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Biomedical subjects

Shinji Uemoto

Publications and source records attributed to Shinji Uemoto.

At least 19 recordsLinked to original sources
PubMed2006

Noradrenalin-secreting retroperitoneal schwannoma resected by hand-assisted laparoscopic surgery: report of a case.

A 66-year-old woman was admitted to our hospital for investigation of a retroperitoneal mass. She was asymptomatic but her serum noradrenalin and vanillylmandellic acid levels were increased remarkably. Computed tomographic angiography showed a mass in the left side of the superior mesenteric artery (SMA) divergence, 6 x 4 cm in size, supplied mainly by the left adrenal artery. We performed hand-assisted laparoscopic surgery (HALS) using a Cavitron ultrasonic surgical aspirator. Abdominal exploration revealed that the tumor was located in the left side of the SMA root, but was not adhered to the adjacent organs. Her vital signs remained stable during the operation. Microscopic examination revealed a palisade formation, confirming a histopathological diagnosis of degenerated schwannoma (Antoni type B). Immunohistologically, the tumor cells were stained with S-100 protein and neuron-specific enolase. Her noradrenalin level normalized immediately after the operation and she remains in good health 3 years 2 months later.

Aged↗
PubMed2006

Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes.

BACKGROUND/AIMS: The development of an efficient in vitro infection system for HCV is important in order to develop new anti-HCV strategy. Only Huh7 hepatocyte cell lines were shown to be infected with JFH-1 fulminant HCV-2a strain and its chimeras. Here we aimed to establish a primary hepatocyte cell line that could be infected by HCV particles from patients' sera. METHODS: We transduced primary human hepatocytes with human telomerase reverse transcriptase together with human papilloma virus 18/E6E7 (HPV18/E6E7) genes or simian virus large T gene (SV40 T) to immortalize cells. We also established the HPV18/E6E7-immortalized hepatocytes in which interferon regulatory factor-7 was inactivated. Finally we analyzed HCV infectivity in these cells. RESULTS: Even after prolonged culture HPV18/E6E7-immortalized hepatocytes exhibited hepatocyte functions and marker expression and were more prone to HCV infection than SV40 T-immortalized hepatocytes. The susceptibility of HPV18/E6E7-immortalized hepatocytes to HCV infection was further improved, in particular, by impairing signaling through interferon regulatory factor-7. CONCLUSIONS: HPV18/E6E7-immortalized hepatocytes are useful for the analysis of HCV infection, anti-HCV innate immune response, and screening of antiviral agents with a variety of HCV strains.

Antigens, CD↗
PubMed2006

Relationship between oxidative stress and antioxidant systems in the liver of patients with Wilson disease: hepatic manifestation in Wilson disease as a consequence of augmented oxidative stress.

The role of oxidative stress in the pathogenesis of liver disease in Wilson disease (WD), a genetic disorder characterized by excess hepatic deposition of copper that generates free radicals, remains unclear. This study investigates oxidative stress on the liver and hepatic antioxidant responses in WD using liver specimens from affected patients showing mild liver damage (group I, n = 3), moderate or greater liver damage (group II, n = 5), and fulminant hepatic failure (group III, n = 5) and from asymptomatic carriers (n = 2). Decreased ratios of reduced glutathione (GSH) to oxidized glutathione (GSSG) and increased thiobarbituric acid reactive substance (TBARS), a lipid peroxidation product, were found in every affected patient, especially in group II and III patients. Activities and protein expressions of Mn-dependent superoxide dismutase (Mn-SOD), CuZn-dependent superoxide dismutase (CuZn-SOD), and catalase were decreased in all patients, especially in group III patients. Glutathione peroxidase (GPx) activity was decreased only in group III patients. Asymptomatic carriers without any clinical manifestations showed normal TBARS level and GSH/GSSG ratio with increases in both GSH and GSSG levels. Their CuZn-SOD, Mn-SOD, and catalase activities were increased. These results suggest that excessive copper-derived oxidants contribute to development and progression of liver disease in WD.

Adult↗
PubMed2006

In vivo luminescent imaging of cyclosporin A-mediated cancer progression in rats.

BACKGROUND: Immunosuppressed individuals undergoing organ transplantation are at increased risk of recurrences of initial cancers, although how immunosuppressive therapy increases early cancer metastasis remains unclear. METHODS: The metastatic fate of luciferase-expressing rat metastatic colon cancer cells (luc-RCN-H4) injected intravenously into the liver of syngeneic and allogeneic rats was examined in the presence of the immunosuppressant cyclosporin A (CsA) by in vivo luminescent technique. With respect to potential tumor-progressing factors, contribution of chemokine receptors and transforming growth factor (TGF)-beta1 to early metastasis was evaluated using their specific signaling inhibitors. RESULTS: F344 rats injected in the liver with luc-RCN-H4 cells did not always exhibit the formation of tumors and showed a dormant state as long as 60 days after inoculation without CsA. However, CsA released early luc-RCN-H4 cells from dormancy within 2 weeks at nearly 100% in liver and preferentially promoted metastasis to the lymph nodes (approximately 40%). A similar dissemination occurred even in minor histocompatibility complex-disparate hosts. As a tumor-progressing factor, RCN-H4 cells aberrantly expressed chemokine receptors CXCR4 and CCR7. The chemokine receptor (CXC) R4-specific antagonist AMD3100 decreased early metastasis of luc-RCN-H4 cells in rats with ischemic liver conditions (P<0.05), but CsA treatment did not enhance early adhesion. Use of CsA was able to facilitate TGF-beta1 expression and the subsequent TGF-beta-mediated random migration was blocked by the use of the specific signaling inhibitor SB431542 in vitro. CONCLUSIONS: Whereas the chemokine receptor expression by cancer cells is implicated with early organotropic dissemination even under CsA-mediated immune suppression, rather, CsA enhances the late-phase progression after tumor adhesion through TGF-beta1 expression.

Adenocarcinoma↗
PubMed2006

Impact of lymph node micrometastasis in hilar bile duct carcinoma patients.

AIM: To immunohistochemically examine micrometastasis and VEGF-C expression in hilar bile duct carcinoma (HBDC) and to evaluate the clinical significance of the results. METHODS: A total of 361 regional lymph nodes from 25 patients with node-negative HBDC were immunostained with an antibody against cytokeratins 8 and 18 (CAM 5.2), and immunohistochemical staining of VEGF-C was performed in 34 primary resected tumors. RESULTS: Lymph node micrometastasis was detected in 6 (24%) of the 25 patients and 10 (2.8%) of the 361 lymph nodes. Patients with micrometastasis showed significantly poorer survival rates than those without (P = 0.025). VEGF-C expression was positive in 17 (50%) of 34 HBDC, and significantly correlated with lymph node metastasis (P = 0.042) and microscopic venous invasion (P = 0.035). CONCLUSIONS: It is suggested that immunohistochemically detected lymph node micrometastasis has an impact on the outcome of HBDC. VEGF-C expression is highly correlated with lymph node metastasis in HBDC and might therefore be a useful predictor.

Adult↗
PubMed2006

Primary liposarcoma of gallbladder diagnosed by preoperative imagings: a case report and review of literature.

A 49-year-old Japanese woman was referred to our department because of high fever and a huge abdominal mass. Computed tomography (CT) and magnetic resonance (MR) imagings revealed a tumor, about 30 cm in diameter,occupied the right hepatic lobe and the peritoneal cavity. Abdominal angiography showed that the tumor was fed mainly by the cystic artery. We preoperatively diagnosed angiosarcoma of the gallbladder and performed tumor resection with cholecystectomy because the tumor was almost capsulated,however the posterior wall of the gallbladder attached to the tumor firmly. Histologically,the tumor was composed of spindle cells including lipoblasts with cellular pleomorphism, which were also detected in the muscular layer of the gallbladder. We finally diagnosed pleomorphic liposarcoma of the gallbladder. At 10 mo and 29 mo after the first operation, she underwent two more operations because of recurrence. Now she has a good quality of life 3 yr and 6 mo after the first operation.

Angiography↗
PubMed2006

Optimal portal venous circulation for liver graft function after living-donor liver transplantation.

BACKGROUND: Previous studies have shown poor outcome after living-donor liver transplantation (LDLT) as a result of excessive portal venous pressure (PVP), excessive portal venous flow (PVF), or inadequate PVF. We investigated optimal portal venous circulation for liver graft function after LDLT in adult recipients retrospectively. METHODS: Between June 2003 and November 2004, 28 adult patients underwent LDLT in our institution. We modulated PVP under 20 mmHg in these 28 cases by performing a splenectomy (n=4) or splenorenal shunt (n=1). The PVF and PVP were measured at the end of the operation. Compliance was calculated by dividing PVF by PVP. RESULTS: PVF and compliance showed a significant inverse correlation with peak billirubin levels after LDLT (r = -0.63: r=-0.60, P<0.01), and with peak international normalized ratio after LDLT (r=-0.41: r=-0.51, P<0.05). Compliance was higher in right-lobe graft with middle hepatic vein cases (148+/-27 ml/min/mmHg), and lower in left-lobe graft cases (119+/-50 ml/min/mmHg). CONCLUSIONS: Liver graft function was better when PVF and graft compliance were higher and PVP was maintained under 20 mmHg.

Adult↗
PubMed2006

K(ICG) value, a reliable real-time estimator of graft function, accurately predicts outcomes in adult living-donor liver transplantation.

Reliable monitoring enabling evaluation of graft function is crucial after living-donor liver transplantation (LDLT). A method to identify poor graft function at an early postoperative period would allow opportune intensive clinical management to bring about further improvements in LDLT outcomes. This study assessed the reliability of the indocyanine green (ICG) elimination rate constant (K(ICG)) value as an estimator of graft function and determined the actual temporal changes of K(ICG) after LDLT. K(ICG) values were measured using a noninvasive method in 30 adult recipients up to 28 days after LDLT. The receptor index (LHL15) based on liver scintigraphy, and graft parenchymal damage score based on histopathological findings were evaluated after LDLT and correlated well with simultaneous K(ICG). Thus, K(ICG) measured by noninvasive method was confirmed as accurately evaluating graft function. Changes of K(ICG) after LDLT in recipients with good graft function were maintained, after some falls in the early periods, and had a significant difference compared with those for recipients without good graft function; moreover, there were already significant differences in K(ICG) 24 hours after LDLT. Mean transit time reflecting systemic hemodynamics revealed that recipients without good outcomes fell into an unstable systemic hemodynamic state, and effective hepatic blood flow has a large influence on liver regeneration after LDLT. In conclusion, we suggested that K(ICG) values can predict clinical outcomes at the early postoperative period after LDLT by sharply reflecting the influence of systemic dynamics on splanchnic circulation.

Adult↗
PubMed2006

The role of living-donor liver transplantation in surgical treatment for hepatocellular carcinoma.

BACKGROUND/PURPOSE: The role of living-donor liver transplantation (LDLT) in the surgical treatment of patients with hepatocellular carcinoma (HCC) has not been established as yet. METHODS: Preliminary experience gained from 24 patients who underwent LDLT for HCC between March 2002 and November 2004, and the results of the 131 patients who underwent hepatic resection (HR) for HCC between January 1990 and December 2003 were retrospectively analyzed. The exclusion criteria for LDLT for HCC included extrahepatic metastasis and major vascular invasion. RESULTS: (1) LDLT: the median age of the patients was 57 years and the Child-Pugh grades (A/B/C) of the patients were 6, 12, and 6, respectively. The tumor size was 3 cm or less in 15 patients, multinodular tumors were present in 23 patients, and 11 patients (45.8%) met the Milan Criteria. The overall 2-year survival rate was 72.3%, without a significant difference as to whether or not patients met the Milan criteria. (2) HR: on multivariate analysis, the Child-Pugh grade, the presence of cirrhosis, and the number of tumor nodules were considered as independent risk factors for unfavorable survival (P < 0.05). The 84 patients who met the Milan criteria and were Child-Pugh grade A had a 5-year survival rate of 71.3%; this was significantly better than those of the other patients (P < 0.005). Among the 57 patients with intrahepatic recurrence, 18 patients who were Child-Pugh grade A, met the Milan criteria, and were treated by re-resection or ablation therapy achieved a significantly better 5-year survival rate, of 73.1%, as compared to 19.7% in the other 39 patients (P < 0.0045). CONCLUSIONS: HR could be a first-line treatment with a favorable prognosis for patients who have resectable HCC, preserved liver function, and who meet the Milan criteria. Salvage LDLT could be employed in patients with recurrent tumors that cannot be controlled by conventional treatment or in patients in whom liver function has deteriorated to Child-Pugh grade B or C.

Adult↗
PubMed2006

Population pharmacokinetic and pharmacogenomic analysis of tacrolimus in pediatric living-donor liver transplant recipients.

OBJECTIVE: Our objective was to investigate the population pharmacokinetics of tacrolimus in pediatric living-donor liver transplant recipients and examine the effects of the multidrug resistance 1 (MDR1) gene and the cytochrome P450 (CYP) genes CYP3A4 and CYP3A5 on the oral clearance of tacrolimus. METHODS: Data were collected retrospectively from 130 de novo pediatric liver transplant recipients treated with tacrolimus during the first 50 postoperative days. Pharmacogenomic data including both the CYP3A5*3 polymorphism and messenger ribonucleic acid (mRNA) expression levels of MDR1, CYP3A4, and CYP3A5 in the native intestine and the graft liver at transplantation were obtained from 65 of the recipients. Population pharmacokinetic analysis was performed with the nonlinear mixed-effects modeling program NONMEM to estimate population mean parameters of apparent clearance (CL/F) and apparent volume of distribution (V/F). RESULTS: Both CL/F and V/F were allometrically related to body weight, and CL/F decreased when the AST value was elevated. CL/F increased linearly in the immediate postoperative period but did not change with time after postoperative day 21. The intestinal MDR1 mRNA level significantly influenced the initial CL/F (P < .005). Furthermore, the increase in CL/F over time was 2 times higher (95% confidence interval, 1.19-2.81 times; P < .005) in recipients of a CYP3A5*1-carrying graft liver than in patients with the hepatic CYP3A5*3/*3 genotype. The Bayesian prediction for tacrolimus concentrations was not significantly biased on any postoperative day, and the mean absolute prediction error was lower than 3 ng/mL after the first 2 weeks of transplantation. CONCLUSIONS: The enterocyte MDR1 mRNA level and the CYP3A5*1 allele in the graft liver contribute differently to the interindividual variability in the oral clearance of tacrolimus after living-donor liver transplantation.

Adolescent↗
PubMed2006

Current role of liver transplantation for methylmalonic acidemia: a review of the literature.

To evaluate the current role of liver transplantation (LT) for methylmalonic acidemia (MMA), we reviewed the literature on outcomes of this treatment, and describe three of our own cases of living-donor liver transplantation (LDLT). The total number of LT cases identified was 18. Transplantation mode was deceased donor LT in 12, including five combined liver-kidney transplantations (CLKT) from deceased donors, and LDLT in six. Three hospital mortalities were noted, because of metabolic decompensation, sepsis and aspergillosis. Although mean postoperative serum MMA level decreased to 13.8% +/- 9.2% (range 1.25-26.1%) of preoperative levels, four patients (22.2%) had renal insufficiency after isolated LT and three (16.7%) had postoperative neurological disability. Continuing metabolic damage to the kidney and brain may occur even after successful LT. Further evaluation is required to determine the long-term suitability of this treatment modality.

Adolescent↗
PubMed2006

[Surgical treatment of carcinoma of the pancreas].

Invasive ductal carcinoma of the pancreas (pancreatic cancer) is mainly treated by operative resection, radio-chemotherapy, or chemotherapy. The survival rate of the patients with each treatment is not good when compared with that in other cancers. Meanwhile, it is still true that surgical resection remains the only method offering pancreatic cancer patients long-term survival or cure. The indications for surgical resection should be considered based on whether margin-free resection can be achieved in individual patients. In addition, the volume of pancreatic cancer patients treated at the institution and the surgeon's personal experience may greatly affect the decision. A recent randomized clinical trial from Japan revealed that surgical resection has a survival advantage over chemo-radiation therapy for locally advanced pancreatic cancer, which is defined as stage IVa in the fourth Japanese edition of the Classification of Pancreatic Carcinoma. Moreover, guidelines for clinical practice for pancreatic cancer by the Japan Pancreas Society have been issued very recently. In addition, the surgical indications should be reevaluated in combination with the adjuvant or neoadjuvant chemotherapy in future.

Carcinoma, Ductal↗
PubMed2005

Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.

Rejection remains a major barrier to successful bowel transplantation, in spite of improved immunosuppressive techniques. Therefore, new, more effective, immunosuppressants, with fewer side effects, are needed. Biodegradable microspheres containing tacrolimus (FK506) were used in an experimental porcine small bowel transplantation. Twenty pigs underwent transplantation and were divided into four groups according to the immunosuppressive regimen. Group A (n = 5): no immunosuppression; group B (n = 6): 0.2 mg/kg per day of FK506; group C (n = 3): 1.0 mg/kg per day of FK506; group D (n = 6): 0.04 mg/kg per day of FK506 contained in biodegradable microspheres. Rejection was diagnosed macroscopically by endoscopic examination and histologically by biopsy specimen analysis. The mean survival time and standard deviation (SD) were 8.8+/-3.5, 11.0+/-1.4, 9.7+/-2.5 and 28.6+/-22.5 days for groups A, B, C, and D, respectively, with a statistically significant difference found between group D, on the one hand, and groups A, B and C, on the other. The mean trough blood concentration of FK506 was 10.5+/-2.2, 27.9+/-6.0 and 10.5+/-3.5 ng/ml in groups B, C and D, respectively. In groups A and B, all pigs died of rejection, without infection. In group C, all died of infection, without rejection. In contrast, none of the pigs in group D developed rejection or infection. Our results clearly show that the drug delivery system using biodegradable microspheres that contain FK506 is effective for controlling rejection with fewer side effects in the porcine small bowel transplantation.

Animals↗
PubMed2005

Hepatitis B virus infection in lymphatic tissues in inactive hepatitis B carriers.

BACKGROUND/AIMS: Hepatitis B virus (HBV) infection in extrahepatic tissues is controversial. To clarify whether episomal HBV can infect nonhepatic tissues, we investigated the molecular forms of HBV in the lymphatic cells of inactive HBV carriers who lacked viremia, thus avoiding contamination with HBV genomes originating from the viral particles present in the serum. METHODS: We assessed HBV genome, replicative forms, and viral integrants in the liver, serum, peripheral blood mononuclear cells (PBMC), and lymph nodes of 21 inactive HBV carriers who tested positive for antibodies against the HBV core antigen (anti-HBc). RESULTS: Of the 21 anti-HBc positive individuals, HBV-DNA was detected in liver samples of 15 (71.4%), in the lymph nodes of 11 (52.4%), and in PBMC of three (14.3%). However, none of the detected HBV genomes from lymphatic tissues included the replicative forms of HBV. In one case, integrated HBV was present in the lymphatic tissues and the host-viral junction was present in the intronic sequences of chromosome 17. CONCLUSIONS: These data suggest that human lymphatic tissues cannot support viral replication in anti-HBc positive inactive HBV carriers, while retaining the viral genome as an integrated form.

Adult↗
PubMed2005

Noninvasive ventilation for pediatric patients including those under 1-year-old undergoing liver transplantation.

Pulmonary complications are an important cause of the mortality associated with liver transplantation. The efficacy of noninvasive ventilation (NIV) in pediatric patients following transplantation is unknown. The purpose of this retrospective study is to investigate the effects of NIV for pediatric patients undergoing liver transplantation. Of 102 pediatric patients who underwent liver transplantation, 15 patients (aged 73 months; range 2.5-179) were supported by NIV because of atelectasis, hypercapnia, hypoxemia, pneumonia, massive effusion, or postextubation ventilatory support. Of 15 patients, 5 were under the age of 1 year (range 2.5-12 months). Of the 15 patients, 7 had required multiple intubations before NIV treatment because of pulmonary complications. NIV treatment was administered to 6 patients because of hypercapnia. Partial pressure of arterial carbon dioxide (PaCO(2)) levels improved from 56.9 (95% confidence interval [CI]: 48.4-65.4) to 41.5 (95% CI: 36.8-46.2) mmHg (P = .028) within 2 days. NIV treatment was very effective for patients with atelectasis with and without other pulmonary complications. Mean inspiratory positive pressure (IPAP) was 7.2 (95% CI: 6.0-8.3) cm H(2)O and expiratory positive pressure (EPAP) was 3.5 (95% CI: 3.2-3.9) cm of H(2)O. Mean duration of NIV was 18.5 (95% CI: 8.6-28.4) days. IPAP and EPAP levels were closely and significantly correlated with height (IPAP: r = .65, P = .016; EPAP: r = .77, P = .004). A total of 13 patients recovered and 2 patients died. However, no patient died of respiratory complications. In conclusion, NIV is effective in pediatric patients undergoing liver transplantation with subsequent pulmonary complications. The IPAP and EPAP levels may be predicted by the height of the patient.

Adolescent↗