Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic fibrosis has been induced in rats by low doses of dimethylnitrosamine (DMN) and special attention has been paid to early morphological events. DMN (10 microliter/kg body wt., i.p.) was given 3 days a week for 3 weeks to Sprague-Dawley rats. Liver samples were taken on days 7, 14, 21, 28 and 35 and examined by light and electron microscopy. Hemorrhagic necrosis, mainly centrolobular, was evident on day 7, with disruption of the sinusoidal lining, and widening or disappearance of the spaces of Disse invaded by erythrocytes and lymphocytes. Large granular lymphocytes similar to pit cells were also present in close contact with hepatocytes. At day 14, fibrotic septa were associated with cells bearing 'transitional' features between those of lipocytes, myofibroblasts and fibroblasts. Hepatocytes showed foci of increased smooth endoplasmic reticulum, and altered sinusoidal and canalicular membranes. At day 21, all animals showed nodularity of the parenchyma, with evidence of micronodular cirrhosis associated with ascites in two animals. At day 35 (19 days after cessation of treatment) there was little residual inflammation, but well-defined micronodules were still present in all animals. This shows that, in the rat, 3-week treatment with a low dose of DMN produces micronodular cirrhosis following diffuse hemorrhagic necrosis without steatosis. The response of the animals was uniform and reproducible. Lesions of the sinusoidal wall and of membranes of liver cells associated with the inflammatory reaction appeared prominent.
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PMID:A morphological study of the early stages of hepatic fibrosis induced by low doses of dimethylnitrosamine in the rat. 369 62

We report the findings in two sisters with active cirrhosis and an anti-liver-kidney microsomal antibody (anti-LKM) of the autoimmune type. This unusual disease is characterized by the presence of high levels of antibodies that react with the smooth and rough endoplasmic reticulum of the liver and other tissues. Our patients had the usual features of chronic hepatitis associated with presence of antibodies: they were young girls, they had anti-LKM antibodies of autoimmune type persisting at a high titer during the whole course of the disease, but with no smooth muscle antibodies; one had a low level of IgA. The occurrence of two cases in the same family has not yet been reported and is probably not coincidental because of the rare occurrence of this disease.
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PMID:Chronic active hepatitis associated with liver-kidney microsomal antibody of an autoimmune type. Two familial cases. 376 10

Histopathological liver changes resembling primary biliary cirrhosis were induced in an experimental animal model. A special strain of rabbit received an antigen prepared from scrapings of bovine gallbladder mucosa. Eventually, 47 out of 84 antigen-treated rabbits displayed histopathological liver features resembling those of chronic non-suppurative destructive cholangitis as seen in humans. In addition, granuloma formation, ductular proliferation and fibrosis were seen in some cases. However, advanced lesions consistent with micronodular cirrhosis have not been found. Lymphocytes seemed to play an important role triggering early pathogenetic mechanisms, judging from the presence of lymphocytes invading the basement membrane of the affected bile ducts. Furthermore, we observed by electron microscopy that the epithelial cells of the involved bile ducts revealed both mitochondrial swelling and dilatation of endoplasmic reticulum cisternae. In summary, our experimental animal model offers interesting possibilities regarding the study of pathogenesis and development of primary biliary cirrhosis.
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PMID:Production of histological changes mimicking primary biliary cirrhosis in rabbits by immunization with bile duct antigen. 377 Mar 55

Monospecific antibodies against collagen types I, IV, fibronectin, and laminin were used to characterize the hepatic extracellular matrix in CCl4-induced cirrhosis. Of the four antigens studied, fibronectin was the first (2 weeks) to be deposited in Disse's space. Synthesis of fibronectin by hepatocytes was demonstrable by 3 weeks. This increased synthesis and deposition of fibronectin continued throughout the cirrhotic process. Type I collagen was deposited in the same areas as fibronectin, but there was a delay of 2 weeks between fibronectin deposition and the subsequent type I collagen deposition. Like fibronectin, type I collagen was localized in the rough endoplasmic reticulum of hepatocytes, but unlike fibronectin type I collagen synthesis was restricted to hepatocytes near zones of necrosis. Type I collagen and fibronectin synthesis were demonstrable only in hepatocytes. Type IV collagen deposition was noticeable after 3 to 4 weeks of CCl4 administration and continued throughout the cirrhotic process. Laminin deposition was delayed, with regard to type IV collagen, by 1 to 2 weeks. Except for this time lag, both basement membrane components codistributed in the space of Disse and were synthesized by the same cells: endothelial, smooth muscle, and Ito cells. The deposition of these two basement membrane components culminated with the formation of continuous endothelial basement membranes. The four extracellular matrix components studied were synthesized and secreted by resident cells of the normal liver. It is proposed that fibronectin deposition in the space of Disse, modulating collagen deposition, may be the crucial event in the cirrhotic process. The interposition of basement membranes between plasma and hepatocytes may have profound effects on hepatic systemic functions.
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PMID:The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. 389 94

Sixteen children (aged between 1 month and 20 years) with alpha-1-antitrypsin deficiency (PiZ) were investigated by liver biopsy on one or more occasions. Eight patients had suffered from neonatal cholestasis, and two of them were investigated during the cholestatic period as well. The clinical status and liver function tests were compared with the light and electron microscopical findings. According to the light microscopical analyses at the latest investigation, the cholestatic and noncholestatic patients were classified as healthy, fibrotic or cirrhotic cases. All livers displayed periodic acid-Schiff positive, diastase-resistant globules in some but not all periportally located hepatocytes. By electron microscopy accumulation of retained secretory material was found in all PiZ patients. This accumulation was most conspicuous in the smooth endoplasmic reticulum of hepatocytes. alpha-1-antitrypsin deficiency seems to affect some, but not all hepatocytes. In the affected cells disappearance or hypotrophy of the Golgi complex could be observed. The intracellular transport of very low density lipoproteins (VLDL) was apparently not affected. The migration block in alpha-1-antitrypsin deficiency seems to occur before transportation to the Golgi complex. The extent of the involvement was not strictly age-dependent. There was no ultrastructural evidence of subclinical cholestasis as a possible triggering factor in the development of cirrhosis.
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PMID:Alpha-1-antitrypsin deficiency and juvenile liver disease. Ultrastructural observations compared with light microscopy and routine liver tests. 613 91

Hepatocytes with orcein-positive ground-glass cytoplasm have been shown to contain abundant hepatitis B surface antigen in the cisternae of excess smooth endoplasmic reticulum. Hepatocytes with similar cytoplasmic changes that did not react with orcein were observed in 26.5% of 49 cases of cirrhosis. These cells exhibited granular, deeply eosinophilic cytoplasm that stained with phosphotungstic acid-hematoxylin and contained numerous densely packed mitochondria as demonstrated by electron microscopy. Therefore, these cells were designated hepatic oncocytes. They were detected predominantly in cases of established cirrhosis, unrelated to etiology. Hepatic oncocytes may form nodular aggregates, but they did not show evidence of regeneration. The nature and pathogenesis of these cells remain unclear. Because of similar appearance, histochemical stains may be necessary to distinguish ground-glass hepatocytes from hepatic oncocytes.
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PMID:Hepatic oncocytes. Incidence, staining characteristics, and ultrastructural features. 616 90

Clinical features and liver biopsy findings were studied in six patients with nonalcoholic steatohepatitis associated with hyalin. A comparative study was made on the ultrastructure of the hyalin in one patient with nonalcoholic steatohepatitis and in one patient with alcoholic hepatitis. The patients, all over 50 years old, comprised two females and one male with steatohepatitis and three females with micronodular cirrhosis. They showed obesity, hepatomegaly, and mild abnormalities on laboratory tests. Three of them showed maturity-onset diabetes. The hyalin was found in the cytoplasm of swollen hepatocytes of the centrilobular or in the peripheral region of nodules and was accompanied by necrosis. Ultrastructurally, the hyalin comprised filamentous structures and vesicular or angular structures resembling disorganized circular or branched rough endoplasmic reticulum. It resembled that found in the liver of patients with alcoholic hepatitis.
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PMID:Nonalcoholic steatohepatitis and cirrhosis with Mallory's hyalin with ultrastructural study of one case. 617 90

A 2-month-old white girl had severe liver disease (but without signs of hepatic necrosis, infection or cirrhosis), urinary cytomegalovirus, transient reduction of alpha 1-antitrypsin concentration and transient abnormal alpha 1-antitrypsin phenotype that were not present in her parents. Five serum specimens that were obtained during the 11/2 months of acute phase liver disease indicated, by polyacrylamide gel isoelectric focusing (PAG-IEF), acid starch gel and agarose electrophoresis as well as immunofixation, an unusual alpha 1-antitrypsin phenotype that we labeled delta (delta). It migrated adjacent to Z, i.e., cathodal of Z and Zpratt on PAG-IEF; anodal of Z but cathodal of X, S, Zpratt on starch gel. We labeled the girl's complete phenotype M delta. After clinical recovery, her phenotype was MM and identical to that of her parents. Hepatic electronmicroscopy of the acute phase specimen showed dilated bile canaliculi. We observed the following in hepatocytes: clusters of globular inclusions surrounded by myelin sheets that, to a lesser extent, also appeared in the liver of CMV-infected children with phenotype MM; dilated endoplasmic reticulum cisternae that contained floccular material; and marked steatosis. These changes were less severe in the convalescent liver specimen.
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PMID:Alpha 1-antitrypsin phenotype: transient cathodal shift in serum of infant girl with urinary cytomegalovirus and fatty liver. 627 90

Sera from 5154 subjects comprising patients with liver diseases (n = 1311), immunological and connective tissue disorders (n = 1098) and other diseases (n = 2421), and healthy people (n = 324), were investigated by immunofluorescence for IgG antibodies (titre greater than or equal to 1:20) against mitochondria (AMA), endoplasmic reticulum (AER), nonorganspecific ribosomes (ARA-1), and liver typical ribosomes (ARA-2). AMA were classified in 10 subtypes. AMA (n = 163 = total 3.2%) were found predominantly in liver diseases (n = 101 = 7.7%) and in autoimmunopathies (n = 34 = 3.1%). AER (n = 59 = total 1.1%) were detected mainly in liver diseases (n = 40 = 3%), ARA-1 (n = 14 = total 3%) in autoimmunopathies (n = 7 = 0.64%), and ARA-2 (n = 7 = total 0.14%) exclusively in liver diseases (n = 7 = 0.5%) (acute and chronic relapsing hepatitis with viral markers). The diagnostic value of antibodies depends among other things on the titre and the subtype. AMA of type 2 and 4 with a titre higher than 1:1280 are a valuable marker of primary biliary cirrhosis or a related disease, even in the absence of other diagnostic signs. AER with a titre higher than 1:320 suggest a special form of autoimmune chronic hepatitis with rapid progress to liver cirrhosis. The diagnostic value of other antimitochondrial antibodies (especially those of type 5 to 10) and of antiribosomal antibodies is not exactly known.
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PMID:[Diagnostic significance of antibodies against cell organelles (mitochondria, endoplasmic reticulum and ribosomes)]. 633 82

Ultrastructural studies with the transmission (TEM) and scanning (SEM) electron microscopes have added greatly to our knowledge of cellular structure and function in the liver. The normal polyhedral hepatocyte has numerous subcellular organelles, such as mitochondria, peroxisomes, lysosomes and complex rough (rer) and smooth (ser) endoplasmic reticulum. The normal hepatocyte stores glycogen, and sometimes lipid droplets, and secretes bile through the bile canaliculi between adjacent liver cells. It receives nutrients from the sinusoidal lumen across a fenestrated endothelium which is separated by the Space of Disse' from the plasma membrane. The Space of Disse' contains a scant network of reticulin fibers but no basal lamina. Two types of parasinusoidal cells are found in Disse's space: the fat storing cells of Ito, and the Pit cells which may have an endocrine function. The diseased liver has yielded much information in studies with TEM and SEM. The studies with TEM have been most helpful in studying the etiology of infectious diseases such as hepatitis B; have revealed organelle changes such as megamitochondria in cirrhosis and the fibrillar nature of alcoholic hyaline; have led to the identification of specific deposits in metabolic and storage diseases such as hemochromatosis (iron). Wilson's disease (copper), and alpha-1-antitrypsin deficiency (glycoprotein) have proven useful in identifying drug induced liver cell changes such as proliferation of SER and cholestasis, and are useful for identifying specific cell types in inflammatory and neoplastic diseases. In the future, both TEM and SEM coupled with histochemical, cytochemical, immunohistochemical and other analytic techniques will continue to add greatly to our understanding of the liver in health and disease.
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PMID:Ultrastructure of the liver and biliary tract in health and disease. 637 90


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