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)

Based on our new finding that an inflammation in which tumor necrosis factor (TNF) is primed or triggered (ontogenic inflammation) can regulate the homeostasis in ontogenesis, we have identified a new lipopolysaccharide from wheat flour (LPSw) that can induce ontogenic inflammation in adult mice. LPSw can prime adult mice to produce TNF when given orally or percutaneously, suggesting that it may maintain homeostasis in adults. LPSw can cure experimental animals of diabetes, hyperlipidemia, ulcer, and herpes. It can also stimulate bone resorption and egg-laying, and shows a strong analgesic effect that is blocked by naloxone. This effect even allows a release from drug addiction. Suppression of serum cholesterol level by oral uptake of LPSw in Watanabe heritable hyperlipidemic (WHHL) rabbit was also observed. Infection of toxoplasma was prevented by oral uptake of LPSw. The realization that a single oral or percutaneous administration of LPSw may be a cure for multiple intractable diseases may lead to the presentation of a nontoxic type of Coley's toxin, which is known to be an efficient cancer treatment, but has high toxicity.
 ...
PMID:Oral or percutaneous administration of lipopolysaccharide of small molecular size may cure various intractable diseases: a new version of Coley's toxin. 147 70

Insulin-dependent diabetes mellitus is characterized by progressive autoimmune destruction of pancreatic Beta cells mediated by ill-defined effector mechanisms. Experimental data suggest that cytokines, e.g. interleukin 1 and tumor necrosis factor, could play a fundamental role. The aim of this study was to analyze the effect of recombinant IL-1 beta (rIL-1 beta) on both islet functional capacity and morphology, using long-term cultures and various glucose concentrations. Islet cultured with 1 g/l (5.5 mmol/l) glucose maintained normal insulin- secretion and morphology for more than two months. In contrast, islets cultured with 2 g/l (11 mmol/l) glucose showed an altered insulin secretion and a shorter survival (40 days). At 11 g/l (60 mmol/l) glucose, islets died by 2 weeks of culture. rIL-1 beta exerted a cytotoxic effect on islet cells only when added to cultures containing supraphysiological glucose concentrations. But, in the presence of 1 g/l glucose, the addition of rIL-1 beta (40 ng/ml) for prolonged periods (14 days), did not alter islet function. Our results suggest that in auto-immune type I diabetes, IL-1 beta represents an aggravating factor in lesion formation more than a primary pathogenic mechanism.
 ...
PMID:The effects of interleukin-1 on pancreatic beta cell function in vitro depend on the glucose concentration. 147 95

The 1991 literature on septic arthritis included a concise review of adult septic arthritis, examples of pseudoseptic arthritis, and two interesting animal studies. One animal study examined the induction of acute synovitis by the intra-articular injection of bacterial endotoxin and the cytokines tumor necrosis factor-alpha, and interleukin-1 beta; and the other studied the effects of early and delayed synovectomy in the management of septic arthritis. The predispositions to septic arthritis can be divided into local joint abnormalities, systemic factors, or both. Examples of the local joint abnormalities include osteoarthritis of the hip and apatite-associated arthropathy. Septic arthritis in a patient with rheumatoid arthritis, in a patient with diabetes mellitus and hip arthropathy associated with hemochromatosis, or in a patient with acquired immunodeficiency syndrome and hemophilic arthropathy are examples of how systemic predisposition is coupled with local joint pathology to increase the vulnerability of the host to joint infection. Other examples of systemic disease that predispose to septic arthritis are systemic lupus erythematosus, hypogammaglobulinemia, and human immunodeficiency virus infection, as well as intravenous drug abuse. Unusual microorganisms causing septic arthritis in the adult include Achromobacter xylosoxidans, Moraxella catarrhalis, meningococci, and diphtheroids. Uncommon pathogenesis is represented by a case of intra-articular inoculation of Mycobacterium gastri into the small joint of the hand and a case of mixed bacterial infection of the hip resulting from an extension of a contiguous pelvic infection associated with trauma. Two cases of immune complex glomerulonephritis illustrate the extra-articular complications of septic arthritis: one due to group G streptococcus and the other due to pneumococcus. Finally, septic bursitis is reviewed from the community practice perspective.
 ...
PMID:Bacterial arthritis. 150 74

In attempt to evaluate biological roles of tumor necrosis factor (TNF), we studied the effects of anti-TNF mAb in non-obese diabetic (NOD) mice. Anti-murine TNF mAb rendered NOD mice hypersensitive to the lethal effects of radiation and prevented the reconstitution of lethally irradiated mice with adoptively transferred lymphocytes. While TNF-alpha reduced the incidence of diabetes development in the adoptive transfer system even when given 6 days post-transfer, mAb to TNF could not reduce or increase the incidence of diabetes compared to control mice. Administration of TNF-alpha for 4 or 8 weeks significantly reduced the incidence of spontaneous insulitis in NOD mice, while anti-TNF mAb given for 8 weeks increased the incidence of insulitis significantly.
 ...
PMID:Monoclonal anti-tumor necrosis factor antibody renders non-obese diabetic mice hypersensitive to irradiation and enhances insulitis development. 151 Jul 87

Polymorphisms were sought between HLA B and tumor necrosis factor (TNF) using three genomic probes. Extensive polymorphism was detected within a panel of 50 cell lines including 37 homozygotes representing 21 different ancestral haplotypes (AH). Following Taq I digestion of genomic DNA, we observed three allelic patterns with probe X (R17A) and four with probe V (R9A). Seven different allelic patterns were found with probe Y (M20A) after Taq I + Rsa I digestion. Family studies showed that the Y, X, and V alleles were inherited and segregated with HLA haplotypes. A striking feature of the allelic patterns detected by these probes was that cells with the same AH had identical Y, X, and V alleles (i.e., the alleles were haplotypic). Of 15 different Y-X-V haplotypes observed, 11 were found to be specific for a particular AH (i.e., were haplospecific). Four were shared by more than one AH, but in these instances there were extensive similarities in other regions within the major histocompatibility complex (MHC), for example, the Japanese 46.2 (HLA Bw46-DRw8) and the Chinese 46.1 (Bw46-DR9) share all alleles between HLA C and C4 and differ only in class II, suggesting their relatively recent divergence by recombination between C4 and DR. Surprisingly, two insulin-dependent diabetes mellitus (IDDM)-resistant but race-specific AHs 52.1 (Bw52-DRB1*1502, Japanese) and 7.1 (B7-DRB1*1501, Caucasoid) carry the same Y-X-V haplotype, suggesting the possibility of localizing gene(s) relevant to IDDM. The present study confirms that MHC AHs have been conserved en bloc, including the region between HLA B and TNF.
 ...
PMID:Haplospecific polymorphism between HLA B and tumor necrosis factor. 156 85

The effects of the cytokines tumor necrosis factor-alpha and interferon-gamma on the adult beta-cell have been well described: a reduction of insulin secretion and content and death of the cell. For this reason and because these cytokines may be released from activated lymphocytes and macrophages that infiltrate islets in insulin-dependent diabetes, they have been implicated in the pathophysiology of this form of diabetes. As to whether the human fetal beta-cell, which differs from the adult beta-cell in not releasing insulin in response to the nutrient glucose and not being adversely affected by the toxin streptozotocin, is similarly affected is unknown. To examine this question we cultured monolayers of a single cell suspension of human fetal pancreas in the presence or absence of 1000 U/mL of these cytokines for 7 days. Chronic insulin release was enhanced for the first 2 days of culture, but unchanged thereafter. Acute insulin release in response to the secretagogue theophylline (10 mM) was enhanced on day 7, but not earlier. There was an increase in the insulin content of the cells by the fourth day, probably due to an increase in the number of beta-cells present (45 +/- 5% vs. 22 +/- 3%). Microscopically, non-beta-cells also seemed to increase in number; there was an increase in both DNA and cell number by the seventh day. In contrast to these beneficial effects on the human fetal beta-cell, treatment of adult rat insulinoma cells, represented by RIN-m5F cells, resulted in inhibition of insulin secretion during the first day of culture and subsequent death of 86% of the cells by the sixth day of culture. It is hypothesized that the functional immaturity and lack of normal (adult) metabolic activity of the human fetal beta-cell somehow confers protection on these cells from the cytotoxic effects of tumor necrosis factor-alpha and interferon-gamma. Indeed, our findings suggest that these cytokines may be trophic for the developing beta-cell.
 ...
PMID:Role of tumor necrosis factor-alpha and interferon-gamma as growth factors to the human fetal beta-cell. 193 17

Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Dec
PMID:Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. 197 29

Diabetes mellitus is recognized as a risk factor for compromised wound healing. This study examines leukocyte infiltration and the appearance of tumor necrosis factor-alpha (TNF) and IL-6 in wound chambers implanted in normal and streptozotocin-induced diabetic mice. Perforated silicone wound chambers containing a strip of polyvinyl alcohol sponge were implanted along the flanks of normal and diabetic mice. Wound fluid aspirated from the chambers 1, 3, and 7 days following implantation was analyzed for the total number of leukocytes and TNF and IL-6 levels. While the number of leukocytes in the wound fluid was similar on Days 1 and 3 following implantation, there were significantly fewer inflammatory cells in wound fluid from diabetic animals (13.8 X 10(6)/ml) than in wound fluid from normal animals (28.5 Z 10(6)/ml) on Day 7 following implantation. TNF levels in the cell-free exudate fluid were similar between the two groups on all days examined. IL-6 levels were similar on Days 1 and 3 following implantation between the two groups, but there was significantly more IL-6 in wound fluid from normal animals (10,998 U/ml) than in wound fluid from diabetic animals (2096 U/ml) on Day 7 following implantation. Histologic evaluation of chambers 8 days following implantation revealed decreased neovascularization and less organization of granulation tissue. These data suggest that delayed healing in diabetes is associated with altered leukocyte infiltration and wound fluid IL-6 levels during the late inflammatory phase of wound healing.
 ...
PMID:Diabetes impairs the late inflammatory response to wound healing. 202 Jan 84

Cultured neonatal rat (F344, RT1(1v1)) islets that were devoid of MHC class II (OX6) antigen and antigen-presenting cells were treated with recombinant murine interferon (IFN-gamma) and/or recombinant murine tumor necrosis factor (TNF-alpha) in vitro. The IFN-gamma and TNF-alpha resulted in some disruption of the integrity of the islets by 7 days of culture, but the combination resulted in disaggregation of the islets within 7-8 days. Insulin release into the medium and secretion in response to glucose were adversely affected by the cytokines. The IFN-gamma resulted in expression of class II antigen on about 10% of the endocrine cells after 3-4 days in culture. This effect of IFN-gamma was potentiated by TNF-alpha resulting in 27% of the cells expressing class II antigen. Islets treated with IFN-gamma and TNF-alpha alone or in combination were not rejected in a subsequent transplant underneath the kidney capsule of WF rats (RT1u). We conclude that expression of class II antigen alone is not sufficient to initiate an allogeneic rejection response, but that cytokine-mediated destruction of endocrine cells could be the basis of immune-mediated islet-cell loss in islet-allograft rejection or autoimmune diabetes.
 ...
PMID:Successful allogeneic transplantation of rat islets expressing cytokine-induced major histocompatibility complex class II antigen. 210 45

Immunoregulatory polypeptides (cytokines) produced by mononuclear cells of the immune system can inhibit insulin secretion and may be cytotoxic to pancreatic islet beta cells. We used a modified 51Cr release cytotoxicity assay to define the interactive cytotoxic effects of interleukin-1 (IL-1), tumor necrosis factor (TNF), and interferon gamma (IFN-gamma) on rat islet cells in monolayer culture. We here demonstrate that (a) IFN-gamma, but not IL-1 or TNF, can sensitize islet cells to subsequent cytolysis by other cytokines (IL-1 or TNF); (b) the cytolytic effect of sequential addition of IFN-gamma, then IL-1 or TNF (approximately 35-40% 51Cr release) is similar to that produced by the concurrent addition of IFN-gamma plus IL-1 or TNF; (c) the priming effect of IFN-gamma persists for 3 to 6 or more days after its removal; and (d) islet cells preincubated with IFN-gamma are also more sensitive to cytolysis by splenic mononuclear cells from diabetes-prone BB/Wor rats. These findings suggest that IFN-gamma produced by activated T lymphocytes and monocytic cells infiltrating islets in Type 1 diabetes may play a direct and important role in sensitizing beta cells to damage by other cytokines (IL-1, TNF) and cytotoxic cells in the immune/inflammatory infiltrate.
 ...
PMID:Interferon-gamma sensitizes rat pancreatic islet cells to lysis by cytokines and cytotoxic cells. 211 Nov 38


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