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Biomedical subjects

S Lucas

Publications and source records attributed to S Lucas.

At least 145 records · Page 8Linked to original sources

Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice.

Within seven weeks of infection with 200 Schistosoma mansoni cercariae, T-cell deprived mice have been shown to suffer from extensive microvesicular damage to hepatocytes, and an inability to excrete parasite eggs at the same rate as comparably infected, immunologically intact controls. Administration of serum (CIS) from chronically infected, immunologically intact donors prevented the development of microvesicular cell damage and partially restored egg excretion rates in infected deprived mice. Serum pools obtained from mice injected either with intact S. mansoni eggs or with a homogenate of eggs emulsified in Freund's complete adjuvant (FCA) were as effective as CIS in preventing hepatotoxicity and restoring the rate of egg excretion in infected deprived recipients. The degree of protection of liver tissue afforded by immune sera could be monitored either by histopathological examination of liver sections or by estimation of serum transaminase concentrations, the results from both assays being generally in agreement. Sera from donor mice injected with cercarial or worm antigens in FCA were relatively inactive either in protecting against S. mansoni-induced liver damage or in reconstituting egg excretion rates in infected deprived mice. Serum from donor mice infected with 25 cercariae became hepato-protective between 49 and 53 days after infection of the donors, and the degree of hepatoprotective activity and egg excretion reconstituting capacity in the serum of 25 cercariae-infected donors was shown to increase between 8 and 16 weeks after infection. Increasing the size of infection of the serum donors to 100 cercariae gave only a marginal increase of hepatoprotective activity at 7 weeks when compared with serum donors infected with 25 cercariae for 7 weeks. Liver parenchymal cells of very heavily infected, immunologically intact mice were found to show microvesicular damage similar to that in livers of infected deprived mice, and administration of CIS to these normal mice was histopathologically protective. However, the elevated serum transaminase concentrations obtaining in the infected normal mice were not reduced to any extent by CIS. The results obtained from serum-reconstituted deprived mice are discussed in terms of the contribution they may make to a better understanding of the host-parasite relationship in immunologically intact mice.

Animals↗

Identification and partial purification of an antigen (omega 1) from Schistosoma mansoni eggs which is putatively hepatotoxic in T-cell deprived mice.

T-cell deprived mice heavily infected with Schistosoma mansoni suffer from severe microvesicular damage to hepatocytes within seven weeks of infection. The damage can be prevented by administration of serum (CIS) obtained from mice chronically infected with S. mansoni or from mice immunized with intact or homogenized S. mansoni eggs. Reaction of serum samples from individual chronically infected mice in immunoelectrophoresis with S. mansoni egg homogenate has enabled the identification of at least 12 distinct immuno precipitation reactions. Precipitating antibody against one S. mansoni egg antigen, omega 1, has been detected in all mice with patent chronic infections, and anti-omega 1 antibody is the most concentrated of the precipitating anti-egg antibody species in pooled CIS. Pooled serum obtained from infected intact mice reacting predominantly against omega 1 was found partially to prevent the hepatotoxicity reaction on transfer to infected deprived mice. Serum samples from mice injected with egg homogenate fractionated either by preparative electrophoresis or by cation exchange chromatography, and containing antibodies reactive with antigen omega 1 in immunoprecipitation, were fully protective against liver cell damage induced by S. mansoni in deprived mice. Sera from mice immunized with other S. mansoni egg fractions, and which did not contain antibodies reactive with omega 1, were not hepatoprotective. Antigen omega 1 is compared and contrasted with other S. mansoni egg antigens that have been described.

Animals↗

Complement and glomerular disease - a natural history study.

Over a 5-year period we have performed sequential measurements of a range of complement components in 127 patients. Each had a well-characterised glomerular lesion and there was no evidence of an underlying connective tissue disorder. In 17 patients with varied histopathology, who did not have C3 nephritic factor, there was a persisting complement defect which was present during remission in the patients we were able to study. The finding of such defects is consistent with the thesis that primary complement system abnormalities predispose to the development of glomerular lesions. Interestingly, these abnormalities did not influence the prognosis of our patients. In 12 other cases without C3 nephritic factor, complement levels were below the normal range when the glomerular lesion was active but returned to it in remission; these were secondary changes. We showed by discriminant analysis that some circulating complement component levels, assessed in relation to each other and without reference to a statistically derived 'normal' range, discriminated between histological subgroups and had prognostic significance as well. These patterns could not be distinguished until the data were stored and analysed by computer.

Analysis of Variance↗

Decreased thyroidal response to thyrotropin in diabetic mice.

The effect of diabetes mellitus on the synthesis and secretion of thyroid hormone ws investigated in mice with streptozotocin-induced diabetes. Thyroid glands were labeled in vivo with 131I for 2 h. In control animals, TSH stimulated the synthesis of PB127I and 131I-labeled iodothyronines and simultaneously decreased the proportion of 131I-. These effects of TSH were not observed in diabetic animals but were demonstrable in diabetic animals treated with insulin. For studies of hormone secretion, labeled thyroid glands were cultured in vitro in medium containing 1 mM mononitrotyrosine. The rate of the hydrolysis of labeled thyroglobulin was measured as the proportion of 131I-labeled iodotyrosines and 131I-labeled iodothyronines recovered at the end of culture and was used as an index of thyroid secretion. TSH in vivo stimulated the rate of thyroglobulin hydrolysis for 6 h, with a peak occurring after 2 h. The diabetic mice had a diminished response to TSH, which improved on treatment with insulin. The addition of TSH and insulin to the culture medium significantly increased the rate of thyroglobulin hydrolysis in glands of diabetic mice over that resulting from the addition of dibutyryl cAMP alone. The generation of thyroidal cAMP in response to TSH was higher in diabetic mice than in controls. The rise in plasma T4 and T3 2 h after the administration of TSH was less in diabetic mice than in control mice or diabetic mice treated with insulin. Our studies, therefore, indicate that the thyroidal response to TSH is decreased in diabetes mellitus. The defect appears to be at a step beyond the generation of cAMP.

Animals↗

The pathological effects of immunosuppression of Schistosoma mansoni-infected mice, with particular reference to survival and hepatotoxicity after thymectomy and treatment with antithymocyte serum, and treatment with hydrocortisone acetate.

The effects of various immunosuppressive regimes on the survival and liver pathology of mice infected with Schistosoma mansoni were investigated. T-cell deprivation before infection (by adult thymectomy and subsequent anti-thymocyte serum administration), or treatment with hydrocortisone or cyclophosphamide or azathioprine after infection, all reduced survival of infected mice when compared with immunologically intact, infected mice. T-cell deprivation or steroids produced severe liver damage in infected mice despite a reduction in the size of the peri-oval granulomatous inflammatory reaction. Administration of chronic infection serum reduced liver damage in both T-cell-deprived and steroid-treated animals, but improved survival only in the deprived animals and not to the level seen in normal infected mice. The liver damage in immunosuppressed mice was not due to opportunistic bacterial infection. Thus, although immunosuppression reduced the granulomatous response to schistosome eggs in the livers of infected mice (as it does to eggs injected intravenously into the lungs), survival time was decreased. The relevance of these findings to human S. mansoni infections is discussed.

Animals↗

Suprascapular entrapment neuropathy: a clinical, anatomical, and comparative study. Part 2: anatomical study.

Two hundred eleven adult scapulae were examined and quantitative data pertaining to the dimensions of the suprascapular notch were obtained. Six types of suprascapular notch were observed. Transitions tended to occur between Types II, III, and IV. A classification function was developed utilizing the measured values of the dimensions of the suprascapular notch, which might help in assigning the scapulae to these transitional types. Dissections of the suprascapular area were performed in 15 cadavers. Static and dynamic relationships of the suprascapular nerve to the suprascapular foramen were examined.

Adult↗

Suprascapular entrapment neuropathy: a clinical, anatomical, and comparative study. Part 3: comparative study.

The suprascapular ligament seems to serve no defined function in the human. A comparative study was undertaken to elucidate its function. The suprascapular region was dissected in species representing seven existing primate families and six subprimate families. A striking dichotomy of pattern was observed. In the New World primates, the suprascapular ligament appeared to be continuous with the coracoclavicular ligament; the former merely served to increase the area of bony attachment of the coracoclavicular ligament. In the Old World monkeys and subprimate mammals, the suprascapular ligament was entirely absent. The human anatomy was comparable to that found in the New World primates. This dichotomy of pattern seems to be related to the function of the upper extremity in the different classes of mammals.

Animals↗