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A 22-year-old male was admitted to our hospital after taking 2450 mg of pilsicainide. On admission, the patient was in cardiac arrest, and percutaneous cardiopulmonary support was introduced to maintain his circulation. After three days of intensive care, he was no impaired consciousness and transferred another hospital for psychological problem.

Cases Case 1: A 63-year-old woman was referred for coughing blood. Although cardiorespiratory dynamics were stabilized by artificial respiration under sedation, severely poor ventilation developed from asphyxia associated with massive respiratory tract hemorrhage. One-lung ventilation was temporarily secured by endotracheal tube insertion into the left main bronchus just prior to cardiopulmonary arrest. Case 2: A 72-year-old man was referred for massive hemoptysis after coughing, then intubated and placed on a respirator. During angiography, blood clots collected with bronchoscopy confirmed extravascular leakage into the right main bronchus. Outcomes Both showed no hemoptysis recurrence after bronchial artery embolization and were discharged. Case 1 required intensive treatment for 6 days, including artificial respiratory management. Conclusion Emergency one-lung ventilation was required for asphyxia in Case 1, and we had difficulties with bleeding point identification and hemostatic therapy. From that experience, we noted hemoptysis during angiography using bronchoscopy in Case 2, enabling prompt bronchial artery embolization.

Correction to: Scientific Reports 7: Article number: 45839; published online: 03 April 2017; updated: 19 March 2018 In this Article, the Authors neglected to include the Data and Material Availability section. This section should read: “Data and material availability The novel mouse strain generatedin this study is available on request from Chugai Pharmaceutical Co.

T cell–mediated immunotherapy is an attractive strategy for treatment in various disease areas. In this therapeutic approach, the CD3 complex is one of the key molecules to modulate T cell functions; however, in many cases, we cannot evaluate the drug candidates in animal experiments because the therapeutics, usually monoclonal antibodies specific to human CD3, cannot react to mouse endogenous Cd3. Although immunodeficient mice transfused with human hematopoietic stem or precursor cells, known as humanized mice, are available for these studies, mice humanized in this manner are not completely immune competent. In this study we have succeeded in establishing a novel mouse strain in which all the three components of the Cd3 complex — Cd3ε, Cd3δ, and Cd3γ — are replaced by their human counterparts, CD3E, CD3D, and CD3G. Basic immunological assessments have confirmed that this strain of human CD3 EDG–replaced mice are entirely immune competent, and we have also demonstrated that a bispecific antibody that simultaneously binds to human CD3 and a tumor-associated antigen (e.g. ERBB2 or GPC3) can be evaluated in human CD3 EDG–replaced mice engrafted with tumors. Our mouse model provides a novel means to evaluate the in vivo efficacy of human CD3–mediated therapy.

Delayed rupture is well-known as a severe complication after splenic injury treated with nonoperative management (NOM). The incidence and timing of splenic pseudoaneurysm (SPA) formation, which is a cause of delayed rupture following splenic injury, have not been thoroughly investigated, and the timing of follow-up computed tomography (CT) is controversial. The objective of this study was to clarify the incidence and timing of both the delayed formation and spontaneous resolution of SPA following splenic injuries treated with NOM in several trauma centers in Japan.This was a retrospective review of all patients with documented blunt splenic injury who were treated with NOM from 2003 through 2010 in five trauma and critical care centers.The present study consisted of 104 patients, including 16 patients (15.4%) with delayed formation of SPA (7 patients with Grade II and 9 with Grade III) during their clinical course. SPA was diagnosed with enhanced CT at a mean (SD) of 4.6 (2.1) hospital days (range, 1-8 days) after admission. Delayed formation of SPA was found in 30.4% of Grade II injuries and in 18.4% of Grade III injuries. Eight patients with delayed formation of SPA were observed without transcatheter arterial embolization during their entire stay. These SPAs were spontaneously occluded on follow-up enhanced CT or angiography. Spontaneous occlusion of SPA was confirmed at 5.2 (2.6) hospital days (range, 2-10 days) after diagnosis of delayed SPA.Delayed formation of SPAs was recognized with enhanced helical CT in 15% of all patients during hospital Days 1 to 8. About one half of the SPAs had occluded spontaneously without therapeutic intervention. Our results suggested that follow-up enhanced CT performed approximately 1 week after splenic injury may be useful to detect delayed SPA formation.Epidemiologic study, level III.

症例は認知症を伴った86歳の男性で，75歳時に左鼠径ヘルニアに対し手術を受けていた．家族が左鼠径部膨隆に気付いたため，救急外来を受診した．腹部所見から左鼠径ヘルニアの嵌頓と診断したが，局所の発赤を認めなかったため，徒手的還納を行った．還納は容易であった．経過観察および待機手術目的で入院していたが，第3病日に腹部全体に筋性防御を認めたため腹部CTを行うと，腹水と小腸拡張像を認めた．急性腹膜炎と診断して開腹手術を行ったところ，S状結腸に壊死，穿孔を認めた．結腸穿孔部縫合閉鎖，ドレナージ，双孔式横行結腸人工肛門造設および腹腔内からのヘルニア門縫縮閉鎖術を施行し，救命した．徒手的還納後の結腸穿孔症例は極めてまれであるが，自覚症状が乏しい高齢者や認知症患者においては，嵌頓腸管が壊死に陥っているかの判断が困難であることもあり，徒手的還納の合併症の危険性を改めて認識すべきと考えられた．

再発鼠径ヘルニアに対する術式選択に関しては定まった見解が得られていないのが現状である．成人再発鼠径ヘルニア62例を検討し，再発手術の術式選択を考察した．62例中43例（69.3％）が内鼠径ヘルニア型の再発であった．再発までの期間はmesh plug法後が4.3±3.6年，Kugel法後が1.2±1.0年であり，tension-repair後の19.2±13.7年に比べ，有意に短かった．2005年までは後方よりの腹膜前腔アプローチで再発手術を多く行ったが，2006年以降はMillikan法が第一選択となった．鼠径管を再解放したにも関わらず，神経損傷による慢性疼痛や精索損傷をきたした症例はなかった．Millikan法は，再発形式として最も多い内鼠径ヘルニア型再発に対して手技が簡便であり，安全面においても問題ないことから，再発症例に対する術式としての有効性が示唆された．

The olfactory system of salmonids is essential for imprinting and the subsequent homing migration. Olfactory imprinting-related genes were identified in the olfactory system of 1- and 3-year-old lacustrine sockeye salmon (Oncorhynchus nerka) using a subtractive hybridization technique of representational difference analysis (cDNA-RDA). We have obtained a partial clone from a subtractive cDNA library of 1-year-old fish that contains a 756 bp open reading frame coding for a putative protein with 252 amino acid residues named the Sockeye salmon Olfactory system Imprinting related Gene (SOIG). By northern hybridization, the SOIG mRNA was only expressed in the olfactory epithelium and not in other tissues. In situ hybridization showed that the expression of SOIG mRNA was observed in the olfactory receptor cells and basal cells of the olfactory epithelium. This suggests that SOIG could have specific and important roles in olfactory system.

The generation of machining defects and their effect on bending strength characteristics are discussed with respect to a TiAl intermetallic compound, which is attracting much attention as a high-temperature structural material because of its high specific strength. The discussion focuses on the mechanism of the formation of edge chipping and machined surface cracks during cutting of a TiAl intermetallic compound. Also, some effects of these machining defects on the bending strength are clarified. The comparison of cutting results with abrasive machining results helps clarify the dependence of strength on undeformed chip thickness during chip generation of machining processes.

Gasless laparoscopic hepatic resection with a 5-cm minilaparotomy was performed in 10 cirrhotic patients with small liver tumors. To maintain good visualization and working space during hepatic resections, we developed a simple retraction system. Mean operative time and blood loss were 291 minutes and 249 mL, respectively. No blood transfusion was required during the operations. No serious complications occurred such as gas embolism. Our laparoscopic procedures had various advantages. Blood, smoke, and water vapor could be aspirated by suction without disturbance of the visual field. There was no risk of gas embolism. It was possible to use conventional instruments through the ports or the wound made by a minilaparotomy. Hemostasis therefore could be performed easily. The procedure could be applicable to cirrhotic patients with some complications. This laparoscopic procedure is recommended for patients with small HCCs associated with liver cirrhosis who are not candidates for major hepatectomy.

Nine cirrhotic patients with liver tumors underwent a gasless laparoscopic hepatic resection with a 5 cm minilaparotomy. To maintain the good visualization and working space during hepatic resections, we developed a simple retraction system. Tumors located in segment II through VI of the liver could be treated by the laparoscopic procedure. In three of the nine patients, laparoscopic microwave coagulation therapy was added for each HCC tumors that were detected by intraoperative sonography. No blood transfusion was necessary during the operations. No serious complications such as air embolism occurred. The procedure was also applicable to cirrhotic patients with some complications. The good indication of the laparoscopic procedure is for the patients with small HCCs associated with liver cirrhosis, who are not candidates for radical hepatic resection.

10カ月,男児の極めて稀な,乳幼児型の十二指腸潰瘍穿孔を経験した.経過は急性激症型で,誘因は多形紅斑あるいはステロイド投与が関与したと考えられた.腹部CTにて腹腔内遊離ガス像が確認され上部消化管穿孔の疑いで開腹すると,十二指腸球部に約1.5cmの穿孔を認めた.乳幼児型は続発性急性潰瘍であり,誘因が取り除かれれば経過が良好なことや将来の成長障害を考慮して,胃温存,穿孔部単閉鎖,大網被覆とドレナージ術を施行した.術後H2-blocker投与にて軽快,第52病日の胃内視鏡では瘢痕期であることが確認された. Helicobacter pylori (以下, HPと略す)は血清抗体価,尿素呼気試験,胃粘膜病理組織同培養ともに陰性であった.

This paper elucidates the formation mechanism of breakouts at the edge of workpiece in cutting of titanium aluminide intermetallic compounds. Furthermore, the relationships between the mechanical strength and the defects including the breakouts and cracks on edge and finished surface is clarified. The results obtained from this study are as follows: The breakouts are formed by propagation of the crack caused by lamellar structure of workpiece. Four-point bending tests in which two types of specimen are prepared, the cutting direction is at right angle to edge and the cutting direction is parallel to edge are conducted. The parallel-specimens are superior to the right-angled-specimen at the average bending strength. Although at the specimens which indicate low strength the breakouts or cracks are observed at the workpiece-edge, there are improvement of the strength by chamfering the specimens. The propagation of the cracks formed at almost right angle to cutting direction on finished surface relates to the strength.

We aimed to assess isolated caudate lobectomy by the anterior approach for the treatment of large hepatocellular carcinomas originating in the paracaval portion of the caudate lobe. The surgical procedures consisted of ligation and dissection of the caudate branch of the portal vein and short hepatic veins from the right side of the hepatic hilum; liver resection cranially from the right side of the process portion; ligation and dissection of the short hepatic veins from the left side; hepatic resection between the lateral segment and Spiegel lobe; and, finally, dissection of the liver at the right of the Cantlie line, reaching the tumor in the paracaval portion of the caudate lobe. The important point in this procedure was the appropriate management of the short hepatic veins, the branches of the hepatic vein, and the glisson's vessels of the paracaval portion. The operative times for the three patients reported here were 430, 355, and 575 min, with blood loss of 1100, 1180, and 2000 ml, respectively. The duration of the operation was short and blood loss was minimal; severe complications were not observed. Complete recovery of liver function after this surgery tended to be slow. Early recurrence was observed during long-term follow-up. This procedure is considered to be a safe method, with optimal surgical vision for caudate lobe tumors of a relatively large size. However, adjuvant therapy to prevent recurrence is required.

We introduced the procedure and the technique of percutaneous microwave coagulation therapy (PMCT) for small liver cancer. PMCT with a microwave electrode for deep lesion was done by an ultrasonic guide under local anesthesia. PMCT may be utilized simply and safely for the treatment of small liver cancer, and also be a useful treatment in combination with conventional palliative managements for recurrent tumors after hepatectomy.

We present efficacy data for the T cell-redirecting antibody (TRAB) with highly potent anti-tumor efficacy. Anti-Glypican-3 (GPC3) TRAB is a humanized IgG4 bispecific antibody that simultaneously binds to GPC3 on the cancer cell surface and to CD3 on the T cell surface. Anti-GPC3 TRAB utilizes T cells as effectors to induce strong TRAB dependent cellular cytotoxicity (TDCC) in the presence of GPC3-expressing cells. Treatment with anti-GPC3 TRAB first activates T cells by increasing the expression of CD25 and CD69 and also upregulating cytokines IL-2, IL-4, IL-6, IL 10, IFNγ, and TNF, and then it enhances the proliferation of T cells. Anti-GPC3 TRAB showed antitumor activity against xenograft tumors derived from various cancer types — MKN-74 (human gastric adenocarcinoma), PC-10 (human lung squamous cell carcinoma), TOV-21G (human ovarian clear cell carcinoma), and KYSE70 (human esophageal squamous cell carcinoma) — in a NOD-SCID mouse model injected with human T cells. Although recent immunotherapy, as represented by immune check point inhibitors PD-1, PD-L1, and CTLA-4 antibodies, showed promising efficacy in human, not every patient can benefit from this immunotherapy, because the significant efficacy shown in patients by a blockade of immune checkpoints is closely related to the tumor microenvironment. The immune check point inhibitors show high efficacy against inflamed tumors, because these have been sufficiently infiltrated by cytotoxic T cells that recognize cancer-specific antigens. However, they do not have efficacy against non inflamed tumors. In an immunocompetent mouse model using human CD3 transgenic mice, neither the inhibitors that block immune checkpoints (such as PD-1, PD-L1 and CTLA-4) nor a conventional ADCC antibody recognizing GPC3 could show significant efficacy against a poorly immunogenic LLC1/hGPC3 tumor. However, anti-GPC3 TRAB showed efficacy against this poorly immunogenic tumor by utilizing any kind of T cell as effectors irrespective of TCR specificity, including not only CD8-positive but also CD4-positive T cells. The studies we present show that anti-GPC3 TRAB is a promising drug with high efficacy utilizing all kinds of T cells as effectors. The compound is expected to have efficacy even in patients with poorly immunogenic tumors, in which an immune checkpoint blockade fails to show efficacy. Citation Format: Yasuko Kinoshita, Takahiro Ishiguro, Yuji Sano, Yumiko Azuma, Toshiaki Tsunenari, Natsuki Ono, Yoko Kayukawa, Otoya Ueda, Naoko A. Wada, Hiroshi Hino, Koichi Jishage, Hirotake Shiraiwa, Mika Kamata-Sakurai, Junichi Nezu, Mika Endo. Anti-GPC3 TRAB, a first-in-class T cell-redirecting bispecific antibody targeting glypican-3 with potent in vitro and in vivo antitumor efficacy against solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1482.

A 65-year-old female was admitted to the hospital because of right low back pain and jaundice. A tumor in the right upper abdomen was palpated. Abdominal ultrasonography and CT revealed gallstones and an 8×7×4cm tumor in the subhepatic space. Gastrointestinal series and endoscopy disclosed no any findings relating to the tumor. Angiography of the abdomen revealed the feeding vessels to the tumor origined from the gastro-duodenal artery. Cholecystectomy was performed and the tumor in the greater omentum was excised. The tumor existing in the large omentum was solid and encapsulated, it being easily removed. Histopathologically the tumor was paraganglioma. Extra-adrenal-paraganglioma arising in the mediastinum or retroperitoneum can be infrequently seen in the literature. The paraganglioma arising in the greater omentum in this case appears the first report in Japan as far as we could review.

The purpose of this study is to obtain the optimum conditions for forming the high precision machined surface by diamond cutting. Therefore, the affections toward the formation of surface by the variation of the tool damage and the whisker orientation were clarified. The results obtained from this study are as follows : The states of tool damage of single crystal and sintered diamond tool and carbide tool had the abrasive type wear, and the tool wear was expressed as the degradation of surface. The most suitable tool for forming the precision surface was the sintered diamond tool with middle size of diamond grain because of the favourable effect of the falling-off of diamond grains. 0.2μm of surface roughness and 0.5μm of surface contour were obtained. And, by setting the whisker orientation parallel to machinedsurface, the whisker was easily fell off and the surface was degraded.

Endometriosis is prevalent among women of reproductive age, and is most commonly found in the gynecologic organs themselves and the surrounding pelvic peritoneum. Endometriosis of the appendix, however, is rare. Preoperative diagnosis is difficult and a definitive diagnosis is usually established following histopathological examination of the appendix. We report a case of endometriosis of the appendix in a 29-year-old woman who presented with right lower quadrant abdominal pain. Rebound tenderness was localized to McBurney's point. Her WBC count was 12,300/mm3 and her CRP was 6.497 mg/dl. Ultrasound and computed tomography detected a calcified region inside the cecum and slight thickening of the wall of the appendix. Based on these findings, the patient was diagnosed with acute appendicitis and underwent an appendectomy. The appendix appeared mildly congested, but the mucosa of the appendix was nearly normal and without macroscopic inflammation. Histopathological examination demonstrated ectopic endometrial glands and stroma in the muscularis. These stroma cells were positive for CD10 on immunohistochemical staining, establishing a diagnosis of endometriosis of the appendix. The patient had a good clinical course and no residual pain postoperatively.

The purpose of this study is to generate higher precision surface of aluminum alloy reinforced by short fibers of alumina experimentally. So, linearly increased depth of cut type cutting is adopted because of being able to vary the cutting force which is concerned with the mechanism of generation of finished surface. As a result, the pore which was caused by fracture and falling-off or falling off thoroughly of fiber was generated in finished surface. As the stress condition around fiber was nearly constant under the same tool geometry, the ratio of depth of pore to the fiber diameter was constant. And, if tool geometry was properly selected with three dimensional cutting, it was feasible to generate the least defect surface.

Up to the present, aluminum alloy reinforced by short fibers of alumina is used as the parts of automobile because this material has wear-resistant. In the future, it is necessary to generate higher precision surface in order to apply to other uses. The purpose of this study is to experimentally generate higher precision surface of this material by means of diamond cutting with an ultra precision lathe. In order to attain the purpose, the first step was to quantitatively estimate surface roughness and defect from three dimensional measurement of the finished surface. After that, the optimum working conditions were selected. The results obtained from this study are as follows : The pore was generated by falling off of fiber, and the swell of matrix around fiber was observed in the finished surface. If tool geometry and another conditions were selected properly, better results were found to be obtained in surface defects, tool wear, and straightness of finished surface.

Background/Aims Parenchymal hepatocytes (PHs) of rat contain colony-forming parenchymal hepatocytes (CF-PHs) as a small fraction. We aimed to demonstrate the presence of CF-PHs in humans and characterize them with respect to growth and differentiation potential. Methods Human PHs were co-cultured with Swiss 3T3 cells in the medium containing human serum, EGF, nicontinamide, and ascorbic acid 2-phosphate. To examine differentiation potential hepatocytes were cultured on gels of Matrigel Matrix. Results Few PHs formed colonies, the colony-forming efficiency being as low as 0.01–0.09%. The CF-PHs could be subcultured up to 7 passages. They showed a liver epithelial cell-like morphology, and immunocytochemically positive for albumin (ALB), cytokeratin (CK) 7, 8, 18, and 19 in a pre- and early phase-confluence, whereas they showed a typical differentiated hepatocyte-like morphology, and positive for α 1 -antitrypsin, but negative for CK7 and 19 in condensed regions at confluence. The CF-PHs at late confluence expressed mRNAs of ALB, HNF4, and isoforms of cytochrome P450 at low levels. However, when cultured on Matrigel, these cells expressed them at high levels comparable to those of original PHs. Conclusions We concluded that the human liver contains highly replicative hepatic progenitor-like cells as a minute population that retain a normal differentiation potential.

Solitary small-sized HCCs tend to be considered as less aggressive cancer, and non-surgical treatments have recently been preferred. The aim of this study was to clarify the clinicopathological features and the prognostic factors of small-sized HCCs and to evaluate the significance of hepatic resection for them.Eighty patients with HCC up to 2cm in diameter who had undergone hepatic resection were enrolled in this study. We investigated the clinicopathological features and evaluated the prognostic factors by univariate and multivariate analyses.The overall survival rates at 3, 5 and 10 years were 83%, 69% and 36%, respectively, and the corresponding disease-free survival rates were 63%, 41% and 10%. Well-differentiated, moderately differentiated and poorly differentiated HCC were detected in 29%, 65% and 6% of the patients, respectively. Furthermore, microscopic portal vein invasion (vp), hepatic vein invasion (vv) and intrahepatic metastasis (im) were positive in 15%, 4% and 10% of the patients, respectively. Multivariate analysis revealed that Child-Pugh classification (p=0.005) and vp (p=0.0008) were independent prognostic factors for survival rate and that platelet count (p=0.002) and tumor differentiation (p=0.0016) were independent prognostic factors for disease-free survival rate.Even solitary small-sized (up to 2cm in diameter) HCC already have the characteristics of advanced HCC. When hepatic function is well preserved, hepatic resection should be the first choice for local control, especially in cases of moderately to poorly differentiated HCC, because the frequency of microscopic vascular invasion is high.

We clarified the indication of partial hepatectomy in hepatocellular carcinoma (HCC) patients with liver cirrhosis classified as Child-Pugh class B. Univariate analysis revealed that adverse prognostic factors were (1) the presence of ascites, (2) elevated total bilirubin (1.5 mg/dl or higher), (3) reduced choline esterase (160 IU/ or lower), (4) elevated alpha-fetoprotein (AFP) (400 ng/ml or higher), (5) microscopic vascular invasion, and (6) non-curative hepatectomy. Microvascular invasion was excluded in the multivariate analysis because this factor could not be predicted before hepatectomy. Multivariate analysis revealed that independent adverse prognostic factors were (1) elevated total bilirubin (1.5 mg/dl or higher), (2) presence of ascites, (3) elevated AFP (400 ng/ml or higher), and (4) non-curative hepatectomy. The overall 5-year survival rate of patients with none of or only one of the four adverse prognostic factors was 45.8%. The overall 5-year survival rate of patients with two or more adverse prognostic factors was only 7.0%. Partial hepatectomy is the first choice of treatment for patients with none of or only one of the four adverse prognostic factors, whereas orthotopic liver transplantation or other conservative treatment should be considered for patients with two or more adverse prognostic factors.

Background The appropriate treatment strategy for transplantable hepatocellular carcinoma (HCC) patients with compensated cirrhosis remains controversial. Methods Surgical outcomes were reviewed in 136 cirrhotic patients with transplantable HCC who had undergone partial hepatectomy. Transplantable HCC was defined as that corresponding to Milan’s criteria. Results The adverse prognostic factors for both survival and disease-free survival were histologic surgical margin of 5 mm or less, Child-Pugh B, and the presence of hepatitis C virus infection. The overall 5-year survival and disease-free survival rates of patients with 1 or none of the adverse prognostic factors were 73% and 33%, respectively, whereas those of patients with 2 or 3 adverse prognostic factors were 36% and 17%, respectively. Conclusions Transplantable HCC patients with 2 or 3 adverse prognostic factors should be considered candidates for liver transplantation, whereas patients with only 1 or none of the adverse prognostic factors are good candidates for partial hepatectomy.

Human hepatocytes were transplanted into urokinase-type plasminogen activator-transgenic SCID mice (uPA/SCID mice), which are immunodeficient and undergo liver failure. The transplanted cells were characterized in terms of their in vivo growth potential and functions. The human hepatocytes progressively repopulated the murine host liver. However, the recipients died when the replacement index (RI) of the human hepatocytes exceeded 50%. The hosts (chimeric mice) survived at RI >50% when treated with a drug that has anti-human complement factor activity, and these mice developed livers with RI values as high as 96%. In total, 36 chimeric mice were generated, and the rate of successful engraftment was as high as 92%. The yield of chimeric mice with RI >70% was 32%. The human hepatocytes in the murine host liver expressed mRNAs for a variety of human cytochrome P450 (hCYP) subtypes, in a manner that was similar to the donor liver. The mRNAs for hCYP3A4 and hCYP1A1/2 were induced in the liver in a CYP type-specific manner when the mice were treated with rifampicin and 3-methylcholanthrene, respectively. These results indicate that human hepatocytes that propagate in mice retain their normal pharmacological responses. We conclude that the chimeric mouse developed in the present study is a useful model for assessing the functions and pharmacological responses of human hepatocytes.

To predict the degree of liver fibrosis and select a safe operative procedure, the correlation between liver fibrotic ratio and preoperative liver function variables were analyzed, and the significance of the molar ratio of branched-chain amino acids to tyrosine determined preoperatively was investigated.Forty-four patients with hepatectomy were enrolled in this study. Liver tissue specimens excised from the patients were stained by Azan-Mallory's method. The liver fibrotic ratio was measured using an Image Cytometer. The correlation between liver fibrotic ratio and preoperative liver function values, including the serum level of branched-chain amino acids to tyrosine, were determined.The degrees of liver fibrosis (normal group, 1.4 +/- 0.7%; chronic hepatitis group, 4.5 +/- 2.8%; cirrhosis group, 8.4 +/- 2.4%) correlated significantly with preoperative liver function values such as branched-chain amino acids to tyrosine, hepaplastin test, type IV collagen 7s domain, total bilirubin, indocyanine green clearance retention rate at fifteen minutes, and platelet count. The serum level of branched-chain amino acids to tyrosine showed the most-significant correlation with the degree of liver fibrosis.The serum level of branched-chain amino acids to tyrosine correlates well with the degree of liver fibrosis, and this value is a useful preoperative parameter for predicting the degree of liver fibrosis and for selecting a safe operative procedure.

TiAl intermetallic compounds are cut in order to examine their machinabilty and to clarify the influence of machined defects on the mechanical strength. The main results are as follows: Diamond tools and cemented carbide tools exhibit streakyabrasiyetype damage. Surface and edge defects are formed along the lamellar layer direction. Bending strength is higher when the cutting direction is parallel to the edge. In the case of lower strength specimens, breakouts or cracks are observed at the edge. The average strength is improved by chamfering.

We studied the relation of perioperative blood transfusion and the outcomes in 175 patients with hepatocellular carcinoma (HCC) who underwent hepatic resection from 1986 to 1994 in our hospital. Hepatectomy was performed in 23 (13.1%) patients with and 152 (86. 9%) without blood transfusions. The cumulative cancer-free survival rates for patients who had received blood transfusion was significantly lower than that for patients who had not received blood transfusions (p = 0.003). Further examinations revealed a significant difference in cancer-free survival rates for stage I-II patients (n = 75) of HCC (p = 0.02) but not for stage III-IV patients (n = 56) (p = 0.06). Cox regression analysis for recurrence revealed that blood transfusion was the most significant prognostic indicator (p = 0.001) for recurrence in stage I-II patients but not in stage III-IV patients (p = 0.99). These results suggest that a perioperative blood transfusion may be a significant prognostic indicator for patients with HCC who had underwent hepatectomy, especially in stage I-II patients of HCC.

The present study succeeded for the first time in cultivating for more than 2 months human normal hepatocytes which showed a high growth potential and expressed their differentiated phenotypes. Constituents of culture medium were critical for this culture, and the medium optimized for their growth contained fresh human serum, fetal bovine serum, Swiss 3T3-cell conditioned medium, L-ascorbic acid 2-phosphate, epidermal growth factor, nicotinamide, and dimethyl sulfoxide. Hepatocytes steadily replicated and formed colonies which continued to increase in size up to around 35 days. The number of hepatocytes in the most replicative colonies increased 17-fold during 31 days. Cells in colonies expressed normal differentiated hepatocytic phenotypes for as long as 35 days. These hepatocytes retained normal liver functions at least for 70 days such as to secrete albumin, and to metabolize lidocaine and D-galactose.

We developed a method for efficient retroviral vector-mediated gene transfer into human hepatocytes, using a human hepatocyte-bearing mouse model. Normal human hepatocytes were transplanted into the livers of immunodeficient and liver-damaged mice. Donor hepatocytes multiplied and replaced the host hepatocytes, which yielded human hepatocyte-bearing mice (human hepatocyte-chimeric mice). As control cells, rat hepatocytes were similarly transplanted. The replacement level reached 86% at 8 weeks and 100% at 5 weeks posttransplantation of human and rat hepatocytes, respectively. Human and rat hepatocytes in the host liver showed a high bromodeoxyuridine-labeling index during the first 2 weeks posttransplantation. Human- and rat-chimeric mice were injected 7 and 10 days posttransplantation, respectively, with retroviral vectors carrying the beta-galactosidase gene and were thereafter injected daily for 20 and 10 days, respectively. The level of beta-galactosidase-positive hepatocytes in the human- and rat-chimeric mice reached 7.1 +/- 1.8% at 8 weeks and 5.3 +/- 0.9% at 5 weeks after transplantation, respectively. The human hepatocyte-chimeric mouse will be useful for testing the ability of vectors to transduce human cells.

Plasma levels of vitamin K, which is composed of phylloquinone and menaquinone and protein C antigen were measured in thirty patients on long-term warfarin therapy after cardiac surgery. Thirty patients were devided in two groups by means of the type of cardiac surgery. Twenty patients of group A were the cases of cardiac valve replacement and ten patients of group B were the cases of coronary artery bypass grafting. Group A was divided further in two grops, group A-(1) and group A-(2) according to the amount of warfarin doses. Vitamin K was measured by high-performance liquid chromatography and protein C antigen was measured by ELISA method.Thrombotest values of groups A and B ranged on an average of 20.2±3.9% and 20.7±5.3%. Plasma levels of vitamin K and protein C antigen in both groups were on an average of 1.36±0.44ng/ml versus 2.64±1.56ng/ml (p