Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The inbred non-obese diabetic (NOD) mouse strain provides a good animal model of the human disease and genetic analysis suggests that, as in man, at least one of the several genes controlling the development of IDDM is linked to the major histocompatibility complex. The NOD mouse does not express I-E owing to a deletion in the promoter region of the I-E alpha-chain gene, and the sequence of NOD I-A beta-chain in the first external domain is unique with His 56 and Ser 57 replacing Pro and Asp, respectively, at these positions. There has been considerable interest in the role amino acid 57 might have in conferring susceptibility to autoimmune diseases, including IDDM. The presence of a charged residue (such as Asp) at this position might affect the conformation of the peptide binding groove. But it could be assumed that Pro 56 gives rise to a different conformation of I-A beta-chain than does His 56. We therefore constructed transgenic NOD mice in which the transgene encoded a modified A beta nod with Pro 56, and studied its effect on the development of IDDM in this mouse strain. Previous studies have suggested that NOD mice expressing I-E as a result of the introduction of an I-E alpha-chain (E alpha) transgene are protected from the development of insulitis and hence IDDM. To explore further the protective effect of this molecule we constructed a second class of transgenic NOD mouse carrying an E alpha d transgene. Both transgenes protected the mice from IDDM, but this was not associated with a complete deletion of any T cells expressing commonly used T-cell receptor V beta genes.
 ...
PMID:Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I-A beta-chain or normal I-E alpha-chain. 197 76

We report a case of symptomatic essential fatty acid deficiency (EFAD) occurring in a free-living individual with type I diabetes mellitus who was voluntarily following a high-carbohydrate, fat-restricted diet. The patient was 43 yr old with type I diabetes for 18 yr and no chronic complications. His self-imposed diet excluded all red meats, fats, and oils. After several months of this diet, the patient developed lethargy and a pruritic, diffuse, scaly, and erythematous rash. Biochemical studies revealed a mildly elevated SGOT and abnormally low levels of linoleic, linolenic, and arachidonic fatty acids. Treatment with linoleic acid supplementation in his diet improved the rash, normalized SGOT, and corrected the fatty acid profile. We conclude that EFAD may occur in a free-living individual after consuming a very-low-fat diet.
 ...
PMID:Diet-induced essential fatty acid deficiency in ambulatory patient with type I diabetes mellitus. 373 94

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.
 ...
PMID:Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. 375 14

Two male infants with severe protracted diarrhoea presenting at 4 months (patient 1) and 10 weeks (patient 2) of age are reported. In both patients jejunal biopsy showed subtotal villous atrophy. Both had specific complement-fixing autoantibodies reacting by immunofluorescence with human duodenal, jejunal, and colonic epithelium. Patient 1 also had hypothyroidism and type 1 diabetes mellitus with thyroid and islet cell autoantibodies. His gut antibodies were of IgG class, reached a titre of 1:512, and remained positive throughout his illness. He died at 16 months of age. Patient 2 had gut antibodies of IgM class, which reached a titre of 1:128 and disappeared at the time of spontaneous recovery of the diarrhoea. The findings suggest that an autoimmune process was the basis for the enteropathy in these patients. We recommend that autoantibody tests should be performed in infants with unexplained protracted diarrhoea.
 ...
PMID:Specific autoantibodies to gut epithelium in two infants with severe protracted diarrhoea. 388 68

A 30-year-old man presented at the diagnosis of an insulin dependent diabetes mellitus with pronounced and multiple complications, such as retino-, nephro-, dermo- and neuropathy. His diabetes had a malignant course and he died from uremia within one year after diagnosis. There were no signs of atherosclerosis at autopsy but in several organs there were pronounced diabetic small vessel lesions.
 ...
PMID:Malignant diabetes mellitus--a case report. 400 39

Serotonin (5-HT) and histamine metabolism was studied in 50 patients with diabetes melitus. Simultaneously the blood and urine content of their precursors and metabolites tryptophane, 5-hydroxytryptophane (5-HTP), 5-hydroxyindolylacetic acid (5-HIAA) and histidine was examined. An increase in 5-HT metabolism intensification (the augmented 5-HTP and 5-HT blood levels and enhanced 5-HTP and 5-HIAA excretion with the urine) was determined, whereas the blood and urine contents of histamine and histadine were within normal. Moreover, significantly higher increase in 5-HT blood level and enhanced 5-HIAA excretion with the urine were seen in patients with juvenile diabetes mellitus comparatively to those with insulin-depending type of the disease. Possible significance of changes, being discovered in 5-HT metabolism of patients with diabetes mellitus, in the disease pathogenesis is discussed.
 ...
PMID:[Metabolism of various biogenic amines in diabetes mellitus]. 617 88

Schmidt syndrome (PGA syndrome type II) is a rare condition characterized by polyglandular failure. It is an autosomal dominant trait with variable expressivity that was inherited over four generations in an the Indiana kindred. Association of HLA-B8 has been reported with Schmidt syndrome. Our proband is a 12-year-old boy with Addison disease, insulin dependent diabetes mellitus (IDDM), and vitiligo. Two of his eight sibs had either IDDM (sister) or vitiligo and hyperthyroidism (brother). His mother had hypothyroidism. Seven members of earlier generations apparently were also affected. We obtained peripheral blood for HLA and genetic analysis from 21 relatives in a family with 8 Schmidt syndrome individuals in three generations. HLA studies on 15 affected and unaffected relatives showed only 2 of 7 persons with B8-containing haplotypes. Therefore, no association exists between the B8-containing haplotype and the syndrome. We identified informative marker loci. No evidence for linkage of the Schmidt locus to any of the 14 markers was found and close linkage to esterase D and adenylate kinase and possibly properdin factor B was excluded.
 ...
PMID:Linkage analysis in a large kindred with autosomal dominant transmission of polyglandular autoimmune disease type II (Schmidt syndrome). 658 52

A 21-year-old patient, since the age of 16, presented a familial type of chronic autoimmune thrombocytopenia that responded only partially to various types of immunosuppressive treatment. His prolonged survival, compared to his decreased siblings, was complicated by the appearance of a severe enteropathy. High doses of corticosteroids induced a type 1 diabetes as a major side effect. The introduction of cyclosporine resulted in both a continuous complete clinical remission and a partial hematological remission and allowed the discontinuation of all other medication for 18 months. In uncommon complex autoimmune disease, cyclosporine may represent a safe and effective alternate therapy when other immunosuppressive agents have failed.
 ...
PMID:Prolonged remission induced by cyclosporine in a patient with familial thrombocytopenia and enteropathy. 764 Jan 83

A pedigree with maternally transmitted diabetes mellitus, deafness, and cardiomyopathy is described. A A-->G mutation at nucleotide pair 3243 in mitochondrial gene was detected by Apa I digestion of PCR amplified genomic DNA from 3 brothers and their mother. The proband, suffering from CHF, showed unique fine granular pattern of hyperechogenic cardiomyopathy as his brother and their mother did. Although he is recently treated with insulin, he was initially NIDDM treated by sulfonylurea. His urinary CPR excretion decreased gradually to as low as less than 10 micrograms/day in these 3 years. The insulin response to oral glucose was decreased in all other family members with the mutation. It is suggested that the defective insulin secretion exists in this family with the mutation and the progressive decrease in insulin secretion might resulted in IDDM in the proband.
 ...
PMID:[A pedigree with maternally transmitted diabetes mellitus, deafness and cardiomyopathy]. 798 86

In some patients with insulin-dependent (type I) diabetes mellitus (IDDM), autoantibodies to insulin are present at diagnosis. After initiation of the treatment with not only animal but also human insulin, anti-insulin, mainly IgG, autoantibodies become a major component of the autoimmune response in virtually all IDDM patients. Their structure, however, is still relatively unknown. We analyzed the structure of the VH and V kappa segments of three human IgG mAb derived from three IDDM patients. The sequences of VH genes of two IgG, mAb13 and mAb48, were 98.3 and 96.6% identical with those of the H11 and 1.9III genes (VHIII family), respectively. The sequence of the VH gene of the third IgG, mAb49, was 98.6% identical with that of the 51p1 gene (VHI family). All three IgG mAb used V kappa III segments. The V kappa III gene sequences of mAb13 and mAb49 were 97.9 and 98.9% identical, respectively, to that of the kv3g gene; the mAb48 V kappa gene sequence was 96.5% identical to that of the kv328 gene. The VH and/or V kappa segments of these anti-insulin IgG mAb are similar to Ig V genes expressed in the fetal, and adult normal and autoimmune B cell repertoires. The nucleotide differences displayed by the three anti-insulin IgG mAb VH gene sequences, when compared with those of the closest reported germ-line genes, were concentrated in the CDR (6.2 x 10(-2) and 0.8 x 10(-2) difference/base in CDR and FR, respectively; p < 0.01, chi 2 test), and yielded a significantly higher putative replacement (R) to silent (S) mutation ratio in the CDR (12.0) than in the framework (0.2). The concentration of nucleotide differences in the CDR and their high R:S putative mutation ratios were consistent with the hypothesis that these expressed VH genes underwent a process of somatic mutation and Ag-driven clonal selection. That such differences constituted somatic point-mutations was formally proved in IgG mAb13, by differentially targeted PCR amplification and Southern blot hybridization of the mAb13-producing cell line DNA. The putative germ-line gene that gave rise to the expressed VH segment was cloned using genomic DNA from PMN of the same patient whose B cells were used for the generation of this mAb. Overall, in the anti-insulin IgG mAb VH and V kappa III genes, the (putative and verified) somatic point-mutations yielded 27 amino acid replacements, of which 14 nonconserved. Four of these resulted in positively charged residues, three Arg and one His.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:VH and V kappa segment structure of anti-insulin IgG autoantibodies in patients with insulin-dependent diabetes mellitus. Evidence for somatic selection. 830 Nov 43


1 2 3 4 5 6 7 8 9 Next >>