Gene/Protein Disease Symptom Drug Enzyme Compound
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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 evaluate beta-cell function in patients with pancreatic cancer, the glucagon stimulation test was performed in seven patients with pancreatic adenocarcinoma, seven patients with type I diabetes mellitus, seven patients with type II diabetes mellitus, and in seven healthy controls. C-peptide serum levels were determined before and after a 1-mg i.v. glucagon injection. Basal C-peptide values were normal or slightly increased in pancreatic cancer and type II diabetic patients and low in type I diabetic patients. Following glucagon stimulation, no significant increase was observed in C-peptide values of type I diabetics and pancreatic cancer patients, whereas significant increases occurred in controls and type II diabetics. It is concluded that the altered beta-cell function found in pancreatic cancer patients may lead to hyperglycemia, which is frequently associated with this tumor type.
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PMID:Beta-cell function in pancreatic adenocarcinoma. 802 55

The pathogenetic mechanism underlying glucose intolerance in pancreatic cancer is still unclear. We studied the pattern of three glucose regulating hormones (C-peptide, glucagon and GH) in pancreatic cancer patients with (N = 34) and without (N = 8) hyperglycemia, and compared the findings made with those from subjects with other hyperglycemic conditions of well-known origin [type I diabetes mellitus (8 cases) and diabetes mellitus secondary to chronic pancreatitis (13 cases) or liver cirrhosis (4 cases)]. In hyperglycemic pancreatic cancer patients, C-peptide was absent in 26% of the cases, reduced in 24%, elevated in 29% and within the normal range in the remaining 21%. In normoglycemic pancreatic cancer this hormone was reduced in two cases (25%) and within the normal range in all the others. GH was within the normal range in all cases: glucagon was below the normal range in some hyperglycemic pancreatic cancer patients (41%) or within the normal range in all the remaining patients. No correlations were found between the three hormones when findings from subjects were considered all together. However, in pancreatic cancer C-peptide and glucagon presented consensual variations. C-peptide, glucagon and GH levels were not related to tumor volume; glucagon was found to be associated with liver metastases. C-peptide was correlated with serum ALT and ALP. We may conclude that hyperglycemia associated with pancreatic cancer may be caused by different mechanisms. In some cases a reduced secretion of both insulin and glucagon was observed, as occurs in chronic pancreatitis. In the majority of patients, beta cell function appears normal, and the hyperglycemic state may depend on an altered peripheral sensitivity to insulin due to the pancreatic pathology itself or to consensual liver involvement.
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PMID:C-peptide pattern in patients with pancreatic cancer. 813 97

Fourteen examples of lymphocytic mastitis (LM) with epithelioid stromal cells characterized by formation of a palpable, hard breast mass composed of a predominantly lobulocentric lymphocytic infiltrate, stromal fibrosis, and an unusual stromal infiltrate of epithelioid cells are presented. The epithelioid cells were so prominent and abundant that the possibility of an infiltrating carcinoma was raised in three cases, and a fourth case was misinterpreted as a granular cell tumor. Interestingly, eight of the 12 women and the only male patient had long standing, insulin dependent diabetes mellitus (IDDM), whereas two had IDDM and hypothyroidism, one had hypothyroidism alone, and one had systemic lupus erythematosus. Contrary to the conclusions in a recent report, our findings indicate that these mammary changes are not exclusive to patients with IDDM, and may also occur in nondiabetic patients particularly those with autoimmune disorders. The morphologic features of the epithelioid stromal cells which have been mistaken for infiltrating carcinoma are emphasized; immunohistochemical and ultrastructural findings favoring their myofibroblastic nature are presented.
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PMID:Epithelioid stromal cells in lymphocytic mastitis--a source of confusion with invasive carcinoma. 815 52

The high frequency of insulin-dependent diabetes (IDDM) in children with congenital rubella suggests that the infectious agent may trigger the autoimmune process. To explore the immunologic relationship between rubella virus and IDDM, we examined a panel of mAb that recognizes rubella virus capsid and envelope glycoproteins for reactivity with islet cell Ag. One mAb, C9, which recognizes a defined domain within the capsid protein of rubella virus, was found to react with extracts from a rat beta-cell tumor and normal rat and human islets. Using one and two dimensional immunoblot analysis of rat beta-cell tumor extracts, the C9-like epitope was found to reside on a 52 kDa protein that is also the target of autoantibodies from human IDDM and nonobese diabetic mice. To confirm this cross-reactivity, antibodies in diabetic sera were absorbed to the recombinant rubella virus capsid protein, eluted, and then shown to react with the 52 kDa insulinoma protein. These data show that an immunogenic epitope on the rubella virus capsid protein is mimicked by a similar structure on a beta-cell protein. These findings suggest that rubella virus has the potential to sensitize susceptible individuals for an autoimmune response to beta-cell Ag and identify one mechanism that may contribute to beta destruction in IDDM.
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PMID:Monoclonal antibody to rubella virus capsid protein recognizes a beta-cell antigen. 845 75

Beta-cell regeneration in adult pancreas is usually considered to be limited. However, various animal models suggest that this tissue is still capable of regeneration under certain conditions. Reg protein could be responsible for this replicative process. The reg gene codes for a 166 amino-acid protein usually synthesized and secreted by pancreatic acinar cells but expressed in islet beta cells during experimental regenerative processes in animals (90% pancreatectomy + nicotinamide, or insulinoma tumor removal in rats, or the "wrapping pancreas model" in the hamster). In addition, recombinant rat reg protein can stimulate beta-cell replication in vivo and in vitro. In animal models of Type 1 diabetes mellitus, reg gene overexpression occurs during active phases of diabetogenesis and could be a defence mechanism. During human pancreatic development, reg gene is expressed at an early stage but is not associated with the expression of other pancreatic genes. Conversely, gene expression for reg and insulin are correlated in adult pancreas. Accordingly, reg protein could be a beta-cell-specific growth factor implicated in the maintenance of beta-cell mass, especially in adult pancreas.
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PMID:Reg protein: a potential beta-cell-specific growth factor? 876 67

A 52 kDa islet protein has recently been identified as the target of autoantibodies in the NOD mouse model of IDDM and humans with IDDM. However, the presence of T cell immunity against the 52 kDa islet protein in IDDM has not been reported. We report the establishment and characterization of a T cell line (19KW) that reacts to purified 52 kDa islet protein (purified p52) from a subject with IDDM. The purified p52 induced a proliferative response as measured by thymidine incorporation in the 19KW T cell line with a stimulating index of up to 48. The proliferative responses were greater with increasing doses of purified p52 (0.1, 0.5, 2.0, and 6.0 microg/well). No reactivity was found to a liver fraction purified in the same manner as 52 kDa protein, BSA, ovalbumin, extracts of rat muscle, fibroblast, adrenal, or pituitary tissue and to a rat exocrine cell tumor. Irradiated PBMC were required as antigen presenting cells (APC) for 19KW reactivity to the purified p52. The addition of anti-HLA DR or anti-HLA DQ antibodies significantly decreased the islet antigen-induced proliferative response. The addition of antibodies to HLA DP and class I MHC had no effect. Flow cytometric analysis revealed that the majority of T cells expressed CD4 and CD45RO molecules. T cell receptors Vbeta6 and Vbeta5.1 were found on 30 and 14% of the CD3+ (T cells) 19KW cells, respectively. In conclusion, a purified p52-reactive human T cell line predominantly consisting of TCR Vbeta6+ and Vbeta5.1+ cells has been established from a subject with IDDM. Reactivity to the purified p52 is antigen dose-dependent, tissue specific, requires irradiated PBMC as antigen presenting cells, and is HLA DR- and HLA DQ-restricted. T cell lines specifically reactive to p52 may be useful for investigating further the role of this antigen in the pathogenesis of IDDM.
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PMID:Characterization of a human T cell line reactive to a 52 kDa islet protein. 923 2

Autoimmunity associated with tumor cell development seems an important mechanism by which to prevent progression to clinical cancer. In this brief review, tumor autoantigens associated with paraneoplastic syndrome, non-HLA-associated organ-specific autoimmune diseases, and the highly cell-specific autoimmune eradication of the islet beta cells in type 1 diabetes are compared and discussed. It is suggested that autoreactivity is important in preventing tumor formation; however, it may be at the expense of the development of autoimmune disease. Although the cytotoxic T lymphocytes (CTL) induction by HLA class I has been studied and used in clinical trials, little is understood about the initiation and HLA class II mediated induction of an immune response to neoplastic cells. This induction apparently takes place because paraneoplastic disorders are often due to an immune response to the tumor cell resulting in a cross-reactivity with a normally expressed autoantigen on a remote nontumor-associated target cell. The problem of immune surveillance to eradicate neoplasm or downregulate pathological autoimmunity are therefore closely related phenomena. An improved understanding of immune mediated tumor suppression should therefore greatly benefit immunotherapy of type 1 diabetes, and the two areas of research would benefit from an interdisciplinary endeavor.
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PMID:Immune surveillance: paraneoplastic or environmental triggers of autoimmunity. 941 31

This study was aimed to establish TSH dependent, transplantable thyroid tumor (TT) in B6C3F1 (BCF1) mice. In addition, transplanted TT was examined for its growth in mice given 17 beta-estradiol (E2), retinoic acid (RA), tamoxifen (TAM), T3 and T4. Both sexes of BCF1 mice were observed for 12 months under IDD and distilled water (DW), starting at 4 weeks of age. Groups of mice received an i.p. injection of radioactive iodine (131I) once at a dose of 60 mu Ci/head and/or given 0.25 mg E2 pellet s.c. One piece of induced pituitary or thyroid tumor was individually dissected aseptically and s.c. grafted under the fat pad of one site of the neck in the same strain of mice at 5 weeks of age. All mice were sacrificed between 7.5 to 13.5 months after grafting the tumors depending on the experiments. The transplantability of both pituitary and thyroid tumor was 100% in IDD mice, but TT was about 50% with a combined treatment of IDD plus E2. A supplement of thyroid hormones of T3 or T4 in mice with IDD completely inhibited the growth of in situ or grafted thyroid tumors. The growth of in situ thyroid gland was significantly promoted by the oral administration of RA in both sexes, whereas the growth of transplanted TT was significantly increased by RA in the female, but not in the male. Oral administration of TAM proved inhibitory upon in in situ and transplanted TT in the male, but not in the female. Thyroid tumor induced by IDD could grow only in mice with IDD and was partially regulated of its growth by RA and TAM.
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PMID:Effect of 17 beta-estradiol, retinoic acid and tamoxifen upon primary and transplanted thyroid tumor in B6C3F1 mice fed an iodine deficient diet. 953 64

Morphologic study of 38 specimens of epiretinal membranes obtained during transciliary vitrectomy in 26 patients with type I diabetes mellitus and 12 with type II diabetes with proliferative diabetic retinopathy of different stages was carried out. In proliferative diabetic retinopathy, new vessels grow mainly along the posterior (retinal) surface of the posterior hyaloid membrane. Sometimes, if there are defects in the posterior hyaloid membrane, proliferative tissue stratifies it and appears on the anterior (hyaloid) surface. We observed no growth of new vessels outside the posterior hyaloid membrane. The impossibility of clinical and mechanical separation of the posterior hyaloid membrane and tumor tissue permits us to regard the stages of proliferative process in diabetic retinopathy as stages in the alteration of the posterior hyaloid membrane proper. Five variants in the structure of proliferative tissue can be distinguished in diabetic retinopathy; we consider that these variants are stages in its development: 1) glial--with predominance of cell-free or hypocellular glial tissue; 2) glial vascular--with growth of thin-wall vessels into glial tissue; 3) glial vascular fibrous--with growth of porous fibrovascular membrane in glial tissue; 4) fibrovascular--with predominance of fibrovascular tissue; and 5) fibrous (cicatricial) hypocellular compact connective tissue with just few vessels or none at all. Reduction of new vessels, involution of proliferative tissue, and development of traction detachment of the retina are associated with the beginning of fibrous proliferation.
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PMID:[Posterior hyaloid membrane as structural base of growth of neovascular tissue in proliferative diabetic retinopathy]. 972 Mar 91

The study of SMS, a rare disease, has resulted in a better understanding of a more common disorder, IDDM, and has allowed investigators to gain insights into the molecular mechanisms of autoimmunity. Many unanswered questions remain, such as the specific site of disease activity in SMS, both at the bedside (cortex, brain stem, or spinal cord) and at the bench (neuronal cytoplasma or synapse). The association of SMS with neoplastic disease and the development of autonomicdysfunction are not understood. The next decade may provide answers to these puzzling issues.
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PMID:Stiff-man syndrome: from the bedside to the bench. 1040 57


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