Publications by authors named "Toshimasa Asahara"

With the widespread and increasing number of cases of Coronavirus Disease (2019) globally, countries have been taking preventive measures against this pandemic. However, there is no universal agreement across cultures on whether wearing face masks are an effective physical intervention against disease transmission. We investigated the relationship between mask wearing and COVID-19 among close contacts of COVID-19 patients in the Hiroshima Prefecture, Japan.

View Article and Find Full Text PDF

Aim: This randomized phase III trial compared hepatic arterial infusion (HAI) chemotherapy with 5-fluorouracil (5-FU) followed by uracil/tegafur (UFT) and leucovorin (LV) versus UFT/LV alone for patients with curatively resected liver metastases from colorectal cancer (CRC).

Methods: The study was designed to include 280 patients to be randomized to receive either HAI with 5-FU followed by UFT/LV (Arm A) or UFT/LV alone (Arm B) to assess whether HAI chemotherapy improved disease-free survival (DFS).

Results: Forty-four patients were randomized.

View Article and Find Full Text PDF

We previously produced mice with human hepatocyte (h-hep) chimeric livers by transplanting h-heps into albumin enhancer/promoter-driven urokinase-type plasminogen activator-transgenic severe combined immunodeficient (SCID) mice with liver disease. The chimeric livers were constructed with h-heps, mouse hepatocytes, and mouse hepatic sinusoidal cells (m-HSCs). Here, we investigated the morphological features of the chimeric livers and the h-hep gene expression profiles in the xenogeneic animal body.

View Article and Find Full Text PDF

This prospective, non-randomized, multicenter cohort study analyzed the safety and efficacy of a steroid-free immunosuppressive (IS) protocol for hepatitis C virus (HCV)-positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assigned the steroid-free IS protocol (Fr group) and 29 the traditional steroid-containing IS protocol (St group). Serum HCV RNA levels increased over time and were higher in the St group until postoperative day 90 (POD 14, p=0.

View Article and Find Full Text PDF

Background: The preferred choice between surgical treatment and radiofrequency ablation (RFA) for the treatment of small resectable hepatocellular [corrected] carcinoma (HCC) has become a subject for debate.

Methods: We compared the results of hepatic resection (n = 199) with those of RFA (n = 87), of which 69 patients were treated with transcatheter arterial chemoembolization followed by RFA, for 286 patients with 3 or fewer nodules, none of which exceeded 3 cm in diameter at Hiroshima University Hospital.

Results: In subgroup analysis of single HCC with tumor size exceeding 2 cm in Child-Pugh class A, the disease-free survival time was significantly longer in the surgical resection group than in the RFA group (P = 0.

View Article and Find Full Text PDF

Background: The appropriate treatment strategy for advanced hepatocellular carcinoma (HCC) that does not meet the Milan criteria (MC) is unclear. The aim of this study was to determine the significance of surgical treatment for such patients.

Study Design: From January 1990 to December 2007, 151 patients with HCC exceeding MC who underwent curative surgical treatment were enrolled.

View Article and Find Full Text PDF

Lipopolysaccharide-stimulated leukocytes secrete proinflammatory cytokines including tumor necrosis factor-α and interleukin-12. Over-activation of host defense systems may result in severe tissue damage and requires regulation. Granulocyte colony-stimulating factor and interleukin-10 are candidate cytokines for inducing tolerance to lipopolysaccharide re-stimulation.

View Article and Find Full Text PDF

Background: This study aimed to evaluate the therapeutic potential of intrasplenic transplantation of culture-propagated homologous hepatocytes in rats suffering from acute liver failure (ALF).

Methods: ALF was induced in dipeptidyl peptidase IV-negative (DPPIV(-)) Fischer 344 rats by totally removing the two anterior liver lobes (68% of the liver) and ligating the pedicle of the right lobe (24% of the liver). Hepatocytes isolated from DPPIV(+) Fischer 344 rats were cultured for 11 d to propagate 3-fold, and the resulting hepatocytes were dubbed "culture-propagated hepatocytes (CPHEPs)".

View Article and Find Full Text PDF

Clinical studies have shown a close association between nonalcoholic fatty liver disease and adult-onset GH deficiency, but the relevant molecular mechanisms are still unclear. No mouse model has been suitable to study the etiological relationship of human nonalcoholic fatty liver disease and human adult-onset GH deficiency under conditions similar to the human liver in vivo. We generated human (h-)hepatocyte chimeric mice with livers that were predominantly repopulated with h-hepatocytes in a h-GH-deficient state.

View Article and Find Full Text PDF

Cryopreserved human (h-) hepatocytes are currently regarded as the best in vitro model for predicting human intrinsic clearance of xenobiotics. Although fresh h-hepatocytes have greater plating efficiency on dishes and greater metabolic activities than cryopreserved cells, performing reproducible studies using fresh hepatocytes from the same donor and having an "on demand" supply of fresh hepatocytes are not possible. In this study, cryopreserved h-hepatocytes were transplanted into albumin enhancer/promoter-driven, urokinase-type plasminogen activator, transgenic/severe combined immunodeficient (uPA/SCID) mice to produce chimeric mice, the livers of which were largely replaced with h-hepatocytes.

View Article and Find Full Text PDF

Liver mass is optimized in relation to body mass. Rat (r) and human (h) hepatocytes were transplanted into liver-injured immunodeficient mice and allowed to proliferate for 3 or 11 weeks, respectively, when the transplants stopped proliferating. Liver/body weight ratio was normal throughout in r-hepatocyte-bearing mice (r-hep-mice), but increased continuously in h-hepatocyte-bearing mice (h-hep-mice), until reaching approximately three times the normal m-liver size, which was considered to be hyperplasia of h-hepatocytes because there were no significant differences in cell size among host (mouse [m-]) and donor (r- and h-) hepatocytes.

View Article and Find Full Text PDF

The estrogen receptor (ER) and progesterone receptor (PgR) status of 163 surgical breast cancer specimens determined on real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using frozen tumor tissue were compared with that determined using three automated immunohistochemistry (IHC) assays including Dako (Glostrup, Denmark), Ventana (Tucson, AZ, USA) and BioGenex (San Ramon, CA, USA) assay. All specimens were semiquantified according to the Allred score and J-score. The cut-offs for ER determined by log (ER/glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) were -3.

View Article and Find Full Text PDF

Ill-located liver metastases close to the cavo-hepatic confluence often require resection and reconstruction of hepatic veins. However, most of the current techniques for reconstruction of the hepatic veins require graft interposition or complex venoplasty. The present case report describes a new surgical procedure which allows reconstructing the middle hepatic vein (MHV) by direct end-to-end anastomosis after a right hepatectomy for colorectal liver metastases invading the right and middle hepatic veins.

View Article and Find Full Text PDF

BACKGROUND.: Although the outcome of liver transplant patients with hepatocellular carcinoma (HCC) has improved with the introduction of strict criteria, tumor recurrence still remains a significant problem. Sphingosine-1-phosphate (S1P) is a phospholipid mediator that can induce diverse cellular responses, such as proliferation, migration, adhesion, and cell-rounding, in cancer cells.

View Article and Find Full Text PDF

After liver transplantation in HCV-infected patients, the virus load inevitably exceeds pre-transplantation levels. This phenomenon reflects suppression of the host-effector immune responses that control HCV replication by the immunosuppressive drugs used to prevent rejection of the transplanted liver. Here, we describe an adoptive immunotherapy approach, using lymphocytes extracted from liver allograft perfusate (termed herein liver allograft-derived lymphocytes), which includes an abundance of NK/NKT cells that mounted an anti-HCV response in HCV-infected liver transplantation recipients, despite the immunosuppressive environment.

View Article and Find Full Text PDF

Hepatocyte transplantation is effective for treating liver failure, but healthy donors as a source of hepatocytes are quite limited. The livers of patients with hepatic fibrosis could be an alternative source; however, few reports have examined the nature of hepatocytes from fibrotic livers (f-hepatocytes). In this study, we compared the growth of f-hepatocytes and hepatocytes from normal livers (n-hepatocytes).

View Article and Find Full Text PDF

Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination.

View Article and Find Full Text PDF

Budd-Chiari syndrome (BCS) results from diverse causative factors. Myeloproliferative disorders (MPDs) including essential thrombocythemia (ET) account for a minority of BCS cases in Japan. ABO-blood-type incompatible living donor liver transplantation (LDLT) in adults has become an acceptable procedure owing to the development of new strategies for preventing antibody-mediated rejection.

View Article and Find Full Text PDF

Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy.

View Article and Find Full Text PDF

Background: Liver transplantation (LT) is known to improve bleeding esophageal varices (EVs) and portal hypertension. However, many issues related to EVs after LT remain unresolved, such as whether LT reduces blood supply to EVs, improves the diameter of unruptured EVs, or improves or worsens EVs. The aim of this retrospective study was to determine the effects of living-donor liver transplantation (LDLT) in patients with hepatic failure on EVs and inflow vessels to EVs and the factors associated with deterioration of EVs after LDLT.

View Article and Find Full Text PDF

A 62-year-old man underwent right hepatectomy with resection of the middle hepatic vein trunk for metastatic liver cancers. Serious congestion of the caudal area of segment 4 occurred just after dividing the middle hepatic vein trunk. The reconstruction of the venous tributary from the caudal area of segment 4 to the inferior vena cava was performed using a saphenous vein graft of 11 cm in length.

View Article and Find Full Text PDF

Background/aims: Although antiviral prophylaxis with the combined high-dose hepatitis B immunoglobulin (HBIg) and lamivudine therapy has effectively reduced post-liver transplantation recurrence of hepatitis B virus infection, its use is limited by cost and availability.

Methodology: Fourteen living-donor liver transplant patients were performed with the mean follow-up of the 23 months (range, 5 to 58 months). We examined the effectiveness of prophylaxis against recurrence of hepatitis B with much lower dose of HBIg.

View Article and Find Full Text PDF

Background: Congestion in the right paramedian sector of a right liver graft without a middle hepatic vein (MHV) may lead to graft dysfunction. To solve this problem, we have developed a technique for reconstructing the MHV tributaries of the right liver grafts by using the preserved recipient's native MHV trunk.

Methods: Between 2005 and 2007, among 34 right liver graft liver transplant patients with significant MHV tributaries (>5 mm in diameter), 21 patients underwent right liver graft living-donor liver transplantation: draining MHV tributaries with recipient's native MHV trunk.

View Article and Find Full Text PDF

Background: The aim of this study was to clarify the characteristics of elderly hepatocellular carcinoma (HCC) patients aged 75 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy.

Methods: Between January 1990 and December 2006, 570 patients underwent curative hepatectomy for HCC. Elderly patients were defined as those aged 75 years or more.

View Article and Find Full Text PDF

Background: Previously, we created, a chimeric mouse (humanized mouse), a severe combined immunodeficiency (SCID) mouse whose liver was >90% repopulated with human (h)-hepatocytes, which are useful for the testing of drug metabolism and toxicity, as well as a hepatitis B virus and hepatitis C virus-susceptible animal model. However, their small body size and small total blood volume limited the utilization for analytical purposes, which led us to develop a method to create a chimeric rat bearing h-hepatocyte-repopulated liver.

Methods: F344 nude rats devoid of T cells were irradiated with X-rays and injected with bone marrow cells (BMCs) from SCID mice (m(SCID)).

View Article and Find Full Text PDF