UMLS:C0023890 - FACTA Search

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Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Excessive accumulation of collagen in the extracellular matrix has a crucial role in fibrosis. Thus pharmacological inhibition of collagen deposition is likely to be beneficial for patients suffering from fibrotic disorders such as liver cirrhosis. Prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline in collagens and other proteins with collagen-like amino acid sequences by the hydroxylation of proline residues in -X-Pro-Gly- sequences. The reaction products, 4-hydroxyproline residues, serve to stabilize the collagen triple helices under physiological conditions. Conversely, collagen chains that contain no 4-hydroxyproline cannot fold into triple helical molecules that are stable at body temperature. The prolyl 4-hydroxylase reaction therefore seems to be a particularly suitable target for the pharmological regulation of excessive collagen formation. The reaction catalyzed by prolyl 4-hydroxylase requires Fe2+, 2-oxoglutarate, O2 and ascorbate and involves an oxidative decarboxylation of 2-oxoglutarate. The active enzyme is an alpha 2 beta 2 tetramer that consists of two types of inactive monomer and has two catalytic sites. Some parts of the catalytic sites may be built up cooperatively of both the alpha and beta subunits, but the alpha subunit appears to contribute the major part. The beta subunit contains the carboxyl-terminal tetrapeptide sequence -Lys-Asp-Glu-Leu which is essential for the retention of a polypeptide within the lumen of the endoplasmic reticulum. Since the alpha subunit lacks the carboxyl-terminal retention signal, one function of the beta subunit in the prolyl 4-hydroxylase tetramer may be to retain the enzyme within the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolyl 4-hydroxylase and its role in collagen synthesis. 166 65

We report on the occasional presence of iron granules in plasma cells in two male patients respectively 64 and 71 years old, both with excessive drinking habits. One patient also had liver cirrhosis. In both patients the bone-marrow biopsy showed a macrocytic anemia without megaloblasts. We refer the morphologic data because the cases reported are not many and the presence of iron granules in plasma cells was a curious and rare aspect. The most important feature appearing from the data issued is the gap concerning both the source and mechanism that cause this phenomenon. Some investigations have suggested that the plasma cell iron is located in mitochondria, others have noted that iron granules were located between the Golgi region and the rough endoplasmic reticulum. Moreover, the morphologic data are not related to the number of plasma cells in the bone-marrow and there is no causal relation between alcoholic abuse and plasma cell iron. The first problem is common, the second is rare.
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PMID:With regards to the presence of iron granules in plasma cells. 181 5

Using in situ immunohistochemistry and a specific monoclonal antibody (mcab R1G10), we analyzed the expression of the human interferon-gamma receptor (HuIFN-gamma R) and its topographical distribution in normal liver biopsies and in biopsies with various inflammatory liver diseases. In normal liver tissue, mcab R1G10 reacted weakly with sinusoidal and vascular endothelial cells, while hepatocytes were distinctly negative. In pathological conditions, mcab R1G10 produced membranous, cytoplasmic and/or perinuclear staining of hepatocytes, in a topographical distribution which varied according to the type of liver disease. In acute hepatitis, R1G10-positive hepatocytes were diffusely distributed throughout the liver parenchyma, and showed strong cytoplasmic, as well as membranous and perinuclear reactivity. In chronic persistent hepatitis, weak membranous staining was found on a number of scattered hepatocytes in acinar zone 1, with more pronounced expression on single hepatocytes in acinar zone 3. In chronic active hepatitis and in active cirrhosis, a diffuse weak membranous reactivity throughout the liver parenchyma was accompanied by enhanced R1G10 expression in areas of inflammation in acinar zone 1. With immunoelectronmicroscopy, R1G10 reactivity was found on the peripheral cell membrane and on the microvillous canalicular cell membrane of hepatocytes in a strikingly discontinuous manner. In the cytoplasm, the reaction product was detected on the cisternae of the rough endoplasmic reticulum and on small vesicles which were especially abundant in the perinuclear area. Our results demonstrate the absence of HuIFN-gamma R on hepatocytes in the normal liver, and its de novo expression during inflammatory liver disease. These findings indicate that hepatocytes, by displaying the HuIFN-gamma R, may act as target cells for the immunoregulatory action of IFN-gamma during liver inflammation.
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PMID:Expression of interferon-gamma receptor in normal and pathological human liver tissue. 182 21

Intralobular changes of the liver in experimental graft-versus-host disease (GVHD) across minor histocompatibility barriers were investigated for up to 14 months after bone marrow transplantation. Sinusoidal lymphocyte infiltration, and necrosis and degeneration of hepatocytes were evident by day 4 and reached a maximum level at 2 weeks after transplantation, then gradually decreased, but they persisted during the entire period of observation, indicating that more or less hepatocyte injury may persist continuously in hepatic GVHD. Piecemeal necrosis was transiently observed around 2 weeks after transplantation, in parallel with the peak of lymphocyte infiltration into the portal area. Similarly, central vein endothelialitis (attachment of lymphocytes to endothelial cells) was transiently observed with a peak activity at 2 weeks after transplantation. Mild centrilobular and portal fibroplasia were evident by 2 weeks after transplantation, but they hardly progressed and no cases developed liver cirrhosis. Frequently lymphocytes were found located beneath endothelial cells and attached to hepatocytes. Ultrastructural observation revealed that sinusoidal lymphocytes were occasionally in contact with endothelial cells by means of cytoplasmic pseudopods. Also lymphocytes were frequently in close contact with hepatocyte plasma membranes over short distances. Lymphocytes occasionally accompanied other inflammatory cells, such as eosinophilic leukocytes and mononuclear phagocytic cells. Hepatocytes in close contact with lymphocyte and other inflammatory cells showed a varying degree of degenerative changes, including condensation of cytoplasm and nucleus with irregular nuclear contours, dilatation of endoplasmic reticulum and mitochondria, formation of cytoplasmic vacuoles, and loss of microvilli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histological changes of the liver in experimental graft-versus-host disease across minor histocompatibility barriers. V. A light and electron microscopic study of the intralobular changes. 188 59

A study was carried out on the evolution of histological and ultrastructural lesions of liver fragments harvested at different time intervals in the course of extracorporeal circulation in 62 patients operated for acquired and congenital heart disease, as well as that of serologic tests, pre-, intra- and postoperatively up to seven days. Morphologically, it is only the ultrastructural examination that detects the accentuation of preexisting hypoxic lesions within the framework of a state of "controlled shock", noting especially accentuated dilation of the endoplasmic reticulum, lysosomal activation, mitochondrial lesions and a tendency to ribosomal and glycogenic depletion. The lesions did not exceed the limits of reversibility, excepting the cases with advanced heart failure and cardiac cirrhosis. Lending support to these data is the decrease of proteinemia and the dynamics of LDH, SDH, G1DH, gamma GT and transaminases increase after 24 h, then fall to normal values within seven days.
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PMID:Contributions to the biology of the hypoxic liver. Note II. Histologic, electron microscopic and biochemical aspects in the course of open heart surgery under extracorporeal circulation. 214 7

Hepatocytes respond to injury by a few basic pathological reactions that are reflected in cell death, different types of degeneration, regeneration, or tumorous transformation. At the ultrastructural level, alterations of cell organelles can be observed in different combinations as a result of the injury, depending on the etiological agent(s) or pathological conditions developed. Nuclear bodies, dilation and fragmentation of rough endoplasmic reticulum (rer), swelling of mitochondria, and an increased number of lysosomes occur during acute viral hepatitis. The core and surface components of the hepatitis B virus can be localized in the liver cells in chronic hepatitis and in carriers. Close contact of hepatocytic and lymphocytic cell membranes were observed in chronic active hepatitis. Hepatocytes surrounded by an increased amount of collagen fibers are characteristic of cirrhosis. Loosely arranged, fine fibrils or condensed forms of Mallory bodies are pathognomic for alcoholic injury. A wide spectrum of alterations are noted after drug treatment: the proliferation of smooth endoplasmic reticulum (ser) as an adaptive phenomenon, focal or complete necrosis of the cell, inflammation, and the like. The fine structural analysis of hepatocytic inclusions in storage diseases has a differential diagnostic value. The storage of copper and other elements can be measured by x-ray microanalysis. The study of the hepatocytic differentiation in liver tumors is highly important in establishing the diagnosis and in proving the hepatocytic origin of the tumor.
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PMID:Fine structure of hepatocytes during the etiology of several common pathologies. 218 62

Homozygosity for alpha 1-antitrypsin deficiency, usually of the genotype PIZZ, is one of the more common single gene defects in infants of European origin, occurring in about 1 in 2000 to 1 in 7000 of the newborn population. About 17% of such infants present with neonatal hepatitis and a small number with intracranial haemorrhage thought to be caused by vitamin K deficiency associated with cholestasis. At least 3% of PIZZ infants will die of cirrhosis in later childhood unless successfully treated by liver transplant. The pathogenesis of the liver disease is not understood and this is unsatisfactory both for treatment and for genetic counselling. The locus coding for alpha 1-antitrypsin (alpha 1AT) is designated PI for proteinase inhibitor. Careful study of the genotypes at this locus in neonatal disease shows that the only certain association is with the homozygous PIZZ genotype. The mutation results in a normal rate of synthesis of a polypeptide that becomes entrapped in the endoplasmic reticulum of the hepatocyte. Some other factor (or factors), as yet unidentified, determines whether severe liver damage results. The low level of alpha 1AT in the plasma seems unlikely to be the primary cause of damage but may play a secondary role. There is some evidence that the other factor(s) may be familial since in one study, though not in all, a high correlation for severity of liver disease was found between PIZZ siblings. The heterogeneity of the clinical course does not result from heterogeneity of PIZ alleles and there is no evidence that it is determined by variation in other related genes on chromosome 14. Only two possible clues have emerged so far. There is some evidence of a protective effect of breast-feeding, and a recent study has found the HLA class II DR3 antigen to be more common than expected in children with alpha 1-antitrypsin deficiency and liver disease. Accumulation of alpha 1AT protein in the hepatocytes may predispose them to some unidentified alteration of the immune response. It is possible that lack of antiprotease activity in the plasma might exacerbate the original damage, so the possibility of useful therapy with alpha 1AT cannot be ruled out entirely. At present, there is no valid way of predicting the severity of disease in a PIZZ child; hence, it is common for parents of a severely affected child to wish to terminate any future PIZZ pregnancy. The most direct method to diagnose the PIZZ genotype of a chorion villus sample is by allele-specific hybridization or sequencing of amplified DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. 218 61

During a 12-year period, 46 children and adolescents with inflammatory bowel disease were followed from the time of diagnosis with regular biochemical tests of liver function. Thirty-four patients had ulcerative colitis and 12 had Crohn's disease. Mean age at the time of diagnosis was 10.2 years (range 7 months-17 years) and the mean follow-up period was 5.2 years (range 1-11 years). Pathological liver function tests were found in 60% of the 34 patients with ulcerative colitis: 9 of these 20 patients demonstrated more severe disturbance, usually at the time of diagnosis. Liver damage was most frequent in patients with total colitis. Liver biopsy was performed in eight patients, demonstrating "pericholangitis", fibrosis and in one case cirrhosis. Morphometry of electron microscopical pictures revealed a significantly increased number of lysosomes and dilated cisternae of the rough endoplasmic reticulum. ERCP was performed in two patients, verifying primary sclerosing cholangitis in one. Four of the 12 patients with Crohn's disease had mildly pathological liver function tests. No correlation was found to the extent, duration or treatment of bowel disease. In our series of juvenile inflammatory bowel disease, liver damage occurred frequently, especially in ulcerative colitis. The more severe changes tended to coincide with the onset of bowel disease.
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PMID:Liver damage in juvenile inflammatory bowel disease. 221 95

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.
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PMID:Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide. 237 79

The so-called novel inclusion body (NIB) is an intrahepatocytic structure which is frequently observed in human cirrhotic liver. It resembles very much to, but definitely differs from Hepatitis B surface antigen (HBsAg) morphologically. The age distribution of liver cirrhosis cases positive for NIB is similar to that positive for HBsAg, except for an existence of a time lag in mean age. One of the best staining methods to demonstrate NIB, for example, is to exhibit it as a reddish body stained by Luna, with a contrast of HBsAg counterstained purple in color by aldehyde fuchsin after thiosulfation. Electron microscopy of the liver obtained from a patient, negative for both HBsAg and Hepatitis B e antigen (HBeAg) but positive for Hepatitis B core antibody (HBcAb) and Hepatitis B surface antigen antibody (HBsAb) clinically, revealed some unfamiliar, tubular and cisternal arrays showing a network pattern and ring-shaped structure at the site exactly corresponding to NIB localization. These are considered to have been induced from the endoplasmic reticulum by an unknown agent, for which non A non B hepatitis virus (NANBV) is rationally postulated as one of the possibilities. A close relation between NIB and NANBV is highly suspected because of much similarities in histology, histochemistry, age distribution, and electron microscopy. The true nature of NANBV should be rescrutinized, especially in relation with Hepatitis B virus infection, since NIB is quite often observed also in cirrhotic liver positive for HBsAg.
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PMID:A study on so-called novel inclusion body in human hepatocyte. 241 47

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