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Biomedical subjects

A Cooke

Publications and source records attributed to A Cooke.

At least 145 records · Page 8Linked to original sources
PubMed1988

X chromosome deletions detectable by flow cytometry in some patients with steroid sulphatase deficiency (X-linked ichthyosis).

The X chromosomes of individuals with isolated steroid sulphatase deficiency (X-linked ichthyosis) from ten families were studied by flow karyotype analysis. In four of the families, a small but significant reduction in the relative fluorescence of the X chromosome was detected consistent with a deletion ranging from 1.2%-3.4% of the X and amounting to a DNA loss of 1.9-5.2 million base pairs. In the remaining six families, three of which demonstrated a molecular deletion of the DNA sequence GMGX9 (DXS237), the relative fluorescence of the X chromosomes was indistinguishable from normal. The phenotypes of those with X deletions detectable by flow cytometry were similar to those of patients without such deletions.

Chromosome Deletion↗
PubMed1988

Delay in onset of insulitis in NOD mice following a single injection of CD 4 and CD 8 antibodies.

Non-obese diabetic (NOD) mice injected with 500 micrograms of both CD 4 and CD 8 antibodies at 5 weeks of age did not develop insulitis until 18 weeks of age, 12 weeks later than the onset of insulitis in parallel uninjected controls. Injection with both antibodies at 2 weeks or 4 weeks of age protected from insulitis for 10 and 14 weeks respectively. Insulitis was not delayed in onset in animals injected at any age with one antibody only, or who were injected at birth. Injection after the onset of insulitis achieved partial but incomplete clearing of islet infiltrates. Salivary gland infiltrates (sialitis) were also delayed in animals injected with both CD 4 and CD 8 antibodies though the degree of protection was less pronounced than that seen for insulitis.

Age Factors↗
PubMed1988

Interferon-gamma induces class II MHC antigens on RINm5F cells.

The ability of recombinant interferon-gamma (rIFN-gamma) to induce major histocompatibility complex (MHC) antigen expression in the rat insulinoma cell line RINm5F was investigated. The cells were stained with monoclonal antibodies specific for rat class I and class II MHC antigens. RINm5F cells endogenously expressed class I antigens; this was enhanced by rIFN-gamma. Class II antigens could not be detected on RINm5F cells, but both I-A and I-E were induced by rIFN-gamma.

Adenoma, Islet Cell↗
PubMed1988

Distinct macrophage subpopulations in pancreas of prediabetic BB/E rats. Possible role for macrophages in pathogenesis of IDDM.

Use of monoclonal antibodies directed against rat macrophages and serial pancreatic biopsy in the prediabetic period have enabled us to document the involvement of macrophages in the pancreatic events leading to onset of diabetes in the spontaneously diabetic BB/E rat. A few weeks before onset of disease, there is marked recruitment and accumulation of ED1+ macrophages at periductal and perivascular locations adjacent to noninfiltrated islets. These recruited cells, distinct from the resident ED2+ tissue macrophages, then infiltrate the islets. Infiltration of the pancreas by ED1+ macrophages is therefore a very early event in the prediabetic period and suggests a possible role for macrophages in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) in this animal model.

Animals↗
PubMed1988

An investigation of the nature of induced suppression to experimental autoimmune thyroiditis.

When mice are pretreated with soluble mouse thyroglobulin (MTg), subsequent induction of autoantibodies in experimental allergic thyroiditis (EAT) is suppressed. This suppression can be reproducibly transferred to low-level irradiated syngeneic recipients and is specific for MTg. Injection of normal cells does not reverse this tolerance, also indicative of an active suppression. Neither can the induced unresponsiveness be overcome by immunization with cross-reactive xenogeneic Tg; although antibodies are formed which will bind to MTg, these are not to epitopes to which antibodies are normally formed on immunization or towards which tolerance is induced. This implies that tolerance might be induced at least at the B-cell level, a view supported by the inability of DNP to provide a new carrier to break tolerance when conjugated to MTg. The poorer response to DNP in these animals also suggests anergy of the MTg-specific T helpers.

Animals↗
PubMed1988

Epitope specificity of spontaneous and induced thyroglobulin autoantibodies in the rat.

We have investigated the epitope specificities of rat thyroglobulin (Tg) autoantibodies arising either spontaneously in BB hybrid and BB rats or following induction in normal rats with thyroglobulin and adjuvant. Using a panel of thyroglobulins from different animal species it was possible to identify three different patterns of reactivity. These were: 1) recognition of all species of thyroglobulin; (2) recognition restricted to rat and mouse thyroglobulins and 3) recognition biased towards dog, rat and mouse thyroglobulins. Furthermore, using human thyroglobulin manifesting different levels of iodination, it was possible to show that sera with recognition pattern 1 recognized the iodination site of thyroglobulin and that this was inhibitable by thyroxine. Taken together these data provide evidence of restricted epitope recognition by Tg autoantibodies in the rat.

Animals↗
PubMed1988

Clinical specialist head nurse: managing toward primary nursing.

What is the role of the head nurse on a primary nursing unit in psychiatry? What if that head nurse is also a clinical specialist in psychiatric nursing? And what if this is happening in a small regional hospital where the concept of primary nursing is new, inpatient psychiatry is new, and there is only one clinical specialist in the hospital. The author discusses the clinical specialist in a management position and the benefits inherent in such a joint appointment.

Hospitals, Psychiatric↗
PubMed1988

The relationship between induced and spontaneous autoantibodies in MRL mice: the role of Ly-1 B cells?

The murine response to bromelain-treated mouse red blood cells (BrMRBC) is derived from Ly-1 B cells. It has been proposed that this B-cell subset produces a variety of other autoantibodies and is elevated in autoimmune mouse strains. We have studied the ability of MRL lpr/lpr and the non-autoimmune congenic MRL +/+ mice to make autoantibodies to BrMRBC and immunoglobulin (rheumatoid factors, RF). Following lipopolysaccharide (LPS) stimulation we found the numbers of autologous plaque-forming cells (PFC) to be low in both lpr and MRL +/+ mice, suggesting low Ly-1 B-cell numbers. This observation is consistent with the view that Ly-1 B cells in the mouse may not give rise to pathologically relevant RF.

Animals↗
PubMed1988

Heterogeneity in rheumatoid factor isotypes and specificities in MRL mice.

MRL/lpr mice spontaneously develop an arthritis which, in several respects, is similar to human rheumatoid arthritis, including joint inflammation and circulating rheumatoid factors. In human disease, circulating IgM rheumatoid factor (RF) predominates but, surprisingly, in these mice we have detected much more IgA rheumatoid factor. This IgA rheumatoid factor has a major specificity for IgG2a, but heterogeneity in binding specificity was seen between different mice. IgG rheumatoid factors were determined in a heterologous mouse IgG assay, in which each subclass of rheumatoid factor was tested for its ability to bind to the remaining IgG subclasses. Rheumatoid factor activity was detected in all the IgG subclasses, but particularly elevated levels were seen in IgG3 and IgG1. Both the levels and specificities of IgG rheumatoid factors were markedly different between each mouse.

Animals↗
PubMed1987

Mapping the testis determinants by an analysis of Y-specific sequences in males with apparent XX and XO karyotypes and females with XY karyotypes.

A number of patients with paradoxical sex chromosome complements (so-called XY females, XX and XO males) have been investigated with a series of 19 Yp and 4 Yq DNA probes to establish which region of the Y is essential for male sexual differentiation. Of the 23 XX males, 18 possessed one or more Yp probe sequences with only 5 lacking such sequences. Of 9 XY females examined, only one showed evidence of a deletion in Yp occurring either as a result of X-Y interchange or interstitial deletion. This suggests that the majority of XY females are not commonly deleted for those Y sequences which are found to be transferred to the X in XX males. The DNA of two XO males both contained different portions of the Y. From a comparison of the patterns of Yp sequences in these patients, it has been possible to elaborate a model of Yp in terms of the order of probe sequences and to suggest a location for the testis determining region in distal Yp.

Chromosome Deletion↗
PubMed1987

Manipulation of idiotype networks in autoimmunity.

The spontaneous occurrence of anti-idiotypes associated with the amelioration of disease activity in some autoimmune disorders encourages the view that one may be able to develop a therapeutic strategy based upon manipulation of idiotype networks. Attempts to abrogate autoimmunity by using heterologous anti-idiotype reagents have been rather disappointing and there may well be an expansion of idiotype-negative antibody clones. We argue that idiotypic reagents based on T cells or antibodies derived from the species being treated are more likely to lead to success because they interact more profoundly with the individual's own networks than do heterologous antibodies.

Animals↗
PubMed1987

High efficiency antigen presentation by thyroglobulin-primed murine splenic B cells.

B cells primed in vivo with mouse or rat thyroglobulin present these antigens at very low concentrations to CH9, an Ly 1+2- T cell hybridoma specific for mouse and rat thyroglobulin. Presentation measured by interleukin 2 release from CH9 is sensitive to treatment with a monoclonal antibody eliminating splenic B cells but is unaffected by anti-Thy-1.2 or 33D1 (which destroy T cells and dendritic cells, respectively). Presentation is specific for the priming antigen and is blocked by preincubation of the B cells with sheep anti-mouse F(ab')2. We suggest that in this system, primed B cells present thyroglobulin and that this may represent a means by which an initial triggering event priming both B and T cells could allow maintenance of autoreactive responses in vivo in the presence of low concentrations of circulating antigen.

Animals↗
PubMed1987

Cytotoxicity of tumor necrosis factor for thyroid epithelial cells and its regulation by interferon-gamma.

The FRTL-5 line of differentiated rat thyroid epithelial cells was shown to be sensitive to the cytotoxic action of recombinant tumor necrosis factor. The sensitivity of the cells varied with the conditions of culture. It was markedly increased by preincubation with recombinant interferon-gamma, and the magnitude of this enhancement was affected by the presence of thyroid-stimulating hormone. The increased susceptibility of the cells to the cytotoxicity of tumor necrosis factor was clear as early as 2-4 h after the addition of interferon-gamma and greatly preceded the induced expression of major histocompatibility complex class II antigen. Since cells secreting interferon-gamma and tumor necrosis factors may co-exist in inflammatory infiltrates, our observations suggest that these factors may be early mediators of cell destruction in autoimmune thyroid disease.

Animals↗
PubMed1987

Class-II and IL2 receptor positive cells in the pancreas of NOD mice.

The aberrant expression of Class-II molecules on pancreatic B cells in Type 1 (insulin-dependent) diabetes is still a matter of debate. In order to verify if Class-II molecules are expressed on islet cells in the NOD mouse we have studied 21 female mice of different ages (5 to 22 weeks). Serial cryostat pancreas sections were stained with monoclonal rat antibodies against Class-II antigens (P7/7) and the IL2 receptor (AMT-13). Our results show no Class-II expression by endocrine cells at any age, whereas about 25-32% of mononuclear cells infiltrating the islets were Class-II positive, and only 6-9% were IL2 receptor positive. No staining, except of occasional tissue macrophages, was observed in the pancreas of BALB/c, CBA or B10.SCSN mice. Our data are in contrast with those recently published and therefore the reality of expression of Class-II molecules by islet cells of NOD mice should be viewed with caution.

Animals↗
PubMed1987

The potential of family flow karyotyping for the detection of chromosome abnormalities.

Chromosomes from the mother, father, and child of nine families were stained with ethidium bromide and analysed in flow. These flow karyotypes on average resolved separately the homologues of 4.8 of the offspring's chromosomes. A homologue's relative DNA content (calculated from the flow karyotype) was found to be an accurate marker which could be used to trace that chromosome in a family. In this way the parental origin of 74.4% of the offspring's resolved homologues was determined. In the karyotypically normal families studied no chromosome was found in a child which was clearly different from a homologue present in one of the parents. Using parental flow karyotypes to identify familial heteromorphisms, a number of dysmorphic children were studied in an attempt to detect small "de novo" abnormalities. Although no chromosome abnormality was detected in these cases, the usefulness of family studies was illustrated. In one family a large chromosome 4 homologue was found in the child and this was shown to be similar to one found in the father, suggesting an inherited heteromorphism rather than a clinically significant duplication. Flow analysis of the parents of a patient diagnosed cytogenetically as having an interstitial deletion of the X chromosome revealed the abnormality to be a "de novo" 3;X translocation. It is suggested that flow karyotype analysis in families has potential for the detection of chromosome rearrangements at the limits of resolution of conventional cytogenetics.

Chromosome Aberrations↗
PubMed1987

The role of autoantigen in autoimmunity.

Autoimmunity in disease is driven by autoantigen. Cell surface molecules may stimulate autoreactive T-helpers if class II MHC is expressed; special factors may predispose to the ease of class II induction. Soluble autoantigens may be focused by primed B cells and processed for presentation to T cells. Autoantigenicity may be influenced by metabolic events: (a) Poorly iodinated thyroglobulin does not induce thyroiditis, and (b) IgG in rheumatoid arthritis has galactose deficient Fc oligosaccharides. Glycosylation defects may prove to have wide implications.

Animals↗