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)

Mast cells have been shown to play a role in many chronic inflammatory and fibrotic disorders. However, their possible contribution to the pathological changes that occur in liver cirrhosis is unknown. To explore this, we examined whether changes in hepatic mast cell number and mediator content were associated with fibrotic changes in experimental biliary cirrhosis. Rats were studied 7, 14, or 21 days after bile duct resection (BDR). Hepatic mast cells were identified by histochemical and immunohistochemical stains. Rat mast cell protease II (RMCP-II), a marker of mast cell degranulation, was measured in liver by enzyme-linked immunosorbent assay. Hepatic collagen deposition was assessed by Sirius Red F3BA staining. In day 21 BDR rats, there was a one- to twofold increase (P < .001) in the number of hepatic mast cells, but this was not observed in day 7 or 14 BDR rats. Mild fibrotic changes were noted in BDR rat livers as early as 7 days after induction of cholestasis. Significant expansion and organization of fibrous tissue had occurred in day 14 BDR rats which progressed to bridging fibrosis by day 21. Liver RMCP-II levels were decreased by 50 percent (P < .05) and mast cell degranulation was apparent as shown by histamine immunostaining. These results suggest that hepatic mast cell hyperplasia and degranulation occur during prolonged cholestasis in the rat. Although these changes do not correlate with the onset of hepatic fibrosis, they do occur at a time during which there is significant deposition and organization extracellular matrix elements. Hepatic mast cells, by releasing profibrogenic mediators, may contribute to fibrotic changes in biliary cirrhosis.
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PMID:Hepatic mucosal mast cell hyperplasia in rats with secondary biliary cirrhosis. 866 46

Four patients with systemic mastocytosis, two men and two women, are presented. Three of them (patients 1, 2, and 4) developed portal hypertension and ascites without histological evidence of cirrhosis in liver biopsy. The remaining patient (patient 3) had severe bone lesions with multiple vertebral fractures. None of the patients had skin or lymph node involvement. Two patients (patients 1 and 2) died 12 and 9 months after diagnosis with acute nonlymphocytic leukemia and overt mastocytic leukemia, respectively, while the other two (patients 3 and 4) are alive 58 and 14 months after diagnosis. Treatment with hydroxyurea or cytosine arabinoside had not any beneficial effect in two patients, while a substantial amelioration of back pain had been obtained by local irradiation and recombinant human interferon-alpha-2b administration in one patient (patient 3). All patients had laboratory findings compatible with autoimmune cholangitis. We concluded that systemic mastocytosis is a rare cause of noncirrhotic portal hypertension often simulating autoimmune cholangitis and leading to the erroneous diagnosis of liver cirrhosis. Diagnosis is based on the presence of mast cells in Giemsa-stained liver histological sections, and it may be confirmed by immunohistochemical detection of tryptase in the cytoplasm of these abnormally proliferating cells.
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PMID:Systemic mastocytosis: a rare cause of noncirrhotic portal hypertension simulating autoimmune cholangitis--report of four cases. 944 86

Our pilot study disclosed that tryptase-positive mast cells (MC) were densely distributed around the intrahepatic bile ducts (peribiliary MC). In this study, the pathophysiologic roles of these MC were examined with respect to the microcirculation around the bile duct in 71 cases of histologically normal liver, 24 cases of chronic hepatitis, and 45 cases of liver cirrhosis. The tryptase-positive MC were very close to the microvessels of the peribiliary vascular plexus (PVP), which supply the intrahepatic biliary tree. The tryptase-positive MC were frequently found adjacent to vascular smooth muscle cells, including pericytes. The location of the tryptase-positive MC was confirmed by ultrastructural analysis. In cirrhosis, the numbers of both microvessels of PVP and peribiliary MC increased in parallel. Peribiliary MC were immunoreactive for endothelin 1 (ET-1), and were variably immunoreactive for histamine, chymase, inducible nitric oxide synthase (iNOS), and endothelin A and B (ET(A) and ET(B)) receptors, particularly in cirrhotic livers. On vascular endothelial cells of PVP, endothelial nitric oxide synthase (eNOS) and ET-1 were consistently detectable, and ET(A) receptors, ET(B) receptors, and iNOS were variably detectable. Pericytes of PVP expressed ET(A) and ET(B) receptors in addition to ET-1 and iNOS. Biliary epithelial cells also focally expressed iNOS, ET-1, and ET(A) and ET(B) receptors. These vasoactive substances were strongly expressed on the cellular components in cirrhotic liver. By in situ hybridization, iNOS mRNA signals were observed on iNOS-immunoreactive cell components, including peribiliary MC. These morphologic and immunohistochemical findings suggest that the cellular components displaying vasoactive substances in the milieu of the intrahepatic biliary tree are very dynamic in the vasoregulation of PVP in normal livers, even more so in cirrhosis, and that peribiliary MC exert local effects on the microcirculation of PVP, directly and indirectly.
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PMID:Evidence of the participation of peribiliary mast cells in regulation of the peribiliary vascular plexus along the intrahepatic biliary tree. 1090 46

Chronic liver diseases commonly result in liver fibrosis, and eventually liver cirrhosis. In the last decade, a new theory explaining liver fibrosis has been established. Accordingly, the development of liver fibrosis due to chronic liver diseases is thought to be mediated by inflammatory cells. They release fibrogenic mediators such as transforming growth factors (TGF)-beta, which are considered to be responsible for the activation and transformation of fat-storing cells. Recently, the involvement of mast cells and peripheral and autonomic nervous system in the fibrogenesis has been suggested. This study was aimed to establish the presence and distribution of mast cells and nerve fibers in the rat liver in the light of their implication in liver inflammatory and fibrotic disorders. Mast cells and afferent (sensory) fibers were detected immunohistochemically. An immunofluorescent method was applied to demonstrate tryptase and serotonin (SER) in the mast cells, while the primary sensory neuronal processes were identified by using antibodies against their marker calcitonin gene-related peptide (CGRP) and the proinflammatory mediator substance P (SP). The portal tracts and fibrous septa contained numerous mast cells, which exhibited strong immuno-reactivity to tryptase and SER. SER-positive nerve fibers were also found. It is generally accepted that no nerve fibers are present in the hepatic lobules, but the current investigation clearly demonstrates availability of CGRP-, SP, and SER-immunoreactive nerve fibers there. Our results indicate that in the rat liver portal tracts and hepatic lobules there are numerous mast cells, sensory and autonomic nerve fibers, which may be involved in liver injury by the inflammatory mediators they release.
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PMID:Relevance of mast cells and hepatic lobule innervation to liver injury. 1547 May 32

Reported herein is an autopsy case of mast cell leukemia, a rare form of systemic mastocytosis, complicated with portal hypertension. A 52-year-old woman presented with urticaria-like skin symptoms, anemia, and thrombocytopenia. Atypical mast cells (CD2+, CD25+, CD117+) with toluidine blue metachromasia were found in the peripheral blood and on bone marrow aspiration smears. Chemotherapy with cytosine arabinoside and idarubicin was ineffective and the patient died of multi-organ failure with rapidly progressing hepatosplenomegaly and large-volume ascites 3 months after admission. At autopsy the bone marrow, spleen, liver, and lymph nodes were extensively infiltrated by atypical tumor cells with occasional bi- or multi-lobated nuclei. They were positive for mast cell tryptase and possessed an activating mutation of the c-kitgene (D816V). Ascites (2200 mL) and non-ruptured esophageal varices with submucosal hemorrhage indicated the presence of severe portal hypertension. Although there was no evidence of liver cirrhosis, the hepatic sinusoids were clogged with tumor cells, with a tendency to be more severe in the perivenular areas, and the lumens of central veins were obliterated by tumor cell infiltration. The present case demonstrates that non-cirrhotic portal hypertension due to blocking of sinusoidal and venous flow could be a serious complication in mast cell leukemia.
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PMID:Mast cell leukemia with rapidly progressing portal hypertension. 1988 34