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)

We compared the expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in normal human liver, in which the endothelial lining of hepatic sinusoids is discontinuous and devoid of basement membrane, and in cirrhosis, during which sinusoids might undergo a process of capillarization and acquire a continuous lining and a typical basement membrane. In normal liver, sinusoidal endothelial cells displayed a very restricted repertory of cell-adhesion molecules: the intercellular adhesion molecules PECAM-1 and CD34 were undetectable and only two integrins, alpha 1 beta 1 and alpha 5 beta 1, were present, whereas the laminin receptors alpha 6 beta 1 and alpha 2 beta 1 were undetectable and the beta 3 integrins were faintly expressed. In capillarized sinusoids, sinusoidal endothelial cells displayed striking changes in their repertory of cell-adhesion molecules, including the expression of PECAM-1 protein and messenger RNAs and the induction of the laminin receptors alpha 6 beta 1 and alpha 2 beta 1. Such changes co-localized with subendothelial laminin deposits. In conclusion, normal sinusoidal endothelial cells express a distinctive set of cell-adhesion molecules, adapted to their structural and microenvironmental characteristics, and this repertory is dramatically modified during sinusoidal capillarization, possibly as a consequence of the concomitant matrix changes.
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PMID:Expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in the normal and cirrhotic human liver. 836 73

The immunohistochemical expression of CD34 (human hematopoietic stem cell and endothelial cell marker) and laminin were studied in chronic liver diseases and hepatocellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non-cancerous sinusoids and sinusoid-like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and laminin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and perinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid-like tumor vessels. However, early-stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid-like vessels. Laminin was strongly expressed in advanced HCC but not in early-stage HCC. The results indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothelial cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.
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PMID:Enhanced CD34 expression of sinusoid-like vascular endothelial cells in hepatocellular carcinoma. 891 44

To clarify the relationship between angiogenesis and hepatocarcinogenesis on progression of hepatocellular carcinoma (HCC), we quantitatively evaluated angiogenesis by CD34 immunohistochemistry in liver cirrhosis (LC), adenomatous hyperplasia (AH), and HCC, and proliferative activity estimated by Ki-67 immunohistochemistry. Angiogenesis was evaluated by CD34 immunohistochemistry using monoclonal antibody HPCA-2, and tumor proliferative activity was evaluated using monoclonal antibody MIB-1. We used an image analysis system to assess the microvessel density as the area percentage of the endothelial area. Angiogenesis was generally observed in HCC and there was no significant difference among all clinical stages and histological grades of HCC. On the other hand, the staining of CD34 was partly observed in sinusoids of AH, although no positive staining was seen in any sinusoids of LC. The proliferative activity was significantly correlated with the clinical stage and histological grade of HCC. Our results indicate that the quantitation of angiogenesis does not provide significant prognostic information in HCC, but that it may have diagnostic value in distinguishing HCC from non-HCC. Meanwhile, AH, which is not morphologically diagnosed as cancer, shows positive staining for CD34, suggesting that some portion of AH contains cancerous characteristics.
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PMID:Angiogenesis in hepatocellular carcinoma as evaluated by CD34 immunohistochemistry. 954 62

This study was aimed to evaluate the source of endothelin-1 (ET-1) in cirrhotic patients. ET-1 is implicated in the pathogenesis of portal hypertension. However, the mechanism and source for increased plasma ET-1 in cirrhotic patients are still obscure. Plasma ET-1 levels in systemic (SV), superior mesenteric (SMV), and splenic venous (SPV) blood were measured in 23 patients with cirrhosis and 8 controls with normal liver. Fourteen removed spleens were immunohistochemically studied for ET-1, CD34, CD68, and CD20. In situ hybridization was done to localize ET-1 messenger RNA (mRNA). In cirrhosis, ET-1 levels in both SMV and SPV were higher than in SV. ET-1 in SV and SPV were significantly higher in cirrhotic patients than in control patients. Three groups of cells in the spleen expressed both protein and mRNA of ET-1: endothelial cells in the sinus, which were also stained for CD34; cells in the germinal center; and cells in the marginal zone of lymphoid sheaths and follicles, which were also stained for CD20 but not for CD34 and CD68. The ET-1 concentration released from the spleen was in parallel with the grade of ET-1 expression in the spleen. The spleen is one of the major sites of ET-1 release in cirrhotic patients. Endothelial cells of the splenic sinus and possibly B lymphocytes in the germinal center and marginal zone of lymphoid sheaths and follicles seem to be the sites of ET-1 production in the spleen.
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PMID:Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis. 1079 86

This is a report of a post-mortem histological, histochemical, and immunohistochemical examination of a rare case of sclerosing encapsulating peritonitis (SEP) and non-occlusive mesenteric infarction (NOMI), two serious complications of continuous ambulatory peritoneal dialysis (CAPD), with which a man suffering hepatitis C virus (HCV)-induced liver cirrhosis for 7 years and trauma-induced paraplegia for 50 years had been treated for 1 year. The direct cause of death was encephalopathy caused by extreme hyperammonemia (11 250 microg/dL in serum). The autopsy revealed that the SEP had drastically reduced the length of the small intestine to 210 cm, 180 cm of which presented acute ischemic enteritis with Gram-negative bacterial infection. Histological examination of the SEP revealed that the exterior was composed of normal serosal elastic lamina, but with a cocoon-like appearance remarkably thickened by fibrosis to 3-8 times that of the normal subserosal layer and consisting of spindle cells and blood vessels, with some infiltration of mast cells and lymphocytes. The immunohistochemical examination of the spindle cells revealed few AE1/AE3(+) cells, HHF35(+) cells, and CD34(+) cells, many CD117(+) cells with slight proliferative activity based on MIB-1 positivity (proliferation index <1%), but no CD44(+) cells. It was concluded that either the few CD34(+) and/or the many CD117(+) cells were mesenteric stem cells that had originated from the serosa, proliferated, then differentiated into myofibroblasts or fibroblasts, producing collagen and hyaluronic acid in the matrix, leading to the gradual formation of the SEP, which was induced by the continual irritation of CAPD.
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PMID:Sclerosing encapsulating peritonitis and non-occlusive mesenteric infarction found at autopsy in a man who had undergone continuous ambulatory peritoneal dialysis: a histochemical and immunohistochemical study. 1097 66

Purging tumor cells from peripheral blood stem cells (PBSCs) used to treat patients with malignancy is important in the prevention of relapse. Positive selection of CD34+ stem cells using either immunomagnetic methods or an avidin-biotin conjugated CD34 monoclonal antibody binding column can reduce the number of contaminating tumor cells. We describe the management of three patients with malignancy treated using high-dose chemotherapy and enriched CD34+ cell transplantation. PBSCs were mobilized with cyclophosphamide plus recombinant granulocyte-colony stimulating factor (rG-CSF), and then leukophoresis was performed to harvest the PBSCs. The collected cells were positively selected for CD34+ cells using the Cellpro system. The CD34(+)-enriched PBSCs were then cryopreserved in the vapor phase of liquid nitrogen for future reinfusion. All three patients recovered smoothly after transplantation. The mean time to full hematologic recovery was 12 days for white blood cells (> or = 1 x 10(9)/L) and 14 days for platelets (> or = 20 x 10(9)/L), respectively. Partial remission occurred in two patients who were disease free for more than 4 years, and in one patient who died of hepatic failure with liver cirrhosis 5.5 months posttransplantation.
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PMID:CD34+ stem cell transplantation in malignancies: report of three cases. 1176 Mar 75

Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.
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PMID:Hepatocellular carcinoma: an update. 1178 14

In surgical pathology, focal nodular hyperplasia (FNH) is sometimes difficult to diagnose, and liver cirrhosis (LC) and hepatocellular adenoma (HA) are often among the differential diagnoses. Recently, we found a reduced expression of angiotensin I-converting enzyme (CD143) in FNH compared with cirrhotic and noncirrhotic liver. Intrigued by this observation, we investigated the expression pattern of CD143 in FNH, LC, and HA and its possible diagnostic value. The expression of CD143 was studied by immunohistochemistry in 20 FNHs, 13 corresponding extralesional noncirrhotic liver parenchyma, 20 patients with LC, and four HAs. Endothelial cells were identified with antibodies directed against CD31 and CD34. CD31+, CD34+, and CD143+ sinusoidal endothelial cells were found in extralesional liver, LC, HA, and FNH. However, the number of CD143+ sinusoidal endothelial cells and the intensity of immunostaining were significantly reduced in FNH compared with extralesional liver, LC, and HA. The expression of CD143 was further assessed using a numerical scoring system ranging from 0 to 6. The mean immunoreactivity score for CD143 was 2.4 +/- 1.7 for sinusoidal endothelial cells in FNH, 5.7 +/- 0.6 in extralesional liver, 4.8 +/- 1.1 in LC, and 5.8 +/- 0.5 in HA. The differences between the mean immunoreactivity scores for CD143 were highly significant. The difference between FNH and extralesional liver was confirmed on transcriptional level by fluorescence-mediated real-time RT-PCR, which also showed a significantly decreased level of CD143 mRNA in FNH. Our study provides evidence that CD143 is down-regulated in FNHs and that the phenotype of endothelial cells lining the sinusoids in FNH differs from those in non-neoplastic liver, LC, and HA. The observed variations in expression patterns for CD143 might be of diagnostic use in surgical pathology.
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PMID:Angiotensin I-converting enzyme (CD143) is down-regulated in focal nodular hyperplasia of the liver. 1470 68

Progenitor cells, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma (HCC) in animal models. By immunolabeling for c-kit and CD34 in human hepatitis B virus-associated cirrhosis with HCC (50 cases) and those with cirrhosis alone (10 cases), we found c-kit+ tumor cells in tumor tissue in 40 of 50 HCCs. The proportion was less than 0.1% of total tumor cell volume in most HCCs. Immunostaining for c-kit also was detected in sinusoidal endothelial cells in 43 of 50 HCCs. The incidence of oval cell occurrence in the adjacent nonneoplastic tissue in cases of HCC was high (44/50). The occurrence of oval cells, c-kit+ tumor cells, and c-kit+ sinusoidal cells in cases of human hepatitis B virus-associated HCC suggests that oval cell proliferation might be associated with the development of human hepatitis B virus-associated HCC. Furthermore, the c-kit+ sinusoidal cells might have a role in angiogenesis and progression of human hepatitis B virus-associated HCC.
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PMID:Occurrence of c-kit+ tumor cells in hepatitis B virus-associated hepatocellular carcinoma. 1592 63

We here report nine liver cirrhosis (LC) patients that underwent autologous bone marrow cell infusion (ABMI) from the peripheral vein. Subjects were patients with LC with total bilirubin of less than 3.0 mg/dl, platelet count of more than 5 (10(10)/l), and no viable hepatocellular carcinoma on diagnostic imaging. Autologous bone marrow (BM; 400 ml) was isolated from the ilium under general anesthesia. Mononuclear cells (MNCs) were separated by cell washing and were infused via the peripheral vein. MNC characteristics were confirmed by fluorescence-activated cell sorting analysis (CD34, CD45, and c-kit). After ABMI therapy, liver function was monitored by blood examination for 24 weeks. From 400 ml of BM, we obtained 7.81 +/- 0.98 x 10(9) MNCs. After washing, 5.20 +/- 0.63 x 10(9) MNCs were infused into patients with LC. Significant improvements in serum albumin levels and total protein were observed at 24 weeks after ABMI therapy (p < .05). Significantly improved Child-Pugh scores were seen at 4 and 24 weeks (p < .05). alpha-Fetoprotein and proliferating cell nuclear antigen (PCNA) expression in liver biopsy tissue was significantly elevated after ABMI therapy (p < .05). No major adverse effects were noted. In conclusion, ABMI therapy should be considered as a novel treatment for patients with decompensated LC.
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PMID:Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. 1754 Aug 55


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