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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune disease. This concept is exemplified in the Obese strain (OS) chicken model which develops a spontaneous autoimmune thyroiditis closely resembling human Hashimoto disease. Three modulating factors are specifically addressed, viz. (a) the lower threshold of OS thyroid epithelial cells for the gamma-interferon-induced MHC class II antigen expression as compared to normal controls, (b) the decreased glucocorticoid tonus of the OS and (c) the presence of a new endogenous virus (ev 22) locus in the OS that has so far not been found in any normal strain and which seems to influence the glucocorticoid-mediated immunoregulatory process.
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PMID:The multi-factorial pathogenesis of autoimmune disease. 312 34

Pretreatment variables that could predict the response of chronic hepatitis C to interferon alfa treatment have not been fully assessed. Eighteen baseline variables were evaluated in a series of 100 consecutive patients treated with a 12 month course of interferon alfa. For the purposes of this study, response was defined as the return to normal of aminotransferase activities before the third month of treatment. Seventy per cent of the patients responded to treatment. Six variables were associated with an increased likelihood of response assessed by univariate analysis. With stepwise multiple regression analysis assessment, however, only three variables remained independently predictive of response: low gamma glutamyltransferase (gamma GT) activities (p < 0.001), absence of obesity (p = 0.005), and absence of cirrhosis (p = 0.01). The response rate in patients with gamma GT activities < 0.66 mu kat/l (n = 55) was 78% and 60% in patients with values > 0.66 mu kat/l (n = 45) (p = 0.048). Response was attained in 75% of non-obese patients (n = 80), compared with only 50% of obese patients (n = 20) (p = 0.03). Finally, 80% of patients without cirrhosis (n = 76) responded, while among those with cirrhosis (n = 24) the response rate was only 37% (p < 0.001). All 23 patients without cirrhosis, <40 years old, and with gamma GT activities <0.66 mu kat/l responded to treatment, while only 28.5% of 14 patients with cirrhosis, >40 years old, and with gamma GT activities >0.66 mu kat/l responded to interferon alfa (p<0.001). Those findings may be useful when evaluating interferon alfa trials and it is suggested that this treatment should be applied early in the course of chronic hepatitis C.
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PMID:Prediction of the response of chronic hepatitis C to interferon alfa: a statistical analysis of pretreatment variables. 790 52

Renal cell carcinoma (RCC) continues to be a frustrating tumor for clinicians to manage and treat. Progress has been made in the identification of risk factors, particularly dietary risk factors. An increased risk has been seen with frequent consumption of fried meat and poultry. Citrus fruits, vitamin C, beta-carotene, and alpha-tocopherol have demonstrated a protective effect against RCC. Other factors that have been associated with the risk of RCC are smoking (which doubles the risk), obesity, hypertension, and exposure to asbestos and petroleum products. Response rates for systemic treatment of RCC continue to hover at about 20%; however, some nonchemotherapy treatments may provide palliation with few side effects. In addition, lower dose combinations of interleukin-2 and interferon alfa may be as beneficial as higher dose regimens, but with less toxicity. Molecular prognostic factors, including proliferation markers, karyometric analyses, oncogenes, and cell adhesion molecules and proteases are areas of intense investigation and may provide mechanisms for identifying patients who require more (or less) aggressive treatment.
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PMID:Renal cell carcinoma. 961 63

Although decreased T-cell function has been observed in obese human subjects and genetically obese animals, the precise role of immune functions in obesity is still unclear. To investigate immune functions in obesity, we examined the proliferative responses of splenic lymphocytes and their capacity to produce cytokines in the presence or absence of leptin, the protein produced by the obese gene, in diet-induced obese and control mice. For induction of obesity, C57BL/6J mice were fed a high-fat diet for 13 weeks. In mice fed the high-fat diet, body weight, fat pad weight, and tumor necrosis factor (TNF) alpha production by adipocytes were significantly increased relative to mice fed the normal diet. Lipopolysaccharide (LPS) stimulated proliferation of cultured splenocytes from diet-induced obese mice was also increased. However, production of interleukin (IL)-2 by splenic lymphocytes from obese mice was suppressed, whereas interferon (IFN)-gamma and IL-4 production was increased. Exogenous lepitn regulated the cytokine production by cultured splenocytes from control and obese mice, respectively (upregulation of IFN-gamma and downregulation of IL-2 in control mice, and downregulation of IL-4 in obese mice). These results suggest that changes in cytokine production by splenic lymphocytes in obesity are indicative of altered immune functions that might contribute to related complications, although the effect of difference in nutrient intake (macro and micro) may also have contributed to the changes.
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PMID:Change of cytokine balance in diet-induced obese mice. 1107 19

In developmental terms, the endocrine system of neither the gut nor the pancreatic islets has been characterized fully. Little is known about the involvement of cholecystokinin (CCK), a gut hormone, involved in regulating the secretion of pancreatic hormones, and pancreatic growth. Here, we tracked CCK-expressing cells in the intestines and pancreata of normal mice (BALB/c), Non Obese Diabetic (NOD) mice and interferon (IFN)-gamma transgenic mice, which exhibit pancreatic regeneration, during embryonic development, the postnatal period and adulthood. We also questioned whether IFN-gamma influences the expression of CCK. The results from embryonic day 16 showed that all three strains had CCK in the acinar region of pancreata, and specifically in alpha cells that also expressed glucagon. However, in adulthood only BALB/c and NOD mice continued this pattern. By contrast, in IFN-gamma transgenic mice, CCK expression was suppressed from birth to 3 months of age in the pancreata but not intestines. However, by 5 months of age, CCK expression appeared in the regenerating pancreatic ductal region of IFN-gamma transgenic mice. In the intestine, CCK expression persisted from fetus to adulthood and was not influenced by IFN-gamma. Intestinal cells expressing CCK did not co-express glucagon, suggesting that these cells are phenotypically distinct from CCK-expressing cells in the pancreatic islets, and the effect of IFN-gamma on CCK varies depending upon the cytokine's specific microenvironment.
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PMID:Cholecystokinin expression in the developing and regenerating pancreas and intestine. 1131 40

Some epidemiologic surveys have demonstrated that asthma is more prevalent in obese children and adults. However, the mechanism of association between obesity and asthma has not been fully clarified. This report investigates a murine model for antigen-induced asthma and diet-induced obesity from an immunologic perspective. For the induction of obesity, C57BL/6J mice were fed a high-fat diet supplemented with lard or soybean oil. Mice were then sensitized and challenged with ovalbumin (OVA) to induce allergic lung inflammation. OVA-specific serum immunoglobulin levels were lower in obese mice compared with non-obese control mice. The decline of OVA-specific IgE in the soybean oil group was found to be especially pronounced. However, obese mice with OVA-induced asthma showed a higher sensitivity of antigen-induced T-cell responses, and increased gamma interferon (IFN-gamma) production of splenocytes with phytohemagglutinin (PHA) stimulation. Furthermore, mast cell numbers in the tracheal mucosa were increased in obese mice upon sensitization by OVA. These results suggest that obesity-induced changes in T-cell function may be partly involved in the pathophysiology of asthma in human obesity, rather than Ig E-mediated allergic responses.
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PMID:Effect of diet-induced obesity on ovalbumin-specific immune response in a murine asthma model. 1237 Aug 41

Although renal cell carcinoma accounts for only 3% of adult malignancies, it has been increasing in incidence by 2-4% per year since the 1970's. Cigarette smoking, obesity and end-stage renal disease are important risk factors. Genetic syndromes such as von Hippel-Lindau disease are also associated with an increased incidence of renal cell carcinoma. Localized disease should be treated with surgical resection. However, approximately 30% of patients present with metastatic disease. Complete resection of metastases can result in long-term survival in some individuals. Removal of the primary renal tumor in patients with unresectable disseminated disease has also been shown to improve survival in selected good performance status patients receiving systemic immunotherapy. While chemotherapy has been relatively ineffective in the treatment of renal cell carcinoma, biologic therapy with interleukin-2 or interferon does lead to responses in a minority of patients, with occasional long-term survivors. Recently, promising results have been reported with allogeneic stem cell transplantation using a non-myeloablative conditioning regimen. However, therapy for metastatic renal cell carcinoma remains inadequate. Ongoing trials with novel approaches such as anti-angiogenesis agents, cyclin-dependent kinase inhibitors, and tumor vaccines will hopefully lead to improved outcomes in this disease.
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PMID:Renal cell carcinoma: current status and future directions. 1260 28

The evolution in therapy for chronic hepatitis C virus (HCV) infection to the more recent use of peginterferons in combination with ribavirin has dramatically increased the sustained virological response (SVR) rates versus standard interferon/ ribavirin combination therapy. However, although peginterferon and ribavirin therapy has markedly improved treatment responses overall, factors such as high viral load, genotype 1 infection, obesity, HIV co-infection and African American race continue to pose challenges to optimizing SVR rates. Application of mathematical models may be helpful in understanding why these groups and/or individuals appear to be resistant to interferon (IFN)-based therapy. This article focuses on the viral kinetics and viral kinetic differences among patients infected with HCV genotypes 1 and 2, obese and nonobese patients, and African Americans and Whites.
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PMID:Viral kinetics in hepatitis C virus: special patient populations. 1293 66

The aim of this study was to determine if body mass index (BMI) was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. A retrospective review was performed of all patients at a single center with chronic hepatitis C treated with antiviral medication from 1989 to 2000. A sustained response was defined as either negative hepatitis C virus (HCV) RNA by polymerase chain reaction and/or normal alanine aminotransferase (ALT) level (only in those treated before availability of HCV RNA testing) 6 months following completion of therapy. All patients were classified into one of 3 groups according to BMI (normal, <25 kg/m(2); overweight, 25-30 kg/m(2); obese, >30 kg/m(2)). A total of 253 patients were treated with either interferon (IFN) monotherapy or IFN in combination with ribavirin. Patients were excluded if predetermined clinical characteristics were unavailable. Using logistic regression, and after adjusting for the examined variables (age, sex, history of alcohol consumption >50 g/d, cirrhosis on pretreatment biopsy, and BMI), likelihood ratio tests showed significant differences in response to treatment according to BMI group (P =.01), genotype (P <.01), and cirrhosis (P <.01). Those with genotypes 2 or 3 had an odds ratio (OR) for success of 11.7 compared with those with genotype 1, cirrhotic patients had an OR of 0.15 compared with noncirrhotic patients, and obese patients had an OR of 0.23 compared with normal and overweight patients. Hepatic steatosis was not an independent risk factor for response to antiviral treatment. In conclusion, obesity, only when defined as a BMI greater than 30 kg/m(2), is an independent (of genotype and cirrhosis) negative predictor of response to hepatitis C treatment.
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PMID:High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. 1293 81

Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized clinico-pathologic entity typically associated with obesity, type II diabetes and hyperlipidemia. It has been noted to recur after orthotopic liver transplantation (OLT). We report four patients who developed de novo NAFLD within 3 months of OLT without the typical predisposing factors of diabetes mellitus or obesity. Three of the four patients underwent OLT for hepatitis C-related cirrhosis, and the other for alcoholic cirrhosis. Examination of the liver explants revealed no evidence of steatosis. No surreptitious alcohol use or a drug-induced process could be identified in these patients. Treatment of recurrent hepatitis C infection in one patient with interferon and ribavirin led to sustained suppression of the viral RNA to undetectable levels, but no improvement in histology or liver enzymes. All four patients had histologic evidence of preservation injury on the initial post-OLT biopsies, but the significance of this finding in relationship to the development of NAFLD is unknown. NAFLD can develop without any of the known predisposing conditions after transplantation, and this raises further questions about the pathogenesis of this condition.
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PMID:De novo non-alcoholic fatty liver disease following orthotopic liver transplantation. 1452 3


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