Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes mellitus is the late consequence of a chronic autoimmune disease directed to the B islet cell, that begins long before the hyperglycemic state. Experimental evidence suggests a central pathogenic role for autoreactive T lymphocytes. Immunointervention studies, particularly those using cyclosporin, have shown that it is possible to stop B cell destruction, even at the late stage of overt diabetes. New therapeutic approaches will be focused on the use of specific agents such as monoclonal antibodies and immunotoxins, and on earlier interventions allowed by the detection of genetic and immunological markers of prediabetes.
 ...
PMID:[Immunotherapy of type 1 diabetes]. 149 32

Most autoimmune diseases are HLA-associated which supports the notion that they are dependent upon specific immune activation of a limited set of T cell clones. Findings which imply that induction of autoimmune reactivity probably does not differ from normal immune responses are discussed. The possibility of transferring autoimmune disease using T cell clones indicates that target structures for auto-immune attack are also present in healthy individuals. In the present article, it is argued that autoimmune reactions and immunity against nominal conventional antigens in principle are effected and regulated by similar mechanisms. It is assumed that persistent tissue damage occurs if immune attack is directed against tissues that cannot be regenerated, such as in diabetes, or are only slowly reconstituted, such as in rheumatoid arthritis. Normal immune responses are regulated by various inflammatory mediators and cytokines/interleukins. The joint of patients with rheumatoid arthritis is discussed as a model for propagation of immune reactions and tissue destruction in autoimmune disease. Of the different cytokines which are present in the synovial fluid or produced by cells in the synovial tissue, most are presumed to have originated in macrophages/monocytes such as IL-1, IL-6, IL-8, TNF-alpha and TGF-beta. Even so, T cells are believed to have an important role for the continued reactivity associated with autoimmune disease. This discrepancy can be explained in different ways. T cell products might escape detection because they are short-lived, they are immediately consumed or they are produced only during short time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Specific and non-specific autoreactive immunity. 150 34

Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on blockade of MHC class II molecules in the treatment of HLA-linked autoimmune diseases.
 ...
PMID:Inhibition of T cell activation by MHC blockade: a possible strategy for immunointervention in autoimmune diseases. 150 37

Type 1, insulin-dependent diabetes mellitus is an autoimmune disease with destruction of beta-cells in islets of Langerhans by activated (antigen-positive) infiltrating mononuclear cells accompanied by serological immune phenomena. The pathological mechanism has not yet been clarified in detail, and some inversion in the proportion of epidermal antigen expression has recently been described in spontaneous diabetes. The BB rat is one of the animal models most closely resembling human type 1 diabetes of autoimmune origin. We compared the class I and class II antigen expression in the islets of Langerhans and in the skin of spontaneously diabetic (BBD) and normoglycaemic (BBND) BB rats in the prediabetic, diabetic and non-diabetic states. Class I and class II antigen expression increased significantly in the islets of BBD rats from prediabetes to diabetes and compared with non-diabetic controls. In the same period, the dermal antigen expression (class I and class II) did not decrease and was not lower in BBD than in BBND animals. These results do not support a loss of activated (antigen-positive) dermal cells at the onset of diabetes in the BB rat and do not show a clear correlation with the antigen expression in infiltrated islets of Langerhans.
 ...
PMID:A comparative study of antigen expression by skin and pancreas in the prediabetic and diabetic state of the BB rat. 157 58

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.
 ...
PMID:Transgenic mouse as a tool for the study of autoimmune disease: insulin-dependent diabetes mellitus. 161 97

Heat shock proteins (hsp) are highly conserved from bacteria to man. Bacterial hsp, with approximate molecular weights of 60 kDa (hsp60), are immunodominant antigens that are immunologically cross-reactive with their mammalian counterparts. Hsp molecules are therefore useful in studies of fundamental questions concerning immune responses to foreign as opposed to self antigens. The finding that immune responses to hsp are associated with both experimentally-induced and spontaneous autoimmune diseases in animals has prompted intensive research to assess the role of bacterial hsp as the etiological agents involved in the development of autoimmune diseases. Recent evidence from animal models of autoimmune disease has clearly demonstrated the involvement of hsp in both the pathogenesis and the immunoregulation of autoimmune diseases. Studies with arthritogenic and diabetogenic T cell clones have identified immunogenic epitopes of hsp. These have been shown to ameliorate adjuvant arthritis in Lewis rats, and insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. Such studies may have important therapeutic implications for the future treatment of human autoimmune disease.
 ...
PMID:Heat shock proteins in autoimmune disease. From causative antigen to specific therapy? 163 73

Type I diabetes mellitus is an autoimmune disease resulting from the interaction of genetic and environmental factors. A virus that was identified serologically as Kilham's rat virus (KRV) was isolated from a spontaneously diabetic rat and reproducibly induced diabetes in naive diabetes-resistant (DR) BB/Wor rats. Viral antigen was not identified in pancreatic islet cells, and beta cell cytolysis was not observed until after the appearance of lymphocytic insulitis. KRV did not induce diabetes in major histocompatibility complex-concordant and discordant non-BB rats and did not accelerate diabetes in diabetes-prone BB/Wor rats unless the rats had been reconstituted with DR spleen cells. This model of diabetes may provide insight regarding the interaction of viruses and autoimmune disease [corrected]
 ...
PMID:Induction of type I diabetes by Kilham's rat virus in diabetes-resistant BB/Wor rats. 165 38

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)
 ...
PMID:Prevention of cyclophosphamide-induced and spontaneous diabetes in NOD mice by syngeneic splenocytes treated with cytotoxic drugs. 166 36

Insulin-dependent diabetes mellitus (IDDM) is generally believed to be an autoimmune disease resulting from T-cell dysfunction that produces beta-cell damage, but it is conceivable that some forms of IDDM are not immunologically mediated. The effect of the expression of a foreign transgenic MHC class I antigen (H-2Kb), restricted to pancreatic islet beta-cells, was tested in vitro and in nude (athymic) mice to determine whether beta-cell dysfunction was due to non-immune mechanisms. The models used clearly excluded immune involvement in beta-cell damage. Fetal pancreas from transgenic and littermate control mice was maintained in organ culture for up to 18 days and insulin secretion into the medium assessed. For the initial 3-4 days in vitro, fetal control and transgenic pancreas secreted similar amounts of insulin, but thereafter insulin secretion by the transgenic tissue decreased in comparison with the controls. When the cultured pancreas was transplanted into nude mice, the transgenic issue produced smaller grafts than the control pancreas, but there was wide variation in graft size. Expression of H-2Kb antigens in beta-cells of nude transgenic mice also resulted in early-onset diabetes. The insulin content in the pancreas of young H-2Kb transgenic euthymic mice, (previously shown not to have insulitis), was reduced but glucagon content was normal. The reduction in in vivo insulin production was similar chronologically to the reduced insulin production by transgenic islets in vitro. These data confirm the non-immune loss of beta-cell function in MHC-transgenic mice and they may be a model for atypical Type I diabetes.
 ...
PMID:Inherent beta-cell dysfunction induced by transgenic expression of allogeneic major histocompatibility complex class I antigen in islet cells. 166 46

Stiff-man syndrome (Moersch-Woltman syndrome) is a rare disorder of motor function characterized by involuntary stiffness of axial muscles and superimposed painful muscle spasms, which are often induced by startle or emotional stimuli. The standard treatment has been benzodiazepines. An association has been reported between stiff-man syndrome and epilepsy, insulin-dependent diabetes, and a variety of organ-specific autoimmune disorders. Antibodies directed against glutamic acid decarboxylase and against pancreatic islet cells have been detected in the serum and cerebrospinal of patients with stiff-man syndrome. These findings suggest that stiff-man syndrome may be an autoimmune disease. Preliminary reports indicate that patients with stiff-man syndrome have a favorable response to plasma exchange and corticosteroid therapy.
 ...
PMID:Stiff-man syndrome. 167 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>