Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of cytochalasin B-induced intrahepatic cholestasis was examined using electron cytochemical techniques. Since previous studies suggested that the earliest lesions were in hepatic canaliculi, markers were used for three canalicular membrane components, namely ruthenium red for the glycoprotein-rich surface coat, the Mg2+-ATPase reaction as an example of a membrane-bound protein, and uranyl acetate en bloc and ruthenium red staining for the canalicular membrane-associated microfilaments. In rat liver infused in vivo with cytochalasin B, reduction in bile flow correlated with bile canalicular dilation, loss of the ruthenium red-positive surface coat from the canalicular membrane, and loss of demonstrable Mg2+-ATPase activity. In addition, structural alterations in microfilaments with widening of the ectoplasmic zone were noted. In isolated liver cells in vitro, identical changes were found. Bile canaliculi isolated from the in vivo cytochalasin B-infused rat liver lacked their normal investment of microfilaments. Detachment of the filaments from the bile canalicular membrane may be involved in the mechanism of cytochalasin B-induced cholestasis.
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PMID:Bile canalicular membrane pathology in cytochalasin B-induced cholestasis. 14 51

This study was performed in order to evaluate the role of various local and systemic alterations in influencing serum glycoproteic markers in patients with pancreatic cancer, and in healthy and diseased controls. Cancer antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and ferritin were determined in the sera of 23 control subjects, 30 patients with pancreatic cancer, 27 with chronic pancreatitis, and 27 with extra-pancreatic diseases mainly of gastrointestinal origin. A number of acute-phase proteins and indices of liver function and cholestasis were also assayed. The three antigens increased only in patients with pancreatic cancer. Higher CA 19-9 and CEA, but not ferritin, levels were found only in patients with hepatic metastases. Acute-phase proteins and synthetic functional indices were found to be higher and lower, respectively, in patients with pancreatic malignancy when compared with controls. Multiple regression analysis documented the dependence of circulating ferritin, but not of CA 19-9 and CEA, on the systemic indices. Canonical correlation showed a similar trend for CA 19-9 and CEA, which differed from that of ferritin. Ferritin was found to depend on the presence of systemic and hepatic alterations, especially of cholestasis. We can conclude that the variations of serum glycoprotein markers in patients with pancreatic cancer depend on various regional and systemic factors. CA 19-9 and CEA are related mainly to the extent of the neoplasia. The influence of a decreased liver function capacity associated or not to cholestasis and the interrelation with the acute-phase response may also be suggested. Ferritin, on the other hand, is related to a higher degree than CA 19-9 and CEA to hepatic dysfunction and also behaves similar to an acute-phase protein.
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PMID:Role of local and systemic factors in increasing serum glycoprotein markers of pancreatic cancer. 177 Mar 22

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.
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PMID:How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? 213 20

Techniques have been studied which distinguish two variants of human alpha-fetoprotein (AFP) on the basis of characteristics of the carbohydrate moiety of this glycoprotein. AFP in serum samples from six children with tumors of yolk sac origin showed little concanavalin-A (Con A) binding. In contrast, Con A binding of AFP was almost complete in serum samples from 14 other subjects with elevated AFP, including two with liver-cell tumors, eight with neonatal cholestasis, and four normal newborn infants. Differences were confirmed by immunoelectrophoretic studies. Thus, AFP from cells of yolk sac origin can be distinguished from AFP from liver cells or from tumors of hepatic cell origin.
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PMID:Differences in the structure of alpha-fetoprotein and its clinical use in pediatric surgery. 240 60

Alpha-1-antitrypsin is a blood glycoprotein synthesized in the liver. It is a protease inhibitor of the serpine group and has a specific action for elastase. Alpha-1-antitrypsin electrophoresis shows about 20 phenotypes, the normal one being PiM. The allele PiZ is usually responsible for liver or lung disease in children or adults, respectively. Eleven per cent of PiZZ infants present with prolonged neonatal cholestasis. Twenty-five of 45 PiZZ infants with prolonged neonatal cholestasis presented with later cirrhosis. Persistence of jaundice beyond the sixth month of age, early development of splenomegaly, persistence of hard hepatomegaly and liver function abnormalities, and early portal fibrosis have a poor prognostic significance. The most severe course occurs in infants with an early histologic pattern of paucity of interlobular bile ducts. Portal hypertension was present in 19 of 25 children presenting with cirrhosis; 8 of 25 PiZZ children with cirrhosis died during childhood.
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PMID:[Alpha 1-antitrypsin deficiency in childhood]. 387 73

Biliary glycoprotein I (BGP I), a constituent of normal bile and serum, is a glycoprotein (mol. wt. approximately 90,000) containing about 40% carbohydrate. Serum BGP I (S-BGP I) was determined by means of a double-antibody radioimmunoassay in patients with liver and gastrointestinal disease and in healthy individuals. The serum levels of five liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (S-ALP), gamma-glutamyltranspeptidase (S-GT), and lactic dehydrogenase), bilirubin (total and conjugated), and bile acids (cholic and chenodeoxycholic acid) were determined in parallel. Healthy individuals had 0.5 +/- 0.3 mg/l of S-BGP I (mean +/- 2 S.D.; range, 0.2-0.9 mg/l). Most patients with liver disease (chronic hepatitis, alcoholic cirrhosis, primary biliary cirrhosis) had elevated levels, up to 5-10 times the upper reference limit, whereas most patients with gastrointestinal disease (ulcerative colitis, Crohn's disease, other GI diseases) had normal values. In patients with liver disease S-BGP I was positively correlated (p less than 0.0005) to S-GT. In primary biliary cirrhosis a positive correlation (p less than 0.005) between S-BGP I and S-ALP was also obtained. All other comparisons between S-BGP I and the other liver function tests showed non-significant correlations. It is concluded that S-BGP I is a determinant of cholestasis of similar use as S-GT.
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PMID:Serum level of biliary glycoprotein I, a determinant of cholestasis, of similar use as gamma-glutamyltranspeptidase. 611 67

CEA is a glycoprotein with a molecular weight of 200,000 containing 55%-65% carbohydrate. The removal of only two sialic acid residues result in rapid uptake from the circulation by the liver and catabolism in the lysosomes. There is a receptor on the plasma membrane of the hepatocyte (hepatic binding protein) which recognizes galactosyl residues. About 70% of 125I-labeled intact CEA is cleared by the liver in 1 hr. The exposure of terminal galactose residues by removing sialic acids determines the rate of clearance. CEA is probably initially taken up by Kupffer cells and transferred to hepatocytes. About 10% of CEA added to an isolated perfused liver appears in bile. Biliary duct obstruction and cholestasis may elevate plasma CEA levels due to detergent effects on the liver cell receptors.
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PMID:Role of the liver in clearance and excretion of circulating carcinoembryonic antigen (CEA). 633 95

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

Differential value of ACE activity and acid alpha 1-glycoprotein was evaluated in the selected liver and biliary tract diseases. The study involved 75 patients divided into 4 subgroups, according to the character of their disease: patients with the acute viral hepatitis, chronic viral hepatitis, liver cirrhosis, and cholelithiasis. It was found that ACE activity was significantly increased in all pathologies involving liver parenchyma, and normal in patients with extrahepatic cholestasis. It was also shown that simultaneous assays of ACE and acid < alpha 1-glycoprotein may serve as a sensitive test differentiating jaundice in parenchymal hepatic diseases from that in the course of extrahepatic pathology.
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PMID:[Activity of angiotensin converting enzyme I and levels of acid alpha glycoprotein in selected liver and biliary tract diseases]. 823 40

Extrahepatic cholestasis is one of the main factors causing liver fibrosis. Surgical biopsies of six patents were studied: one with normal liver (control patient), and five with different degrees of extrahepatal cholestasis with hepatocellular degenerative and necrotic changes. Monospecific antibodies directed against type IV collagen and fibronectin were localized by light microscopical immunohistochemistry. Type IV collagen was found in all basement membranes: ductal, vascular, neural, Intensive, almost continuous deposits of it were found along the entire length of the sinusoid. Fibronectin, the structural glycoprotein, was codistributed with type IV collagen in portal matrix and in perisinusoidal location. It did not decorate the basement membranes of bile ducts and stained more intensely than type IV collagen at the border between portal stroma and parenchyma. The intensity of the two antibodies increased corresponding with the heaviness of parenchymal deterioration. There was weaker staining behavior of the extracellular matrix regarding collagen IV and fibronectin in the area of heavy bilirubin impregnation. The sinusoid morphology in the regions with fibrosis and increased extracellular matrix formation in periportal areas was reported. Disses's space was distended and occupied by collagen bundles, amorphous matrix, swollen hepatocyte microvilli, and basement membrane-like material. Ito cells transformed into transitional cells or myofibroblast-like cells. Sinusoidal changes and increased collagen IV as well as perisinusoidal fibronectin formation coincided with the aggravation of cholestasis.
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PMID:Electron microscopic investigation on Ito cells and Disse's space in patients with extrahepatic cholestasis. Immunohistochemistry of collagen type IV and fibronectin in hepatic sinusoids. 870 81


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