UMLS:C0028754 - FACTA Search

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Query: UMLS:C0028754 (obesity)
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The pathology of the liver in 19 cases of malabsorption is reported. Five of these were proven to have adult coeliac disease, in the others that diagnosis was presumed by exclusion of other causes of malabsorption and by the coincidence of other conditions known to be associated with coeliac disease. Of these cases, three had liver changes of chronic hepatitis and two of these were in the proven coeliac group, including a case with cirrhosis and a hepatoma. In addition, less severe liver changes such as portal tract fibrosis and portal tract infiltration by inflammatory cells were present greatly in excess to that of the controls. The reasons for the occurrence of liver damage in coeliac disease are outlined and discussed in relation to the liver disorders associated with jejunoileal bypass used in the treatment of obesity. Possible mechanisms of liver injury in coeliac disease are described.
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PMID:The liver in coeliac disease. 21 Jan 3

Thirty patients with alcoholic cirrhosis, ascitic during 13.6 +/- 13 months (mean +/- S.D.) were cured of ascites and followed up during 2 to 9 years (4.3 +/- 2.7 years). Twenty six were compared with a same number of cirrhotics, matched for age and sex, who died during the year after the first admission. Many biological data show statistical difference. Nevertheless no valuable prognosis can be predicted in an individual case. The clinical improvement is associated with major, sometimes total biological recovery. Other complications of cirrhosis (gastro-intestinal bleeding, hepatoma) may occur (7 cases with 5 deaths) or alcoholic hepatitis if alcohol withdrawal is stopped (3 cases, 2 deaths). Some associated diseases look unexpectedly frequent: diabetes (4 cases), obesity (9), nodular lipomatosis (14 cases) whose frequency looks higher than that can be calculated for a similar group of healthy subjects.
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PMID:[Recovery after treatment for cirrhotic ascites : a study of 90 cases. Frequency of arterial hypertension (author's transl)]. 49 44

During studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in Richardson's ground squirrels. Of 12 Richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. Serological tests for hepadnavirus surface antigen, anti-core antibody and virion DNA that recognize the ground squirrel hepatitis virus of California ground squirrels (Spermophilus beecheyi) were uniformly negative. Southern blot analyses of EcoRI digests of liver cell DNA demonstrated 3.2 kb fragments that hybridized with a ground squirrel hepatitis virus-specific probe in nontumorous liver tissue from 6 of 10 ground squirrels and in hepatocellular carcinoma specimens from 2 of 5 squirrels indicating infection with a hepadnavirus related to ground squirrel hepatitis virus. Failure, however, to detect serum antibody to ground squirrel hepatitis core antigen suggested probable antigenic differences between the ground squirrel hepatitis virus of California ground squirrels and the putative Richardson's ground squirrel agent. Further studies are required to fully characterize the hepadnavirus of Richardson's ground squirrels and to determine its relationship to hepatocarcinogenesis in this species.
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PMID:Hepatocellular carcinoma in Richardson's ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection. 164 62

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension. Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol- or acetaldehyde-altered proteins, and questionably enhanced by viral hepatitis. Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug-induced injuries, jejunoileal bypass, and related "shortcircuiting" of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen is the prime example.
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PMID:Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. 205 45

Forty-two patients with nonalcoholic steatohepatitis were followed for a median of 4.5 yr (range = 1.5 to 21.5 yr). Except for two patients with lipodystrophy, all were obese; 35 of 42 were women, 26 of 32 were hyperlipidemic and 15 were hyperglycemic. Upper abdominal pain was the most common reason for presentation. Initial liver biopsy specimens showed the presence of macrovesicular fatty infiltration, lobular (acinar) inflammation, apoptosis, Mallory bodies (in four cases) and fibrosis (in 18 cases). Cirrhosis was present at initial diagnosis in one subject and in another two subjects liver biopsy showed marked fibrosis with disturbed architecture. Serial liver biopsy specimens revealed minimal or no apparent progression of the disorder in most of the patients, in keeping with their benign clinical course. However, one patient showed progression from fibrosis to cirrhosis during the 5-yr observation period, and in the patients with extensive fibrosis the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation. The patient with cirrhosis later died of hepatocellular carcinoma. The severity or type of hepatic change did not correlate with the degree of obesity, hyperlipidemia or hyperglycemia. However, in individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis. We conclude that nonalcoholic steatohepatitis is a cause of hepatic inflammation histologically resembling that of alcohol-induced liver disease but usually slowly progressive and of low-grade severity. However, the disorder may ultimately result in cirrhosis. Nonalcoholic steatohepatitis should be distinguished from alcoholic steatohepatitis and recognized as a further cause of "cryptogenic cirrhosis."
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PMID:The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years. 1503 Sep 72

Obese mottled yellow Avy/a, lean pseudoagouti Avy/a and lean black a/a (YS X VY) F-1 hybrid female mice were fed diet containing 160 p.p.m. lindane (gamma-hexachlorocyclohexane) for 6, 12, 18 or 24 months. Clara cell hyperplasia was present in a majority of the mice after six months of lindane ingestion; however, more yellow mice (77%) than pseudoagouti (50%) or black (56%) mice had developed this lesion. Continued ingestion of lindane increased the incidence of Clara cell hyperplasia and resulted in similar prevalences in the three phenotypes. Lung tumors associated with lindane ingestion for 24 months were found only in yellow (19%) and pseudoagouti (14%) mice but not in the black mice. Prevalences of hepatocellular adenomas and carcinomas were very low (less than 10%) in untreated pseudoagouti and black mice. Lindane ingestion for 24 months resulted in an hepatocellular adenoma prevalence of 12% in pseudoagouti mice and 3% in black mice; comparable hepatocellular carcinoma prevalences were 5% and 1%. Among yellow mice fed lindane diet for 24 months, adenoma prevalence was 35% (9% among untreated controls) but carcinoma prevalence was only 17% (13% among controls). The tumorigenic responses evoked by lindane feeding in the lean pseudoagouti Avy/a mice but not in the black a/a mice indicate, for the first time, that the Avy gene itself, in the absence of obesity, sensitizes cells to transformation. The greater prevalence of hepatocellular adenomas in obese yellow Avy/a than in lean pseudoagouti Avy/a mice implicates obesity-associated factors in tumor promotion. Similarly, the increased prevalence of hepatocellular carcinomas in untreated obese yellow Avy/a mice, as compared to lean pseudoagouti mice, implicates obesity-associated factor as favoring histiotypic progression of liver tumors. Thus, the Avy gene not only sensitizes cells to respond to tumorigenic stimuli but also, by the induction of obesity, enhances promotion and progression of transformed cells.
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PMID:Tumorigenic responses to lindane in mice: potentiation by a dominant mutation. 244 99

An insulin-sensitive subcellular system was developed from rat adipocytes consisting of plasma membranes and mitochondria. Direct addition of insulin, concanavalin A or anti-insulin receptor antibody to this system resulted in the production of a mediator substance from the plasma membrane that caused dephosphorylation of the alpha subunit of pyruvate dehydrogenase in the mitochondria with concomitant activation of the enzyme. The mediator activated pyruvate dehydrogenase by activating the pyruvate dehydrogenase phosphatase and not by inhibiting the pyruvate dehydrogenase kinase. This was similar to the mechanism by which insulin causes activation of the enzyme in the intact cell. The insulin-sensitive mediator material from the adipocyte plasma membrane was acid-stable with a molecular weight of 1,000 to 1,500. Our laboratory has shown that the mediator that activates pyruvate dehydrogenase was present in intact adipocytes, hepatoma cells, and IM-9 lymphocytes. Insulin altered the amount or activity of the mediator consistent with the effect of the hormone on the cell. Other laboratories have shown similar effects on skeletal muscle and liver. We have shown the mediator to mimic insulin action on the low Km cyclic adenosine monophosphate (AMP) phosphodiesterase and the (calcium++-magnesium++)-adenosine triphosphatase (Ca++-Mg++)-ATPase of adipocyte plasma membranes in addition to pyruvate dehydrogenase. Other laboratories have shown the mediator to activate glycogen synthase. A body of direct and indirect evidence exists that demonstrates that more than one mediator exists. The chemical nature of the mediator is unknown but probably represents a new family of intracellular mediators of hormone action. These mediators may have clinical relevance in postreceptor defects of obesity and type II diabetes (noninsulin-dependent diabetes mellitus).
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PMID:The chemical mediators of insulin action: possible targets for postreceptor defects. 633 85

Tumor necrosis factor-alpha (TNF) has been suggested to be the mediator of insulin resistance in infection, tumor cachexia, and obesity. We have previously shown that TNF diminishes insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). The current work examines potential mechanisms that mediate this event. TNF effect on IRS-1 in Fao hepatoma cells was not associated with a significant reduction in insulin receptor tyrosine kinase activity as measured in vitro but impaired the association of IRS-1 with phosphatidylinositol 3-kinase, localizing TNF impact to IRS-1. TNF did not increase protein-tyrosine phosphatase activity and protein-tyrosine phosphatase inhibition by vanadate did not change TNF effect on IRS-1 tyrosine phosphorylation, suggesting that protein-tyrosine phosphatases are not involved in this TNF effect. In contrast, TNF increased IRS-1 phosphorylation on serine residues, leading to a decrease in its electrophoretic mobility. TNF effect on IRS-1 tyrosine phosphorylation was not abolished by inhibiting protein kinase C using staurosporine, while inactivation of Ser/Thr phosphatases by calyculin A and okadaic acid mimicked it. Our data suggest that TNF induces serine phosphorylation of IRS-1 through inhibition of serine phosphatases or activation of serine kinases other than protein kinase C. This increased serine phosphorylation interferes with insulin-induced tyrosine phosphorylation of IRS-1 and impairs insulin action.
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PMID:Tumor necrosis factor alpha-induced phosphorylation of insulin receptor substrate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. 755 52

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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PMID:Weaning of immunosuppression in long-term liver transplant recipients. 783 42

To aid understanding of markers of disease and predictors of outcome in alcohol-exposed systems, we undertook a literature survey of more than 700 articles to view the morphological characteristics and the clinical and experimental epidemiology of the Mallory body. Mallory bodies are filaments of intermediate diameter that contain intermediate filament components (e.g., cytokeratins) observable by conventional light microscopy or immunohistochemical methods, identical in structure regardless of initiating factors or putative pathogenesis. Although three morphological types can be identified under electron microscopy (with fibrillar structure parallel, random or absent), they remain stereotypical manifestations of hepatocyte injury. A summary of the conditions associated with Mallory bodies in the literature and their validity and potential etiological relationships is presented and discussed, including estimates on the combined light microscopic and immunohistochemical prevalences and kinetics. Emphasis is placed on proper confounder control (in particular, alcohol history), which is highly essential but often inadequate. These conditions include (mean prevalence of Mallory bodies in parentheses): Indian childhood cirrhosis (73%), alcoholic hepatitis (65%), alcoholic cirrhosis (51%), Wilson's disease (25%), primary biliary cirrhosis (24%), nonalcoholic cirrhosis (24%), hepatocellular carcinoma (23%), morbid obesity (8%) and intestinal bypass surgery (6%). Studies in alcoholic hepatitis strongly suggest a hit-and-run effect of alcohol, whereas other chronic liver diseases show evidence of gradual increase in prevalence of Mallory bodies with severity of hepatic pathology. Mallory bodies in cirrhosis do not imply alcoholic pathogenesis. Obesity, however, is associated with alcoholism and diabetes, and Mallory bodies are only present in diabetic patients if alcoholism or obesity complicates the condition. In addition, case studies on diseases in which Mallory bodies have been identified, along with pharmacological side effects and experimental induction of Mallory bodies by various antimitotic and oncogenic chemicals, are presented. Mallory bodies occur only sporadically in abetalipoproteinemia, von Gierke's disease and focal nodular hyperplasia and during hepatitis due to calcium antagonists or perhexiline maleate. Other conditions and clinical drug side effects are still putative. Finally, a variety of experimental drugs have been developed that cause Mallory body formation, but markedly different cell dynamics and metabolic pathways may raise questions about the relevance of such animal models for human Mallory body formation. In conclusion, the Mallory body is indicative but not pathognomonic of alcohol involvement. A discussion on theories of development and pathological significance transcending the clinical frameworks will be presented in a future paper.
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PMID:The Mallory body: morphological, clinical and experimental studies (Part 1 of a literature survey). 792 9

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