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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To compare the protective effects of IGF-1 and insulin on the autoimmune process of beta-cell destruction, permissive NOD recipients were adoptively transferred with 7 x 10(6) autoreactive T cells from diabetic NOD mice and then administered either 10 micrograms of rhIGF-1 or 0.5 unit of regular insulin subcutaneously twice daily for three weeks. The final incidence of successful transfers of diabetes observed at day 22 was significantly reduced in 1/12 mice (8.3%) treated with IGF-1, while diabetes was observed in 4/10 (40%) receiving insulin and 7/11 (63.4%) controls. A marked reduction of insulitis during histological analysis of the pancreatic glands of IGF-1 or insulin-treated mice was also observed. Non-diabetic mice treated with rhIGF-1 had a higher mean +/- SD percentage of intact islets (68.9 +/- 36% vs 10.7 +/- 13%, p < 0.01) and a lower percentage of severely infiltrated islets (5.7 +/- 9.8% vs 30.3 +/- 21%) than non-diabetic control mice. Insulin reduced islet-cell infiltration, though to a lesser extent, with a high percentage of normal islets (55.2 +/- 31%, p < 0.02). Some mice developed diabetes and severe islet-cell infiltration despite rhIGF-1 or insulin, thus indicating that some committed T cells were still able to invade islets and cause beta-cell destruction. To evaluate the effects of rhIGF-1 and insulin on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1, 2 mice injected into congenic NOD-N Thy-1, 1 mice were monitored three weeks after adoptive cell transfer. The percentage of Thyq-1.2+ T cells was significantly reduced in the spleen (10.8 +/- 1.3% vs 17.2 +/- 3.9%, p = 0.004) of rhIGF-1 treated mice as compared to the thymus (68.4 +/- 7.9% vs 72.87 +/0 6.2, p = 0.306). Similar experiments performed in mice treated with insulin revealed no significant differences in the percentages of Thy-1,2+ T cells compared to controls in the spleen (l4.3 +/- 1.4%), thymus (84 +/- 2.5%) or pancreatic lymph nodes (21.5 +/- 1.6% vs 23.4 +/- 1.5%) of treated animals. These results suggest that rhIGF-1, as compared to insulin, could influence T-cell trafficking to the lymphoid organs in addition to affecting beta cells. These findings may have important implications for new preventive strategies in human Type 1 diabetes mellitus.
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PMID:Effects of insulin like growth factor-1 and insulin on effector T cells generating autoimmune diabetes. 876 68

The number and the size of the Langerhans islets in the pancreata of most of investigated cases with diabetic foetopathy is increased (polynesia and macronesia). The B endocrine cells are immunoreactive for both insulin and IAPP, the reaction for IAPP being weaker in comparison with the controls. In one of the cases (the mother with long history of treated type 1 diabetes, who died during delivery) no presence of insulin-immunoreactive of PAF positive B cells is discovered. The reactivity for glucagon and somatostatin in the pancreata with diabetic foetopathy is found to be similar to the controls. In the vicinity of some islets lymphoid cell infiltrations are observed.
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PMID:[Immunohistochemical studies of the pancreas in newborns with diabetic fetopathy]. 896 31

Previous studies have shown that anti-gamma-interferon (IFN-gamma) antibody reduces the frequency of autoimmune IDDM in the DP-BB rat. We tested the effects of systemically administered recombinant rat IFN-gamma in both DP-BB and DR-BB rats. Unexpectedly, IFN-gamma markedly reduced the incidence of IDDM as compared with control rats when administered six times per week at a dosage of 280,000 U between ages 30-35 to 105 days or ages 60-64 to 105 days. A lower dosage (28,000 U on alternate days) was also protective when administered to DP-BB rats between birth and age 60 days. However, long-lasting protection against IDDM development over the 1-year study period was achieved only by the highest dosage of IFN-gamma administered from age 30 to 105 days. Ex vivo production of tumor necrosis factor-alpha from splenic lymphoid cells (SLCs) and peritoneal macrophages of the rats treated with IFN-gamma was comparable with that of controls; however, SLCs from the IFN-gamma-treated animals secreted lower amounts of IFN-gamma after stimulation with concanavalin A. IFN-gamma treatment also markedly reduced the frequency of phenotypically activated SLC-expressing class II antigens and interleukin-2 receptor. Finally, in agreement with the observed antidiabetogenic effects, exogenously administered IFN-gamma induced neither insulitis nor IDDM development in DR-BB rats, a subline of DP-BB rats in which autoimmune diabetes rarely occurs spontaneously but can be induced by administration of polyinosinic-polycytidilic acid.
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PMID:Paradoxical antidiabetogenic effect of gamma-interferon in DP-BB rats. 942 71

Inflammation represents the consequence of capillary dilation with accumulation of fluid (edema) and the immigration of leukocytes. By the end of the last century, Metchnikoff noted the power of certain blood cells to move toward bacteria and foreign substances and ingest them. In fact, leukocytes adhere to the vascular endothelium, and subsequently leave the circulation by transendothelial migration driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to endothelium, basement membranes, and other surfaces on which they crawl is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation can become chronic. The acute process, characterized by neutrophil infiltration and edema, gives way to a subsequent predominance of mononuclear phagocytes or lymphocytes. Insulin-dependent diabetes mellitus is the result of organ-specific autoimmune destruction of the insulin secreting beta-cells in the pancreatic islets of Langerhans. It has become evident that diabetes mellitus is a multifactorial disease caused in part by infiltrating T-lymphocytes, comparable to situations of inflammation. After presentation of the different effectors of the immune system and their fluxes through the body, this review will propose a general model of adhesion between leukocytes and endothelial cells. It will emphasize how the homing specificity of lymphocyte subsets to different lymphoid organs is ensured, and how leukocyte migration to sites of inflammation is regulated. Finally, general therapeutic perspectives based on adhesion molecules leading to cure or prevention of chronic inflammation will be discussed.
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PMID:Basic mechanism of leukocyte migration. 949 98

Insulin dependent diabetes mellitus type I. (IDDM) is often connected with other autoimmune diseases. The most frequently concomitant disease is autoimmune thyroiditis. The authors present the results of the observation of 33 patients. The age of patients at the beginning of the study was 39.5 (24-65) years (median + confidential intervals). In all these patients, there were performed the assessment of thyroid stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (AbTPO) and TSH receptor antibodies (TRAK). An ultrasound examination and percutaneous aspiratory biopsy were performed in all patients. The control examination was realised 5 years later. In 1991, primary hypothyroidism due to lymphoid thyroiditis in 12.1% and autoimmune hyperthyroidism in 3% of all patients were found. During the observation period 2 patients died. In 1996 the diagnosis of primary hypothyroidism in 9.6% and M. Graves-Basedow in 3% of all patients were confirmed. Thyroid peroxidase antibodies have been positive in 33.4% of all patients with primary hypothyroidism and they correlated with ultrasound and cytology findings. (Tab. 3, Ref. 13.)
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PMID:[Autoimmune thyroid disease in patients with type 1 diabetes mellitus]. 958 75

Immune responses are best initiated in the environment of lymphoid tissues wherein circulating lymphocytes enter by interacting with endothelial adhesion molecules. In type 1 diabetes, immune responses against pancreatic islets develop, but the environment in which this occurs remains unidentified. To determine whether lymphocyte homing to lymphoid organs is involved in the pathogenesis of diabetes in nonobese diabetic (NOD) mice, we blocked the function of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is a vascular addressin-mediating lymphocyte homing into mucosal lymphoid tissues, in these mice. While ineffective if started later, a blockade started at 3 wk of age reduced the incidence of diabetes from 50% to 9% (p < 0.01). This finding is associated with Peyer's patch atrophy, a marked decrease of naive (CD44(low) CD45RB(high)) T lymphocytes, and a reduction in the relative numbers of memory (CD44(high)) T lymphocytes in the spleen. The potential of these spleen cells to cause diabetes was diminished. Anti-MAdCAM-1 treatment also inhibited both lymphocyte entry into the pancreas and diabetes development in NOD/SCID recipients after the transfer of lymphocytes derived from the mesenteric lymph nodes of young, but not of diabetic, NOD donors. Therefore, MAdCAM-1 may be required during two distinct steps in an early phase of diabetes development: for the entry of naive lymphocytes into the lymphoid tissues in which diabetes-causing lymphocytes are originally primed, and for the subsequent homing of these lymphocytes into the pancreas. The role of MAdCAM-1 as a mucosal vascular addressin suggests that mucosal lymphoid tissues are involved in the initiation of pathologic immune responses in NOD mice.
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PMID:Mucosal addressin is required for the development of diabetes in nonobese diabetic mice. 963 17

Interleukin (IL)-13 is a cytokine primarily produced by the T-helper (Th)-2 subset of lymphocytes that possesses powerful anti-inflammatory properties. Here, we have evaluated the impact of IL-13 treatment on development of type 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice. Prolonged treatment with recombinant human IL-13 (hIL-13) markedly diminished the incidence of spontaneous type 1 diabetes in the mice. Female NOD mice treated from age 5-16 weeks with hIL-13 also showed significantly milder insulitis than control mice. The preventive action of hIL-13 was associated with a slight but significant change from a type 1 to a type 2 cytokine response. Accordingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted less interferon (IFN)-gamma upon ex vivo stimulation with Concanavalin A than controls, and anti-CD3 monoclonal antibody-induced activation of T-cells in vivo resulted in lower blood levels of IFN-gamma and tumor necrosis factor-alpha and augmented blood levels of IL-4 in NOD mice pretreated with hIL-13. hIL-13 treatment also increased the blood levels of IgE and inhibited the transfer of type 1 diabetes by spleen cells from a diabetic donor to irradiated recipients. Taken together, these data add hIL-13 to the list of cytokines capable of downregulating immunoinflammatory diabetogenic pathways in NOD mice, and further support the concept that IL-4-related anti-inflammatory cytokines might have a role in the prevention of type 1 diabetes.
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PMID:Interleukin-13 prevents autoimmune diabetes in NOD mice. 1042 68

Diabetic mastopathy, an uncommon form of lymphocytic mastitis and stromal fibrosis, typically occurs in longstanding type 1 diabetes. Nineteen cases meeting predetermined histopathologic criteria for diabetic mastopathy were correlated as to clinical history and disease recurrence. Physical examination revealed palpable discrete masses or diffuse nodularity, both predominantly in the subareolar region. One nonpalpable lesion was detected incidentally during reduction mammoplasty. All cases contained lymphocytic ductitis and lobulitis with varying degrees of keloidal fibrosis, vasculitis, epithelioid fibroblasts, and lymphoid nodule formation. Single mammary lesions were found in 11 patients with type 1 diabetes, 1 with type 2 diabetes, and 3 without diabetes. Four cases were bilateral (3 patients with type 1 and 1 patient with type 2 diabetes). Six of 19 cases recurred (3 ipsilateral, 2 contralateral, and 1 bilateral). We confirm the histopathologic constellation for diabetic mastopathy. However, we question the specificity of these features because of identical findings in patients with type 2 diabetes and nondiabetic patients. We found diabetic mastopathy in men and women, as a solitary mass or bilateral disease, and recurrence in either breast, sometimes multiple. Recognition of potential recurrence is important because it might spare patients with documented diabetic mastopathy from repeated breast biopsies.
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PMID:Diabetic mastopathy. A clinicopathologic review. 1076 56

The concept of oral tolerance refers to a form of peripheral tolerance in which mature lymphocytes in the peripheral lymphoid tissues are rendered nonfunctional or hyporesponsive by prior oral administration of an antigen. The primary mechanisms mediating oral tolerance include deletion, anergy of antigen-specific T cells and active cellular suppression, the primary determining factor being the dose of fed antigen. Low doses favor active suppression, whereas high doses favor deletion and anergy. Active cellular suppression is mediated by the induction of regulatory T cells in the gut-associated lymphoid tissue, which migrate to the systemic immune system. One of the primary mechanisms of active cellular suppression is via secretion of suppressive cytokines such as TGF-beta, IL-4, and IL-10 following antigen-specific triggering. TGF-beta is produced both by CD4+ and CD8+ GALT-derived T cells and is an important mediator of the active suppression component of oral tolerance. CD4+ cells that primarily produce TGF-beta appear to be a unique T-cell subset and termed Th3 cells. Oral tolerance was successfully studied in a variety of experimental models for autoimmune diseases, among them experimental autoimmune encephalomyelitis, experimental arthritis, experimental anti-phospholipid syndrome, experimental autoimmune uveoretinitis, experimental insulin dependent diabetes mellitus (IDDM), and experimental autoimmune myasthenia gravis. The results obtained in experimental animal models have led to the conduction of several clinical trials of oral tolerance in patients with multiple sclerosis, rheumatoid arthritis, uveitis, and IDDM. Conflicting results were obtained, and although some improvement has been noted in some of the patients, broad ranging clinical improvement has not yet been observed. A more accurate choice of antigens, as well as more precise dosing and timing of antigen-administration might lead to better results in the future.
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PMID:Immunomodulation of experimental autoimmune diseases via oral tolerance. 1077 Feb 68

Recent reports indicate that genes with tissue-restricted expression, including those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512), are transcribed in the thymus. The reported modulation of diabetes susceptibility by genetically determined differences in thymic insulin levels and studies in transgenic mice provide correlative and functional evidence that thymic expression of peripheral proteins is crucial for immunological self-tolerance. However, there are no specific data about the existence, tissue distribution, phenotype, and function of those cells that express insulin and other self-antigens in the human thymus. We find that the human thymus harbors specialized cells synthesizing (pro)insulin, GAD, and IA-2, mainly localized in the medulla, and we demonstrate such cells also in peripheral lymphoid organs (spleen and lymph nodes). Phenotypic analysis qualifies these cells as antigen-presenting cells (APCs), including both dendritic cells and macrophages. These cells often appear surrounded by apoptotic lymphocytes, both in thymus and spleen, and may therefore be involved in the deletion of autoreactive lymphocytes. Our findings demonstrate the existence of, and define the tissue distribution and phenotype of, a novel subset of APCs expressing self-antigens in human lymphoid organs that appear to be involved in the regulation of self-tolerance throughout life.
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PMID:Self-antigen-presenting cells expressing diabetes-associated autoantigens exist in both thymus and peripheral lymphoid organs. 1123 56


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