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Biomedical subjects

K S Warren

Publications and source records attributed to K S Warren.

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

Suppressive effect of a chronic helminth infection, schistosomiasis mansoni, on the in vitro responses of spleen and lymph node cells to the T cell mitogens phytohemagglutinin and concanavalin A.

Chronic murine schistosomiasis mansoni is associated with depressed cell-mediated immune responses to Schistosoma mansoni egg antigens. The present study has examined the possibility that factors develop during infection that are capable of altering the response of lymphocytes to stimuli other than specific schistosomal antigens. Egg production begins at 5 weeks, and 1 to 3 weeks later there is a moderate degree of unresponsiveness of lymph node and spleen cells to the mitogens concanavalin A and phytohemagglutinin. This was associated with an altered dose response curve to the mitogens similar to that observed in antigenic systems. Seven weeks after the initiation of antigenic stimulation (egg prodiction lymph node and spleen cells from chronically infected animals were profoundly unresponsive to all concentrations of concanavalin A and phytohemagglutinin tested. These investigations suggest that, in addition to possible blockade by serum antibody, other suppressive factors may be involved in the spontaneous modulation of immunopathology in chronic schistosomiasis. These are detectable 1 to 3 weeks after the onset of egg production and are prominent at 12 weeks. Such findings are consistent with, but do not prove, the existence of suppressor T cells in chronic schistosomiasis.

Animals↗
PubMed1976

Suppression of giardiasis during the intestinal phase of trichinosis in the mouse.

The interaction of the intestinal phases of Giardia muris and Trichinella spiralis was investigated in Swiss albino mice. Intraoesophageal inoculation of G. muris cysts seven days before, or seven days after, similar inoculation of T. spiralis larvae resulted in significant reduction in the numbers of Giardia trophozoites in small bowel and Giardia cysts in stools. This effect was not observed when G. muris cysts were administered after resolution of the intestinal phase of trichinosis. Giardiasis had no effect on trichinosis as assessed by numbers of adult worms in small bowel and larvae in skeletal muscles. Studies of small bowel morphology showed that the intestinal phase of trichinosis was associated with increased numbers of inflammatory cells in the lamina propria, a significant increase in Paneth cells in crypts, and a marked reduction in the villus:crypt ratio of jejunum. These observations suggest that the intestinal phase of trichinosis induced environmental changes in small bowel, perhaps related to inflammation, which resulted in suppression of proliferation of Giardia trophozoites.

Animals↗
PubMed1976

Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection.

These investigations delineate the recently described suppression of a form of cellular hypersensitivity in mice with streptozotocin-induced diabetes mellitus using a variety of cell-mediated immunologic responses in animals with several different forms of diabetes. Streptozotocin- and alloxan-induced diabetic mice and db/db genetically determined diabetic mice showed reductions in the areas of inflammation around Schistosoma mansoni eggs injected into the pulmonary vasculature of 68, 70, 77%, respectively. In contrast, streptozotocin-induced diabetes had no effect on the nonimmunologic foreign body granuloma around divinyl benzene copolymer beads injected into the pulmonary arterioles. Animals protected from diabetes by treatment with nicotinamide before streptozotocin administration did not develop hyperglycemia and had normal areas of immunologic granuloma formation around schistosome eggs. Treatment with insulin reversed the suppression of schistosome egg granuloma formation in both streptozotocin- and alloxan-diabetic animals. Two additional in vivo parameters of cellular immunologic reactivity were examined in streptozotocin-induced diabetes: delayed footpad swelling was essentially eliminated; skin graft survival across the H-2 area was significantly prolonged from 10.2 days in the controls to 14.4 days in moderately diabetic A/J mice. These observations suggest that diabetes mellitus is associated with suppression of cell-mediated reactions in vivo and that the defect is reversible with insulin treatment.

Animals↗
PubMed1976

Relation of intensity of infection to disease in hamsters with acute schistosomiasis mansoni.

Groups of young hamsters were exposed to 3, 20, 40, 80, or 160 cercariae. A highly significant correlation was observed between the number of cercariae, worm burdens, and liver and fecal egg counts. The most heavily infected animals were the first to lose weight and die. Hamsters exposed to 20 or more cercariae and harboring a mean of 4.2 or more worm pairs developed significant hepatosplenic disease by 10 weeks after infection as assessed by hepatomegaly, splenomegaly and the development of portal hypertension. Lightly infected animals with single worm pairs did not develop significant disease.

Acute Disease↗
PubMed1976

Schistoma mansoni soluble egg antigens: determination of the stage and species specificity of their serologic reactivity by radioimmunoassay.

Three highly purified Schistosoma mansoni egg antigens reactivity with sera from mice with chronic schistosomiasis mansoni (major serologic antigens-MSA1, MSA2, and MSA3) were utilized in radioimmunoassays for determining their stage and species specificity. Inhibition studies revealed that MSA1 was completely stage specific, since its binding to S. mansoni chronic infection serum (CIS) could not be inhibited either with cercarial or adult worm antigen. MAS2 and MSA3 were specific with regard to adult worm antigen but their binding to CIS was slightly inhibited by cercarial antigen. Immature eggs in comparison with mature eggs contained only negligible amounts of MSA1 whereas MSA2 and MSA3 were present in large quantities. Fluid from eggs hatched in spring water (hatch fluid-HF) contained considerable amounts of MSA1 as well as MSA2 and MSA3. With regard to species specificity, MSA1 essentially did not cross-react with crude soluble egg antigen (SEA) from Schistosoma japonicum and Schistosoma haematobium whereas MSA2 and MSA3 showed partial cross-reactivity. Antibody dilution studies with sera from animals and humans infected with heterologous schistosome species (i.e., S. japonicum and S. haematobium) indirectly confirmed the high degree of species specificity of MSA1. The degree of serologic specificity of MSA1 as demonstrated in this study parallels that of the sensitizing activity of S. mansoni eggs and SEA for granuloma formation, as demonstrated in previous investigations. This study, therefore, indicates that MSA1 may be a major immunopathologically active egg antigen. In addition, the high degree of species specificity of MSA1 suggests its use in the serodiagnosis of schistosomiasis mansoni.

Animals↗
PubMed1976

Field studies of a rapid, accurate means of quantifying Schistosoma haematobium eggs in urine samples.

A new means of quantifying schistosome eggs has been adapted from the laboratory to the field. Urine from 510 individuals in areas of Kenya with a high prevalence of schistosomiasis haematobia was injected in aliquots of 10, 5 and 1 ml on to transparent Nuclepore filters, 13 mm in diameter. The filters were placed face down on glass slides and were read without staining at x40 magnification. The method has been shown to be accurate, sensitive, and reproducible, and also extremely rapid.

Adolescent↗
PubMed1976

Giardiasis in the mouse: an animal model.

An animal model for giardiasis was developed using Giardia muris in Swiss albino mice. Intraesophageal inoculation of G. muris cysts caused a reproducible pattern of infection, with trophozoite and cyst counts reaching a maximum on days 5 to 14 after cyst inoculation and thereafter showing a progressive decline. Spontaneous resolution of infection occurred in most mice after 21 to 28 days. When compared to uninfected controls, Giardia-infected mice had significant impairment of weight gain and a significant reduction in the villus to crypt ratio of jejunal mucosa. Although maximal trophozoite and cyst counts were independent of the size of the cyst inoculum, those mice receiving inoculations of larger numbers of cysts showed earlier attainment of maximal counts, greater impariment of weight gain, and earlier and more severe small bowel changes than mice receiving inoculations of smaller numbers of cysts. This model offers unique opportunities for study of this poorly understood gastrointestinal parasite.

Animals↗
PubMed1976

Schistosoma mansoni soluble egg antigens. I. Identification and purification of three major antigens, and the employment of radioimmunoassay for their further characterization.

A cell-mediated immunologic granulomatous response to Schistosoma mansoni eggs is now generally accepted as being responsible for the hepatosplenic disease of chronic schistosomiasis. Previous investigations have demonstrated that a soluble extract of S. mansoni eggs (SEA) both induces and elicits granulomatous hypersensitivity and other forms of cell-mediated immunologic reactivity. Mice with chronic light S. amnsoni infections show spontaneous suppression of granulomatous hypersensitivity in the presence of high levels of anti-SEA antibodies. Immunodiffusion analysis using antiserum obtained from these mice and SEA resulted in the identification of three major serologic antigens which have been designated MSA1, MSA2, and MSA2. Initial studies with Sephadex G-200 gel filtration and polyacrylamide gel electrophoresis indicated that the three antigens were markedly different in m.w. and at least two of the three were glycoproteins. The antigens were then extracted from crude SEA by adsorption to a concanavalin A Sepharose affininity column. The eluted antigens were separated from each other by ion exchange chromatography on DEAE cellulose. On polyacrylamide gel electrophoresis (PAGE) MSA1 and MSA2 were homogenous; MSA3 was estimated to be 70% pure. The purified antigens were radiolabeled and were passed through Sephadex G-200 or Bio-Gel A 1.5 columns to determine their m.w. These studies have shown that MSA1 and MSA2 are glycoproteins of m.w. 137,000 and 465,000 daltons, respectively; the m.w. of MSA3 is in the range of 50,000 to 70,000 daltons. PAGE of the purified antigens revealed the following R.F.s: MSA1=0.34, MSA2=0.20, and MSA3=0.48. MSA1 and MSA2 were employed in radioimmunoassays using the ammonium sulfate method of Farr. On the basis of immunodiffusion analysis and radioimmunoassay, MSA1 exhibits a degree of stage and species specificity consistent with the granulomatous response to S. mansoni eggs. The potential specificity of the MSA1 radioimmunoassay and its great sensitivity suggest a role in the immunodiagnosis of schistosomiasis.

Animals↗
PubMed1975

A role for the eosinophil in acquired resistance to Schistosoma mansoni infection as determined by antieosinophil serum.

Partial immunity to schistosomiasis mansoni has been demonstrated in mice and has recently been transferred passively with serum, but not with cells. In vitro studies using human and rodent materials have demonstrated antibody-dependent cell-mediated damage to immature schistosomes (schistosomula); the cell involved in some of these in vitro systems appears to be the neutrophil and in others the eosinophil is suspected. In the present study the effect of antileukocyte sera on partial immunity to schistosomiasis was tested in vivo using quantitative assay systems for schistosomula in the lungs and adult worms in the portal venous system. Mice infected with 10 cercariae of Schistosoma mansoni 16 and 32 wk before challenge with 500 cercariae showed reductions in the recovery of schistosomula at 4 and 6 days of approximately 40%; adult worm recovery was reduced by 60%. Treatment with antilymphocyte, antimacrophage, or antineutrophil serum had no effect on the numbers of schistosomula recovered from the lungs of immune animals, but in the mice treated with antieosinophil serum the numbers of schistosomula and adult worms recovered increased to the levels seen in normal nonimmune animals. Furthermore, sera collected from the partially immune mice and passively transferred to uninfected mice conferred a marked resistance to infection as measured by recovery of schistosomula; this was also abrogated by treatment with antieosinophil serum. These studies suggest that antibody-dependent cell-mediated immunity to schistosomiasis occurs in vivo, and also establishes a role for the eosinophil in immune systems.

Animals↗