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Blood purification therapy is indispensable for liver transplant recipients. The case of a living donor liver transplant recipient who represented graft insufficiency and was supported by novel blood purification "plasma diafiltration" immediately after operation is presented. A 60-year-old woman was referred for living donor liver transplant because of liver cirrhosis due to hepatitis C. Elective living donor liver transplant was performed, but the graft was small for size. Thus, the signs of graft insufficiency appeared immediately after the operation, and plasma diafiltration was used as a bridge to graft regeneration. After plasma diafiltration was started, the recipient recovered promptly, and withdrawal was performed 35 hours after induction without any complications. Plasma diafiltration is a useful and safe liver support for liver transplant recipients, including immediately after liver transplantation.

This report presents a case that was successfully treated for acquired factor VIII inhibitor after extensive visceral surgery. A 71-year-old male who underwent surgery for bile duct cancer had active bleeding in the abdominal drainage tube on postoperative day (POD) 5, and prolonged activated partial thromboplastin time (aPTT) was detected (83.1 s) on POD 7. An extensive coagulation work-up revealed factor VIII deficiency (1 %), and a diagnosis of an acquired factor VIII deficiency was established when a factor VIII inhibitor of 8 Bethesda units was demonstrated. The patient was treated with activated prothrombin complex concentrate (aPCCs) and bloody discharge was stopped within 3 days. Inhibitor elimination was started using prednisolone on POD 20; rituximab, was administered on POD 74 and 81. Factor VIII inhibitor had disappeared by POD 124, and factor VIII (72 %) and aPTT recovered to 45.9 s. This case report demonstrated the efficacy of aPCCs and rituximab in the treatment of acquired hemophilia associated with visceral surgery.

Aims: To determine the expression of CXCL12 in human spleens with extramedullary haematopoiesis (EMH) for clarifying the association of splenic haematopoietic stem cells (HSCs) with CXCL12, which has been demonstrated to be a marker of bone marrow niches., Methods: We examined the expression of mRNA for CXCL12 by quantitative reverse transcription polymerase chain reaction (RT-PCR) and localised the CXCL12 protein by immunohistochemical staining in EMH negative and positive spleen samples from autopsy cases., Results: Expression of CXCL12 was significantly higher in samples from EMH positive cases than those from EMH negative cases. CXCL12 was localised to the endothelial cells of the sinuses of the red pulp in EMH positive spleens while vascular endothelial cells of the white pulp expressed CXCL12 throughout the spleen. c-kit positive/CD34 negative cells were identified in contact with CXCL12 positive endothelial cells of sinuses in EMH positive cases, although the number was few. In contrast, erythroblastic islands were frequently observed in EMH positive cases and dominantly localised to the intrasinusoidal spaces in association with CD68 positive macrophages., Conclusions: Our results suggest that endothelial cells of splenic sinuses expressing CXCL12 may contribute to attracting circulating haematopoietic precursor cells and constitute bone marrow niche-like regions of EMH in humans. Differentiating haematopoietic cells may move into intrasinusoidal spaces to form EMH foci such as erythroblastic accumulation.

We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying a mixed adenoneuroendocrine carcinoma (MANEC). A 74-year-old woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET.

Analytical electron microscopy revealed the structure and growth of hard coating Cr(Al)N/SiOx nanocomposite films prepared in a differential pumping cosputtering (DPCS) system, which has two chambers to sputter different materials and a rotating substrate holder. The substrate holder was heated at 250 °C and rotated at a speed as low as 1 rpm. In order to promote the adhesion between the substrate and composite film, transition layers were deposited on a (001) Si substrate by sputtering from the CrAl target with an Ar flow and a mixture flow of Ar and N2 (Ar/N2) gases, subsequently, prior to the composite film deposition. Then, the Cr(Al)N/SiOx nanocomposite film was fabricated on the transition layers by cosputtering from the CrAl target with the Ar/N2 gas flow and from the SiO2 target with the Ar gas flow. The film had a multilayer structure of ∼1.6 nm thick crystallite layers of Cr(Al)N similar to NaCl-type CrN and ∼1 nm thick amorphous silicon oxide layers. The structure of the transition layers was also elucidated. These results can help with the fabrication of new hard nanocomposite films by DPCS.

Imaging mass spectrometry (MS) is an emerging technique that can detect numerous biomolecular distributions in a non-targeting manner. In the present study, we applied a mass imaging modality, mass microscopy, to human lung tissue and identified several molecules including surfactant constituents in a specific structure of the lung alveoli. Four peaks were identified using imaging MS, and the ion at m/z 772.5, in particular, was localized at some spots in the alveolar walls. Using an MS/MS analysis, the ion was identified as phosphatidylcholine (PC)(16:0/16:0), which is the main component of lung surfactant. In a larger magnification of the lung specimen, PC (16:0/16:0) was distributed in a mottled fashion in a section of the lung. Importantly, the distribution of PC (16:0/16:0) was identical to that of anti-SLC34A2 antibody immunoreactivity, which is known to be a specific marker of type II alveolar epithelial cells, in the same section. Our experience suggests that imaging MS has excellent potential in human pathology research., (© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Aims:   Multidrug resistance (MDR) in B-cell lymphomas still constitutes a major obstacle to the effectiveness of chemotherapy even in the anti-CD20 antibody therapy era. The aim of this study was to investigate the expression of MDR-associated molecules in reactive lymphadenopathy (RL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL)., Methods and Results:   The expression of mRNA for ABC-transporter family genes was determined by real-time RT-PCR in lymph nodes from RL, FL, and DLBCL cases. MDR1 exhibited significantly stronger expression in RL, FL, and DLBCL than Raji B-cell lymphoma cells. RL and FL showed significantly higher expression than DLBCL. Immunohistochemically, MDR1 positive cells were localized in the germinal centers of RL and center of the nodular lesions of FL showing associations with CD21 positive follicular dendritic cells (FDCs). Raji cells were co-cultured with FDC sarcoma-derived cells and the expression of MDR1 and drug resistance were analyzed. The co-culture of Raji cells with FDCs induced strong expression of MDR1 and introduced resistance to doxorubicin-induced apoptosis., Conclusions:   These results suggest that FDCs induce MDR1 expression in reactive as well as neoplastic B-cells. Inhibition of the interaction of FDCs with B-cells may provide a novel strategy for treating the chemotherapy resistant fraction., (© 2013 Blackwell Publishing Ltd.)

Objectives: The most serious, life-threatening complication after living-donor liver transplant is a hepatic arterial thrombosis. Although possible therapies for acute hepatic arterial thrombosis include revascularization to salvage the graft, or retransplant, these may be difficult to perform owing to technical aspects and donor shortages. Previously, we reported the usefulness of partial portal arterialization in such cases., Materials and Methods: Four cases of partial portal arterialization for hepatic arterial occlusion after living-donor liver transplant were reviewed. The surgical procedure of partial portal arterializations involves making an arteriovenous shunt via a side-to-side anastomosis, using mesenteric vessels approximately 2 mm in diameter., Results: After partial portal arterialization, hepatic arterial flow was not detected, but graft injury owing to hypoxia gradually improved in all cases. In 1 case, occlusion of the arteriovenous shunt itself and the collateral artery to the graft were identified by angiography 45 days after partial portal arterialization. In another case, massive ascites, pleural effusion, and variceal changes of the mesenteric veins owing to portal hypertension were identified, and surgical closure of the shunt was performed 152 days after partial portal arterialization. In the other 2 cases, there were no definite problems related to partial portal arterialization, but the patients died owing to other complications., Conclusions: When hepatic arterial thrombosis occurs after living-donor liver transplant, revascularization should be performed first. However, this sometimes may be difficult, as when the arterial dissection reaches into the graft. Partial portal arterialization is an easy and effective surgical procedure. Therefore, partial portal arterialization appears to be a useful option to gain time until collateral arterial vessels develop or retransplant, even if revascularization cannot be performed.

Background/objective: Recently, endoscopic and radiological procedures for various symptoms related to cirrhosis have improved. Thus, the role of Hassab's operation (gastroesophageal decongestion and splenectomy) has changed for cirrhotic patients., Methods: Hassab's operation was performed on patients who had gastroesophageal varices that were difficult to control with balloon occluded retrograde transvenous obliteration or an endoscopic procedure, or had hypersplenism. Thirteen consecutive patients underwent this operation, and the outcomes of all patients were reviewed retrospectively., Results: There was no operative morbidity or rebleeding varices. In the preoperative endoscopic injection sclerotherapy treated group (n=6), only one patient (16.7%) developed recurrent varices. Mean platelet counts were significantly higher 6 months after surgery (201 ± 65 × 10(3)/mm(3)) than preoperatively (64 ± 54 × 10(3)/mm(3)). In patients with hepatocellular carcinoma, percutaneous therapies, such as radio frequency ablation, were safely performed with adequate therapeutic effect. Interferon therapy was given to patients with hepatitis C virus (HCV)-related cirrhosis without interruption., Conclusion: Hassab's operation is a satisfactory approach to controlling varices, especially when combined with preoperative endoscopic treatment. Platelet counts were significantly higher after surgery. This therapy was important for cirrhotic patients contraindicated for liver transplantation in that they could continue their therapy for hepatocellular carcinoma (HCC) and HCV as needed., (Copyright © 2012. Published by Elsevier B.V.)

Na+/H+ exchangers (NHEs) are a group of secondary active antiporters that regulate cellular pH, cell volume and ion homeostasis. In humans, nine isoforms (NHE1-NHE9) were identified and characterized as functional NHEs. While a growing body of evidence indicates that NHE1 generates an acidic tumor environment and thereby contributes to tumor invasion, little is known about the role of other NHE isoforms in tumor progression. NHE7 is a unique member of the NHE gene family that dynamically shuttles between the trans-Golgi network, endosomes and the plasma membrane, and regulates the luminal pH of these organelles. Here we show that NHE7-overexpression in breast cancer MDA-MB-231 cells enhances cell overlay, cell-cell adhesion, invasion, anchorage-independent tumor growth and tumor formation in vivo. In contrast, NHE1-overexpression enhances tumor invasion, but it has little effect on cell adhesion or anchorage-independent tumor growth. Pathological examinations of the tumor samples derived from NHE7-overexpressing cells showed a similar appearance to aggressive tumors. Together, these results suggest that NHE7 enhances tumor progression. This is the first report to show the involvement of an organellar NHE in oncogenic processes.

Metastasis of the small intestine that derives from a primary hepatic neoplasm is rare. We encountered a case of intrahepatic cholangiocarcinoma (ICC) with jejunal metastasis after resection of a primary lesion. A 61-year-old male patient was referred to us with a diagnosis of liver tumors. Partial hepatectomy was performed, and the pathological diagnosis was ICC. Seventeen months after surgery, the patient was found to have a mass in the jejunum and lymph node swelling by positron emission tomography-computed tomography. The jejunal tumor was preoperatively diagnosed as a metastasis of ICC from a biopsy specimen obtained by double balloon endoscopy, and the tumor was resected. The patient received systemic chemotherapy but succumbed with ICC recurrence 46 months after the primary surgery. To the best of our knowledge, this case is the first report of jejunal recurrence of ICC. In addition, this report suggests the usefulness of double balloon endoscopy to make the correct diagnosis of the jejunal tumor.

Hepatic metastasis is a common cause of treatment failure after curative resection of pancreatic cancer. We report a pilot study of hepatic arterial infusion (HAI) chemotherapy with gemcitabine and 5-fluorouracil (5-FU) for postoperative liver metastases from pancreatic cancer. Five patients who had undergone curative resection of liver metastases from pancreatic cancer received HAI of gemcitabine and 5-FU between October 2008 and September 2010 at Kanazawa University Hospital. Gemcitabine at a dose of 800 mg was infused over 30 min via a bedside pump. After gemcitabine administration, 250 mg of 5-FU was infused continuously over 24 h on days 1-5, comprising one cycle of therapy. These treatment cycles were continued biweekly. In the evaluation according to RECIST criteria, a partial response was obtained in 2 of the 5 cases, with stable disease being achieved in the remaining 3 cases (response rate, 100%). In 4 of the 5 cases, a decrease in serum tumor marker CA19-9 was observed after 10 HAI treatment cycles. The median time to treatment failure was 10 months (range 3-17). As to adverse events, leukocytopenia was grade 3 in 1 of 4 affected cases and all 5 were anemic, although 4 of the 5 cases had anemia prior to HAI therapy. Grade 2 thrombocytopenia was observed in 2 cases. No nonhematologic events, such as nausea, diarrhea, liver injury and neuropathy, occurred. There were no life-threatening toxicities, but 4 cases (80%) developed catheter complications, and the HAI catheter and subcutaneous implantable port system had to be removed. HAI delivers high doses of chemotherapeutic agents directly into tumor vessels, producing increased regional levels with greater efficacy and a lower incidence/severity of systemic side effects. In conclusion, HAI chemotherapy is useful and safe for the treatment of malignancies confined to the liver.

Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis.

Here, we present a case of post-operative liver metastases from pancreatic head cancer in a patient with leukocytopenia, who was safely treated by hepatic arterial infusion (HAI) chemotherapy consisting of gemcitabine and 5-FU. The patient was a 61-year-old woman who underwent pancreaticoduodenectomy for pancreatic head cancer, but was found to be an unsuitable candidate for adjuvant systemic chemotherapy due to the presence of leukocytopenia. Five months after surgery, a follow-up CT revealed two liver metastases. Intravenous systemic chemotherapy was also contraindicated due to the leukocytopenia. In the apparent absence of recurrence, excepting the liver metastases, we decided to administer HAI chemotherapy, which had already been administered following the curative surgery. HAI chemotherapy has been shown to be associated with a lower incidence of systemic side effects. Gemcitabine at a dose of 400 mg was administered via a bedside pump and infused over 30 min. After gemcitabine infusion, 250 mg of 5-FU was infused continuously over 24 h from days 1 to 5. This comprised 1 cycle of therapy. The treatment cycles were continued biweekly. After 10 cycles without severe side effects, it was found that though the size of the metastatic tumors was not reduced, tumor vascularity was. However, after the 13th treatment cycle, local recurrence and lymph node metastases were detected. By this time, the patient had recovered from the leukocytopenia, and could thus be administered systemic chemotherapy. In conclusion, HAI chemotherapy is useful and safe for the treatment of malignancies confined to the liver, even in cases where the patient is in a reduced physical condition.

Serous microcystic adenomas are rare and account for 1-2% of all exocrine pancreatic tumors and 25% of all pancreatic cystic neoplasms. Recently, with advances in imaging techniques, these adenomas have been identified at an increasing frequency. A 63-year-old woman visited her doctor in 1999 due to a gastric deformity detected by upper gastrointestinal endoscopy. An abdominal computed tomography scan revealed a cystic lesion measuring 6.0 cm in diameter, resulting in a diagnosis of serous microcystic adenoma of the pancreatic head. During follow-up, the tumor increased steadily in size, measuring 6.0 cm in diameter in 1999 and 13.0 cm in 2008, while remaining asymptomatic throughout this period of time. The risk of malignant transformation appears to be low even over the long-term. However, some cases of malignant transformation to serous cystadenocarcinoma have recently been reported. In this case, assessment of the relationship between the tumor and adjacent vascular structures, such as massive drainage vein development on the surface or tumor flow into the portal and superior mesenteric veins and the celiac and superior mesenteric arteries, was critical for determining tumor resectability. The risk of massive intra-operative hemorrhage was felt to be considerable, given the extent of the veins on the surface of the tumor, as well as the size and location of the primary pancreatic mass. Therefore, preoperative embolization of the tumor-feeding arteries arising from the celiac axis (gastroduodenal, splenic and dorsal pancreatic arteries) was performed. Tumor resection with pancreaticoduodenectomy was performed without a blood transfusion, with an estimated blood loss of 570 ml. The final pathology confirmed the diagnosis of serous microcystic adenoma. The patient is currently alive and disease-free. Preoperative partial embolization of the tumor feeding arteries and intra-operative resection of the right gastric and inferior pancreatoduodenal arteries, allowed the tumor blood supply to be arrested without preoperative tumor necrosis. Subsequently, intraoperative blood loss was reduced. Preoperative partial embolization of the feeding arteries is useful for the resection of hypervascular large tumors of the pancreas.

We report on photocurrent switching based on photoisomerization for the nondestructive readout of photochromic optical memory. The photoisomerization of a diarylethene (DAE) memory layer switched the photocurrent generated in a light-absorbing phthalocyanine layer upon irradiation of a laser light. This switching is based on the ionization potential change of the DAE molecules. Switching characteristics of the photocurrent were investigated for the laser light with a wavelength of 410 nm, 630 nm, or 780 nm. Excellent on-off ratios of the photocurrent were achieved by irradiation at 630 nm and 780 nm. When the pulsed laser light with a wavelength of 780 nm was repeatedly irradiated to the colored and uncolored memory devices, no change of the photocurrent signal levels was observed, even after 8 x 10(5) cycles, indicating a successful demonstration of the nondestructive readout.

In primary malignant liver tumors, trypsinogen-immunoreactivity was present in 70% of intrahepatic cholangiocarcinoma (ICC) specimens, but absent in hepatocellular carcinoma (HCC) specimens. We suggest the secretion of trypsinogen to be a key difference in biological behavior between ICC and HCC cells. The purpose of this study was to investigate the secretion of tumor-derived trypsin and the expression of its specific receptor, protease-activated receptor-2 (PAR-2), in ICC using cell lines and surgical specimens. The expression of trypsinogen-1 mRNA was observed in three of four ICC cell lines, but none of three HCC cell lines. Western blot analysis detected trypsinogen-1 in serum-free conditioned medium from one of the ICC cell lines positive for the mRNA. Gelatin zymography revealed a gelatinolytic activity for trypsin, the activated form of trypsinogen, in the same conditioned medium. PAR-2 mRNA and protein were observed in ICC cell lines. The proliferative activity of ICC cells was increased by concentrations of trypsin as low as 10 nM, and peaked at 100 nM. The effect of trypsin was suppressed by a serine protease inhibitor, gabexate mesilate. PAR-2 expression was detected in 64% of ICC surgical specimens immunohistochemically. In addition, stroma fibroblasts expressed PAR-2 in 52% of ICC specimens. These results suggest that trypsinogen-1 contributes to the growth of ICC cells and also tumor-associated fibroblasts.

Radiofrequency ablation (RFA) has been reported to be a minimally invasive and effective procedure for the treatment of hepatocellular carcinoma (HCC). However, the pattern of recurrence and complications following RFA have yet to be fully identified. During the period January 2000 to December 2006, we performed HCC resections in 15 patients who developed local recurrence after RFA, as well as in 144 patients without RFA. In patients with local recurrence of HCC after RFA, the tumors showed a more invasive growth, more vascular invasion and less differentiation compared with tumors of patients without RFA. In 6 of the 15 patients with recurrence after RFA, needle biopsy of the HCC was performed before tumor ablation. In five of these 6 patients, dedifferentiation of the tumor was observed. These findings suggest that heat shock due to RFA induces dedifferentiation of HCC. Recurrence after RFA may result in an aggressive tumor that precludes any possibility of cure. RFA must not be considered a suitable alternative to surgery in patients with a low surgical risk. Instead, RFA should be performed according to strict indications by skilled operators using the latest devices.

Objective: To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan., Methods: Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed., Results: The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived., Conclusion: PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.

Na+/H+ exchanger isoform 5 (NHE5) is a brain-enriched NHE that may play important roles in ion homeostasis and cell-volume regulation. However, the regulation mechanism of NHE5 has not been fully elucidated. Here, we show that Receptor for Activated C-kinase 1 (RACK1) directly binds to NHE5 and positively regulates the transporter function. NHE5 co-localized with RACK1 as well as beta1 integrin, paxillin and vinculin, suggesting that NHE5 associates with focal adhesions. By using RACK1 dominant-negative mutants and siRNA, we further show that RACK1 regulates NHE5 both directly and through an integrin-dependent pathway. The NHE5-RACK1 interaction, but not the RACK1-beta1 integrin interaction, was reinforced when cells were spread on an integrin-substrate fibronectin. We propose that RACK1 activates NHE5 both by integrin-dependent and independent pathways, which may coordinate cellular ion homeostasis during cell-matrix adhesion.

Genome-targeting molecules would have broad application as probes in genomic study. We recently developed the ligands (Bpy-H) connecting the Hoechst33258 skeleton for DNA binding and 2,2'-bipyridine for Cu(2+) complexation. It was shown that L-Bpy-H with a long linker exhibited Cu(2+)-mediated assembly on the DNA template having two A(3)T(3) sites in a ratio of 1:2:1 DNA-ligand-Cu(2+). Binding selectivity depends on the distance between the two A(3)T(3) sites of DNA. In contrast, S-Bpy-H having a short linker tended to form 1:2:2 DNA-ligand-Cu(2+) complex.

We performed combined therapy with trastuzumab-vinorelbine for 6 HER2 positive metastatic breast cancer patients from which informed consent was obtained. As the initial dosage, we administered 4 mg/kg of trastuzumab, followed by a dosage of 2 mg/kg every week thereafter. At the same time, 25 mg/m2 of vinorelbine was administered for 2 weeks, followed by a week of rest. Total administration frequency of trastuzumab was 13-34 times (median: 27 times) and vinorelbine was 8-22 times (median: 17 times). A partial response was seen in 4 patients and no change in 2, for a response rate of 66%. A fixed period effect was recognized in each case, and the TTP was 112-274 days (median: 205 days). The side effects recognized were leukopenia of grade 3 in 1 patient, but she recovered during a withdrawal period. After that, continuous administration was possible. Trastuzumab-vinorelbine combined therapy expanded treatment alternatives for HER2 positive metastatic breast cancer patients and might prolong life.

A case of an unresected, advanced gastric cancer with Sister Mary Joseph nodule was presented. It was treated with new combination chemotherapy of low-dose S-1 and cisplatin producing complete response of periumbilical metastasis. Few treatments are efficacious for umbilical invasion of peritoneal dissemination. A complete response for Sister Mary Joseph nodule from gastric adenocarcinoma has not been ever reported.

A fast and controlled radical polymerisation of acrylates and acrylamides can be achieved with a combination of a highly active metal catalyst, Fe2Cp2(CO)4, and a mild radical scavenger, iodine, in the presence of an iodide initiator.

We report the case of an 84-year-old woman with vulval extramammary Paget's disease associated with pancreatic cancer who was successfully treated. At first, biweekly low-dose FP (cisplatin 10 mg/body, 5-fluorouracil 250 mg/body) was administered by intravenous infusion. Next, we attempted a regimen of gemcitabine (1,000 mg/body) was administered weekly by intravenous infusion. As a result, the size of the pruritic lesion of the vulva was reduced more than 50%, and the serum level of CA19-9 decreased clearly. These treatments would be a valid option in certain cases of pancreas cancer and extramammary Paget's disease.

TS-1, a novel oral formation of 5-fluorouracil, consists of tegafur (5-FU), CDHP and Oxo. Low-dose cisplatin (CDDP) and TS-1 was evaluated in 12 patients with advanced or recurrent gastric cancer. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 80 mg/body of TS-1 was orally administered as many times as possible. The response rate was 41.7%. Median survival time was 13.3 months. In one case, an adverse reaction of grade 3 leucopenia was observed. Thus, thought it is necessary to watch for leucopenia, this chemotherapy could well be effective for patients with advanced or recurrent gastric cancer.

Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many times as possible. The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic head cancer with liver and para-aortic lymph node metastases received this therapy 38 times, and lived for 54 months. No severe side effects occurred in any of these cases. Thus, this chemotherapy could well be effective for the outcome of cases of advanced gastrointestinal carcinoma.

We have generated a mouse model for hepatic ischemia in which surgical subcutaneous transposition of the spleen allows hepatic ischemia to be applied without affecting other tissues. Using this mouse model we investigated the relationship between the length of ischemic periods in the liver and subsequent liver function; furthermore, we assayed the activation of c-Jun N-terminal kinase (JNK) during ischemia and reperfusion. Although prior to this study only the activated form of JNK was known to be translocated to the nucleus, we found that JNK translocates to the nucleus during ischemia without activation and is then activated during reperfusion. These results suggest a novel mechanism of JNK activation.

The authors present the results of a clinical and endoscopic controlled trial of outpatients with duodenal ulcer treated with carbenoxolone (CBX) and carbenoxolone plus antacids (CBX + AA). They observed complete healing of the duodenal ulcer in 77%-83,3% in both groups of patients. They concluded that CBX is important in the treatment of duodenal ulcer been equally effective alone or in association with antacids.

Wegener's granulomatosis is a disease characterized by necrotizing vasculitis and granulomatous inflammation. Gastrointestinal (GI) involvement is uncommon in this disorder. Only a few cases of perforation of GI tract have been reported, but vasculitis has not been demonstrated to be a cause of perforation in these cases. We report a case of Wegener's granulomatosis in which a single perforation in the terminal ileum was disclosed on laparotomy and active necrotizing vasculitis was found in the submucosal layer of the resected specimen.