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Query: UMLS:C0751781 (NOD)
 6,696 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Nonobese Diabetic mouse (NOD mouse) is an established model of autoimmune diabetes mellitus. While all colonies of NOD mice are derived from a single diabetic female detected during the breeding of a cataract-prone strain of mice, some of the dispersed colonies have been separated for many generations and express varying levels of diabetes. It is unclear to what extent this is due to environmental factors such as diet factor or a result of the varied origins of the colonies. Here we compare the incidence of diabetes and severity of insulitis in two divergent lines of NOD mice that differ in incidence of disease, but are maintained in the same environment. F1 crosses were performed and the progeny found to express the disease incidence of the low incidence line. This finding is consistent with either a dominant resistance gene(s) being responsible for reduced penetrance of disease or a transmissible environmental agent reducing the severity of the autoimmune process.
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PMID:High and low diabetes incidence nonobese diabetic (NOD) mice: origins and characterisation. 166 48

The non-obese diabetic mouse (NOD mouse) is widely used as a model of organ-specific autoimmunity because it develops specific autoimmune destruction of pancreatic beta cells mediated by T cells and culminating in insulin-dependent diabetes mellitus. Here, we report that the NOD mouse also develops Coombs'-positive hemolytic anemia, a B cell-mediated autoimmune disease. Aged NOD mice were found to have splenomegaly and jaundice predominantly due to raised unconjugated serum bilirubin. Their hematocrits were markedly lowered, and there was a reciprocal increase in the reticulocyte count. Red blood cells (RBC) from anemic mice showed a normal lytic response to hypotonicity. RBC from non-anemic mice had normal half lives in non-anemic, non-diabetic NOD mice by 51Cr labeling but, dramatically shortened half lives in anemic mice. Similar results were obtained with RBC from anemic mice. Hemolysis could be transferred with serum from anemic mice resulting in reticulocytosis. The antibody-mediated nature of the anemia was confirmed with the direct Coombs' test. Anemia was found only in mice aged greater than 200 days and was more common in diabetic (4/8) than non-diabetic (1/16) mice at 300 days. However, by 550 days, 14/17 non-diabetic mice were affected.
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PMID:Hemolytic anemia in non-obese diabetic mice. 188 56

Type 1 (insulin-dependent) diabetes mellitus results from an autoimmune disease which is directed to insulin-secreting islet cells. In man, it is closely associated to definite major histocompatibility complex alleles. The islets are infiltrated by inflammatory cells (insulitis). Anti-islet cell autoantibodies are present in most patients and represent a valuable marker for the autoimmune reaction. The major role of autoreactive T lymphocytes has been demonstrated in animal models of spontaneous insulin-dependent diabetes (the BB rat and the NOD mouse). Such pathophysiological concepts already have clinical applications. The presence of anti-islet cell antibodies identifies patients with type 1 diabetes of slow onset who initially present with non-insulin dependent diabetes. In the same respect it is now feasible to predict the possible occurrence of diabetes in 'at risk' subjects (such as siblings of a diabetic patient) on the basis of HLA typing and the presence of markers of anti-beta cell immunity. Lastly, both in animal models and in human diabetes, it has been demonstrated that immune intervention can alter the course of anti-islet autoimmunity. From these results one may hope in the future to get preventive treatment of type 1 diabetes before the onset of metabolic disturbances.
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PMID:[Type 1 diabetes mellitus, autoimmune disease: physiopathologic aspects and practical applications]. 206 84

Microencapsulated rat islets of Langerhans (alginatepolylysine microcapsules) were implanted into the peritoneal cavity of diabetic mice (500 rat islets per mouse) in order 1) to evaluate the ability of this xenograft in correcting hyperglycemia in different models of diabetes and 2) to examine the implanted material recovered from the recipients after several weeks. 1) In the high-dose streptozotocin model in Balb/c mice (n = 14), 6 had a sustained (over one month) decrease in plasma glucose concentration from 401 +/- 7 to 171 +/- 7 mg/dl, with no effect in the other. 2) In the low dose streptozotocin model in C57BL/6J mice (n = 17), plasma glucose levels decreased in 9 mice, from 439 +/- 27 to 180 +/- 30 mg/dl, and remained below 250 mg/dl up to 60 days. In 8 mice, only a transient effect was observed. Empty capsule transplantation had no effect. Plasma insulin in successfully transplanted mice was higher in fed than in fasted state. 3) Microencapsulated rat islets had no effect on plasma glucose in male NOD mice made diabetic by cyclophosphamide treatment (n = 10). Thus, microencapsulated rat islets can improve the diabetic state in some, but not all diabetic mice. In this study, microcapsules were consistently surrounded by an inflammatory reaction, which remains a major concern.
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PMID:Comparative study of microencapsulated rat islets implanted in different diabetic models in mice. 208 71

The dependency of a high level of serotonin (5-hydroxytryptamine, 5HT) in the lung on blood 5HT was examined. The whole lung excised from NOD/Shi mice (male, 8-12 week old) immediately after being sacrificed by cervical dislocation contained 2.86 +/- 1.21 micrograms/g of 5HT per wet tissue. This amount was much higher than that explained by the included blood which was estimated by the hemoglobin concentration in the lung extract. In order to decrease 5HT level in the blood, platelet was depleted by an exposure to gamma-ray. On the 10th day after the irradiation the amount of 5HT in the lung and blood decreased to about 3.1% and 1.5% of the respective normal values. The progressive decrease in 5HT in the lung and blood of the irradiated mice was prevented by the transplantation of normal bone marrow cells (10(7) cells/mouse). 5HT in the intestine did not change significantly. The correlation between 5HT in the excised lung and the number of platelets in the blood was statistically significant (correlation coefficient r = 0.61). The irradiated, platelet-deficient mice were incapable of accumulating serotonin in the lung, while normal mice increased the lung serotonin more than 3-fold, when high doses of 5HT were administered. The results indicated that the high level of 5HT in the dissected lung was closely related to platelet in the blood. A question remained where the majority of the measured 5HT was located in the lung tissue.
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PMID:Serotonin in the lung. Demonstration of a close correlation to blood platelet. 352 83

In vivo expansion and multilineage outgrowth of human immature hematopoietic cell subsets from umbilical cord blood (UCB) were studied by transplantation into hereditary immunodeficient (SCID) mice. The mice were preconditioned with Cl2MDP-liposomes to deplete macrophages and 3.5 Gy total body irradiation (TBI). As measured by immunophenotyping, this procedure resulted in high levels of human CD45(+) cells in SCID mouse bone marrow (BM) 5 weeks after transplantation, similar to the levels of human cells observed in NOD/SCID mice preconditioned with TBI. Grafts containing approximately 10(7) unfractionated cells, approximately 10(5) purified CD34+ cells, or 5 x 10(3) purified CD34+CD38- cells yielded equivalent numbers of human CD45+ cells in the SCID mouse BM, which contained human CD34+ cells, monocytes, granulocytes, erythroid cells, and B lymphocytes at different stages of maturation. Low numbers of human GpA+ erythroid cells and CD41+ platelets were observed in the peripheral blood of engrafted mice. CD34+CD38+ cells (5 x 10(4)/mouse) failed to engraft, whereas CD34- cells (10(7)/mouse) displayed only low levels of chimerism, mainly due to mature T lymphocytes. Transplantation of graded numbers of UCB cells resulted in a proportional increase of the percentages of CD45+ and CD34+ cells produced in SCID mouse BM. In contrast, the number of immature, CD34+CD38- cells produced in vivo showed a second-order relation to CD34+ graft size, and mice engrafted with purified CD34+CD38- grafts produced 10-fold fewer CD34+ cells without detectable CD34+CD38- cells than mice transplanted with equivalent numbers of unfractionated or purified CD34+ cells. These results indicate that SCID repopulating CD34+CD38- cells require CD34+CD38+ accessory cell support for survival and expansion of immature cells, but not for production of mature multilineage progeny in SCID mouse BM. These accessory cells are present in the purified, nonrepopulating CD34+CD38+ subset as was directly proven by the ability of this fraction to restore the maintenance and expansion of immature CD34+CD38- cells in vivo when cotransplanted with purified CD34+CD38- grafts. The possibility to distinguish between maintenance and outgrowth of immature repopulating cells in SCID mice will facilitate further studies on the regulatory functions of accessory cells, growth factors, and other stimuli. Such information will be essential to design efficient stem cell expansion procedures for clinical use.
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PMID:Transplantation of human umbilical cord blood cells in macrophage-depleted SCID mice: evidence for accessory cell involvement in expansion of immature CD34+CD38- cells. 949 Jun 79

Dendritic cells (DCs) comprise a small population of cells in the normal thyroid. These excellent antigen-presenting cells (APCs) are thought to be involved in the initiation of thyroid autoimmune reactions. However it is not known whether the APCs involved in this process are indeed DCs, or thyrocytes. Our aims were as follows: (1) to isolate DCs from the thyroid of normal Wistar rats and BB-DP rats prior to the development of lymphocytic thyroiditis; (2) to determine the T-cell stimulatory capability of such isolated thyroid DCs and to compare this capability to that of BB-DP thyrocytes and splenic DCs; and (3) to investigate the phenotype of isolated thyroid DCs and to compare it to that of splenic DCs; and (4) to investigate the capability of such thyroid DCs to regulate thyrocyte growth and function, and to compare it to our earlier reports demonstrating such capability with splenic DCs. Leukokcytic cell fractions were isolated from the thyroids of BB-DP and control Wistar rats of 7-20 weeks of age. The isolation steps included gentle enzymatic tissue disruption, the collection of non-plastic adherent cells and density gradient centrifugation of these cells to yield a low and a high density non-adherent fraction. The low density cell (LDC) fraction was composed of 50-75% leukocytes in both strains. These leukocytes were almost exclusively ED1+ monocytes or MHC-class II+ DC. The high density cell (HDC) fractions of both strains were composed of about 70% MHC-class II-negative thyrocytes and 30% ED1+ monocytes. The thyroid LDCs of both strains had an APC capability in syngeneic(syn)-MLR comparable to that of splenic DCs. However, the HDCs were extremely poor in syngeneic T cell stimulation. There was a difference in composition between the Wistar and the BB-DP LDC fractions: The Wistar LDCs were composed of 30-35% ED1+ monocytes and 15-20% typical MHC-II+ DCs, while BB-DP LDC fractions contained more ED1+ monocytes (about 70%), but fewer DCs (5-10%). In comparison to splenic DCs, thyroid DCs had a low CD80 and CD86 expression in both strains (i.e., an 'immature' phenotype). The LDCs of both animal strains were shown to decrease both basal and TSH-stimulated thyrocyte proliferation and T(3)release by about half. This report shows that a cell fraction enriched for monocytes and DCs can be isolated from the thyroids of both Wistar and BB-DP rats. The cells in this fraction were as capable as splenic DCs to act as T cell stimulators in syn-MLR. Since the thyroid HDCs (predominantly thyrocytes) were very poor at such T cell stimulation, thyroid monocytes and DCs (and not thyrocytes) are the prime candidates to act as immune accessory cells in the initiation of thyroid autoimmunity in the rat. Wistar thyroid LDCs differed in phenotype from BB-DP LDCs. The latter contained a lower percentage of DCs and a higher percentage of their precursors, the monocytes. Interestingly, a defect in the transition of monocytes to DCs has been described in another animal model of autoimmune thyroiditis/insulitis (the NOD mouse), as well as in thyroiditis and diabetic patients.
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PMID:A functional and phenotypic study on immune accessory cells isolated from the thyroids of Wistar and autoimmune-prone BB-DP rats. 1109 Feb 40

Sulfatide (3'sulfogalactosylceramide) is a glycosphingolipid present within the nervous system and in the islets of Langerhans. Anti-sulfatide antibodies have been observed in both pre-diabetic and newly diagnosed type 1 diabetic patients. The aim of this study was to test in vivo, the therapeutic effect of sulfatide on the development of diabetes in the NOD mouse. In four separate experiments diabetogenic splenocytes from newly diabetic NOD mice were injected iv into 7-8 week old irradiated (700R) female NOD mice (4-10 million cells/mouse). Each experiment consisted of four treatment groups to which the mice were randomly divided: 1) sulfatide; 2) galactosylceramide (the precursor to sulfatide without sulfate); 3) GM1, a glycosphingolipid negatively charged as sulfatide but with a different sugar composition; and 4) phosphate buffered saline (PBS). The mice received 100 microg glycosphingolipid iv on the day of cell transfer and 1-3 times thereafter at four day intervals, and were screened for diabetes three times a week the next 52 days. Among all the 35 sulfatide-treated mice 54% became diabetic compared to 93 % of 43 PBS-treated animals (p < 0.00001). Correspondingly, galactosylceramide reduced diabetes incidence to 52% (25 mice, p < 0.00001). On the other hand, 86% of GM1-treated mice (n=28) became diabetic indicating that no effect was obtained by this glycosphingolipid. In two experiments in which less spleen cells were transferred (4-5 mill.) and glycosphingolipids were given 4 times, 35% of the sulfatide-treated animals (n = 17) developed diabetes compared to 85% of PBS-treated mice (n = 20, p < 0.001). A robust proliferative response to sulfatide, but none to GM1, was observed when spleen cells were rechallenged with glycosphingolipid in vitro. Thus, like insulin and GAD, sulfatide is able to prevent diabetes in NOD mice.
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PMID:Treatment with sulfatide or its precursor, galactosylceramide, prevents diabetes in NOD mice. 1168 95

The nonobese mouse model of autoimmune diabetes (NOD mouse) exhibits a strain-dependent preponderance of disease in females. Castration of male NOD mice leads to an increased incidence of diabetes, suggesting that testosterone directly modulates the expression of diabetes in the NOD mouse. However, castration also modulates hypothalamic and pituitary hormone production via removal of the negative feedback effects of testosterone. One hypothalamic hormone with immunomodulatory properties whose expression is increased by castration is GnRH. To test whether the increased incidence of diabetes in castrated male NOD mice is related to an increase in GnRH activity, we treated castrated male NOD mice with Antide, a GnRH receptor antagonist, to determine the effect on the incidence and timing of onset of diabetes. The prevalence of diabetes at 40 wk of age in male NOD mice was 50% in sham-operated mice, compared with an 83% prevalence in castrated males. Antide administration prevented the increased incidence of diabetes in the castrated male mice. Antide reduced total serum IgG levels, IL-6 cytokine expression in cultured splenocytes, and the lymphocytic infiltration of islets. GnRH administration exerted reciprocal effects, leading to earlier timing of onset of diabetes and increases in serum total IgG levels. We conclude that GnRH modulates the expression of diabetes in the NOD mouse independently of gonadal steroids.
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PMID:Modulation of diabetes with gonadotropin-releasing hormone antagonists in the nonobese mouse model of autoimmune diabetes. 1295 92

Type 1 diabetes is an immune-mediated disease critically dependent upon the interaction between antigen-presenting cells and T cells. Clearly, both CD4+ and CD8+ T cells are required, but activated CD4+ T cells are both necessary and sufficient in causing disease. The mechanism of the Th1/Th2 immunoregulatory imbalance is unclear and needs to be further investigated. CD8+ T cells are not commonly sufficient in causing disease, but CD8 T cells are necessary in initiation (<14 weeks in the NOD mouse), but not in the later (>14 weeks) effector phase of the disease. It is still unclear whether the CD8+ T cell exerts its function as a classical effector cell or mainly as an immunomodulatory cell acting in synergy with the CD4+ T cell. The relative role of T cell effector mechanisms such as Fas/FasL, perforin/granzyme, and the TRAIL systems is unclear. Proinflammatory cytokines, reactive oxygen species, and other immune mediators seem to be involved in beta cell destruction, but much is to be learned about signaling, molecular mechanisms, and in vivo importance.
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PMID:Beta cell death and protection. 1467 38


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