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)

The risk factors of retinopathy associated with administration of interferon have not been fully clarified. We prospectively examined the retinal condition in 50 patients with type C chronic active hepatitis during alpha-interferon treatment. 43 patients (86%) were shown to have retinopathy during the course of interferon treatment, and were divided into three groups. Grades I, II and III were patients having a single episode of transient retinopathy with soft exudate or hemorrhage (34%), frequent episodes of retinopathy (42%), and exacerbating retinopathy requiring change or cessation of interferon treatment (10%), respectively. The patients with grade II and III were found to have the first retinal changes within 8 weeks after initiation of the interferon therapy. Early onset of retinopathy and presence of systemic disease such as diabetes mellitus or hypertension were risk factors for serious retinopathy with statistical significance. The grades of retinopathy were also well correlated with dosage and duration of interferon treatment. These results suggest that careful fundus examination is required up to 8 weeks after initiation of interferon treatment, especially for the patients with risk factors such as early onset of retinopathy, presence of systemic diseases, and large dosages and long duration of interferon therapy, in order to prevent serious ocular complications.
 ...
PMID:[Evaluation of risk factors of interferon-associated retinopathy in patients with type C chronic active hepatitis]. 864 32

A variable region gene of the T-cell receptor, V beta 8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2u mice after immunization with myelin basic protein (MBP). Vaccination of these mice with naked DNA encoding V beta 8.2 protected mice from EAE. Analysis of T cells reacting to the pathogenic portion of the MBP molecule indicated that in the vaccinated mice there was a reduction in the Th1 cytokines interleukin-2 (IL-2) and interferon-gama. In parallel, there was an elevation in the production of IL-4, a Th2 cytokine associated with suppression of disease. A novel feature of DNA immunization for autoimmune disease, reversal of the autoimmune response from Th1 to Th2, may make this approach attractive for treatment of Th1-mediated diseases like multiple sclerosis, juvenile diabetes and rheumatoid arthritis.
 ...
PMID:Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity. 870 50

Nitric oxide (NO) is a critical mediator of a variety of biological functions. A range of micro-organisms, including viruses, bacteria, protozoa and helminths, is sensitive to NO produced by macrophages activated with gamma-interferon (IFN-gamma) and lipopolysaccharide. In contrast, NO is involved in a number of important immunopathologies, including diabetes, graft-vs-host reaction, rheumatoid arthritis, systemic lupus erythematosus, experimental autoimmune encephalomyelitis and multiple sclerosis. Thus, it is crucial that the synthesis of NO is under tight regulation. This is achieved, in part, through the opposing cytokines produced by T helper 1 (Th1) and Th2 cells. Th1 cells produce IFN-gamma, which is the most powerful inducer of inducible NO synthase (iNOS). In contrast, interleukin 4 is produced by Th2 cells and inhibits the induction of iNOS at the level of transcription. Furthermore, NO is also produced by Th1 cells, whose proliferation can be inhibited by high concentrations of NO. Thus, apart from being a mediator of Th1/Th2 interaction, NO may also be an important self-regulatory molecule that prevents the over-expansion of Th1 cells which are implicated in a range of severe immunopathologies.
 ...
PMID:Nitric oxide in infectious and autoimmune diseases. 872 41

The involvement of macrophages in protection against diabetes mellitus in mice of BALB/c (susceptible) and C57BL (resistant) strains infected with the B (non-diabetogenic) or D (highly diabetogenic) variant of encephalomyocarditis (EMC) virus was examined. Pretreatment with the B variant of EMC virus (EMC-B), avirulent interferon (IFN) inducer, or Corynebacterium parvum inhibited diabetes in BALB/c mice infected with the D variant of EMC virus (EMC-D). Treatment of C57BL mice with carrageenan to compromise macrophage function rendered C57BL mice susceptible to EMC-D-induced diabetes. In macrophage culture for BALB/c mice, EMC-B induced IFN at an earlier stage than did EMC-D. The C57BL mouse-derived macrophages produced more IFN than did BALB/c mouse-derived macrophages after stimulation with EMC-D. Moreover, C. parvum increased IFN production in macrophage cultures from BALB/c mice, whereas carrageenan inhibited that in macrophage cultures from C57BL mice. These results suggest that IFN derived from macrophages may have an important role in protecting mice against EMC virus infection.
 ...
PMID:Protective effects of macrophage-derived interferon against encephalomyocarditis virus-induced diabetes mellitus in mice. 874 25

The development of autoimmune diabetes in the NOD strain of mice (H-2g7) is marked by the presence of T-cells reactive to the p277 peptide of the 6O-kDa heat shock protein (hsp60). We have found that the p277 peptide can be used as a therapeutic vaccine to arrest NOD diabetes. Recently, we found that T-cell autoimmunity to p277 also develops spontaneously in C57BL/KsJ mice (H-2d) during the induction of autoimmune diabetes by a very low dose of the beta-cell toxin streptozotocin (STZ). We now report the inhibition of STZ toxin-induced autoimmune diabetes by p277 peptide therapy. Administration of two doses each of 100 micrograms of peptide p277 in mineral oil given 1 week after toxin induction and 85 days later was most effective. The effect of p277 on STZ toxin-induced diabetes was marked by a shift in p277 autoimmunity from a T-cell proliferative response to the production of anti-p277 antibodies. The anti-p277 antibodies were predominantly of the IgG1 and IgG2b isotypes, known to be regulated by Th2 type cytokines; IgG2a antibody, known to be dependent on interferon (IFN)-gamma, was induced to a much lesser degree. Peptide p277 therapy was specific: treatment of the mice with an immunogenic peptide from the sequence of another antigen, GADp34, failed to prevent the development of diabetes. The GADp34 peptide induced lower titers of specific antibodies, and the antibodies were predominantly of the IgG2a class. Thus, p277 peptide therapy, marked by the induction of Th2-type antibodies, can be effective in toxin-induced autoimmune diabetes.
Diabetes 1996 Sep
PMID:The hsp60 peptide p277 arrests the autoimmune diabetes induced by the toxin streptozotocin. 877 17

The objective of this study was to evaluate the metabolic effects and opthalmologic effects of alpha-interferon therapy in diabetes mellitus patients with proliferative diabetic retinopathy (PDR). Three volunteer patients [insulin-dependent diabetes mellitus (IDDM), insulin requiring non-insulin-dependent diabetes mellitus (NIDDM), and maturity onset diabetes of the young (MODY)] threatened with blindness due to progressive PDR were treated with alpha interferon for 4 months and were evaluated at intervals of 1-2 weeks to monitor the drug effects on carbohydrate tolerance and possible beneficial therapeutic effects on the preexisting PDR. Metabolic studies included basal and postsustacal glucose, c-peptide and glucagon, fasting serum cortisol, free fatty acids, growth hormone, insulin-like growth factor-1, and urinary microalbumin excretion. Ophthalmologic studies included visual acuity, slit lamp examination, gonioscopy, fluorescein angiography, and standard colored fundus photographs. In all subjects, hyperglycemia worsened with duration of increasing dosage of interferon therapy, requiring progressively higher daily insulin requirements of 17%-68% above pretreatment values. Lowered levels of stimulated C-peptide were observed in the NIDDM and MODY subjects. The counterregulatory hormones (cortisol, growth hormone, and glucagon) were elevated during the 4 months of interferon therapy. In all subjects, visual acuity appeared to stabilize. No new retinal hemorrhages occurred during the 4 months of interferon administration, although all subjects experienced hemorrhage within 6 weeks of termination of the drug. Although only three subjects were investigated, the 1-2 week frequency of metabolic and opthalmologic studies permit some conclusions. The metabolic effects of alpha interferon in our diabetic subjects were consistent worsening of carbohydrate tolerance associated with impaired beta-cell secretion and increased insulin resistance. The extensive opthalmologic investigation suggested protection from retinal hemorrhage while receiving interferon, but further studies are indicated to validate these proposed and antiangiogenic properties.
J Diabetes Complications
PMID:A pilot study of chronic recombinant interferon-alfa 2a for diabetic proliferative retinopathy: metabolic effects and opthalmologic effects. 877 37

Immunogrammes of 31 patients with grave forms of insulindependent diabetes mellitus were reviewed. The illness has been characterized as a systemic immunopathologic process combining autoimmune and infectious-and-allergic components realized by organ and tissue abnormalities; it evolves against the manifest background of allergy of both delayed anl immediate types, impairement of the humoral and cell-mediated immunity function, pathogenetic activity of endogenous proteases, the complement system components and interferon.
 ...
PMID:[The role of immunopathological factors in severe forms of insulin-dependent diabetes mellitus]. 881 57

To assess the clinical value of determination of the interferon (IFN)-producing capacity of patients, IFN production induced by Sendai virus (HVJ) in vitro was measured in cell cultures of whole blood from patients with various diseases. IFN production in patients with lung cancer, myelodysplastic syndromes, noninsulin-dependent diabetes mellitus, pulmonary tuberculosis, and asymptomatic HIV-1 infection was lower than that in healthy persons. Furthermore, periodic measurements of IFN production revealed decreasing IFN producing capacities in patients with lung cancer with progression of the tumor stage. However, increased IFN-producing capacities were observed in patients with tuberculosis after standard therapy. Further experiments showed that the main type of IFN induced in whole blood cultures was IFN-alpha, and decreased IFN production in patients did not result from a decreased number of leukocytes but rather from an impairment of cellular IFN production. The evaluation of IFN production in whole blood cell cultures may be a feasible method of assessing the impaired immune status.
 ...
PMID:Determination of interferon-alpha-producing capacity in whole blood cultures from patients with various diseases and from healthy persons. 893 66

Oncogene amplification is frequent in many epithelial tumors and often associated with advanced tumor progression. In different epithelial neoplasias it helps to provide prognostic information on individual patients. The present study was performed to evaluate the hitherto unknown prevalence of INT-2 gene amplification and its potential usefulness as prognostic marker in patients with human thyroid cancer. We used differential quantitative polymerase chain reaction and fluorescent DNA technique as a reliable method to detect low copy-number amplification of oncogenes from archival carcinoma specimens. Sequences from the int-2 gene and the single copy gamma-interferon gene were amplified simultaneously by PCR and quantified on a fluorescence activated sequencer. Native tumor tissue from 63 patients with differentiated thyroid cancer (43 papillary, 3 oncocytary, and 17 follicular) and from 12 goiters was analyzed by differential quantitative polymerase chain reaction. The study group contained many far advanced tumors. 40% of tumors were recurrent, 35% were staged T4 tumors and 70% presented with lymph node metastases. The prevalence of INT-2 amplification was 12% for follicular and 7% for papillary carcinomas. In goiter tissue no amplification was found. Amplification was only 2-4fold in positive cases. Low grade amplification is of no apparent importance in differentiated thyroid cancer.
Exp Clin Endocrinol Diabetes 1996
PMID:INT-2 gene amplification in differentiated human thyroid cancer. 898 Oct 13

Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies (ICAs) in IDDM patients were associated with high levels of Th1 and Th2 cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. Also, HLA-DQ types did not significantly correlate with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory cytokines appeared to be the most reliable marker of the individual disease process. This study provides first evidence of a systemic bias in the immune regulation of humans, which might be either toward cell-mediated immunity (Th1) in IDDM or humoral immunity (Th2) in Graves' disease.
Diabetes 1997 Feb
PMID:Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease. 900 Jul


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