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 authors define pro-thrombotic states as conditions associated with a high frequency of thrombosis; this association is based on pathogenetic or simply clinical and epidemiological relationships. Thrombophilic states have well-defined, specific causes: antithrombin III, protein C and S and similar deficiencies for inherited thrombophilias, and lupus anticoagulant, antiphospholipid antibodies for the acquired forms. Another identifiable group is made up of several conditions predisposing to thrombosis (CPT) characterized by less specific and multiple mechanisms (e.g. malignancy, inflammatory bowel disease, nephrotic syndrome, diabetes, obesity, etc.). These conditions may induce thrombosis by themselves or contribute to its clinical onset in patients with true thrombophilic states. This is especially the case for patients who are taking contraceptive drugs, are pregnant, have undergone surgery or trauma. The term hypercoagulability states is by no means equivalent to either thrombophilia or CPT. In fact, hypercoagulability may be defined as "activation of blood coagulation" in the presence of specific markers such as fibrinopeptide A and prothrombin fragment F1 + 2. Hypercoagulability is therefore a laboratory rather than a clinical condition and can be a transient feature appearing during certain phases of thrombophilia or CPT. Lastly, conditions involving the presence of hemostatic risk factors for atherothrombosis are simply terms used to describe a statistical-epidemiological relationship between certain hemostatic variables (fibrinogen, factor VII, PAI, etc.) involving the risk of cardiovascular morbidity and mortality but not necessarily indicating a hypercoagulability state.
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PMID:Pro-thrombotic states and their diagnosis. 800 87

Thrombomodulin is an endothelial cell surface glycoprotein that forms a 1:1 complex with thrombin. In this form, thrombin can activate approximately 1,000-fold more protein C than thrombin alone and does not activate coagulation factors, V and VIII, and platelets. Activated protein C inactivates factors Va and VIIIa. Thus thrombomodulin converts thrombin from a procoagulant protease to an anticoagulant. The soluble thrombomodulin present in human urine and plasma appears to represent a truncated form that lacks the transmembrane and cytoplasmic domains of tissue thrombomodulin. The plasma level of thrombomodulin has been used as a marker for endothelial injury in vivo. Elevated levels of soluble thrombomodulin were reported in the plasma from the patients with disseminated intravascular coagulation, adult respiratory distress syndrome (ARDS), and diabetes mellitus retinopathy.
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PMID:[Soluble thrombomodulin: as a marker of endothelial injury]. 805 97

To investigate diabetes resistance to T cell-mediated disease transfer, we administered islet-specific T cell clones to the F1 progeny of nonobese diabetic (NOD) mice that were crossed with various nondiabetes-prone inbred mouse strains. We investigated four diabetogenic CD4+ T cell clones and all induced insulitis and full development of diabetes in (SWR x NOD)F1, (SJL x NOD)F1, and (C57BL/6 x NOD)F1 mice. In contrast, (BALB/c x NOD)F1 and (CBA x NOD)F1 mice were susceptible to disease transfer by some T cell clones but not others, and (C57/L x NOD)F1 mice seemed to be resistant to both insulitis and disease transfer by all of the clones tested. Disease induced by the T cell clones in susceptible F1 strains was age dependent and could only be observed in recipients younger than 13 days old. Full or partial disease resistance did not correlate with the presence or absence of I-E, different levels of Ag expression in islet cells, or differences in APC function. The results from this study suggest that there may be multiple factors contributing to susceptibility of F1 mice to T cell clone-mediated induction of diabetes, including non-MHC-related genetic background, the immunologic maturity of the recipient, and individual characteristics of the T cell clones.
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PMID:Islet-specific T cell clones transfer diabetes to nonobese diabetic (NOD) F1 mice. 807 83

We isolated CD4+ and CD8+ T cell clones from pancreatic islets of non-obese diabetic (NOD) mice and studied their interactions with pancreatic islets, in culture. The three CD4+ T cell clones proliferated when cultured with islet cells from NOD, BALB/c, or C57BL/6 (B6) mice. For proliferation to the allogeneic islets, however, APC from NOD mice were required in the culture. Two of the clones also produced IFN-gamma upon culture with NOD islet cells. The Ag from islet cells responsible for T cell stimulation were not released into the supernatant but were cell associated. Paraformaldehyde treatment of islet cells, in fact, preserved their antigenicity. The fixed islet cells could present Ag to CD4+ T cell clones, provided live, syngeneic APC were added to the culture. We conclude from these experiments that islet cells donate Ag to the APC for presentation and that the function of APC is to process the Ag. The two CD8+ T cell clones proliferated and released IFN-gamma upon reaction with islet cells from either NOD or BALB/c but not B6 mice. The CD8+ T cell clones also reacted with the insulinoma NIT-1 cell line, derived from NOD mice. Fixation of NIT-1 cells did not impair recognition when live APC were present in the culture. In this case, however, the APC could be allogeneic. We conclude that CD8+ T cells directly recognized a MHC class I-restricted Ag on target cells, but needed the costimulatory effect of APC. We also found that CD8+ T cells killed islet cells. Two of the CD4+ T cell clones produced diabetes when transferred into male, irradiated NOD mice. For optimal transfer of disease, the CD4+ T cell clones had to be co-injected with CD8+ T cells from NOD diabetic mice. The two CD8+ T cell clones did not transfer disease.
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PMID:Presentation of beta-cell antigens to CD4+ and CD8+ T cells of non-obese diabetic mice. 810 46

Urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in healthy subjects of all ages. The urinary gamma-Gla levels were highest in infants (0-1 years), then fell in an age-dependent manner, again in subjects reaching a minimum value in adults, then gradually increased over 60 years of age. Urinary gamma-Gla levels therefore change markedly with aging. The relationships between the urinary gamma-Gla excretion and plasma levels of prothrombin and protein C in patients with various hepatic diseases or diabetes mellitus were examined and compared with those in healthy adults. Both plasma prothrombin and protein C levels were decreased in all patients with liver disease compared with healthy adults. In patients with hepatitis and liver cirrhosis, the decrease did not, however, affect the gamma-Gla excretion. In addition, in patients with hepatoma or carcinoma with liver metastases, the urinary gamma-Gla levels were increased. In patients with diabetes mellitus, the urinary gamma-Gla levels and plasma levels of prothrombin and protein C tended to increase, but this was not significant. The present results indicate that simultaneous measurement of the levels of urinary gamma-Gla and plasma prothrombin and protein C is a useful tool for the diagnosis of liver diseases and diabetes mellitus.
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PMID:Urinary levels of gamma-carboxyglutamic acid and its clinical significance. 814 4

The immunogenicity of murine pancreatic islets can be reduced by culture in 95% O2 prior to transplantation. Such cultured tissue can reverse diabetes indefinitely in nonimmunosuppressed, allogeneic recipients. Although the cultured graft does not trigger a rejection response, the graft retains recognizable alloantigens in that the graft is acutely rejected when the host is immunized with donor-type antigen-presenting cells. However, over time the recipients bearing cultured islet allografts become increasingly resistant to rejecting the established graft following APC challenge. Data show that this process of graft "stabilization" is a function of time postgrafting and initial graft mass. Graft stabilization is not due to a change in the vulnerability of the graft to immune recognition--that is, stabilization cannot be accounted for by the spontaneous adaptation of the long-term graft. Rather, graft stabilization is associated with a change in host reactivity (tolerance induction). This conclusion is based on the findings that (1) recipients of long-term established grafts (> 120 days) resist rejection of both the primary and secondary donor-type grafts, and (2) donor-specific tolerance can be transferred to severe-combined-immune-deficient (scid) recipient mice.
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PMID:Tolerance induction to cultured islet allografts. I. Characterization of the tolerant state. 817 46

Parameters of haemostasis, endothelial cell markers and lipid peroxide levels were studied in 64 Type 1 (insulin-dependent) and 94 Type 2 (non-insulin-dependent) diabetic patients according to their urinary albumin excretion rate in comparison with age-matched control subjects. We determined plasma levels of fibrinogen (Clauss' method), coagulation factor VII:activity (clotting assay), factor VII antigen, protein C and S antigen, von Willebrand factor antigen, D-dimer concentration (ELISA), and lipid peroxide levels (thiobarbituric acid) in relation to urinary albumin excretion rate (RIA). Significant positive correlations were found between urinary albumin excretion rate and plasma fibrinogen (p < 0.005, p < 0.02), factor VII activity (p < 0.0002, p < 0.002), factor VII antigen (p < 0.0001, p < 0.001), protein C (p < 0.003, p < 0.05), and lipid peroxides (p < 0.02, p < 0.004) in Type 1 as well as in Type 2 diabetes. Von Willebrand factor (p < 0.001) and protein S (p < 0.0005) correlated with albuminuria only in patients with Type 1 diabetes. Although most of the haemostatic abnormalities are already found in normoalbuminuric patients, the significant positive correlations to urinary albumin excretion indicate that endothelial cell damage and coagulation disorders deteriorate with the progression of diabetic nephropathy.
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PMID:Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. 824 53

Hypercoagulability is a condition where as a result of certain pathological changes in the blood inadequate cumulation of thrombocytes or fibrin occurs which finally can lead to arterial or venous thrombosis, depending on vascular wall damage. In the submitted review the authors analyze the most important inborn and acquired causes of hypercoagulation states. As to inborn causes, deficiens of natural anticoagulation proteins (antithrombin III, protein C, protein S) are most important as well as dysfibrinogenaemia, impaired fibrinolysis associated with deficiency of natural activators of fibrinolysis or increased activity of their inhibitors and homocystinuria. The most frequent acquired causes of hypercoagulation states are the presence of anticardiolipin antibodies ("lupus anticoagulans"), pregnancy, the use of oral contraceptives, malignity, nephrotic syndrome, postoperative conditions, diabetes mellitus and some other diseases.
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PMID:[Hypercoagulation states]. 828 11

We have shown previously that a 500-bp region of the human insulin receptor promoter (-0.3 to -1.8 kb) was able to stimulate transcription from a heterologous thymidine kinase promoter in HepG2 hepatoma cells but not in HeLa fibroblasts. Footprint analysis localized the transcription factor binding sites to a 36-bp region at -1420. In this paper, we analyze the factors that recognize this element and show that it contains binding sites for the CAAT/enhancer binding protein C/EBP and nuclear factor 1 (NF-1). In addition we show that both C/EBP alpha and the C/EBP beta can transactivate the human insulin receptor promoter in a dose-dependent manner.
Diabetes 1994 Feb
PMID:An upstream element from the human insulin receptor gene promoter contains binding sites for C/EBP beta and NF-1. 828 55

There are a number of predisposing factors to thrombosis. Blood stasis and hypercoagulability are two important factors for the development of venous thrombosis. Several clinical situations are associated with these two factors. Congenital deficiencies in antithrombin III, protein C or protein S, the antiphospholipid antibodies represent well established risk factors. Arterial hypertension, dyslipidemia, tobacco, diabetes and obesity represent risk factors for arterial thrombosis. Hypofibrinolysis high levels fibrinogen and factor VII increases the risk of arterial thrombosis.
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PMID:[Predisposing factors for thrombosis]. 833 21


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