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

The relationship between increased risk in relatives over population prevalence (lambda R = KR/K) and probability of sharing zero marker alleles identical by descent (ibd) at a linked locus (such as HLA) by an affected relative pair is examined. For a model assuming a single disease-susceptibility locus or group of loci tightly linked to a marker locus, the relationship is remarkably simple and general. Namely, if phi R is the prior probability for the relative pair to share zero marker alleles identical by descent, then P (sharing 0 markers/both relatives are affected) is just phi R/lambda R. Alternatively, lambda AR, the increased risk over population prevalence to a relative R due to a disease locus tightly linked to marker locus A, equals the prior probability that the relative pair share zero A alleles ibd divided by the posterior probability that they share zero alleles ibd, given that they are both affected. For example, for affected sib pairs, P (sharing 0 markers/both sibs are affected) = .25/lambda S. This formula holds true for any number of alleles at the disease locus and for their frequencies, penetrances, and population prevalence. Similar formulas are derived for sharing one and two markers. Application of these formulas to several well-studied HLA-associated diseases yields the following results: For multiple sclerosis, insulin-dependent diabetes mellitus, and coeliac disease, a single-locus model of disease susceptibility is rejected, implying the existence of additional unlinked familial determinants. For all three diseases, the effect of the HLA-linked locus on familiality is minor: for multiple sclerosis, it accounts for only a 2.5-fold increased risk to sibs over the population prevalence, compared to an observed value of 20; for coeliac disease, it accounts for approximately a 5.25-fold increased risk to sibs, while the observed value is on the order of 60; for insulin-dependent diabetes mellitus, it accounts for a 3.42-fold increased risk in sibs, while the observed value is 15. In all cases, the secondary determinants must be outside the HLA region. For tuberculoid leprosy, an unlinked familial determinant is also implicated (increased risk to sibs due to HLA = 1.49; observed value = 2.38). For hemochromatosis and Hodgkin's disease, there is little evidence for HLA-unlinked familial determinants. With this formula, it is also possible to examine the hypothesis of pleiotropy versus linkage dis-equilibrium by comparing lambda AS with the increased risk to sibs due to the associated allele(s).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Assessing the role of HLA-linked and unlinked determinants of disease. 346 4

Chronic debilitating diseases such as multiple sclerosis, demyelinating inflammatory polyradiculoneuropathy, rheumatoid arthritis, diabetes mellitus type I, Hashimoto thyroiditis, forms of uveitis and interstitial nephritis, share many characteristics. They are all organ-specific inflammatory diseases of unknown etiology but with strong evidence of tissue-destructive activity of the cellular immune system in the organs respectively affected, i.e. the central or peripheral nervous system, the joints, the islets of Langerhans, the thyroid gland, the retina, or the tubulo-interstitial renal tissue. Recognized animal models of all these diseases are experimentally induced autoimmune conditions that are transferable with autoreactive T-lymphocytes, in contrast to autoantibodies in humoral autoimmune diseases. In recent years, disease-transferring T-lymphocytes, have been successfully grown as lines and clones in vitro, thus finally proving the primary pathogenic role of autoreactive T-lymphocytes in these animal models. Such T-cell lines are valuable tools in further defining autoantigens, studying mechanisms of T-cell activation in vitro, following T-cell migration and organ-specific homing in vivo, and analyzing effector functions in the infiltrated organs. In addition, questions concerning the breakdown of immunological selftolerance and the basic principles of resistance to disease can be addressed, and possibilities of treatment can be approached. Although the basic etiology of the human organ-specific immune diseases is still unknown, these animal models have helped to throw light on some of the pathogenic mechanisms common to these various diseases.
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PMID:[The role of T-lymphocytes in organ-specific autoimmune diseases]. 349 35

This article deals with the use of oral contraceptives and IUDs by chronically ill adolescent females. Results of controlled studies of contraceptive choices and problems are reviewed for teenagers with cardiac disease, epilepsy, multiple sclerosis, migraine headaches, asthma, cystic fibrosis, inflammatory bowel disease, hepatitis, diabetes mellitus, thyroid disease, oligomenorrhea and amenorrhea. If oral contraceptives (OC) are prescribed for use in teens with cardiac disease, a contraceptive with 35ug or less of estrogen and the equivalent of 1 mg or less of norethindrone should be used. The low-dose progestin only pill can be prescribed, but should be used in conjunction with a back-up barrier method. Reports to date have failed to reveal increased seizure activity in epileptic pattients on OCs, and there is no significant evidence to date that OCs alter the course of multiple sclerosis. Although the evidence is inconclusive, the physician should use extreme caution in prescribing OCs for teens with prior migraines. Regarding asthmatic patients, no problems have been reported with IUD use except in regard to steroid therapy and its possible effect on reducing IUD effectiveness. No adverse effects 2ndary to the use of OCs in asthmatic patients have been reported. OCs should be avoided or used with extreme caution in the cystic fibrosis patient. Teens with active inflammatory bowel disease should be advised that OCs may be ineffective or dangerous; there are no reports available on the effects of the IUD on the disease. The pill is contraindicated during active liver disease or cirrhosis. The IUD is not highly recommended for contraception in diabetic teenagers, whereas a low-dose combined OC can be used with extreme caution. However, OCs should be avoided in the diabetic patient with nephropathy, vascular complications or retinopathy. There is at present no contraindication for contraceptive use by women with thyroid disease. Finally, patients with prolonged post pill amenorrhea and infertility are generally females with amenorrhea or oligomenorrhea before pill use.
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PMID:Contraceptive use in the chronically ill adolescent female: Part I. 351 58

We have studied in 22 informative families typed for HLA the segregation of DNA restriction fragments obtained with five restriction enzymes and hybridized with one class I and three class II probes. Most of the fragments correlate with serologically defined specificities. Many fragments can be grouped in clusters, whose genetic significance is discussed. The RFLP distribution in patients with insulin-dependent diabetes mellitus, multiple sclerosis or narcolepsy, three diseases known to be associated with some HLA-DR specificities, has been also studied. Many fragments allow to distinguish between patients and HLA-DR matched controls. Hybridization of genomic DNA with synthetic oligomers will refine moreover the understanding of the HLA system polymorphism.
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PMID:New methods for detection of HLA genes polymorphism useful for associated diseases studies. 353 98

Eight families (121 individuals) with two or more members affected with systemic lupus erythematosus (SLE) were analyzed for histocompatibility antigens (HLA-A, B, C, DR, MT, and MB) and complement antigens (C4A, C4B, and BF). These data were correlated with serological markers (antinuclear antibodies, single- and double-stranded anti-DNA, anti-SM, anti-nRNP, anti-Ro [SS-A], anti-La [SS-B], and biological false-positive tests for syphilis and clinical features. Fifteen members had SLE, and 19 had other immune diseases (subacute cutaneous lupus erythematosus, discoid lupus erythematosus, hypothyroidism, insulin-dependent diabetes mellitus, primary Sjogren's syndrome, immune thrombocytopenic purpura, rheumatoid arthritis, and multiple sclerosis). Twenty-three healthy relatives (seroreactors) had significant titers of circulating antibodies, as did 2 of 17 spouses. There was an increased frequency of null C4 alleles in those individuals with SLE (60%) and healthy relatives (50%) as compared with spouses (24%). Multivariate analysis showed a significant association between SLE and female sex (P =.006), whereas there was no significant association revealed between female sex and other immune diseases. Patients with SLE also had a higher frequency of either C4A or C4B null alleles (P = .01) than those with immune diseases. The C4A homozygous null phenotype was more common in SLE patients than in seroreactors (P = .02). There was a higher frequency of HLA-DR2 and DR3 in individuals with SLE than in those with immune disease (P = .08), seroreactors (P = .02) and normal relatives (P = .002). One totally C4-deficient patient with SLE was identified. These families demonstrate an important association between SLE and the C4 null allele and the HLA-DR2 and DR3. These risk factors, however, cannot account for the development of disease in all individuals.
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PMID:Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus. 387 10

A defined general population of 159,200 male and female native Swedes born in the period 1911-1940 from an urban catchment area of the then only general hospital, was followed over a decade (1970-79) with regard to in-patient hospitalization for all kinds of diagnoses. As a part of this population cohort study, multiple sclerosis cases (n = 351) and epilepsy cases (n = 648) were studied for association with other diseases. Unexpectedly, a cluster of diseases encompassing tuberculosis, bronchial asthma, diabetes mellitus and myocardial infarction, among the diseases associated with multiple sclerosis, also forms a gradient; this suggests a quantitative rather than a qualitative multifactorial model of disease for the understanding of the pathogenesis of MS. In epilepsy, heterogeneity was suggested as being mainly linked to the presence or absence of co-existing alcoholism. Brain tumours in cases of epilepsy were found almost exclusively in the latter subset and prevailing among younger people independent of sex (with an almost 100-fold excess rate of that disease combination as expected by chance only).
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PMID:Diseases associated with multiple sclerosis and epilepsy. A population cohort study of 159,200 middle-aged, urban, native Swedes observed over 10 years (1970-79). 387 80

Regular fundus oculi examination is not necessary for normal, healthy women taking oral contraceptives. Ophthalmological complications have been observed in women with a history of cardiovascular disease, diabetes, and multiple sclerosis, however. A detailed medical history should be taken in these cases. Slight aggravation of myopia and astigmatism is sometimes observed.
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PMID:[Letter: Fundus oculi examination following administration of contraceptives?]. 445 17

The isoelectric focusing (IEF) properties of human alpha 2-macroglobulin (alpha 2M) and alpha 2M-proteinase complexes from crude and partially purified preparations were studied by column IEF. The average isoelectric point (pI) of the major form was 6.5 for alpha 2M from crude plasma but was 5.3 for purified samples. Following preincubation with either trypsin, chymotrypsin or pancreatic elastase the crude alpha 2M-proteinase complexes displayed pI values ranging from 5.3 to 6.1 and the purified alpha 2M-proteinase complexes ranged from pH 6.0 to 6.1. A comparison of recoveries for focused crude or purified alpha 2M and trypsin-preincubated alpha 2M indicated enhanced recovery for the trypsin-preincubated samples suggesting that the binding of the proteinase enhances the stability of alpha 2M. alpha 2M thus displays column IEF properties which appear to be dependent upon the state of purity of the molecule. These findings are of particular significance to investigators concerned with using expressions of altered alpha 2M electrophoretic patterns for clinical diagnostic purposes in such diseases as multiple sclerosis, diabetes and cystic fibrosis.
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PMID:Differential isoelectric focusing properties of crude and purified human alpha 2-macroglobulin and alpha 2-macroglobulin-proteinase complexes. 619 30

Recent advances in nutritional and biochemical research have substantiated the importance of inositol as a dietary and cellular constituent. The processes involved in the metabolism of inositol and its derivatives in mammalian tissues have been characterized both in vivo and at the enzyme level. Biochemical functions elucidated for phosphatidylinositol in biological membranes include the mediation of cellular responses to external stimuli, nerve transmission, and the regulation of enzyme activity through specific interactions with various proteins. Inositol deficiency in animals has been shown to produce an accumulation of triglyceride in liver, intestinal lipodystrophy, and other abnormalities. The metabolic mechanisms giving rise to these latter phenomena have been extensively studied as a function of dietary inositol. Altered metabolism of inositol has been documented in patients with diabetes mellitus, chronic renal failure, galactosemia, and multiple sclerosis. A moderate increase in plasma and nerve inositol levels by dietary supplementation has been suggested as a means of treating diabetic neuropathy, although excessively high levels, such as are found in uremic patients, may be neurotoxic. A thorough consideration of the biochemical functions of inositol and a further characterization of various diseases with the aid of appropriate animal models may suggest a possible role for inositol and other dietary components in their prevention and treatment
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PMID:The nutritional significance, metabolism, and function of myo-inositol and phosphatidylinositol in health and disease. 627 2

HLA-DR2 allele is negatively associated with insulin-dependent diabetes and positively associated with multiple sclerosis (MS). A 2.2-kilobase-pair EcoRI DNA restriction fragment detected with a beta-chain HLA-DC cDNA probe was found to be strongly correlated with HLA-DR2 in the normal population, but was absent in HLA-DR2 insulin-dependent diabetic patients. This fragment was found in HLA-DR2 multiple sclerosis patients with the same frequency as in controls. A beta-chain HLA-DC 12-kilobase-pair BamHI fragment might differentiate multiple sclerosis patients from healthy individuals.
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PMID:Class II HLA-DC beta-chain DNA restriction fragments differentiate among HLA-DR2 individuals in insulin-dependent diabetes and multiple sclerosis. 632 15


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