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A Cooke

Publications and source records attributed to A Cooke.

At least 163 records · Page 9Linked to original sources
PubMed1987

Interferon-mediated enhancement of thyroid major histocompatibility complex antigen expression. A flow cytometric analysis.

Epithelial expression of class II antigens encoded by the major histocompatibility complex (MHC) has been proposed as a means by which autoimmune thyroid disease may be initiated and maintained. We studied a rat thyroid epithelial cell line (FRTL-5), which constitutively expresses class I (OX18) but not class II (OX6 or OX17) determinants to quantify in vitro MHC antigen induction using flow cytometry. Recombinant rat gamma interferon (rIFN-gamma) induced dose-dependent expression of OX6 (I-A) antigen at greater than 48 h (maximum 80-90% of cells in culture at 100 U/ml), which was abrogated by DB-1, a monoclonal antibody to rat IFN-gamma. OX17 antigen (I-E) was also induced (86%) and OX18 (class I) markedly increased under these conditions. Other thyroid-active agents including the calcium ionophore A23187, dibutyryl cyclic AMP, thyroid-stimulating autoantibodies from Graves' disease patients (LATS), and TSH, caused no I-A induction. Supernatants from spleen cells stimulated with plant lectins (concanavalin A or phytohaemagglutinin), but not lectin alone, evoked substantial class II induction, which was inhibited by DB-1. These findings suggest that IFN-gamma is the central mediator of thyroid epithelial class II expression. FRTL-5 provides a powerful model for the analysis of thyroid MHC class II dynamics and a potential means of analysing the role of epithelial class II in autoimmune pathogenesis.

Animals↗
PubMed1987

Confirmation of a suspected 16q deletion in a dysmorphic child by flow karyotype analysis.

Cytogenetic examination of a dysmorphic infant with multiple congenital abnormalities revealed a possible de novo interstitial deletion in the long arm of chromosome 16. Conclusive proof of the deletion was obtained by flow karyotype analysis of the patient and both parents, which showed that the deleted segment was approximately 7000 kb in size.

Abnormalities, Multiple↗
PubMed1987

Pre-diabetes in the spontaneously diabetic BB/E rat: pancreatic infiltration and islet cell proliferation.

A cohort of BB/E rats derived from litters with a high and low incidence of IDDM was studied prospectively to examine the relationship between circulating autoantibodies, islet insulin secretion, pancreatic infiltration, and islet cell replication during the pre-diabetic period. Although a higher incidence of islet cell surface (ICSA) and insulin autoantibodies (IAA) was detected in the diabetes-prone than in the low diabetic-incidence BB/E rats there was no correlation between the two antibodies in individual animals. Moreover, ICSA, but not IAA, were associated with loss of first phase islet insulin release. Between 75 and 105 days of age the number of diabetes-prone rats with ICSA and impaired islet insulin secretory function increased. Over the same period, there was a concomitant increase in the proportion of diabetes-prone animals with pancreatic infiltration, and increased islet endocrine cell proliferation. All these interrelated phenomena were observed in diabetes-prone BB/E rats at a time when the animals were normoglycaemic.

Animals↗
PubMed1987

A cross-reactive idiotype on anti-DNA and lymphocytotoxic antibodies.

The possibility that shared idiotypes may be present on antibodies of different specificities was explored using sera from 13 patients with systemic lupus erythematosus. Eleven sera had anti-DNA and seven carried the 16/6 idiotype (ID). Two of the sera with 16/6 ID also had lymphocytotoxic antibodies, the activity of which was blocked by antibody to the 16/6 ID. Our studies reveal that 16/6 ID is present on two antibodies with different binding specificities.

Antibodies, Antinuclear↗
PubMed1987

Insulin autoantibodies, islet cell surface antibodies and the development of spontaneous diabetes in the BB/Edinburgh rat.

The presence of insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) was sought in two longitudinal studies, involving BB/Edinburgh rats of high (BB/E/H, n = 157) and low (BB/E/L, n = 61) susceptibility to diabetes development. Both studies were designed to correlate pancreatic morphology with cellular and humoral immunity. In Study I, groups of eight male and eight female non-diabetic rats of the BB/E/H line were killed at 15 day intervals from 30-105 days and plasma samples were obtained by cardiac puncture. In study II, 61 BB/E/H and 41 BB/E/L rats underwent pancreatic biopsy 1-3 times from 30 days of age until onset of diabetes or 150 days, plasma samples being taken from the tail vein at biopsy. Both studies revealed a higher prevalence for ICSA than IAA in BB/E rats. Whereas a highly significant association of ICSA with diabetes development was observed in study II (chi 2 = 8.30, P less than 0.005), IAA were associated with diabetes development only weakly (P less than 0.03, Mann-Witney U-rank test). No correlation between the presence of ICSA and IAA in individual rats was observed and IAA were not significantly associated with BB/E/H in preference to BB/E/L rats, although positive IAA values were significantly elevated in the former compared with the latter (P less than 0.01). These observations support the concept that IAA form part of a background of heightened autoimmunity against which frank diabetes develops in some animals.

Aging↗
PubMed1987

Immunological responses of the BB rat colony in Edinburgh.

Several immunological responses of the spontaneously diabetic BB rat colony in Edinburgh designated (BB/E) have been studied. The proliferative responses to Con A and LPS, ability to make IL-2 and to show NK activity have been studied using diabetic and non-diabetic BB/E rats and normal Wistar rats. Our data suggest that the diabetic animals in the BB/E colony do not have marked deficiencies in any of these parameters. Lymphopenia and depressed T-cell responses do not appear to be a prerequisite for the development of diabetes in the BB/E colony.

Animals↗
PubMed1986

Variable transfer of Y-specific sequences in XX males.

A series of twelve XX males and their relatives have been examined by Southern blot analysis with fourteen different Y recombinants. The pattern of Y sequences present shows considerable variation between XX males. Furthermore, on the basis of the terminal transfer model, anomalous patterns of Y sequences are evident in certain XX males in that sequences located as proximal Yp by means of a Y deletion panel are found to be present in the absence of distal sequences. These anomalies can be resolved by proposing that the order of Yp sequences varies in the population in the form of inversion polymorphisms in the Y chromosomes of normal males. Alternatively, it is necessary to invoke multiple recombination events between the X and Y chromosomes to explain the patterns of Y sequences in these XX males. Southern analysis on DNA prepared from flow sorted X chromosomes of XX males indicates that the Y sequences in these patients are linked to X chromosomes.

Chromosome Mapping↗
PubMed1986

Duchenne muscular dystrophy due to familial Xp21 deletion detectable by DNA analysis and flow cytometry.

We report two male cousins with Duchenne muscular dystrophy (DMD) in whom cytogenetic studies have shown a small interstitial deletion at Xp21. The lesion is readily detectable in patients and carriers by flow cytometry which indicates that approximately 6000 kb of DNA are deleted in each case. The DNA markers OTC, C7, and B24 are present in the deleted X chromosome but 87-8, 87-1, and 754 are absent. Despite apparently identical deletions one affected boy has profound mental handicap while the other is only mildly retarded. The results confirm the assignment of familial DMD to Xp21 and illustrate the value of flow cytometry in improving the precision of chromosome analysis. We have also undertaken flow cytometry in a cell line from a previously reported DMD patient with a de novo Xp21 deletion who had, in addition, chronic granulomatous disease, retinitis pigmentosa, and the McLeod syndrome. The results indicate that the amount of DNA deleted from the X is similar in both families despite the striking differences in phenotype.

Child↗
PubMed1986

Induction of class II MHC antigens in vitro on pancreatic B cells isolated from BB/E rats.

The ability of recombinant Interferon-gamma to induce class II expression in vitro on pancreatic islet B cells has been investigated by exposing islets isolated from BB/E and normal Wistar rats to Interferon-gamma and then staining successively with monoclonal antibodies specific for rat class II MHC antigens and insulin. Induction of class II expression was never observed on islet cells obtained from either normal Wistar rats or rats from the BB/E low diabetes incidence (less than 2%) subline. In contrast, pancreatic B cells from rats from the BB/E high diabetes incidence (60-70%) subline expressed class II antigen following culture with Interferon-gamma.

Animals↗
PubMed1986

Antibody-mediated modulation of the immune response.

We have studied the ability of monoclonal IgM and IgG antibodies to enhance or suppress immune responses and attempted to dissect the underlying mechanisms. Both IgM and IgG1 antibodies increased the rate of clearance of antigen from the circulation. Monoclonal IgM antibody to SRBC was found to specifically increase antibody responses, enhancement being insensitive to low doses of irradiation (150 R). IgM antibody specifically depressed the delayed hypersensitivity response to SRBC in vivo. Following administration of IgM in vivo, in vitro responses to SRBC were also enhanced. This in vitro enhancement appeared to depend on both T cells and B cells. In contrast, monoclonal IgG1 antibody to SRBC specifically depressed antibody responses in vivo. Such depressed antibody responses were also seen in vitro following IgG1 in vivo and did not appear to be due to the induction of suppressor T cells.

Animals↗
PubMed1986

Connective tissue abnormalities in MRL/1 mice.

Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal infiltrates of polymorphs or large mononuclear cells, or both, were seen both in synovial lining and subcutaneous tissue. Infiltrates were associated with vasculitis in some cases. Deposits of amorphous material were seen in and around joints and in foot pads. The material was more particulate and refractile than typical 'fibrinoid' and showed a positive Feulgen reaction. It was not surrounded by palisading cells and when seen in synovial tissue was not usually associated with changes in synovial lining cells. No obvious difference was seen between intra-articular and extra-articular lesions. Lesions in subcutaneous tissue occurred exclusively in the foot pads. Lymphocyte infiltration was not prominent at any site and no follicle formation was seen. Of two colonies studied, only one showed a significant increase in lining cell numbers in synovial tissue. Exercised animals had a similar distribution and severity of disease to those of matched controls. All lesions described were distinguishable from non-specific inflammatory lesions in normal control mice and MRL/++ mice on assessment of unmarked sections. The relation between these connective tissue lesions and the changes found in human chronic synovitis is discussed.

Animals↗
PubMed1986

Helper and suppressor activities of an autoreactive mouse thyroglobulin-specific T-cell clone.

An autoreactive T-cell clone, MTg9B3, specific for mouse thyroglobulin, has been characterized. This clone has properties consistent with it an being autoreactive T helper cell. It is I-A restricted, with a surface phenotype of Thy 1+, L3T4+, Ly2-, and produces a number of non-specific lymphokine activities following specific triggering with antigen. Furthermore, antigen-stimulated clone cells were capable of providing bystander help in SRBC-specific antibody responses. Surprisingly, MTg9B3 cells had a profound suppressive effect on thyroglobulin autoantibody responses in vitro.

Animals↗
PubMed1986

Immunological defects in SJL mice.

SJL mice are shown to be defective in their ability to develop suppressor cells following stimulation with Con A, a polyclonal T-cell activator. They make a normal proliferative response to this mitogen. In addition to this suppressor T-cell defect, the SJL mouse (unlike most mouse strains) does not develop a spontaneous antibody response to bromelain-treated autologous red blood cells (BrMRBC) in vitro. Although the SJL makes a normal proliferative response to LPS, antibody-forming cells against bromelain-treated autologous red blood cells are not increased following LPS in vivo nor does it manifest an increased response to SRBC or TNP. This may signify the presence of a functional B-cell defect in these animals. DBA mice are also shown, in this report, to have small numbers of antibody-forming cells to bromelain-treated autologous red blood cells but to be capable of responding to LPS in vivo with an increase in SRBC and TNP antibody responses.

Animals↗
PubMed1986

Cyclosporine affects the function of antigen-presenting cells.

The immunosuppressant drug cyclosporine (CsA) is known to affect T-cell function. We have studied the effect of CsA on the specific proliferative response of T-cell lines to antigen. In addition to blocking IL-2 release by specifically activated T-cell lines, CsA also affected the ability of irradiated spleen cells to present preprocessed antigen to T-cell lines. Irradiated spleen cells pulsed with antigen for 2 hr were able to stimulate a proliferative response in T-cell lines. Following a 2-hr pulse with CsA, antigen presentation by these irradiated spleen cells was reduced significantly, suggesting that CsA not only affects T cells, but also affects the function of antigen-presenting cells.

Animals↗
PubMed1985

Quantitative variation in cystic fibrosis-associated proteins in cystic fibrosis patients, carriers, and controls.

Serum samples from patients with cystic fibrosis (CF), obligate heterozygotes, and normal controls have been examined by isoelectric focusing (IEF). Our results suggest that cystic fibrosis protein (CFP) is a normal serum protein exhibiting quantitative variation primarily dependent on possession of the CF allele. It is concluded that detection of CFP by IEF is an inappropriate screening test for the CF gene due to lack of specificity.

Alleles↗
PubMed1985

Pre-diabetes in the spontaneously diabetic BB/E rat: lymphocyte subpopulations in the pancreatic infiltrate and expression of rat MHC class II molecules in endocrine cells.

Use of monoclonal antibodies specific for rat lymphocyte subsets and an anti-insulin marker has allowed us to document the following sequence of events leading to the development of clinical diabetes in this animal model. The first change observed in the pancreas is increased expression of MHC class II molecules on vascular endothelium and this precedes lymphocytic infiltration. Next, T cells of the T helper phenotype infiltrate the pancreas around blood vessels. Many of the infiltrating T cells show class II expression indicating that they are activated. A few cytotoxic and suppressor cells and B lymphocytes are also present and their numbers increase proportionately with rat age. Some macrophages are also seen. Finally, at a late stage class II MHC molecules can be detected in partially destroyed islets on beta cells which are still actively synthesising insulin. We have never observed expression of class II molecules on glucagon or somatostatin secreting cells which are invariably well preserved.

Animals↗