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)

The concentrations of total glycogen (TG) and its labile (LF) and stable (SF) fractions were determined in hepatocytes of portal and central zones of the normal human liver and in the liver of patients with cirrhosis of viral and alcohol aetiologies. Using PAS reaction, TG, LF and SF were revealed in histological sections of the material obtained by the liver punch biopsies. The concentrations of TG and its fractions were measured by televisional cytophotometry. In liver cirrhosis, the concentrations of TG, LF and SF in both zones of the hepatic lobule have been found to be much higher than in the normal liver. It has been shown that the ratio of the hepatocyte TG concentrations in the portal zone to the central zone both in the normal liver and in viral cirrhosis exceeds 1.0, amounting to 1.264 +/- 0.021 and 1.030 +/- 0.009, respectively. The glycogen fraction composition in the cells of both the liver lobule zones in viral cirrhosis does not differ significantly from the norm. On the contrary, in the liver of patients with alcoholic cirrhosis, the ratio of the TG concentrations in the portal zone to the central zone is reduced to 0.815 +/- 0.016 and is accompanied by qualitative changes of the glycogen composition.
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PMID:Metabolic heterogeneity of glycogen in hepatocytes of patients with liver cirrhosis: the glycogen of the liver lobule zones in cirrhosis. 1143 96

Using cytophotometric method, the content of glycogen was studied in hepatocytes of the portal and central zones of a liver lobule in norm, in cirrhosis, and 1, 3, and 6 months after a partial hepatectomy of the normal and cirrhotic rat liver. As we showed earlier, glycogen content in cirrhotic liver hepatocytes rose 2-3-fold, along with obvious impairment of glycogen metabolic heterogeneity in these. In cirrhotic liver glycogen dominates in the central zone, whereas in norm more glycogen is observed in the portal one. The objective of this study was to find out to what degree a partial hepatectomy of cirrhotic liver may promote recovery of the metabolic glycogen heterogeneity in hepatocytes. Glycogen was determined in hepatocytes, using a quantitative variant of PAS-reaction on sections of the material obtained from serial supravital punctate liver biopsies. Glycogen amount in hepatocytes of different liver lobule zones was determined by an image analyzer technique that allows to bring together the cytophotometric analysis of the substance with its localization in a particular liver lobule. Results of these studies have shown that a partial hepatectomy of cirrhotic liver promotes restoration of the hepatocyte metabolic heterogeneity in the liver lobule.
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PMID:[Effect of partial hepatectomy on the glycogen level in hepatocytes in the portal and central lobule zones in cirrhotically-changed rat liver]. 1155 50

FAP is an autosomal dominant inherited disease, characterized by systemic deposition of amyloid fibrils in various tissues. The purpose of this study is to describe the gross and microscopic findings of the explanted livers for FAP.10 patients were transplanted for FAP at our institution. Diagnosis was supported by positive familiar history, clinical data and detection of mutated TTR by electrospray ionization mass spectrometry with Val30Met mutation verified by PCR. All the explanted livers were photographed, fixed in formol and processed according to protocol. Later they were examined with HyE, reticulin, PAS diastasa, Masson trichromic, Congo red with polarised light and immunoreactivity against TTR. The gross aspect was normal. We obtained multiple samples representative of the organ and the hepatic hilium. All of the patients presented with deposits of amyloid substance in the lymph nodes and the nerves of the hepatic hilium These deposits were Congo red positive with a greenish birefringence to polarized light Deposits show immunoreactivity with antihuman TTR. Whereas liver transplantation restores hepatic function in patients with cirrhosis, liver transplantation cures the FAP patient of their genetic defect. Domino transplantation is a procedure in which the index patient receives an organ, while the explanted organ is reused for transplantation into another patient. In conclusion, exclusion of hepatic amyloid deposits which can cause functional alterations in the FAP liver is vital; and is important to study the explanted livers of patients with FAP to confirm the results of the scarce published series.
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PMID:Transthyretin familial amyloidotic polyneuropathy: histopathological study of the explanted livers. 1511 56

Hypofibrinogenemia is a rare inherited disorder characterized by low levels of circulating fibrinogen, caused by mutations within 1 of the 3 fibrinogen genes. We report here the case of a 61-year-old man with chronic liver function test alterations. Liver biopsy examination revealed chronic hepatitis complicated by cirrhosis and weakly eosinophilic globular cytoplasmic inclusions within the hepatocytes, faintly stained with PAS-diastase. On immunohistochemistry, the inclusions reacted strongly with human antifibrinogen antibodies. Coagulation investigations of the propositus and his 2 sons showed low functional and antigenic fibrinogen concentrations that were indicative of hypofibrinogenemia. A liver biopsy performed on the 28-year-old son demonstrated the same globular cytoplasmic inclusions, albeit without associated chronic liver disease. PCR amplification followed by sequencing showed that all 3 were heterozygous for a CGG>TGG mutation at codon 375 of the fibrinogen gamma-chain gene (FGG), corresponding to an Arg>Trp substitution. This is the first in an adult male and the second published case with a discernible hepatic fibrinogen endoplasmic reticulum storage disease due to an FGG Arg375Trp (fibrinogen Aguadilla) mutation. Our results suggest that familial hypofibrinogenemia should be considered in the differential diagnosis of a progressive liver disease associated to hepatocellular intracytoplasmic globular inclusions.
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PMID:Fibrinogen gamma375 arg-->trp mutation (fibrinogen aguadilla) causes hereditary hypofibrinogenemia, hepatic endoplasmic reticulum storage disease and cirrhosis. 1681 36

Schistosomiasis mekongi was shown to be endemic, along the Mekong River, in northern Cambodia, affecting many patients with portal hypertension. Surgical procedures were proposed to some patients with digestive haemorrhage history to avoid fatal recurrence. The aim of our study was to evaluate the intensity of the liver fibrosis among these patients. During surgical treatment, liver biopsies were collected, fixed in Bouin or in formalin and processed at the Institut Pasteur of Cambodia. Sections were stained by H&E, Masson's trichrome, PAS, Ziehl-Neelsen's method and Congo Red. A total of six biopsies from patients aged 16-36 were analysed. There was complete disorganization of hepatic architecture with fibrous enlargement of portal tracts and some portal-portal bridging fibrosis, but there was no cirrhosis. In portal areas, there was blood vessel congestion and thrombosis with inflammation. Bile ducts were normal. In the parenchyma, congestion of sinusoidal capillaries was combined with focal mononuclear inflammatory infiltrate. There was no steatosis, no necrosis, no cholestasis, no iron accumulation and no amyloidosis. Numerous eggs of Schistosoma mekongi were observed in five cases, mostly in fibrous areas and more rarely in the parenchyma. Eggs were round or oval, measuring 60 x 40 microns with an acid-fast thin hyaline wall. Some eggs were surrounded by epithelioid and giant cell reaction. In conclusion, our findings illustrated a surprisingly high degree of fibrosis among young adults which contrasts with other schistosomiasis.
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PMID:[Histology of liver lesions due to Schistosoma mekongi. About six cases with severe portal hypertension operated in Cambodia]. 1725 54

We report on clinicopathological and whole body MRI analyses of the index patient of a large nonconsanguineous German-Ukraine family with homozygous and heterozygous AGL gene mutations at position p.W1327X (c.3980G > A). There are only limited reports on this phenotype with a homozygous genotype. The index patient, a 49-year-old woman presented with hepatomegaly, cardiomyopathy and moderate progressive proximal limb myopathy. Skeletal muscle showed severe vacuolar myopathy with storage of PAS-positive non-membrane-limited glycogen. An increase in glycogen content and completely decrease of debranching enzyme activity was measured in erythrocytes. Mutational analysis of the AGL gene showed a homozygous p.W1327X mutation. In the family, two brothers had been affected by severe infantile onset hepatomegaly and died within their first years of life by fatal liver cirrhosis. Furthermore, another sister severely affected by hepatomegaly, cardiomyopathy and proximal skeletal myopathy died at age 33. Three younger heterozygous sisters and a brother noticed exercise-induced myalgia and weakness since their teens. In sum, a homozygous p.W1327X mutation leads to a severe generalized glycogenosis types 3a and 3b within the same family. Even heterozygous p.W1327X mutation carriers may present with mild non-progressive neuromuscular symptoms, such as exercise-induced myalgia and fatigue.
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PMID:Clinicopathological analysis of the homozygous p.W1327X AGL mutation in glycogen storage disease type 3. 1892 25

Glycogen storage disease type IV (GSD IV, or Andersen disease) is an autosomal recessive disorder due to the deficiency of 1,4-alpha-glucan branching enzyme (or glycogen branching enzyme, GBE1), resulting in an accumulation of amylopectin-like polysaccharide in muscle, liver, heart and central and peripheral nervous system. Typically, the presentation is in childhood with liver involvement up to cirrhosis. The neuromuscular form varies in onset (congenital, perinatal, juvenile and adult) and in severity. Congenital cases are rare, and fewer than 20 cases have been described and genetically determined so far. This form is characterized by polyhydramnios, neonatal hypotonia, and neuronal involvement; hepatopathy is uncommon, and the babies usually die between 4 weeks and 4 months of age. We report the case of an infant who presented severe hypotonia, dilatative cardiomyopathy, mild hepatopathy, and brain lateral ventricle haemorrhage, features consistent with the congenital form of GSD IV. He died at one month of life of cardiorespiratory failure. Muscle biopsy and heart and liver autoptic specimens showed many vacuoles filled with PAS-positive diastase-resistant materials. Electron-microscopic analysis showed mainly polyglucosan accumulations in all the tissues examined. Postmortem examination showed the presence of vacuolated neurons containing this abnormal polysaccharide. GBE1 biochemical activity was virtually absent in muscle and fibroblasts, and totally lacking in liver and heart as well as glycogen synthase activity. GBE1 gene sequence analysis revealed a novel homozygous nonsense mutation, p.E152X, in exon 4, correlating with the lack of enzyme activity and with the severe neonatal involvement. Our findings contribute to increasing the spectrum of mutation associated with congenital GSD IV.
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PMID:Neuropathological study of skeletal muscle, heart, liver, and brain in a neonatal form of glycogen storage disease type IV associated with a new mutation in GBE1 gene. 1935 89

The paper describes a patient who has developed Whipple's disease in the presence of infantile cerebral palsy and hepatitis B virus cirrhosis. After 5-year treatment with co-trimoxazole (480 mg b.i.d.), the clinical manifestations subsided and PAS-positive macrophages were no longer detectable in the small intestinal mucosal biopsy specimens. Subsequent worsening of the patient's condition was associated with the progression of liver cirrhosis.
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PMID:[Whipple's disease in a patient with infantile cerebral palsy and hepatitis B virus cirrhosis]. 2477 11

We investigated the immunoexpression of the intermediate filament proteins, cytokeratin and desmin, and the morphological changes in the liver of rats during experimental fasciolosis at 4, 7 and 10 weeks post-infection. Rats were infected with 30 Fasciola hepatica metacercariae. Paraffin sections of the liver were stained using H & E, PAS and azan stains. Immunohistochemical reactions were performed using antibodies against cytokeratin and desmin. The experimental F. hepatica infection led to fibrosis and cirrhosis of the liver, and to inflammation of the common bile ducts. The expression of cytokeratin was increased in the epithelial cells of both the liver bile ductules at 4, 7 and 10 weeks post-infection and in the common bile ducts at 7 and 10 weeks post-infection compared to uninfected rats; expression in the common bile ducts was more intense. The myofibroblasts of the liver and smooth myocytes of the interlobular bile ducts and common bile ducts, showed a slight increase in desmin expression compared to the uninfected rats. The increased expression of cytokeratins in the hyperplastic rat common bile duct epithelium during the biliary phase of fasciolosis at 7 and 10 weeks post-infection may be explained by mechanical irritation by the parasite and an inflammatory reaction in the bile duct epithelium and in periductal fibrous tissue.
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PMID:Immunoexpression of intermediate filaments and morphological changes in the liver and bile duct of rats infected with Fasciola hepatica. 2592 46

We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8-20.9 mm in size on liver cirrhosis received CA4P intravenously at 10 mg/kg. Tumor-diameter was measured by T2-weighted imaging (T2WI) to define microcancers (< 5 mm) versus larger HCCs. Vascular responses and tissue necrosis were detected by diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (CE-T1WI) and dynamic contrast enhanced (DCE-) MRI, which were validated by microangiography and histopathology. MRI revealed nearly complete necrosis in 5 out of 7 micro-HCCs, but diverse therapeutic necrosis in larger HCCs with a positive correlation with tumor size. Necrosis in micro-HCCs was 36.9% more than that in larger HCCs. While increased diffusion coefficient (ADCdiff) suggested tumor necrosis, perfusion coefficient (ADCperf) indicated sharply decreased blood perfusion in cirrhotic liver together with a reduction in micro-HCCs. DCE revealed lowered tumor blood flow from intravascular into extravascular extracellular space (EES). Microangiography and histopathology revealed hypo- and hypervascularity in 4 and 3 micro-HCCs, massive, partial and minor degrees of tumoral necrosis in 5, 1 and 1 micro-HCCs respectively, and patchy necrotic foci in cirrhotic liver. CD34-PAS staining implicated that poorly vascularized micro-HCCs growing on liver cirrhosis tended to respond better to CA4P treatment. In this study, more complete CA4P-response occurred unexpectedly in micro-HCCs in rats, along with CA4P-induced necrotic foci in cirrhotic liver. These may help to plan clinical applications of VDAs in patients with HCCs and liver cirrhosis.
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PMID:Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P. 2890 14


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