Hitoyoshi Ohta

Measurement of Immunoreactive Prothrombin Precursor and Vitamin-K-Dependent Gamma-Carboxylation in Human Hepatocellular Carcinoma Tissues: Decreased Carboxylation of Prothrombin Precursor as a Cause of Des-Gamma-Carboxyprothrombin Synthesis

Des-gamma-carboxyprothrombin is an abnormal prothrombin which is drastically increased in the plasma of patients with hepatocellular carcinoma. To investigate the process of the abnormal prothrombin synthesis, the amount of prothrombin precursor was measured with an enzyme-linked immunosorbent assay using a specific antibody directed to human prothrombin; the vitamin-K-dependent gamma-carboxylation of prothrombin precursor was determined in human liver tissues. The tissue content of prothrombin precursor was increased in hepatoma tissues compared with noncancerous liver tissues, while the vitamin-K-dependent carboxylation of prothrombin precursor was markedly decreased in hepatoma tissues of the patients with increased plasma des-gamma-carboxyprothrombin. The present study indicates that in hepatocellular carcinoma an increase in prothrombin precursor concentration does not induce vitamin-K-dependent carboxylase activity, which is ordinarily observed in normal liver; probably an overproduction of prothrombin precursor with reduced gamma-carboxylation causes an increase in plasma des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma.

Serum immunoreactive β-glucuronidase determined by an enzyme-linked immunosorbent assay in patients with hepatic diseases

An enzyme-linked immunosorbent assay (ELISA) was developed for human beta-glucuronidase, using a specific polyclonal antibody raised against the purified enzyme. beta-Glucuronidase from human liver consisted of three subunits with molecular mass of 76, 64 and 18 kDa. The assay offered a specific, sensitive and convenient means of measuring immunoreactive beta-glucuronidase in human sera. beta-Glucuronidase activity determined by the conventional method appeared to be extremely low, indicating that in human sera beta-glucuronidase exists in an enzymatically inactive form. The sensitivity of the assay permitted the detection of 1-100 ng of purified beta-glucuronidase. A mean serum level in normal subjects was 108 +/- 25 ng/ml (mean +/- S.D.). A high level of beta-glucuronidase was found in sera of patients with severe hepatocellular necrosis, including liver cirrhosis (152 +/- 130 ng/ml) and chronic active hepatitis (220 +/- 99 ng/ml), whereas no significant increase of the enzyme protein was observed in chronic persistent hepatitis (102 +/- 42 ng/ml). beta-Glucuronidase was also increased in sera of patients with primary hepatoma (156 +/- 125 ng/ml). The immunoreactive beta-glucuronidase determined in this assay was thought to be a supplementary serological indicator for hepatocellular necrosis.

C ASE R EPORT: Mucinous cholangiocarcinoma featuring a multicystic appearance and periportal collar in imaging

A case of mucinous cholangiocarcinoma (CC), a rare histological type of CC, featuring unusual images is reported. The patient was hospitalized because of acute development of jaundice and fever. Computed tomography demonstrated multiple cystic lesions in the liver and a band‐like low density area parallel to the intrahepatic portal vein, a so‐called ‘periportal collar’. Endoscopic cholangiography revealed a stricture of the hepatic duct with slight upstream dilatation. Cytology of the bile juice and fine‐needle aspiration of the cystic lesion in the liver disclosed mucinous carcinoma. The patient died of multiorgan failure 3 weeks after admission. The autopsied liver showed that multiple mucus lakes were lined with adenocarcinoma cells and signet ring cells were floating in the mucus lakes. The cancer cells had spread along the portal tract and invaded into the hepatic parenchyma.

Altered intrahepatic pathway of para-umbilical vein in portal hypertension

The object of this study was to determine the frequency and characteristics of altered paraumbilical vein in the hepatic parenchyma, developed from portal hypertension, using computed tomography (CT). Two hundred and ninety‐two patients who presented with portal hypertension from 1986 to 1996 were studied retrospectively. The pathway of the dilated para‐umbilical vein was demonstrated by contrast‐enhanced CT. Thirty‐one (11%) patients had a dilated para‐umbilical vein arising from the left portal vein into the falciform ligament. In 24 (77%) of these patients, the para‐umbilical vein followed the expected route, passing through the fissure of ligamentum teres hepatis. The remaining seven patients (23%) displayed the unusual pathway, with the vein arising from the left branch of the portal vein and passing into the hepatic parenchyma. In these seven patients, four had one collateral vein, and three patients had two collateral veins in the liver parenchyma. The dilated para‐umbilical vein frequently passes through the hepatic parenchyma in patients with portal hypertension.

The effect of IL-6 on the des-gamma-carboxy prothrombin synthesis in human hepatoma cells

SummaryEffects of several cytokines on des-gamma-carboxy prothrombin (PIVKA II) synthesis in human hepatoma cells were investigated to know the process of PIVKA II production during a liver allograft rejection. Human recombinant interleukin-6 (IL-6) significantly stimulated the PIVKA II synthesis without any influence on the cell proliferation. The effect was almost completely neutralized by the specific anti-IL-6 antibody. Neither tumor necrosis factor (TNF), interleukin-1 (IL-1) nor interferon-gamma (IFN-gamma) had such a stimulative effect. IL-6 appears to stimulate PIVKA II production, and would be a candidate of factors that enhance the production of PIVKA II during a liver allograft rejection.

Paraumbilical Vein Aneurysm: Case Reports

Two cases of paraumbilical vein aneurysm are reported. The patients were diagnosed as having cirrhotic liver with portal hypertension. Angiography and contrast-enhanced computed tomography demonstrated a dilated paraumbilical vein arising from the left branch of the portal vein. Furthermore, localized dilatation of a paraumbilical vein was demonstrated. The focal aneurysmal dilatation of the dilatated paraumbilical vein is rare.

Recurrence of hepatocellular carcinoma after medical treatment.

肝細胞癌に対する内科的治療後の再発に関して検討を行った.対象は直径4cm以下の単発の肝細胞癌症例49例中,内科的治療を行った37例である.うちわけはTAE 17例,PEIT 13例,TAE・PEIT併用7例である.TAE後の再発例は9例で,再発様式は局所再発5例,非治療部再発3例,びまん再発1例であった.PEIT後,TAE・PEIT併用後の再発例は12例で,再発様式は局所再発はなく,非治療部再発11例,びまん再発1例であった.再発時期・再発部位関しては一定の傾向はなかった.局所効果の増強のためには,TAE例でも可能であればPEITの併用が望ましい.2年以内の再発例(18例)と無再発例(7例)を比較し,再発に関する因子を検討したところ,患者背景や治療法によって差はなかったが,腫瘍の肉眼分類で単結節周囲増殖型は単結節型より再発が多い傾向をみた.また,個々の病変に対して十分治療し得たかどうかも再発を左右する因子といえる.

Unique properties of cathepsin D purified from alcoholic cirrhotic liver

Abstract In order to show the possibility of the impaired function of Golgi apparatus in alcoholic cirrhotic liver, we studied the property of sugar chains on purified cathepsin D, which was an aspartic protease in lysosome. Alcoholic cirrhotic liver contained a large amount of cathepsin D which had no binding affinity for concanavalin A. On the other hand, no cathepsin D was detected in concanavalin A-unbound fractions from normal liver, viral cirrhotic liver and hepatoma tissues. In the treatment with exogenous hydrolases to cleave carbohydrate moieties, abnormal cathepsin D purified from alcoholic cirrhotic liver contained altered sugar chains. Since the processing of oligosaccharide moieties on lysosomal hydrolases are performed in Golgi apparatus, the alteration of sugar chains suggests that the abnormal intracellular processing is caused by the dysfunction of Golgi apparatus. Unique cathepsin D described here may support the hypothesis that the impaired function of Golgi apparatus is associated with the mechanism of alcoholic liver injury.

Molecular form of IgM antibody to hepatitis B core antigen in sera from the patients with chronic hepatitis B virus infection.

IgM型HBc抗体の分子性状を,B型肝炎ウイルスの一過性感染と持続感染で比較するとともに,持続感染において,その抗体価の変動に伴う分子性状の変化を検討した.その結果,一過性感染では急性期・回復期ともにその抗体活性は19S IgMのみに認められた.それに対し,持続感染では19S IgMばかりでなく7S IgMも抗体活性が認められた.さらに,持続感染ではIgM型HBc抗体が陰性時には7S IgMが主体であるが,急性増悪時など抗体陽性になる時にほ19S IgMが主体となっており,この様な分子性状の変化は同一症例でも確認された.つまり,持続感染例では急性肝炎と異なり7S IgMもIgM型HBc抗体活性を示すが,その急性増悪に際しては,19S成分のIgM型HBc抗体が増加すると考えられた.