Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751781 (NOD)
 6,696 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of oral administration of THI, a compound present in ammonia caramel food colouring, was studied in spontaneous and induced murine diabetes mellitus. Continuous administration of THI at 400 ppm in drinking water reduced the prevalence of spontaneous diabetes in female NOD/Lt mice from 63% in untreated controls to 8% in treated animals. Since cyclophosphamide (CP) accelerates and intensifies diabetes in NOD mice, we also studied the effect of THI in this model. Diabetes incidence was reduced from 100% in mice given only CP to 13-14% in mice given THI either concurrently or from 14 days previously. Histologically, THI greatly reduced the severity of insulitis. As measured by flow cytometry, all THI-treated mice had a 60-80% reduction in splenic CD4+ and CD8+ T cells. THI-treated mice showed no untoward effects and specifically no weight loss, or pathological changes in their livers, kidneys or lungs. However, there was moderate atrophy of the thymus cortex. THI is a small imidazole-containing compound with structural similarity to histamine and urocanic acid, both known to have immunosuppressive properties. It is a widely used food additive with no known long-term toxic effects at low dosage. Thus, THI could be a useful immunosuppressive agent.
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PMID:Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutylimidazole (THI), a component of caramel colouring III. 160 24

Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction.
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PMID:Dimethyl sulfoxide modulation of diabetes onset in NOD mice. 291 23

Strain differences in the induction of hepatocellular preneoplastic lesions by amitrole were examined in NOD, ICR and DS mice. Amitrole was administered to mice in drinking water at a dose of 1% for 6 months. After 3 months, hyperplastic nodules (HN) and severe fibrosis were prominent in NOD mice but not in other strains. On examination at 6 months, both number and size of HN were greatest in the NOD strain. Furthermore, a hepatocellular carcinoma was found in a NOD mouse, suggesting that this strain is more susceptible to amitrole-induced hepatocarcinogenesis than are ICR or DS mice.
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PMID:Amitrole: strain differences in morphological response of the liver following subchronic administration to mice. 408 83

According to our previous studies the Arabidopsis gene AthH2 which is inducible by blue light and phytohormones codes for an intrinsic membrane protein. It bears a resemblance to several distinct channel proteins of plant and animal species classified as the MIP/NOD-26/GlpF family. In the present study biochemical analyses and electron microscopic immunochemistry were used to elucidate the subcellular location of the AthH2 protein. The results clearly demonstrate that it is an exclusive constituent of the plasmalemma. Furthermore, the expression of the AthH2 gene in transgenic Arabidopsis plants containing the promoter region of AthH2 fused to the beta-glucuronidase (gus) reporter gene was studied. The in situ localization of gus activity revealed that the specific promoter is temporally activated by light in expanding and/or differentiating cells comprising newly formed tissues and organs: root elongation zone, guard cells of stomata, vascular bundle sheaths, filaments of stamen and young siliques. Several sites of gus expression coincide spatially with those of in situ hybridization and the immunocytochemical reaction, respectively, suggesting that the AthH2 promoter had correctly responded to light as an important exogenous factor with relevance to the complex pattern of differentiation. Studies with protoplasts from plants transformed with an antisense construct revealed a water transport capacity of the AthH2 protein.
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PMID:The blue light-responsive AthH2 gene of Arabidopsis thaliana is primarily expressed in expanding as well as in differentiating cells and encodes a putative channel protein of the plasmalemma. 753 55

17 members of MIP family from bacteria, yeast, plants and animals are compared in this review. These proteins appear to function in (1) water channels (CHIP, WCH-CD, MIWC, AQP3, gTIP, RD28, TobRB7), (2) neurogenesis (Bib), (3) small-molecule-permeating channels (MIP, AQP3, NOD, Glpf), (4) unknown function (WCH-3, AtRB7, Pea R7A, FPS1). However, the biological functions are not well established. The most conserved residues in the first and the second halves of all MIP family proteins are asparagine-proline-alanine (NPA) sequences in the loops (NPA boxes). This structural similarity may lead to functional similarity (water and/or small molecule permeation). This signature sequence for the MIP family will facilitate the identification of new protein members of this family.
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PMID:[Water channel family proteins]. 753 36

The major intrinsic protein (MIP) of the bovine lens fiber cell membrane was the first member of the MIP family of proteins to be sequenced and characterized. It is probably a homotetramer with transmembrane channel activity that plays a role in lens biogenesis or maintenance. The polypeptide chain of each subunit may span the membrane six times, and both the N- and C-termini face the cell cytoplasm. Eighteen sequenced or partially sequenced proteins from bacteria, yeast, plants, and animals have now been shown to be members of the MIP family. These proteins appear to function in (1) metazoan development and neurogenesis (MIP and BIB), (2) water transport across the human erythrocyte membrane (ChIP), (3) communication between host plant cells and symbiotic nitrogen-fixing bacteria (NOD), (4) transport across the tonoplast membrane during plant seed development (alpha-TIP), (5) water stress-induced resistance to desiccation in plants (Wsi-TIP), (6) suppression of a genetic growth defect on fermentable sugars in yeast (FPS1), and (7) transport of glycerol across bacterial cell membranes (GlpF). One other sequenced member of the MIP family (ORF1 of Lactococcus lactis) has no known physiological function. The biochemical functions of the eukaryotic proteins are not well established. Computer analyses have revealed that the first and second halves of all MIP family proteins probably arose by a tandem, intragenic, duplication event. Thus, the primary structure of putative transmembrane helices 1 to 3 is similar to that of putative transmembrane helices 4 to 6 even though they are of opposite orientation in the membrane. Among the most conserved residues in these two repeated halves are a membrane-embedded glutamate (E) in helices 1 and 4, an asparagine-proline-alanine (NPA) sequence in the loops between helices 2 and 3 (cytoplasmically localized) and helices 5 and 6 (extracellularly localized), and a glycine within helices 3 and 6. Statistical analyses suggest that the two halves of these proteins have evolved to serve distinct functions: the first half is more important for the generalized or common functions of these proteins, while the second half of these proteins is more differentiated to provide specific or dissimilar functions of the proteins. The apparent origin of MIP family proteins by duplication of a three-spanner precursor protein suggests an evolutionary origin distinct from other transport proteins with six transmembrane spanners.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins. 832 40

We have previously shown that diabetes in the NOD mouse can be prevented if mice are placed from weaning on an infant formula diet in which the protein source is replaced with casein hydrolysate (Pregestimil) or soy protein (Prosobee), or if 1% nicotinamide is given in the drinking water. Nicotinamide somewhat suppresses insulitis but the hydrolysed casein formula does not. In this study, Prosobee was given concurrently with oral nicotinamide from weaning and their effects on the development of insulitis and diabetes measured. These effects were also assessed in mice given Prosobee alone from conception (day -20) or from weaning. Unlike the earlier experiments, a marked suppression of insulitis was observed when the diets and nicotinamide were given concurrently (mean insulitis scores +95% confidence intervals (back transformed): day 40 = 0.4% [0.03, 1.17] vs. 12.5% [2.52, 28.40] and at day 90 = 8.8% [3.65, 15.68] vs. 48.1% [33.89, 62.49], P = 0.0001). A similar suppression was observed on day 90 with Pregestimil combined with nicotinamide 7.3% [3.88, 11.70] vs. 43.8% [32.59, 55.35] (P = 0.0001). Qualitatively, introduction of Prosobee from conception appeared to elicit a greater degree of suppression of insulitis than when introduced from day 21. Insulitis lesions were examined immunohistochemically for CD4, CD8 and MAC-1 cells. The proportion of these cells was not different for any regime despite the great differences in total number of inflammatory cells in and around the islets of mice fed the combined diet. All the three dietary treatments (Prosobee from day -20, Prosobee from day 21, Prosobee+nicotinamide from day 21) resulted in substantial protection from diabetes in mice followed until 250 days. We conclude that the complete prevention of diabetes in the NOD mouse fed a casein-free diet together with nicotinamide is accompanied by marked inhibition of insulitis, which is not seen when either dietary agent is introduced alone. The somewhat greater suppression of insulitis in mice given the soy diet from conception compared to those fed from day 21 may indicate that even maternal diet during gestation may influence diabetes outcome in the offspring.
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PMID:A combined casein-free-nicotinamide diet prevents diabetes in the NOD mouse with minimum insulitis. 859 3

Dentato-rubro-pallido-luysian atrophy (DRP-LA) is a rare autosomal dominant neurodegenerative disorder. Recently the genetic abnormality has become clear. We encountered four patients with DRPLA (including a 14-year-old boy and his father) in whom the final diagnosis was made by DNA analysis. In addition to performing conventional MRI, we quantified brain metabolites by proton MR spectroscopy. We also compared the expanded repeat size of CAG trinucleotide in a gene on the short arm of chromosome 12 to the MR findings which consisted of the findings of clinical severity and age of onset. The method reported by Nagafuchi et al. was used to determine the size of the CAG repeat on the focus chromosome. Repeat size was closely correlated with age at onset and disease severity. The MR studies were performed with a Magnetum H-15SP (Siemens, 1.5 Tesla) equipped with a C-P type head coil. Axial T2-WIs (TR = 2000 ms, TE = 90 ms) and T1-WIs (TR = 200 ms, TE = 15 ms) were measured. Atrophy of the brainstem, the tegmentum, and the cerebellum, and periventricular hyperintensity could be seen. The sequence for 1H-MRS was PRESS, voxel size was 8 ml, and regions of interest were placed on right basal ganglia and right parietal white matter. After compensating the observed signals, we obtained metabolite concentrations by using compensated water intensity as an internal standard. Despite the absence of abnormalities of the basal ganglia on MRI, NAA concentrations differed from patient to patient and were low in severe clinical cases. We propose that the CAG repeat size of the focus chromosome and NAA concentration quantified by 1H-MRS are closely correlated with clinical severity and age of onset. In conclusion, DNA analysis may be useful in early diagnosis and 1H-MRS can detect metabolic abnormalities non-invasively even when no markedly abnormal findings can be detected with other clinical modalities.
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PMID:[Magnetic resonance studies of dentato-rubro-pallido-luysian atrophy--correlation with clinical severity and age of onset]. 888 30

Recently, the synthetic immunomodulator Linomide (quinoline-3-carboxamide, LS 2616) was reported to prevent IDDM and insulitis in NOD mice. The mechanism for this protective effect is not known. The cytokine interleukin 1 (IL-1) may be a pathogenetic factor in the initial destruction of the beta-cells leading to IDDM. This study was undertaken to investigate the influence of Linomide on IL-1beta induced diabetogenic and hormonal changes in the rat in vivo, and on IL-1beta mediated synthesis of NO and inhibition of insulin secretion in isolated islets of Langerhans ex vivo. Normal male Wistar Kyoto rats received 4.0 microg/kg of recombinant human IL-1beta (rhIL-1beta) i.p. daily for 5 days with or without Linomide (8-9 mg/kg/day) in the drinking water. Litters of neonatal Wistar rats were pretreated for 3 days with injections of 10 mg/kg of Linomide i.p., and pancreatic islets of Langerhans were isolated for ex vivo studies. Linomide alone caused significant hypercorticosteronemia, hypoglucagonemia, lymphopenia and neutrophilia. Linomide had no effect on IL-1beta induced hyperglycemia, hyperglucagonemia, lymphopenia, neutrocytosis, or hypercorticosteronemia on day three and hypocorticosteronemia on day five. Further, Linomide did not prevent rhIL-1beta mediated reduction in insulin secretion or increase in NO synthesis ex vivo. In conclusion, Linomide does not seem to exert its protective effect on IDDM development via inhibition of interleukin 1 action on islet insulin release or NO production, but the increase in plasma corticosterone may contribute to the understanding of the immunomodulatory effects of Linomide.
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PMID:Linomide increases plasma corticosterone in normal rats, but does not prevent the inhibitory action of IL-1 on beta-cells in vivo or ex vivo. 891 32

Excess iodine ingestion has been implicated in induction and exacerbation of autoimmune thyroiditis in human populations and animal models. We studied the time course and sex-related differences in iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. This strain, derived from a cross of NOD with B10.A(4R), spontaneously develops autoimmune thyroiditis but not diabetes. NOD-H-2h4 mice were given either plain water or water with 0.05% iodine for 8 weeks. Approximately 54% of female and 70% of male iodine-treated mice developed thyroid lesions, whereas only 1 of 20 control animals had thyroiditis at this time. Levels of serum thyroxin (T4) were similar in the treatment and control groups. Thyroglobulin-specific antibodies were present in the iodine-treated group after 8 weeks of treatment but antibodies to thyroid peroxidase were not apparent in the serum of any of the animals. Levels of thyroglobulin antibodies increased throughout the 8-week iodine ingestion period; however, no correlation was seen between the levels of total thyroglobulin antibodies and the degree of thyroid infiltration at the time of autopsy. The thyroglobulin antibodies consisted primarily of IgG2a, IgG2b, and IgM antibodies with no detectable IgA, IgG1, or IgG3 thyroglobulin-specific antibodies. The presence of IgG2b thyroglobulin-specific antibodies correlated well with the presence of thyroid lesions.
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PMID:Iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. 893 7


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