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Biomedical subjects

K Tanikawa

Publications and source records attributed to K Tanikawa.

At least 19 recordsLinked to original sources

The morphologic transition in hepatocellular carcinoma. A comparison of the individual histologic features disclosed by ultrasound-guided fine-needle biopsy with those of autopsy.

In hepatocellular carcinoma (HCC), it has been strongly suggested that as the tumor increases in size, foci of less-differentiated malignant tissues arise in the well-differentiated tumor and increase until they replace the well-differentiated tumor tissues. It has also been suggested that tumor growth is attributed to such dedifferentiation. In the current study, the individual histologic features of ultrasound-guided fine-needle biopsy specimens, taken from 12 small HCC in an early stage, were compared with those of autopsy to confirm the dedifferentiation of HCC. In all 12 cases, autopsy was performed 6 months or more after the initial biopsy. Dedifferentiation was demonstrated in 9 of 12 cases (75.0%). Most of the biopsy specimens from minute HCC were well-differentiated. All tumors that had been well-differentiated when evaluated by biopsy were found to have become moderately differentiated at autopsy. This comparative study confirmed the dedifferentiation of HCC with tumor growth.

Aged

Orthotopic liver transplantation for urea cycle enzyme deficiency.

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measurable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and argininosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and argininosuccinic acid synthetase. Seven other patients--six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency--are known to have been treated elsewhere with liver transplantation 1 1/2 yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1 1/2 to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all.

Adult

Vitronectin in liver disorders: biochemical and immunohistochemical studies.

The concentration of plasma vitronectin was determined and compared with various parameters of liver function including the blood coagulation system in patients with liver diseases. The severity of cirrhosis was graded according to Child's criteria and compared with the plasma vitronectin level. Furthermore, the distribution of vitronectin in the liver of patients with liver diseases was studied by light and electron microscopy using the indirect immunoperoxidase method. The plasma vitronectin level was low in all liver disease groups as compared with the healthy controls. The difference from the controls was significant in patients with hepatocellular carcinoma and decompensated cirrhosis. Moreover, the plasma vitronectin level was positively correlated with the levels of serum cholinesterase, albumin, plasma alpha 2 plasmin inhibitor-plasmin complex and the prothrombin time and results of the hepatoplastin test. Plasma vitronectin decreased with increasing severity of cirrhosis according to Child's criteria. These results suggest that the plasma vitronectin level is a useful parameter of hepatic synthetic function in patients with liver diseases; it may also reflect the severity of cirrhosis. Light microscopy revealed vitronectin in the area of focal necrosis and the portal tracts in the liver of patients with acute viral hepatitis, in the area of piecemeal necrosis in the liver of patients with chronic hepatitis and along the area of fiber deposition in the liver of patients with cirrhosis. Immunoelectron microscopy showed vitronectin in the rough endoplasmic reticulum of hepatocytes. Moreover, vitronectin was seen around inflammatory cells, endothelial cells, Ito cells and hepatocytes in the perisinusoidal area near focal necrosis and piecemeal necrosis and on collagen fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Indication of liver transplantation for hepatocellular carcinoma in Japan.

Approximately 20,000 patients die of hepatocellular carcinoma (HCC) annually in Japan and most of them are hepatitis B virus (HBV) or hepatitis C virus (HCV) carriers. Recently, small HCC, less than 3 cm in diameter, have frequently been found by ultrasonography in the follow-up of patients with chronic liver diseases. Such cases are mainly treated by either surgical resection or percutaneous ethanol injection therapy (PEIT) with a satisfactory 5 year survival rate of 50%. In addition, the survival rate of advanced cases has gradually improved thanks to transcatheter arterial chemo-embolization combined with PEIT, radiation, hyperthermia, or immune therapy. On the other hand, our autopsy study has indicated a high frequency of extrahepatic metastasis in advanced cases. From these results, liver transplantation for HCC does not seem to be the treatment of first choice, at present, in Japan. In the future, the means to control the underlying infection of HBV or HCV as well as making an accurate imaging diagnosis for the detection of extrahepatic metastasis will become inevitably more important for successful liver transplantation in HCC.

Administration, Cutaneous

Incidence of anti-HTLV-1 antibody in liver disease.

Positivity for serum anti-HTLV-1 antibody (anti-HTLV-1) in 171 patients with various chronic liver diseases and 22 asymptomatic hepatitis B virus (HBV) carriers was compared with that of 200 healthy controls in the Chikugo district of Japan. The rate of anti-HTLV-1 positivity in patients with liver disease was 8.1% (14/171) and was higher than that (3.5%: 7/200) in healthy controls, but the difference was not significant. However, in patients with liver disease with a history of blood transfusion, the positive rate was 18.4% (7/38) which was significantly higher than that for healthy subject (P less than 0.001). On the other hand, in 133 liver disease patients without blood transfusion, anti-HTLV-1 positivity was significantly higher (P less than 0.05) in patients with hepatitis B surface antigen (11.3%: 6/53) than in those without it (1.3%: 1/80). These data suggest that the high incidence of anti-HTLV-1 in our patients with liver disease was due to the transmission of HTLV-1 by the same routes (maternal transmission and blood transfusion) and probably at the same time as the hepatitis viruses (HBV and hepatitis C virus).

Adult

Clinical evaluation of tissue plasminogen activator (t-PA) levels in patients with liver diseases.

Tissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n = 30); fulminant hepatitis (FH, n = 36); chronic inactive hepatitis (CIH, n = 57); chronic active hepatitis (CAH, n = 39); compensated liver cirrhosis (cLC, n = 78); decompensated liver cirrhosis (dLC, n = 84); hepatocellular carcinoma (HCC, n = 64); advanced hepatocellular carcinoma (aHCC, n = 28); and compared with that of a control group (n = 106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin alpha 1-plasmin inhibitor complex (PIC), plasminogen (Plg), FDP, AT III and alpha 2-plasmin inhibitor (alpha 2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers

A case of an undifferentiated small cell carcinoma of the esophagus with a primary abdominal mass.

This paper reports a case with an undifferentiated carcinoma of the esophagus which primarily developed symptoms due to metastatic lesions. The case was a 59-year-old woman with a primary manifestation of an abdominal mass and with subsequent dysphagia. A protruding lesion with ulceration was found at the lower third of the thoracic esophagus by endoscopic examination and was histologically proved to be an undifferentiated carcinoma by biopsy. The abdominal mass was initially thought to be due to metastasis to an abdominal lymph node based on the diagnosis image finding at admission, but it was consequently found by autopsy to be a metastatic tumor in the liver. Therefore, undifferentiated carcinoma of the esophagus should be take into account for differential diagnosis of an abdominal mass.

Abdominal Neoplasms

Portal hypertensive gastropathy in patients with cirrhosis.

Portal hypertensive gastropathy is a recently recognized important complication of cirrhosis. In the present study, the clinical features, portohepatic hemodynamics, and hepatic function were investigated in a series of 47 patients with cirrhosis. Mild gastropathy was found in 15 patients (32%) and severe gastropathy in 17 patients (36%). The presence of gastropathy seemed to be independent of age, sex, cause of cirrhosis, or grade of gastroesophageal varices. However, severe gastropathy was associated with an increase in portal venous pressure gradient (vs. control, P less than 0.01; vs. mild gastropathy, P less than 0.01), an increase in hepatic sinusoidal resistance (vs. control, P less than 0.01; vs. mild gastropathy, NS), and a decrease in hepatic blood flow (vs. control, P less than 0.01; vs. mild gastropathy, NS). In addition, patients with severe gastropathy had impaired metabolic activity of the liver, which was assessed by intrinsic clearance of indocyanine green (vs. control, P less than 0.01; vs. mild gastropathy, NS). These observations may have important therapeutic implications in patients with cirrhosis and portal hypertensive gastropathy.

Aged

Role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats.

The present experiments were designed to study the role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats. Administration of 2 mg/kg body weight of endotoxin caused severe hepatic injury in chronic alcohol-fed rats as compared with controls. This injury was significantly less in those whose spleens had been resected 1 week prior to endotoxin administration. There were no differences in plasma endotoxin levels 16 h after intravenous injection of endotoxin between sham-operated control rats, and chronic alcohol-fed rats with and without splenectomy. The plasma tumor necrosis factor (TNF) level 1 h after intravenous injection of endotoxin was significantly higher in chronic alcohol-fed rats than in controls. However, TNF levels were significantly lower in those with splenectomy. Neutrophil infiltration was seen in the liver sinusoid of sham-operated chronic alcohol-fed rats as early as 1 h after injection of endotoxin, and was observed even 15 h later. These results suggest that endotoxin-induced liver injury is closely related to factors derived from the spleen and induced by plasma endotoxin, especially when Kupffer cell function is reduced by chronic alcohol feeding. In addition, TNF and neutrophils may play an important role in this type of liver injury.

Alanine Transaminase

Comparative study of magnetic resonance imaging, computed tomography and histology in the assessment of liver iron overload.

Magnetic resonance imaging, computed tomography, and liver biopsy findings were compared in ten patients with serum ferritin levels over 500 ng/ml. The liver was observed as a low-intensity area on magnetic resonance imaging in all four patients with serum ferritin levels above 2,000 ng/ml, while no abnormalities were detected in four of the six patients with a serum ferritin level below 2,000 ng/ml. Computed tomography revealed the liver to be a high density area in five of the seven patients tested. However, it demonstrated no abnormality in a patient with steatosis despite a high serum ferritin concentration. Liver biopsy demonstrated iron deposits in nine of the ten patients. These findings indicate that liver biopsy remains the most accurate mean of detection of liver iron overload. Both magnetic resonance imaging and computed tomography could be used to be monitor the progress of a patient with liver iron overload treated by phlebotomy.

Adult

Sclerosing hepatocellular carcinoma with hypercalcemia--a case report.

A case of sclerosing hepatocellular carcinoma (SHCC) with hypercalcemia was reported. Clinical studies revealed a tumor at the liver hilum with invasion into the bile duct. Light microscopy of the tumor disclosed a moderately differentiated hepatocellular carcinoma (HCC) of the trabecular type with diffuse fibrous stroma. Abundant dense granules were observed in the cytoplasm of the tumor cells with electron microscopy. The elevated serum calcium (13.9 mg/dl) returned to the normal range after resection of the tumor.

Carcinoma, Hepatocellular

Immunological study of the association between hepatocyte damage and HBc antigen.

To identify the target antigen during hepatocyte damage in hepatitis type B virus (HBV) infections, the expression of HBc and HBs antigens, and beta 2-microglobulin (BMG) were studied in liver tissue. Serial changes of serum DNA-polymerase (DNA-P) activity and HBV DNA were also measured. After the onset of acute hepatitis, HBs antigen in liver tissues was observed from many patients; but HBc antigen was rarely detected. In liver tissues of patients with chronic hepatitis, HBs antigen was consistently positive, irrespective of the changes in sGPT. On the other hand, HBc antigen was frequently positive both preceding and during the culmination period for sGPT. The distribution of HBc antigen in the hepatocyte was mostly cytoplasmic. During the same period the serum DNA-P and HBV DNA were frequently positive. Immunoelectron microscopy showed that reaction products with HBc antigen existed in the cytoplasm and the cell membrane. These results indicate that HBc antigens become the target, when HBV infected hepatocytes are eliminated.

DNA, Viral

Significance of serum type-IV collagen levels in various liver diseases. Measurement with a one-step sandwich enzyme immunoassay using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen.

Serum type-IV collagen levels determined with a one-step sandwich enzyme immunoassay (EIA) using monoclonal antibodies with specificity for pepsin-solubilized type-IV collagen were compared with histologic changes in liver biopsy specimens from 107 patients with various liver diseases. Serum type-IV collagen levels were increased in the groups with liver diseases compared with controls. The serum type-IV collagen levels in the group with alcoholic cirrhosis showed significantly higher values than the other groups (P less than 0.05). A significant positive correlation was found between the serum type-IV collagen level and the degree of fibrosis or cell infiltration in 107 patients. Immunolocalization of type-IV collagen was observed around blood vessels and bile ducts increased in number in the portal tracts, with cell infiltration and fibrosis, increased around vessels in fibrous septa, and sinusoidal walls of areas with cell infiltration or necrosis in hepatic lobules, and along the boundary between fibrous septa and hepatocytes. The present data indicate that serum type-IV collagen may be a sensitive marker for active fibrosis and that the elevation of serum type-IV collagen level primarily reflects the enhancement of type-IV collagen synthesis and deposition in the liver tissue at the stage of active fibrosis in liver disease.

Adolescent

[Clinical study on relationship between hepatocellular carcinoma and hepatitis C virus infection in patients with chronic liver disease].

The relationship between hepatocellular carcinoma (HCC) and hepatitis C virus (HCV) infection was investigated. Antibody to hepatitis C virus was detected in 88.8% and 87.0% of 240 patients with hepatocellular carcinoma and liver cirrhosis, respectively. A history of blood transfusion was shown in only 21.8% (21/96) of the HCV antibody positive HCC patients. Of 196 patients with chronic hepatitis type C and the HCV antibody positive liver cirrhosis, 10 developed HCC during the follow-up period of two years. A high prevalence of HCV antibody was also shown among 83 patients with alcoholic liver cirrhosis and HCC associated with alcoholic liver cirrhosis. HCV-RNA was detected in all patients with alcoholic HCC. These data support a causal association between hepatitis C virus and hepatocellular carcinoma.

Carcinoma, Hepatocellular

Ultrastructure of intracellular membranous system and intracellular transport of asialoglycoproteins in rat hepatocytes.

The ultrastructure of the intracellular membranous system in rat hepatocytes was observed three dimensionally with a scanning electron microscope using the aldehyde prefix osmium-dimethyl sulfoxide-osmium method. Intracellular organelles were clearly observed in three dimensions, and direct connection of tubular structures with the bile canalicular membrane was clearly seen. The transcellular pathway of asialoglycoproteins in isolated cultured rat hepatocytes was also investigated, by affinity cytochemistry, using gold-conjugated asialofetuin, under a transmission electron microscope. Gold particles were clearly seen not only in vesicles, endosomes and lysosomes, but also in the tubular structures. These results suggest that the tubular structures in rat hepatocytes directly participate in the transcellular transport of macromolecules. In addition, the frequent connections of tubular structures with the bile canalicular membrane indicate that these structures around the bile canaliculus may supply membrane components to the bile canalicular membrane.

Animals

[Infection of C type hepatitis virus in patients with alcoholism. Studied by serum HCV antibody of C100-3 and 2nd generation].

To investigate the infectious situation and causes of hepatitis C virus (HCV) in patients with alcoholism, C100-3 antibody (C100-3) and HCV antibody of the 2nd generation (HCV-2nd) were examined on admission, and the factors that affected the infection of HCV were studied in 226 alcoholics. The positive rate of anti-HCV was as high as 16.4% by C100-3 and much higher by HCV-2nd as 33.2%. The incidence of cases with the history for blood transfusion, drug addict and/or tattoos in alcoholics was as high as 39.4% (89/226). To clarify the influence of the background such as blood transfusion, drug addict and/or tattoos on HCV infection, the positive rate of anti-HCV was compared between those with the background and without the background. In alcoholics without the backgrounds, the positive rate of C100-3 and HCV-2nd were significantly (p less than 0.001) higher than patients without the backgrounds, namely 27.0% vs 9.5%, 56.2% vs 18.2%, respectively. In alcoholics without the backgrounds, the positive rate of anti-HCV became higher in proportion as the age of the patients grows older from 20 to 60 years. These results suggest that a high incidence of HCV infection in alcoholics may resulted from increased the backgrounds that can provide chances of HCV infection and that in those without the backgrounds, alcohol and aging may lead the tolerance to HCV infection.

Adult