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Biomedical subjects

R G Bell

Publications and source records attributed to R G Bell.

At least 109 records · Page 6Linked to original sources

Requirement for two discrete stimuli for induction of the intestinal rapid expulsion response against Trichinella spiralis in rats.

Rats subjected to a 7-day abbreviated enteral infection with Trichinella spiralis subsequently reject more than 90% of a challenge infection within 24 h. This process is known as rapid expulsion. In these experiments parabiotic rats were used to examine the factors that establish rapid expulsion in the intestine. Induction with low to moderate doses of worms required exposure to two separate stimuli. These initiated different responses; one was readily transferred between parabiotic rats, whereas the second response was sessile and restricted to the intestine. These two responses interacted synergistically to produce strong rapid expulsion. Stage-specific exposure of parabiotic rats to preadult or adult trichinae (or the unrelated parasite Heligmosomoides polygyrus) showed that only preadult worms induced the transferable factor. Exposure to adult worms or to H. polygyrus induced a strictly local intestinal effect that was nonspecific. It is suggested that preadult worms initiated an immune response specific for preadults. This was transferable between parabionts but was unable to produce rapid expulsion unless the intestine had been non-specifically stimulated. Intestinal stimulation is accomplished by exposure to adult worms in natural infections or artificial regimes. These results suggest novel techniques for the development of enteral antihelminth vaccines.

Animals↗

Rapid expulsion of Trichinella spiralis: coinduction by using antigenic extracts of larvae and intestinal stimulation with an unrelated parasite.

The injection of cell-free extracts of larval Trichinella spiralis with Freund complete adjuvant immunized rats against a challenge infection with T. spiralis. Protection was expressed by a reduction of adult worms in the intestines 8 days after a challenge infection. The quantitatively more important rapid expulsion reaction could also be produced by immunization with antigen, provided immunized rats were also given an intestinal priming infection with adult Trichinella spiralis or an unrelated nematode, Heligmosomoides polygyrus. These parasites stimulated a local change in the intestine that synergistically interacted with immunity to give up to 90% protection through the rapid expulsion response. Intestinal priming had to follow antigen administration by not less than 5 days and was optimal when 10 days elapsed. These experiments provide evidence for an immunological component in the rapid expulsion process. In addition, the technique suggests that the utilization of intestinal priming may provide a new approach for the development of intestinal antihelminth vaccines.

Animals↗

Transfer of immunity against Listeria monocytogenes by T cells purified by a positive selection technique.

Affinity columns prepared with rabbit antibody to the F(ab')(2) fragment of rat immunoglobulin were used to separate rat thoracic duct lymphocytes into sub-populations that differ with respect to the density of their surface membrane immunoglobulin. Using this technique, it was shown that lymphocytes in the DNA synthetic (S) phase of the mitotic cycle are added in increased number to the lymph of rats infected with Listeria monocytogenes. The great majority of these S-phase cells lacked a high density of surface immunoglobulin as indicated by their failure to bind to the immunoabsorbent. Cells which can protect recipient rats against a challenge infection with L. monocytogenes also segregated with nonadherent thoracic duct lymphocytes obtained from Listeria-immune donors. These protective cells realized their full immunological potential only in recipients that shared histocompatibility-gene-coded structures with the immune lymphocyte donors. The above findings accord with the view that immunity to L. monocytogenes is mediated in rats by activated T cells which are formed as part of the animal's cell-mediated response to infection. Although Listeria-protective lymphocytes concentrate in the nonadherent, T-cell-enriched fraction, it was consistently observed that the adherent, B-cell-enriched fractions of immune donor thoracic duct lymphocytes also could transfer a low level of antimicrobial resistance. This immunity was restricted in allogeneic recipients, a finding which implies that the protection afforded by the adherent population is related to its content of T cells. Nonadherent S-phase lymphoblasts moved in substantial numbers from the blood into peritoneal inflammatory exudates induced by L. monocytogenes. The above finding encourages the belief that recently activated T cells realize their protective function locally in centers of infection where they have secondary effects on macrophages.

Animals↗

Comparative virulence and immunodiffusion analysis of Petriellidium boydii (Shear) Malloch strains isolated from feedlot manure and a human mycetoma.

The virulence to mice of a Petriellidium boydii strain isolated from feedlot manure was compared with that of a strain from a human mycetoma. Washed spores suspended in 5% hog gastric mucin were injected intraperitoneally into non-inbred female albino Swiss mice. In 21 days, the mycetoma strain killed 95% of the test animals whereas injection of eight times as many feedlot strain spores resulted in only 28% mortality. A progressive, exclusively sinistral (leftsided) torticollis was the most obvious symptom of experimental petriellidiosis. Mycelia bearing annellospores were observed in PAS-stained sections of most internal organs, including the brains, of the test animals. Immunodiffusion analyses were conducted on soluble antigen preparations with concentrated antisera produced in rabbits using live spore suspensions. The two strains contained common antigen but the proportions of two were significantly different.

Animals↗

Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K--epoxide cycle.

Vitamin K is primarily located in hepatic microsomes, where the vitamin K-dependent carboxylation in prothrombin synthesis occurs. Recent evidence supports the idea that the carboxylation is linked to the metabolism of the vitamin--specifically the cyclic interconversion of vitamin K and vitamin K epoxide. The primary site of action of coumarin and indandione anticoagulants appears to be an inhibition of the epoxide-to-vitamin K conversion in this cycle. There is a correlation between the inhibition of prothrombin synthesis and the regeneration of vitamin K from the epoxide by anticoagulants. In hamsters and warfarin-resistant rats prothrombin synthesis and the epoxide-K conversion are less sensitive to warfarin than in the normal rat. The epoxide-K conversion is impaired in resistant rats, which may explain their high vitamin K requirement. There is also a correlation between vitamin K epoxidation and vitamin K-dependent carboxylation, but the apparent link may be because vitamin K hydroquinone is an intermediate in the formation of the epoxide and also the active form in carboxylation. The vitamin K-epoxide cycle is found in extrahepatic tissues such as kidney, spleen, and lung and is inhibited by warfarin.

1-Carboxyglutamic Acid↗

The influence of dietary protein insufficiency on the murine thymus. Evidence for an intrathymic pool of progenitor cells capable of thymus regeneration after severe atrophy.

Low protein diets initiated at wearning in Balb/c mice cause a rapid and profound reduction in thymus weight and cellularity. Thymus weight falls to less than that of involuted thymus of adult mice and remains depressed for as long as diets are fed. Although most peripheral T cell functions do not appear to be depressed, suppressor cell activity was not as vigorous in deprived animals despite the presence of functional suppressor populations. Thymus growth was reinitiated promptly when high protein diets were fed to deprived animals. Thymus regeneration appeared to be due to both a resident population of stem cells which persisted in the thymus through the period of deprivation and a second, probably bone-marrow derived, population of stem cells. It is suggested that in normal mice the synchronized growth of the first population produces the characteristic innate growth pattern of the thymus. This is superimposed on the growth of the second population which continuously seeds the thymus and is constantly replaced. Protein deprivation severely restricts the growth of the first and second population, but both maintain their capacity for growth during long periods of protein restriction.

Animals↗

Factors determining the effects of chronic protein-deficiency on antibody responses to sheep red blood cells and Brucella abortus vaccine in mice.

Chronic protein-deficiency in weanling mice caused variable suppression of the humoral plaque-forming cell (PFC) responses to sheep erythrocytes. This was most prominent at high antigen doses and did not increase when mice were maintained on the diets for longer periods. Antibody responses produced by deficient mice were often short-lived and involved high levels of IgM. Total PFC counts were depressed slightly more than were circulating antibodies. Antibody responses to Brucella abortus were slightly decreased by protein-deficiency at high antigen doses but were normal or elevated at lower doses, the proportion of IgM produced was increased and the splenomegaly response to B. abortus was severely depressed. These results suggest that the depression of antibody production by protein-deficiency is not simply due to an impairment of helper T cell function, but a reduction in the availability or effectiveness of macrophage and regulatory or suppressor T cells may be important.

Animals↗

Marsupial immunoglobulins: the distribution and evolution of macropod IgG2, IgG1, IgM and light chain antigenic markers within the sub-class Metatheria.

The distribution within Australian and American marsupials of the heavy and light chain antigenic markers identified by antisera to purified quokka (Setonix brachyurus) immunoglobulins is described. Markers for IgM and IgG2 constant region determinants as well as for light chains were widely distributed in Australian species and were also detected in Didelphis, the American opossum, thus indicating a long-term structural conservatism of some immunoglobulins within the marsupials. More detailed analysis of the distribution of quokka IgG2 determinants by quantitative precipitation and sequential absorption procedures suggested that there had been a gradual and cumulative acquisition of these markers with time. The presence of IgG2 markers in species separated for 130 million years (quokka and opossum) suggested that IgG2 was the ancestral IgG present before the divergence of these separate lines. The origin of IgG1 remains obscure as it appears to be limited to a small group of closely related diprotodont marsupials suggesting a recent origin.

Animals↗

The response of protein-deficient mice to tetanus toxoid. Effects of antigen dose, adjuvants, period of deprivation and age on antibody production.

The effects of a 4% albumin diet initiated at weaning on primary and secondary responses to AIPO4-adsorbed and soluble tetanus toxoid (TT) were studied in C57BL mice. Responses of both groups were directly proportional to the dose of antigen over most of the range tested, but at very low doses protein-deficient mice produced higher primary titres than normal mice. In the primary response AIPO4-adsorption of the antigen essentially increased the effective dose irrespective of the diet, but after secondary challenge responses to soluble TT were more severely affected by the diet. Normal secondary titres to AIPO4-adsorbed TT were achieved when deficient mice were given high doses of antigen. Diet also affected the relative proportions of IgG and IgM produced in most responses. Gram-negative bacterial vaccines and lipopolysaccharide increased antibody production in both groups of mice. The low protein diet produced less dramatic effects when initiated at the time of inoculation or later, and mice maintained for longer on the diet produced more nearly normal titres. Mechanisms which may explain these findings are discussed.

Age Factors↗

Mechanism of action of anticoagulants: correlation between the inhibition of prothrombin synthesis and the regeneration of vitamin K1 from vitamin K1 epoxide.

It has been proposed that coumarin and indandione anticoagulants inhibit clotting protein synthesis by preventing the regeneration of vitamin K1 from its 2,3-epoxide metabolic. To test this hypothesis, the effects of nine coumarin and indandiones on prothrombin synthesis and the conversion of vitamin K1 epoxide to vitamin K1 were measured. There was a good correlation between the inhibition of prothrombin synthesis and the epoxide-K1 conversion both in vivo and in vitro. Diphenadione (2-diphenyl acetyl-1,3-indandione) caused a delayed inhibition of prothrombin synthesis which correlated with a delayed inhibition of the epoxide-K1 conversion in vivo. These results provide strong evidence for the proposed mechanism of action of coumarin and indandione anticoagulants.

Animals↗