Toshifumi Yasuyama

Primary biliary cirrhosis in japan: National survey by the subcommittee on autoimmune hepatitis

SummaryA total of 280 cases of primary bijiary cirrhosis were reported from 86 institutes in Japan, of whom 208 were middle aged women. Four clinical stages (asymptomatic, pruritus, icteric and terminal stage) were set up for analysing clinical and histopathological features based on the natural course of the disease. The clinical and histopathological findings were similar to the study reported from the United States and European countries. Out of 270 cases examined, 245 (90.7%), had mitochondrial antibodies. Concerning the prognosis 37 of 120 asymptomatic patients developed symptoms and the average symptom-free period in these patients was 28.7 months. Fifty-eight cases were fatal and causes of death were hepatic failure in 27, gastrointestinal bleeding in 20 and others in 11 cases. Patients were subdivided into three groups to elucidate the survival rate in patients with different symptoms. Asymptomatic patients showed almost the same survival rate as the patients with pruritus alone, showing about 50% survival 8 years after the diagnosis, in contrast to jaundiced cases with only 13.6% surviving 8 years after the onset of this symptom.

Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma*

SummaryA total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4′-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicinlipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%).

The protective effect of pyrroloquinoline quinone and its derivatives against carbon tetrachloride-induced liver injury of rats

Pyrroloquinoline quinone (PQQ) and its derivative, oxazo pyrroloquinoline (OPQ‐G), protected rats from experimental liver injury induced by carbon tetrachloride (CCl4) in vivo. This effect was observed after an intraperitoneal injection of 5 mg/kg PQQ or OPQ‐G, which was given twice, 10 min and 1 h before CCl4 administration. Pyrroloquinoline quinone protected primary cultured rat hepatocytes from CCl4 toxicity in vitro. This protection was most effective at a concentration of 3 μmol/L PQQ. Pyrroloquinoline quinone derivatives (oxazo pyrroloquinoline, methyl‐thioethyl oxazo pyrroloquinoline and PQQ‐allylester) also protected the hepatocytes from CCl4 toxicity. Pyrroloquinoline quinone and its derivatives inhibited the lucigenin‐enhanced chemiluminescence from isolated hepatocytes initiated by CCl4. These results suggest that eliminating free radicals is one of the protective mechanisms of PQQ and its derivatives against CCl4‐induced liver injury.

Intralobular distribution of rat liver aldehyde dehydrogenase and alcohol dehydrogenase

1. The activity of liver microsomal high Km-ALDH and mitochondrial low Km-ALDH, which may be primarily responsible for the oxidation of acetaldehyde after ethanol administration was found to be predominantly distributed in the centrilobular area. 2. The activities of other ALDH isozymes in mitochondrial and soluble fractions were evenly distributed in periportal and perivenous regions. 3. The activity of ADH which is involved in production of acetaldehyde was predominantly located in the periportal area. 4. From these results it seems unlikely that a concentration of acetaldehyde after ethanol ingestion is higher in perivenous hepatocytes than in periportal ones. Additional data would be needed to understand fully the mechanism by which ethanol induces predominantly centrilobular liver injury.

Preferential accumulation of CD103+ T cells in human livers; its association with extrathymic T cells

BACKGROUND/AIMS CD103, a mucosal integrin alphaEbeta7, binds to E-cadherin expressed on hepatocytes and bile duct epithelium in the liver. Although CD103+ T cells are enriched in intestinal intraepithelial lymphocytes, the localization of those cells in the liver is unknown. METHODS We investigated whether CD103+ cells are present in human livers, and how they are associated with the intrahepatic development of T cells by flow cytometry and immunohistochemistry. RESULTS Human livers contain significantly (P<0.001) higher percentages of CD103+ cells in CD4+ and CD8+ T cells (25.7+/-13.5 and 27.1+/-19.3%, respectively) than peripheral blood lymphocytes. Moreover, CD103+ cells in the liver, but not in peripheral blood, contained T cells with intermediate expression level of T cell receptor alphabeta. Those cells consist of mostly CD4+ and CD4-CD8- cells, and expressed low level of CD56 and interleukin-2 receptor beta chain in most of the population. These characteristics are distinct from natural killer T cells, which have been thought to be extrathymic T cells in human livers. Moreover, intrahepatic CD103+ cells expressed mRNA for recombination-activating gene-1, -2 and pre T cell receptor-alpha detected by reverse transcription-polymerase chain reaction. CONCLUSIONS CD103+ T cells are preferentially accumulated in human livers, and those T cells show characteristics of extrathymic T cells.

Induction of allogeneic tumour‐ and lymphokine‐activated lymphocytes against hepatocellular carcinoma

For clinical application of adoptive immunotherapy against hepatocellular carcinoma (HCC), it is not easy to prepare tumour specific effector cells such as cytotoxic T lymphocytes (CTL). To induce potent and broad‐spectrum effectors, allogeneic cultured hepatoma cell lines (JHH‐4 and HuH‐6) were used as stimulators of peripheral blood lymphocytes (PBL) instead of autologous HCC cells. Allogeneic tumour‐ and lymphokine‐activated killer cells (ATLAK) were generated by a mixed culture of lymphocytes and allogeneic cultured tumour cells with recombinant interleukin‐2 (rIL‐2). The tumour‐killing activity of ATLAK induced by HuH‐6 was confirmed against HuH‐6 and other different HCC cell lines (JHH‐2, HuH‐7 and PLC). These activated lymphocytes were significantly more potent than lymphokine‐activated killer cells (LAK) in [51Cr]‐releasing assay. The JHH‐4 stimulated ATLAK was reactive not only with JHH‐4 but also with JHH‐2. The lysis of allogeneic targets could be partially inhibited by anti‐CD8 and anti‐CD3 but not by anti‐CD4. Anti‐tumour cytotoxicity in these cultures might be mediated by CD3+CD56‐ and CD3+CD56+ effectors. These results imply that adoptive immunotherapy for HCC with ATLAK may be more feasible than that with LAK.

Anti-HCV in the medical employees comparison to the voluntary blood donors.

Anti-HCV were tested in 6, 093 voluntary blood donors (male 3, 842, female 2, 251) and 566 medical employees (doctors 219, nurses 297, technologists 50) using ELISA Kit of Ortho Diagnostic Systems Co.In voluntary blood donors, percentage of anti-HCV positivity over 36-year-old was statisticaly higher than that under 35-year-old. It is supposed that this phenomena was caused by the improvement of circumstances of common health and exchanging needls every person in preventive inoculation.In medical employees there is no statistical difference between doctors, nurses technologists and blood donors.In 6 cases anti-HCV positive in ELISA methods, only 3 cases were positive in RIA methods.

A case of Gilbert's disease with constitutional excretory defect of ICG.

BSP試験は正常でICG試験が高度の排泄異常を呈したGilbelt病の1例を報告した.症例は35歳の女性で,黄疸を主訴に入院し,血液生化学的検査において,貧血,溶血を認めず,間接型優位の高ビリルビン血症(総ビリルビン:3.3mg/dl,間接ビリルビン:2.4mg/dl)とICG試験で15分停滞率77.5%と高度の排泄異常を示した以外は,肝機能異常を認めなかった.腹部血管造影,腹腔鏡下肝生検などによる検査においても肝に著変を認めなかった.ニコチン酸投与による内因性ビリルビン負荷により,間接型ビリルビンの増加とその持続を認めた.またICG試験より算出した血中ICG消失率は0.014min-1と著しい低値を示し,かつ消失曲線はほぼ直線を示し,ICGの肝細胞への取り込み障害が示唆された.ICG試験で高度の排泄異常を伴うGilbelt病は少なく,本邦では本症例を含め11例報告されているにすぎず,これらをまとめ考察を加えた.