980

The importance of topical heparin in microvascular anastomoses: a study in the rat.

The importance of heparinised saline irrigation of the vessel ends in microvascular anastomoses may be under-estimated. Recent thrombosis research is reviewed which suggests that heparin is selectively adsorbed onto endothelium, thereby preventing thrombus formation. This evidence is invoked to explain the results of a free flap experiment in the rat and to make some practical recommendations.

Animals↗
PubMed1980

Municipal waterborne giardiasis: an epidemilogic investigation. Beavers implicated as a possible reservoir.

In March 1976, 128 persons in Camas, Washington, had laboratory-confirmed giardiasis. A questionnaire survey of 498 Camas residents revealed that 3.8% had clinical giardiasis, while none of 318 residents in a control town were ill. No associations between illness and sex, pet ownership, travel, time spent in wilderness areas, public gatherings, or food preference were found. Giardia cysts were recovered from raw water entering the city water treatment system via two streams and also from two storage reservoirs containing chlorinated and filtered stream water. Failure to remove Giardia cysts was attributed to the water plants' inadequate flocculation, coagulation, and sedimentation combined with deterioration of the filter media. Investigation of the watershed revealed no signs of human fecal contamination. Animal trapping in the watershed area yielded three beavers (Castor canadensis) infected with Giardia that were infective for specific pathogen-free beagle pups.

Animals↗