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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-mediated immune reactions, such as allogenic skin-graft rejection and PHA or MLC responses, and antibody synthesis against different antigens (sheep erythrocytes, Brucella antigen, bovine serum albumin) have been evaluated in rats suffering from experimentally-induced diabetes and in age-matched sham-treated controls. Cell-mediated immune reactions are strongly depressed diabetic rats. The cellularity of the thymus and of thymus-dependent areas and the number of peripheral blood lymphocytes is significantly reduced in pancreatectomized rats. Moreover, the immunological recovery from heavy cortisonization is also greatly impaired. Daily treatment with insulin may prevent these immunological alterations. By contrast, antibody responses in diabetic rats are not quantitatively altered in respect to either the number of antibody producing cells in the spleen or the circulating antibody titres. The discrepancy between the abnormality of cell-mediated immune reactions in diabetic rats and their physiological capacity to synthetize antibodies suggests that the sensitivity to an insulin-deprived environment is present only in a definite, although yet undefined, subpopulation of lymphoid cells rather than in the whole lymphoid system.
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PMID:Differential effect of pancreatectomy on humoral and cell-mediated immune responses. 14 53

The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been extablished by daily steroid treatment. Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and/or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis).
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PMID:Corticosteroids: clinical pharmacology and therapeutic use. 20 58

Growth and development of the thymus is dependent on secretions from the anterior pituitary, presumably growth hormone. Diabetes mellitus is known to reduce immunological competence. These studies compare the effects of bovine growth hormone (bGH) and the growth factor produced by plerocercoid larvae of the tapeworm, Spirometra mansonoides, on metabolism of lymphoid tissue, thymus and spleen, in hypophysectomized rats made diabetic with a single intraperitoneal injection of alloxan. Whereas the control diabetic-hypophysectomized rats gradually lost weight throughout the experimental period, both bGH and plerocercoid infection caused significant weight gains during the experimental period. The diabetic-hypophysectomized rats treated with bGH had significantly heavier thymuses and spleens than controls. Plerocercoid infection also caused significant increases in thymus weights. Both bGH and plerocercoids stimulated the metabolic activity of thymocytes isolated from treated rats and tested for their ability to incorporate 3H-thymidine into DNA in vitro. Thus, these growth factors have similar effects on the lymphoid tissue of diabetic-hypophysectomized rats which are apparently independent of normal insulin levels. Whether this anabolic effect is direct or mediated by somatomedin remains to be determined.
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PMID:Comparison of the effects of the growth factor produced by Spirometra mansonoides and growth hormone in diabetic-hypophysectomized rats: lymphoid tissue. 66 Mar 78

1. A patient with occasional attacks of hypoglycemia had levels of serum immunoreactive insulin persistently fifty to one-hundred times the normal value. Immunoelectrophoresis revealed presence of monoclonal IgG in his serum. The patient's diagnosis was established as paraproteinemic lymphoid and plasmocytic reticulosis proximate to multiple myeloma; insuloma was not found. 2. On gel filtration of native serum, only part of the total immunoreactivity was found in the elution position of crystalline insulin; the major part emerged in the early fractions together with the large proteins. After acidification of the serum, however, practically the entire immunoreactivity was recovered in ethanol extracts and proved to be "little insulin" on gel filtration. Only, "little insulin" was also detected after gel filtration of serum incubated with urea. 3. It is suggested that the large component with insulin immunoreactivity obtained in gel filtration of native serum is an insulin-protein complex. The nature of the presumed complex is not clear. It is not a complex of the antigen-antibody type. Insulin "trapping" by monoclonal gamma globulin is considered.
Diabetes 1975 Feb
PMID:Inordinately high levels of serum immunoreactive insulin in monoclonal immunoglobulinemia (on the problem of "big, big insulin"). 112 9

The evolution of destructive and restorative alterations was morphologically followed up in 82 tuberculotics that died of non-tiberculous diseases. In the majority of the deceased, the restorative alterations were observed with manifested mesenchymal and immunologic reactions with morphological peculiarities as in the treated with anti tuberculous remedies. The destructive alteration are clearly manifested and the restorative manifestations are depressed in tuberculotics with non-treated diabetes and osteomyelitis treated with cortison. In a negligible part of the patients died of non-tuberculous diseases, a reactivation of the foci developed around the fibrocaseous lung foci, tracheobronchial lymph nodes, kidneys and suprarenals, manifested with filamented neutrophyils in the calcified and caseous matter, fresh necrosis, tubercula, specific granular tissue, friable capsule with appearance of lymphoid cells and specific granular tissue.
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PMID:[Morphological characteristics of the destructive and reparative changes in tuberculosis in those dying of nontubercular diseases]. 122 81

The clinical phenotype of Werner's syndrome (WS) includes short stature, premature cataracts, skin atrophy, osteoporosis, graying and loss of hair, neoplasia, diabetes mellitus, and arteriosclerosis. Cultured cells from patients with this autosomal recessive disorder exhibit chromosomal instability and a markedly reduced replicative lifespan and growth rate. To elucidate the cell cycle alterations associated with the growth deficit, we continuously labeled lymphoid cell lines from five WS patients and from four healthy adult controls with 5-bromodeoxyuridine. Bivariate Hoechst 33258/ethidium bromide flow cytometry revealed a 2.4-h prolongation in the minimal duration of the S phase of WS cells (P less than 0.005). Moreover, the fraction of proliferating cells irreversibly arrested in the S phase (5.4% vs 1.4% in controls) was significantly elevated in WS (P less than 0.001). Other cell cycle compartments were not significantly affected in WS cell lines. As a partial test of the hypothesis that the WS phenotype is due to a defect in DNA topoisomerase I (topo I) or DNA topoisomerase II (topo II) we exposed lymphoid cells from a healthy control to the topo I inhibitor camptothecin or to the topo II inhibitor 4'-(9-acridinylamino)methanesulfon-m-anisidine. The cell kinetic alterations elicited by these compounds differed from that exhibited by untreated WS patients. Thus, a primary defect in topo I or II is unlikely in WS. Our cell cycle results, however, provide important evidence that the biochemical genetic lesion is in fact expressed in lymphoblastoid cell lines, the most readily available cells from such subjects.
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PMID:Impaired S-phase transit of Werner syndrome cells expressed in lymphoblastoid cell lines. 132 51

Several features of the genetics and immunopathology of diabetes in the nonobese diabetic (NOD) mouse, which spontaneously develops type I diabetes, are shared with the human disease. Immunohistochemical studies support the concept that T lymphocytes are the major components of inflammatory cells in the pancreatic islets and these cells may play a critical role in the destruction of the beta cells leading to diabetes. Therefore, we examined whether particular TCR-beta variable region genes were utilized by in situ islet T cells at different stages (4 - 5, 7, 14 - 15 and 16 weeks of age) of the disease process. Dot-blot hybridization was performed using RNA prepared from isolated islets, thymus, spleen, peripheral blood leukocytes and axillary lymph nodes of 10 to 15 mice pooled for each data point. Ten different TCR V-beta probes were used for the analyses. Limited usage of islet V-beta genes was observed only at the early prediabetic stage (4 - 5 weeks old) of the disease. At later stages of the disease (7 - 16 weeks old), no preferential usage of TCR genes was observed in the islets compared to those of peripheral lymphoid organs. These data suggest that only certain types of T cells bearing particular TCR V-beta genes may be responsible for initiating and perpetuating infiltration of immune cells into the islets and these particular T cells are only identified at the very early stages of the autoimmune process.
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PMID:In situ islet T cell receptor variable region gene usage in the nonobese diabetic mouse. 137 82

The authors studied the proliferative response of central and peripheral lymphoid organs of male BALB/c mice with alloxan diabetes to injections of a zinc-insulin suspension (1 u/mouse/24 hours) given for 1, 3, or 5 days. Insulin therapy failed to compensate the diabetes completely, but normalized to a considerable measure the diminished proliferative activity of the young lymphoid cells of the thymus and bone marrow from the third day of the experiment. Autoradiographic study showed that the thymus of diabetic mice was marked by a significant reduction of the percentage of young lymphoid cells bearing insulin receptors on their surface. The results of the experiments point to insulin dependence of central lymphopoiesis in rats.
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PMID:[Lymphopoiesis in mice with alloxan diabetes in experimental insulin therapy]. 148 Apr 16

Transgenic mice have been used for analyses of cis-acting elements which are involved in the tissue-specific and developmental-specific expression, for analyses of physiological function of genes, or for the production of a human disease model. This approach is especially successful in the fields of immunology and oncology. Several years ago it was shown that the major histocompatibility complex (MHC) class II gene is identical to the immune response gene by demonstrating that the immune response can be restored by the new expression of class II molecules on immunocompetent cells. Recent evidence suggests that the class II molecule is involved in the generation of autoimmune disease, such as insulin-dependent diabetes mellitus (IDDM). The NOD (non-obese diabetic) mouse is shown to be a mouse model for human IDDM. Concerning the class II genes, the NOD mouse has two characteristic features, the lack of I-E and the presence of unique I-A. It is discussed how the role of class II molecules in the development of IDDM in the NOD mouse can be analyzed. In addition, the transgenic technique can be applied to the study of differentiation and oncogenesis of lymphoid cells. Factors or molecules that affect these processes will also be discussed.
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PMID:Transgenic mouse as a tool for the study of autoimmune disease: insulin-dependent diabetes mellitus. 161 97

Infusions of syngeneic T-cells, lethally damaged with ultraviolet A light (UVA) and 8-methoxypsoralen (8-MOP), have been reported to prevent or ameliorate a number of autoimmune diseases in humans and in animal models of autoimmune disease. We previously demonstrated that the combination of UVA/8-MOP, or deoxycoformycin and deoxyadenosine (dCF/dAdo), damaged human lymphoid cells by inducing DNA strand breakage and stimulating poly (ADP-ribosyl)ation. These cells subsequently underwent programmed cell death ("apoptosis"). These findings suggested a common mechanism of lymphocyte damage, and that in vitro treatment of T-cells with cCF/dAdo might substitute for UVA/8-MOP. This hypothesis was tested in a model of autoimmune diabetes in the NOD mouse. Young adult female NOD/Wehi mice were given 350 mg/kg cyclophosphamide (CP) on day 1 to induce rapid-onset diabetes and divided into five treatment groups. Four groups received approximately 50 x 10(6) syngeneic mouse splenocytes that had been treated with various cytotoxic agents. 27/40 (68%) of the CP-only control group and 14/30 (48%) of the group given untreated splenocytes developed diabetes. By contrast, only 2/20 (10%) mice of UVA/8-MOP and 3/23 (14%) of dCF/dAdo-treated splenocyte groups developed diabetes (P < 0.01). Diabetes in high spontaneous-diabetes incidence NOD/Lt female mice was also greatly reduced (4/8 untreated vs 1/7 treated; (< 0.05). We postulate that cytotoxic damage to activated splenic T-cells allows their recognition by host T-cells and results in a protective response against autoreactive cells as a form of T-cell vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of cyclophosphamide-induced and spontaneous diabetes in NOD mice by syngeneic splenocytes treated with cytotoxic drugs. 166 36


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