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Biomedical subjects

C B Chapman

Publications and source records attributed to C B Chapman.

At least 37 records · Page 2Linked to original sources
PubMed1982

Proteolytic cleavage of immunoglobulin by enzymes released by Fasciola hepatica.

Immature Fasciola hepatica release a papain or cathepsin B-like proteolytic enzyme which cleaves immunoglobulins (Ig) of mouse, rat, rabbit and sheep in vitro. Mouse IgG and IgM molecules are both susceptible to cleavage as is hemoglobin. Whether single or multiple proteases are responsible for Ig cleavage is unknown. The proteolytic activity of secreted enzyme(s) is optimal at pH 3.5-4.5, but activity is also present at pH 7. Proteolysis is enhanced in the presence of 5 mM dithiothreitol or 100 mM cysteine. Based on studies with protease inhibitors, the F. hepatica enzyme activity has been identified as a thiol protease. It is destroyed by heating at 56 degrees C for 1 h, but retains activity after storage at -20 degrees C for 7 days. Whether inhibition of the proteolytic activity increases the susceptibility of F. hepatica immature worm to any extant immune effector mechanisms in hosts remains to be determined.

Animals↗
PubMed1981

Clonal parasites in the analysis of resistance to reinfection with Fasciola hepatica.

A feature of fascioliasis in mice and rats is incomplete and generally poor resistance to reinfection. The possibility exists that population heterogeneity amongst Fasciola hepatica parasites (in characteristics such as antigenic variability and infectivity) contributes to the incomplete resistance expressed by already infected rodents to challenge infection. Using different exposure regimes, mice and rats were dosed with infective metacercariae of different single snail-derived clones and challenged with the same or different clonal parasites. The results clearly demonstrate that no better resistance to reinfection is seen with parasites of the homologous clone than with heterologous clone challenge. Thus the poor resistance to reinfection seen in fascioliasis cannot be ascribed readily to antigenic or infectivity differences between clonal metacercariae.

Animals↗
PubMed1980

A difference in surface proteins of Fasciola hepatica larvae from intact and nude mice.

Larvae of the trematode, Fasciola hepatica, dissected from the livers of intact mice at 12 to 14 days of infection, bind anti-immunoglobulins in vitro. This is not so for larvae harvested from the livers of infected hypothymic nude (nu/nu) mice. When attempts were made to confirm the presence of surface Ig using lactoperoxidase-catalysed radioiodination and analysis by SDS-polyacrylamide gel electrophoresis, proteolysis at the time of solubilization markedly affected the profiles obtained. Provided protease inhibitors were present during processing, a mu-like Ig heavy chain and a gamma-like Ig heavy chain could be demonstrated on larvae from nu/+ mice but not on larvae from nu/nu mice.

Animals↗
PubMed1979

Should there be a commission on medical education?

In its premedical and preclinical phases our present scheme of education for medicine is intellectually deficient, wasteful of money and time, and in urgent need of overhaul. The author defines conditions under which a national commission might possibly set the educational process on the road to reform.

Education, Medical↗
PubMed1979

Fasciola hepatica: attempts to induce protection against infection in rats and mice by injection of excretory/secretory products of immature worms.

In vitro excretory/secretory products of 4-week (immature) and 8-week-old (mature) Fasciola hepatica parasites, derived from rats, were injected together with adjuvant into naive rats and mice. Resistance to infection was assessed in rats by counting adults in the bile ducts at 9 weeks, or in mice by recording deaths after oral challenge with a high dose of viable metacercariae. Exposure of rats to excretory/secretory products of immature F. hepatica conferred a significant degree of resistance which was comparable to the level of resistance induced following oral administration of a low number of metacercariae. No protection against infection was seen in rats injected with excretory/secretory products from mature, bile duct-derived worms. In mice, no obvious mouse strain variation in susceptibility to first infection existed and hypothymic nude mice were as susceptible to infection as intact mice. As determined by protection against death, vaccination with excretory/secretory products derived from immature F. hepatica was without effect in mice. It is concluded that "host protective antigens", at least for rats, were present in the excretory/secretory products of immature F. hepatica larvae.

Animals↗
PubMed1979

Hybridoma antibody immunoassays for the detection of parasitic infection: development of a model system using a larval cestode infection in mice.

A prototype immunodiagnostic assay has been developed using chronic infection with the larval cestode, Mesocestoides corti, as a model system in mice. The assay is highly sensitive, it appears to be absolutely specific for M. corti infection, and is based on the inhibition of binding (by sera from infected mice) of a radiolabelled anti-M. corti hybridoma antibody to a crude M. corti antigen extract. The hybridoma antibody binds to living M. corti larvae and is an IgG1 protein. In large scale experiments no false positives were detected and the only M. corti-infected mice not detected by the assay were hypothymic nude (nu/nu) mice. Only limited success has been achieved in attempts to convert the assay to one not requiring parasite antigen and based on the inhibition of binding of radiolabelled anti-parasite hybridoma antibody and a large pool of anti-idiotype antiserum. Monoclonal antibodies derived from anti-parasite antibody-secreting hybridoma cell lines will be of particular use in the development of new, highly specific, immunodiagnostic reagents for the detection of parasite infection, exposure and disease.

Animals↗
PubMed1979

IgG1 hypergammaglobulinaemia in chronic parasitic infections in mice: magnitude of the response in mice infected with various parasites.

Mice chronically infected with 3 metazoan and 1 protozoan parasite contain in their circulation levels of IgG1 which are increased over the levels in uninfected mice by at least 10x. In the case of infection with the larval cestode, Mesocestoides corti, the serum IgG1 concentration can reach greater than 50 mg/ml and, with a half-life of less than 2 days, the number of cells engaged in IgG1 production is approximately 2 x 10(8). The IgG1 hypergammaglobulinaemia is not seen in infected hypothymic nude mice. Biosynthetic labelling studies with organ and tissue cultures established that in two of the chronic infections the organs principally involved in IgG1 synthesis were those pathologically involved or those "in line" for antigen capture: i.e. liver and spleen in the case of M. corti which is located in the liver and the peritoneal cavity, and various intestinal lymph nodes in the case of the gut-dwelling nematode, Nematospiroides dubius. This apparently exaggerated response to chronic parasitic infection is of interest simply because of the potential magnitude of the effect and the fact that it involves an Ig isotype with very poorly defined biological function.

Animals↗
PubMed1979

IgG1 hypergammaglobulinaemia in chronic parasitic infections in mice: evidence that the response reflects chronicity of antigen exposure.

The IgG1 molecules in the sera of IgG1 hypergammaglobulinaemic mice chronically infected with the larval cestode, Mesocestoides corti, are a heterogeneous population. Although antibodies to M. corti are present, the question of whether a minority or majority of the serum IgG1 molecules has anti-parasite reactivity remains open. The splenic PFC response to an intravenous injection of SRBC in M. corti-infected mice does not consist of an unusually high proportion of IgG1 anti-SRBC PFC. Moreover, the adoptive anti-DNP PFC response of spleen cells from M. corti-infected mice to DNP-M. corti is not biased towards IgG1 antibody production. Since IgG1 hypergammaglobulinaemia is seen in mice with chronic, "high-dose" infections, an attempt has been made to simulate chronic antigenic exposure with SRBC in uninfected mice. A split, high-dose regime of SRBC injections leads to a high number and high proportion of IgG1 anti-SRBC PFC in the spleen in three strains of mice. The results suggest that the extraordinarily high levels of IgG1 seen in the sera of mice chronically infected with the metazoa, M. corti and Nematospiroides dubius, reflect persistent, high-dose, "strong", T cell-dependent stimulation of the B cell system.

Animals↗