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Biomedical subjects

A Cooke

Publications and source records attributed to A Cooke.

At least 181 records · Page 10Linked to original sources
PubMed1985

Effects of low doses of cyclophosphamide and low doses of irradiation on the regulation of induced erythrocyte autoantibodies in mice.

This paper describes some of the characteristics of a suppressor cell which is capable of regulating a rat RBC-induced autoantibody response against mouse RBCs. This cell, which appears to function as an inducer of suppression on transfer to naive recipients, is sensitive to low doses of cyclophosphamide, and its generation is affected by low doses of irradiation. However, the recipients of these cells are insensitive to cyclophosphamide treatment, suppression still being induced in such animals.

Animals↗
PubMed1985

Autoreactive T-cell lines specific for mouse thyroglobulin.

Autoreactive T-cell specific for mouse thyroglobulin have been established and characterized. These Lyt 1+ T cells proliferated specifically in response to thyroglobulin presented by syngeneic irradiated spleen cells. The antigen-presenting cell requirements of these autoreactive T cells appeared to be the same as those for foreign antigen (PPD) reactive T cells. All lines tested required antigen-presenting cells compatible at the I-A subregion of the H-2 complex. Both T-cell types responded to antigen presented by peritoneal cells and splenic dendritic cells, but only gave optimal responses when whole spleen cells were used. The cross-reactivity patterns of responses to mouse, rat, pig and human thyroglobulins indicated that at least two different epitopes could be recognized by the autoreactive T cells. Furthermore, these epitopes appeared to be different from those recognized by the majority of serum autoantibodies to mouse thyroglobulin.

Animals↗
PubMed1985

Hepatic metabolic function in patients receiving long-term methotrexate therapy: comparison with topically treated psoriatics, patient controls and cirrhotics.

Standard biochemical liver function tests and the clearances of antipyrine and indocyanine green have been compared in psoriatic patients taking methotrexate, psoriatic patients on topical treatment, patient controls and patients with hepatic cirrhosis. The methotrexate-treated patients showed significant elevations in alkaline phosphatase (p less than 0.025) and gamma glutamyl transpeptidase activities (p less than 0.05) compared to topically treated psoriatics and patient controls. The clearance of antipyrine was reduced in the methotrexate treated group but not significantly (p less than 0.1 greater than 0.05). In contradistinction, the weight-adjusted clearance of indocyanine green was significantly impaired in the methotrexate group in comparison with the topically treated psoriatics (p less than 0.01). The clearance of both antipyrine and indocyanine green were markedly lowered in the cirrhotics (p less than 0.001 against all other groups). These data suggest that the serial measurement of alkaline phosphatase and indocyanine green clearance may provide a non-invasive indicator of the development and progression of methotrexate-related liver injury.

Aged↗
PubMed1985

Suppression of induced erythrocyte autoantibodies is dependent on Lyt 1 cells.

When normal mice are immunized with rat RBC, autoantibodies to mouse red cells and antigen-specific suppressor cells are generated. Suppressor cell activity is found in T-enriched populations and suppresses only the induction of autoantibody, not ongoing or secondary autoantibody responses. Using antibodies lytic for either B cells or distinct T-cell subpopulations, we are able to show that suppression is dependent on the presence of Lyt 1+ T cells.

Animals↗
PubMed1985

Partial cross-reactivity by suppressor cells induced during different experimental autoimmune diseases.

Following injection of rat red cells, mice develop anti-red cell autoantibodies and subsequently suppressor T cells specific for these. Likewise, following recovery from non-lethal malaria, they develop suppressor T cells which suppress the anti-lymphocyte autoantibodies induced by lethal malaria parasites. Neither type of suppressor cell affected non-autoantibody components of the response, nor a response to sheep red cells. However, there was variable but significant cross-suppression of the respective autoantibody responses by both types of suppressor cell. Possible reasons for this unexpected cross-reaction are discussed.

Animals↗
PubMed1984

Defective regulation of erythrocyte autoantibodies in SJL mice.

When SJL mice are hyperimmunized with rat red blood cells (RBC), tolerance to self is readily broken and these animals develop a high autoantibody response to their own RBC. However, these mice also fail to generate those antigen-specific suppressor cells which normally regulate this induced autoantibody response.

Animals↗
PubMed1984

Mitogenic effects of glycolipoprotein extract from Pseudomonas aeruginosa.

Glycolipoprotein extracted from the extracellular of slime of Pseudomonas aeruginosa has been tested for its ability to cause murine spleen cells to proliferate and differentiate. The extracted glycolipoprotein was found to be mitogenic for a subpopulation of murine B cells. It also caused an increase in the number of specific antibody forming cells in vitro. The activity of this extract was sensitive to low doses of cyclosporin A. These findings may be important in understanding the mechanism(s) of host resistance to this organism.

Animals↗
PubMed1983

The differential effect of 2-deoxyguanosine on concanavalin A-induced suppressor and cytotoxic activity.

The effect of 2-deoxyguanosine (dGuo) on the generation in vitro of nonspecific suppressor cells in murine spleen cell cultures by concanavalin A (Con A) is examined. The experiments indicate that dGuo abrogates the generation of nonspecific suppressor activity by lectin stimulation of murine spleen cells. When comparisons were made between the effect of this nucleoside on the generation of suppressor and cytotoxic cells by Con A stimulation of murine spleen cells, it was found that dGuo only affected the generation of suppressor cells. The development of lectin-stimulated cytotoxicity was not affected by dGuo. In addition it was found that dGuo does not affect the NK activity of murine spleens.

Animals↗
PubMed1983

Functional evaluation of murine allogeneic T lymphoblasts separated by Vicia villosa lectin positivity.

Mixed-lymphocyte culture-stimulated cells have been fractionated by their ability to bind the lectin Vicia villosa (Vv) and assessed for their cytolytic and suppressor activity in vitro. Vv positive and negative cells were separated either by cell affinity chromatography using Vv-Sepharose 6MB chromatography or by electronic cell sorting with FITC-Vv. Both populations expressed marked cytolytic and suppressor cell activity. Thus this lectin cannot be used to discriminate between these and other functional lymphoid cell population of blastoid cells binding the FITC-Vv appears following allogeneic stimulation; treatment with the immunosuppressive drug cyclosporin A, which affects cytotoxic cells preferentially, results in a considerable reduction of the Vv positive blastoid cells.

Animals↗
PubMed1983

Murine T cell suppression demonstrable in the absence of cytotoxicity and the effect of Cyclosporin A on this system.

In vitro culture of murine spleen cells in FCS without prior immunization or allogeneic stimulation leads to the development of spontaneous cytotoxicity. This cytotoxicity is not H-2 restricted and can affect any subsequent in vitro assays using syngeneic cells, especially if those assays include prolonged culture in FCS. Studies on murine spleen cells cultured in NMS, however, led to the detection of a suppressor system that did not display cytotoxic effects. Furthermore, it was found that this suppression, in contrast to the cytotoxicity and suppression generated during culture in FCS, was not sensitive to CYA. The suppressor cell may be an effector or an inducer of suppression and is sensitive to treatment with anti-Thy-1.2 and complement. It is suggested that some in vitro suppression is really due to cytotoxicity that may be directed toward FCS determinants adsorbed onto syngeneic targets.

Animals↗
PubMed1983

II. IgM-mediated enhancement: dependency on antigen dose, T-cell requirement and lack of evidence for an idiotype-related mechanism.

Passive administration of monoclonal IgM anti-sheep red blood cell antibody 2 hr prior to a low dose of sheep red blood cells (SRBC) markedly enhances the specific antibody response. This IgM enhancement of the response to SRBC is highly reproducible and can furthermore be demonstrated in vitro. The time course and dose dependency of the response indicate that a critical antibody: antigen ratio is necessary for enhancement to occur. The IgM enhancement phenomenon has been demonstrated in several strains of mice, providing strong evidence against an idiotype-related mechanism.

Animals↗
PubMed1983

An in vitro cytotoxicity study of aldehyde-treated pig dermal collagen.

The cytotoxicity of aldehyde-treated collagen was assayed by measuring 3H-thymidine incorporation in adult human skin fibroblasts grown in tissue culture for 1 or 3 days in the presence of pig dermal collagen cross-linked with formaldehyde or glutaraldehyde. A comparison was also made with collagen preparations washed for 2 weeks either at 15 degrees throughout or partly at 15 degrees and partly at 37 degrees. Collagen treated with both formaldehyde and glutaraldehyde proved increasingly toxic with increase in the concentrations of aldehyde used. While the maximum toxic effect was observed after 1 day culture in formaldehyde-treated collagen, with thymidine uptake ranging from 4-48% of control values with 5-0.1% formaldehyde and a 15 degrees wash, the toxic effect of glutaraldehyde treatment increased with longer exposure and at 3 days thymidine uptake ranged from 3-40% of control values with 0.05-0.001% glutaraldehyde and washing at 15 degrees. Washing partly at 37 degrees significantly reduced toxicity, the differences in thymidine uptake as compared with washing at 15 degrees alone ranging from 34-50% with 1 and 0.3% formaldehyde respectively in 1 day cultures and from 14-37% with 0.02 and 0.005% glutaraldehyde in 3 day cultures. While fibroblasts actively grew and migrated when seeded on non-cross-linked collagen, only limited cell survival occurred on aldehyde-treated collagen.

Adult↗
PubMed1982

Independent segregation of NZB immune abnormalities in NZB x C58 recombinant inbred mice.

The study of NZB x C58 recombinant inbred mouse strains has revealed independent segregation of naturally occurring thymocytotoxic antibody and Coombs' anti-erythrocyte autoantibody. The lack of concordance of either of these autoantibodies with known heavy and light chain markers suggests that the autoantibodies are produced as a result of regulatory gene defects rather than alterations of antibody structural genes. Further, lack of concordance of the various autoimmune traits with each other or with H-2 or virus expression suggests that the autoimmune phenotype is not the result of a single "autoimmunity' gene but rather the outcome of faulty regulation of a number of independently segregating genes.

Aging↗
PubMed1982

Newly synthesised DNA in ageing human cells in culture treated with 4-nitroquinoline-1-oxide.

Two lines of normal human embryonic lung fibroblasts, MRC-5 and F2002, were serially subcultured until senescence was attained. When cells were exposed to varying concentrations of the chemical carcinogen 4-nitroquinoline-1-oxide (4-NQO), the rate of DNA synthesis (as measured by thymidine incorporation) was reduced in a dose-dependent fashion in cells from both early and late passages. While the overall amount of incorporation was considerably lower in old cells, the extent of inhibition caused by 4-NQO treatment (relative to appropriate controls) was not related to culture age. Alkaline sucrose density gradient analysis of newly synthesised DNA from cells pre-treated with 4-NQO failed to detect any significant variation in the size of labelled DNA from cells examined immediately after incubation with radioactive thymidine. The shift of this labelled material to high molecular weight in 4-NQO-treated cells also showed no age-related difference.

4-Nitroquinoline-1-oxide↗
PubMed1982

Dermal collagen implants.

The feasibility of using preparations of cell-free, fibrous dermal collagen, prepared by trypsin-treatment of skin, for the repair of soft body tissues has been examined both as subcutaneous implants and as a replacement for dermis in skin wounds in rats. Increased collagen stability, and suppression or reduction of tissue antigenicity in collagen heterografts, was achieved by crosslinking with weak solutions of aldehydes while still allowing implant recellularization and revascularization. Tritium-labelled collagen turnover studies have shown that maintenance of collagen mass in implants crosslinked with glutaraldehyde occurs primarily by inhibition of loss of original implant collagen. Some of the in vitro growth characteristics of human fibroblasts on animal collagen preparations are also described.

Animals↗