[Physiopathology of alcoholic liver cirrhosis--comparison with viral liver cirrhosis].
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Adult↗
Biomedical subjects
Y Hasumura
Publications and source records attributed to Y Hasumura.
Vitamin E deficiency in acquired fat malabsorption.
Thirteen patients with adult-onset vitamin E deficiency due to fat malabsorption were investigated clinically and electrophysiologically. These patients had slightly or moderately decreased serum vitamin E (1.7-4.8 micrograms/ml, normal less than 6.0) or vitamin E/cholesterol ratio (0.21-0.31 mg/g, normal less than 0.35). Only one patient had typical neurological manifestations of vitamin E deficiency, which improved with supplementary vitamin E. The pathological findings in this patient were also compatible with vitamin E deficiency. This patient had poorly controlled diabetes mellitus due to advanced chronic pancreatitis. Reviewing previously reported cases of vitamin E deficiency with diabetes mellitus in chronic pancreatitis, the duration of deficiency until the onset of symptoms was shorter than in those cases without complications. Although adult patients with early, slight deficiency of vitamin E are generally asymptomatic, patients with diabetes mellitus tend to have early neurological symptoms. The vitamin E tolerance test should be used, because even in some patients with vitamin E deficiency due to malabsorption, the deficiency can be overcome by large oral doses of vitamin E.
Adult↗
A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis.
A multi-center double-blind controlled trial of ursodeoxycholic acid (UDCA) for treatment of primary biliary cirrhosis (PBC) was carried out. Twenty two and 23 patients were treated with 600 mg/day UDCA and placebo, respectively, for 24 weeks. In UDCA-treated patients, fall of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase activities started within 4 weeks after start of the trial and continued throughout the trial period. The serum IgM level fell in 7 UDCA-treated patients examined but not in 10 placebo-treated patients examined. Serum bilirubin concentration showed no significant change at the end of the study in either of UDCA- and placebo-treated group of patients. There was no significant difference between these two groups with respect to the frequency of improvement of pruritus. In UDCA-treated patients, serum bile acid composition changed markedly, though its concentration showed no significant change. The percentage of total bile acid which ursodeoxycholic acid took up increased, whereas those which cholic acid, chenodeoxycholic acid and deoxycholic acid took up were decreased.
Alanine Transaminase↗
Urinary polyamine excretion measured by a simple enzymatic method is clinically useful as an expression of hepatic regeneration in liver diseases.
Polyamines have been known to play an important role in hepatic regeneration. In the present study, we measured the amount of urinary polyamine excretion in various liver diseases using a simple enzymatic method. Urinary polyamine excretion was elevated above the normal range in 21 out of 47 cases with fulminant hepatic failure, acute hepatitis, chronic active hepatitis, and liver cirrhosis. No change, however, was observed in 11 patients with chronic inactive hepatitis. In fulminant hepatic failure, two patients with urinary polyamine concentrations above 100 mumoles/g.cr. recovered, while two patients with concentrations of 56.2 and 26.7 mumoles/g.cr., died. In acute hepatitis, urinary polyamine excretion was significantly less in the recovery stage compared with the acute stage. When insulin and glucagon infusion therapy was performed in patients with liver cirrhosis without ascites, urinary polyamine excretion was significantly elevated after three days. These results suggest that measuring the amount of polyamine in urine is clinically useful for monitoring hepatic regeneration.
Biogenic Polyamines↗
A lithium clearance study of sodium reabsorption at the proximal tubule in liver cirrhosis with ascites.
Since the reabsorption of lithium occurs almost exclusively in the proximal tubule and is associated with that of sodium, the fractional excretion of lithium (FELit) ws examined in 18 patients with cirrhosis in order to examine the reabsorption rate of sodium at the proximal tubule. As expected, the fractional excretion of sodium (FENa) was significantly lower in cirrhotic patients with ascites (0.43 +/- 0.10%, mean +/- SEM) than in cirrhotic patients without ascites (0.75 +/- 0.14%, P less than 0.05) and healthy controls (0.82 +/- 0.17%, P less than 0.05). By contrast, there was no significant difference in FELit among cirrhotic patients with ascites (16.7 +/- 2.0%), cirrhotic patients without ascites (15.4 +/- 2.0%) and controls (17.4 +/- 1.5%). It is unlikely, therefore, that in cirrhotic patients with ascites, the impaired sodium excretion is solely caused by the abnormal sodium reabsorption capacity of the proximal tubule.
Absorption↗
In vitro effect of corticosteroid on immunoregulatory functions in primary biliary cirrhosis.
Primary biliary (PBC) has many features, suggesting immunopathogenic mechanisms involved in its etiology. However, none of the therapeutic modalities that are beneficial in many autoimmune diseases have been demonstrated to halt histologic progression of the disease or to induce a complete clinical, biochemical, and histologic remission on this disease. To investigate whether corticosteroids improve the abnormal immunoregulatory functions in PBC, the in vitro effect of corticosteroid on the activity of suppressor T cells and interleukin 2, an inducer of immunoregulatory cells, was evaluated in eight patients with PBC. Defective suppressor T cell activity was found in PBC; however, no clear improvement of T cell activity was observed after in vitro treatment of lymphocytes with corticosteroid. In PBC, interleukin 2 activity was normal, and the same decrease of activity as occurring in healthy controls was observed after corticosteroid treatment. These results suggest that a defect in the responsiveness of suppressor T cell activity to corticosteroid may play, at least in part, a role in the pathogenesis of corticosteroid ineffectiveness in PBC.
Cells, Cultured↗
In vitro effect of prednisolone on peripheral blood suppressor T cell activity in patients with alcoholic hepatitis.
An immunological process is suggested to play some role in the pathogenesis of alcoholic hepatitis; however, its nature has not been clarified. In the present study, we examined, in 30 patients with alcoholic liver disease, an in vitro effect of prednisolone on suppressor T cell activity to see whether an altered cellular immunoregulatory mechanism is affected by corticosteroid. Suppressor T cell activity, which was induced by concanavalin A (Con A), was assessed by inhibition of phytohemagglutinin-stimulated blast transformation of autologous lymphocytes, and prednisolone (10 micrograms/ml) was added when suppressor T cells were induced. Low suppressor T cell activity was found in alcoholic patients with hepatic fibrosis, alcoholic hepatitis, and cirrhosis with hepatitis; these reductions recovered to a normal range when lymphocytes were incubated in vitro with prednisolone, suggesting an improvement in the altered immunoregulation by prednisolone. Although immunotherapy is shown to be of no benefit in the treatment of alcoholic hepatitis, we propose a need to elucidate further the therapeutic modalities for correction of the immunoregulatory abnormalities in such patients.
Female↗
Clinical significance of serum antibodies against alcohol-altered hepatocyte membrane in alcoholic liver disease.
The clinical significance of serum antibodies against alcohol-altered rabbit hepatocytes was evaluated in 91 patients with alcoholic liver disease. Patients were divided into two groups according to the presence or absence of those antibodies at the time of first admission, and their clinical, biochemical, and histological findings were compared. In 38 seropositive patients, the total amount of ethanol consumption as well as serum activity of glutamate-oxaloacetate transaminase, serum levels of total bilirubin, gamma-globulin, IgG, and IgA were all significantly higher than in 53 seronegative patients. In addition, the extent of fibrosis, alcoholic hyalin, cholestasis, and lymphocytic and polymorpholeukocytic infiltrations in the liver were all significantly greater in the seropositive patients. Histological changes were compared in the 16 patients who continued to drink alcohol and who received repeated liver biopsies. Seven out of eight patients who were seropositive at the time of the first liver biopsy showed histological deterioration, whereas one of the eight seronegative patients showed a slight progression. These results suggest that the presence of serum antibodies against alcohol-altered liver cell membrane delineates a group of alcoholic patients with severe, advanced liver disease characterized by a tendency to progress with continued alcohol ingestion.
Alanine Transaminase↗
Prostaglandin-E-producing hepatocellular carcinoma with hypercalcemia.
An autopsy case of prostaglandin E-producing hepatocellular carcinoma with hypercalcemia is presented in this article. A 72-year-old man showed high serum calcium levels (14.2 to 17.3 mg/100 ml) and hypophosphatemia. The plasma level of immunoreactive parathyroid hormone was below the normal range. Administration of oral indomethacin 50 mg daily was effective in decreasing the serum calcium concentration. However, this effect lasted only 5 days, after which it returned to pretreatment levels. The patient died in a hypercalcemic coma. By an autopsy, hepatocellular carcinoma was found in the right lobe of the liver. However, no obvious bone metastases nor abnormalities in the parathyroid glands were detected. The immunoreactive prostaglandin E level assayed in the neoplastic tissue (2278 ng/g) was significantly high when compared with level in the nonneoplastic liver tissue (194 ng/g). The production of prostaglandin E by the tumor itself appears to be the most likely mechanism for the hypercalcemia in this patient.
Aged↗
Case of mixed connective tissue disease associated with autoimmune hepatitis.
A 56-year-old female with mixed connective tissue disease (MCTD) who developed autoimmune hepatitis is described. Hepatitis was controlled effectively by the corticosteroid therapy. Biopsy of the liver revealed swelling and hydropic degeneration of hepatocytes, accompanied by Councilman's body formation and focal necrosis. These histological findings differ from those in three previously described cases. A relationship between MCTD and liver involvement appears possible.
Autoimmune Diseases↗
Differences of liver membrane antibody frequency in alcoholic liver disease. Detection of IgG and IgA classes using radioimmunoassay.
The presence of liver membrane antibody in IgG and IgA was investigated by radioimmunoassay using isolated rabbit hepatocytes as target cells. This technique was more sensitive than the immunofluorescent method. IgG liver membrane antibodies were positive in 24% of patients with alcoholic liver disease. IgA liver membrane antibodies were detected in 58% of patients with alcoholic liver disease, whereas they were detected only in 21% of those with nonalcoholic liver disease, except for cases of autoimmune chronic active hepatitis. In alcoholic liver disease, IgA liver membrane antibodies were detected at a high frequency in a group of patients with alcoholic hepatitis and active cirrhosis (94%) as compared with that of fatty liver, hepatic fibrosis, and inactive cirrhosis (42%). These results suggest that alcoholic liver disease is characterized in part by a humoral immune response of IgA liver membrane antibodies.
Cell Membrane↗
Immunological mechanisms of corticosteroid therapy in chronic active hepatitis: analysis of peripheral blood suppressor T-cell and interleukin 2 activities.
To investigate the immunological mechanisms underlying corticosteroid therapy in chronic active hepatitis (CAH), in vitro effects of prednisolone on suppressor T-cell and interleukin 2 (IL-2) activities were examined in six corticosteroid therapy-effective and six therapy-ineffective patients with CAH prior to the therapy. Whereas low suppressor T-cell activity and decreased response to IL-2 in T cells were found in the corticosteroid therapy-effective group, these reductions recovered to the normal range when the activity or response was tested in the presence of prednisolone (1 and 10 micrograms/ml). Corresponding with these recoveries, suppressor T-cell activity arrived at normal values after corticosteroid therapy for 8 weeks. By contrast, in the corticosteroid-ineffective group, no apparent effects of prednisolone on suppressor T-cell activity and the response to IL-2 were observed. The relationship between the clinical effect of corticosteroid therapy and in vitro improvement in suppressor T-cell activity or in the response to IL-2 by prednisolone suggests that, in CAH, the corticosteroid effect is likely to be due to an immunomodulation in T-cell function.
Female↗
Localization of cytoplasmic and mitochondrial aldehyde dehydrogenase isozymes in human liver.
Aldehyde dehydrogenase isozymes (ALDH1 or E1 and ALDH2 or E2 according to the classification by Greenfield NJ, Pietruszko R, Biochim Biophys Acta 483:35, 1977) were purified from the human liver to homogeneity by the use of ion exchange chromatography on CM-Sephadex, DEAE-Sephadex, and QAE-Sephadex and affinity chromatography on 5'-AMP Sepharose 4B, and preparative isoelectric focusing agarose electrophoresis. These were injected in rabbits to elicit antibodies against ALDH1 and ALDH2, respectively and their specificities were tested by double immunodiffusion. By gel filtration, the antibodies were separated into F'ab fragments, conjugated with horseradish peroxidase, and served to detect ALDH1 and ALDH2 proteins in normal liver tissue. Immunoelectron microscopy by the preembedding method revealed that the electron-dense materials reacted with anti-ALDH1 antibody were located in the cytoplasm of hepatocytes, mainly around the nuclear membrane, mitochondria, and endoplasmic reticulum; in the mitochondria, however, no staining was demonstrated. In contrast, the reaction with anti-ALDH2 antibody was observed only in the mitochondria. Immunostaining, performed by the enzyme-labeled antibody method demonstrated that in the hepatic lobule, there were no differences of the intensity of ALDH1 antigenicity and that of ALDH2 antigenicity between periportal (zone 1) and pericentral (zone 3) hepatocytes. These results suggest that in the human liver ALDH1 and ALDH2 are distributed equally in the periportal and centrilobular regions.
Aldehyde Dehydrogenase↗
Functional heterogeneity of rat hepatocytes: predominance of aryl hydrocarbon hydroxylase activity in perivenular zone.
To elucidate the hepatic intralobular distribution of aryl hydrocarbon hydroxylase (AHH) activity biochemically, periportal (PP) and perivenular hepatocytes (PV) from male Sprague-Dawley rats were separated by a fluorescence-activated cell sorter after labeling the PP zone with fluorescein diacetate and the perivenular zone with fluorescein isothiocyanate. AHH activity was higher in PV than in PP. The enzyme activity was induced about 6-fold in hepatocytes of rats pretreated with 3-methyl-cholanthrene, and the induction was more prominent in PP than in PV. Neither phenobarbital pretreatment nor altered lipid content of the diet induced the change in the enzyme activity.
Animals↗
[A case of splenic abscess occurring in ulcerative colitis and successfully treated by antibiotic therapy].
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Abscess↗
[Clinical study of ethanol-induced liver injuries].
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Alcoholism↗
[The incidence of alcoholic liver disease in Japan (1976-1985)].
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Carcinoma, Hepatocellular↗
A case of hepatocellular carcinoma associated with ossification. A case report.
A 54-year-old man with hepatocellular carcinoma (HCC) of the typical trabecular pattern exhibiting unusual histologic features, both osteoid and bone formations, is reported. The tumor was associated with well-developed cirrhosis; thus, this may be different from mixed hepatic tumors of adults with bone formations because the latter are characterized by their prevalence in noncirrhotic livers and by the formation of myxoid connective tissue. Computed tomography of the current case revealed calcification within HCC.
Carcinoma, Hepatocellular↗