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Biomedical subjects

A Cooke

Publications and source records attributed to A Cooke.

At least 73 records · Page 4Linked to original sources
PubMed1995

In vivo activity and in vitro specificity of CD4+ Th1 and Th2 cells derived from the spleens of diabetic NOD mice.

CD4+ T cell lines were generated from the spleens of diabetic NOD mice against crude membrane preparations derived from a rat insulinoma. Adoptive transfer of these lines into neonatal mice confirms that overt diabetes is induced by gamma-IFN-secreting Th1 cells, whereas transfer of IL-4-secreting Th2 cells resulted in a nondestructive peri-islet insulitis. Analysis of the antigens recognized by individual T cell clones from the Th1 line included reactivity against an insulinoma membrane fraction enriched in proteins of approximately 38 kD. Immune responses to the same antigen preparation have been associated with T cell clones derived from human insulin-dependent diabetes mellitus. The specificity of Th2 cells includes reactivity to a fraction enriched in proteins of 30 kD. The data suggest that in insulin-dependent diabetes mellitus the balance between beta cell destruction, associated with intra-islet infiltration, and nondestructive (potential protective) peri-islet insulitis may depend on both the antigens recognized, and the prevailing cytokine environment.

Animals↗
PubMed1995

Comparative study of the protective effect afforded by intravenous administration of bovine or ovine insulin to young NOD mice.

Soluble bovine or ovine insulin given intravenously to female NOD mice shortly after weaning had a downregulating effect on several autoimmune parameters associated with insulin-dependent diabetes. The titer of spontaneous anti-insulin antibodies was reduced, insulitis was delayed and less severe, and only 25% of treated mice were diabetic at 30 weeks compared with 70% of untreated mice. An interesting paradox occurred in that bovine insulin, although poorly immunogenic in NOD mice and ineffective as a tolerogen for complete Freund's adjuvant-induced cellular and humoral responses to ovine insulin, was nearly as effective as immunogenic ovine insulin in protecting against diabetes and better than ovine insulin at downregulating spontaneous autoantibodies to insulin. Bovine and ovine insulins differ by only one amino acid on the A-chain loop, but whereas modulation of the induced response to ovine insulin appeared to be sheep-specific, modulation of the induced and spontaneous autoimmunity was achieved almost equally well by bovine or ovine insulin. We suggest therefore that modulation of the induced and spontaneous responses are dependent on different T-cell epitopes and that modulation of spontaneous autoimmunity appears to be governed by an epitope common to both insulins.

Amino Acid Sequence↗
PubMed1994

How can nurses build trusting relationships with people who have severe and long-term mental health problems? Experiences of case managers and their clients.

Despite the shift in recent policy toward people with severe and long-term mental health problems, there is considerable evidence that mental health nurses tend to prioritize clients with acute, neurotic or short-term problems and become demoralized when working with people with persistent needs and disabilities. Mental health nurses need to find ways of developing effective relationships with these people in order to offer a service which the client is not only willing to engage in, but takes an active part in, and which allows care providers to derive satisfaction from their work. Through 46 in-depth interviews with case managers (working specifically with people with long-term mental health problems) and their clients, this qualitative study provides some guidelines for mental health nurses working in this field. Analysis of the interviews revealed that both clients and case managers focused on the problems and strategies associated with developing and maintaining relationships with one another. Furthermore, the interviews suggested that case managers adopted a philosophy for working that enabled both clients and case managers to feel positive about the work. The principles of this value base, and the way it was used in the process of case management, are explored in this account.

Adult↗
PubMed1994

Mycobacteria precipitate autoimmune rheumatic disease in NOD mice via an adjuvant-like activity.

NOD mice spontaneously develop organ-specific autoimmunity and are widely used as a model for diabetes. NOD mice also exhibit some features of non-organ specific autoimmune rheumatic disease such as thymocytotoxic and anti-nuclear autoantibodies and they develop haemolytic anaemia in senescence. A single dose of 2.6 x 10(7) heat-killed Bacillus Calmette-Guerin (BCG) i.v. in 8-week-old NOD mice prevented diabetes but precipitated a syndrome similar to systemic lupus erythematosus (SLE), in which treated mice rapidly developed haemolytic anaemia, high titre anti-DNA and anti-Sm antinuclear autoantibodies, perivascular lymphocytic infiltration in the kidneys and glomerular immune complex deposition. Here, we examined the mechanism of action by which BCG precipitated rheumatic autoimmune disease in NOD mice. Two weeks after injection, reticuloendothelial cell function was dramatically increased in BCG-treated NOD mice. By 4 weeks, treated mice had a three- to four-fold increase in Mac-1+ and class-II+, B220-negative splenocytes and in vitro antigen-presentation capacity was enhanced two- to four-fold. In vivo responses to SRBC confirmed enhancement of DTH 4 weeks after BCG injection, consistent with an adjuvant-like activity.

Adjuvants, Immunologic↗
PubMed1994

Non-diabetogenic insulitis in NOD<-->B10.GD allophenic mice in spite of permissive class I MHC antigens.

Allophenic mice (embryo aggregation mouse chimeras) enable us to dissect the process of spontaneous autoimmunity under physiological conditions. Our previous experiments showed that the autoimmune process in allophenic mice of the NOD<-->C57B1/6 strain combination does not progress from insulitis to diabetes. One possible explanation for this protection is that H-2 Kd-restricted CD8+ T cells kill only NOD beta cells (Kd,Db) in the chimeric islets, while the B6 beta cells (Kb,Db) are spared from destruction. To test this hypothesis we analysed 22 NOD<-->B10.GD chimeras in which the class I MHC are shared by both parental strains. Therefore all the beta cells in these chimeras express H-2 Kd molecules. Ten allophenic mice were killed at 7 weeks and studied for early pathology. No evidence for intra-islet infiltration was obtained at this age, suggesting that the autoimmune process in NOD<-->B10.GD chimeras is slower than in NOD mice. Twelve chimeras were followed up for 1 year for disease development and all failed to progress to full-blown diabetes, despite the occurrence of intra-insulitis in six out of 12 mice. The lack of disease in NOD<-->B10.GD chimeras demonstrates that class I MHC chimerism does not account for diabetes resistance in NOD-allophenic mice.

Animals↗
PubMed1994

Diagnosis in Prader-Willi syndrome.

Thirty one patients with the putative diagnosis of Prader-Willi syndrome were reassessed clinically and by DNA analysis. Eleven patients were judged not to have Prader-Willi syndrome and 20 to have the condition. This was confirmed by DNA analysis in all but one case. The diagnosis of Prader-Willi syndrome, especially in early infancy, should be made with caution unless confirmed by molecular genetic studies.

Adolescent↗
PubMed1994

Renin gene restriction fragment length polymorphisms do not show linkage with preeclampsia and eclampsia.

OBJECTIVE: To investigate linkage between the renin gene restriction fragment length polymorphisms in families with a history of preeclampsia/eclampsia. METHODS: Nine Icelandic families with at least three affected females in two or three generations were investigated. DNA from lymphocytes was digested with the endonuclease restriction enzyme Bgl I and restriction fragments were transferred by Southern Blotting. Hybridisation was effected with the 32P-oligonucleotide-labeled diallelic genomic probe pHRnX 0.8. LOD scores were calculated by the Liped program for two forms of inheritance patterns. Affected sib pairs were analysed. RESULTS: Frequencies of the 9.0 kb and 5.0 kb alleles were 0.67 and 0.33, with no significant differences between affected females and spouses and combined LOD scores of -2 for recombination values of 3%. Allele sharing in affected sibs was not different from the expected random assortment. CONCLUSION: The linkage analysis provides evidence to exclude alteration of the renin gene in pregnancy as being directly responsible for the manifestations of preeclampsia or eclampsia in these families.

Alleles↗
PubMed1994

Studies on the thymus of non-obese diabetic (NOD) mice: effect of transgene expression.

The non-obese diabetic (NOD) mouse is a good model of insulin-dependent diabetes mellitus. Autoreactive T cells may play a fundamental role in disease initiation in this model, while disregulation of such cells may result from an abnormal thymic microenvironment. Diabetes is prevented in NOD mice by direct introduction of an E alpha d transgene (NOD-E) or a modified I-A beta chain of NOD origin (NOD-PRO or NOD-ASP). To investigate if disease pathology in NOD mice, protection from disease in transgenic NOD-E and NOD-PRO and partial protection from disease in NOD-ASP can be attributed to alterations in the thymic microenvironment, immunohistochemical and flow cytometric analysis of the thymi of these mouse strains was studied. Thymi from NOD and NOD-E mice showed a progressive increase in thymic B-cell percentage from 12 weeks of age. This was accompanied by a concomitant loss in thymic epithelial cells with the appearance of large epithelial-free areas mainly at the corticomedullary junction, which increased in size and number with age and contained the B-cell clusters. Such thymic B cells did not express CD5 and were absent in CBA, NOD-ASP and NOD-PRO mice as were the epithelial cell-free spaces, even at 5 months of age. Therefore the mechanisms of disease protection in the transgenic NOD-E and NOD-ASP/NOD-PRO mice may differ if these thymic abnormalities are related to disease.

Animals↗
PubMed1994

Mycobacteria precipitate an SLE-like syndrome in diabetes-prone NOD mice.

Non-obese diabetic (NOD) mice spontaneously develop organ-specific autoimmunity and are widely used as a model for diabetes. Aged NOD mice also exhibit some features of non-organ-specific autoimmune rheumatic disease such as anti-nuclear antibodies and late-onset haemolytic anaemia. Here, we report that a single dose of 2.6 x 10(7) heat-killed bacillus Calmette-Guérin (BCG) i.v. in 8-week-old NOD mice prevented diabetes but precipitated a syndrome similar to systemic lupus erythematosus (SLE). Treated mice developed haemolytic anaemia, anti-DNA and anti-Sm anti-nuclear autoantibodies and an increased severity of sialadenitis. Perivascular lymphocytic infiltration in the kidneys and glomerular immune complex deposition were also found. The action of BCG appeared to be mediated by an adjuvant-like activity as treated mice showed a substantial increase in reticuloendothelial cell function and enhanced antigen presentation capacity.

Anemia, Hemolytic, Autoimmune↗
PubMed1993

Active suppression induced by anti-CD4.

Treatment with a non-depleting monoclonal antibody to CD4 in the presence of mouse thyroglobulin (MTg) inhibits the development of murine autoimmune thyroiditis. This unresponsiveness was transferrable since such treatment generated a population of donor cells which could suppress the thyroiditis induced in lightly irradiated recipients by subsequent challenge with specific antigen. The suppression appears to be both antigen specific and antigen dependent and seems to discriminate between TH1 and TH2 helper subsets in that there is no significant effect on anti-MTg autoantibodies after challenge.

Animals↗
PubMed1993

The effect of bone marrow and thymus chimerism between non-obese diabetic (NOD) and NOD-E transgenic mice, on the expression and prevention of diabetes.

The non-obese diabetic (NOD) mouse is an established animal model of the autoimmune disease, insulin-dependent diabetes mellitus (IDDM). The NOD-E mouse is a transgenic mouse which expresses the I-E molecule (absent in NOD mice). Expression of I-E protects these mice from both insulitis and IDDM. We have investigated the possible mechanisms of this protection by constructing bone marrow, and combined bone marrow and thymus chimeras between NOD and NOD-E mice. Our data suggest that thymic epithelium may play no direct role in either protection against, or promotion of, IDDM. Protection from diabetes is provided either by NOD-E donor bone marrow or NOD-E recipient non-thymic radioresistant cells. The means by which protection may be achieved in this system are discussed.

Animals↗
PubMed1993

Prevention of diabetes but not insulitis in NOD mice injected with antibody to CD4.

Non-obese diabetic (NOD) mice were injected with a rat monoclonal antibody to CD4 from birth every two weeks through 6 months of age. These animals gained weight normally but < 11% of their spleen T cells were CD4+, compared with 28% of CD4+ in controls injected with polyclonal rat IgG. The reduction in CD4 cell percentage was associated with a reduction in the number of cells in the thymus and spleen following the injection. CD4+ cells which survived the injections were nevertheless able to enter cell cycle when stimulated by Con A. None of the CD4-treated NOD mice became diabetic by 6 months of age and none of the animals studied histologically at this time had insulitis. At 9 months of age (three months after stopping the CD4 injections) the mice made antibody to human IgG. At 1 year of age most of the male mice had insulitis, although none of the male or female mice had become spontaneously diabetic. Two thirds of animals injected with cyclophosphamide at 16 months became diabetic within 3 weeks. The results confirm that treatment with CD4 antibody in the first 6 months suffices to reduce the incidence of diabetes in NOD mice. The treatment does not prevent the subsequent development of insulitis in injected mice and does not prevent the accumulation of cells capable of causing overt diabetes after cyclophosphamide injection.

Animals↗