HapMap scanning of novel human minor histocompatibility antigens.

Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation.

Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells.

Background/aims: Septins are ubiquitous and multifunctional scaffold proteins involved in cytoskeletal organization, exocytosis and other cellular processes. We disclose the quiescent hepatic stellate cells (HSCs)-specific expression of a septin subunit Sept4 in the liver, and explore the significance of the septin system in liver fibrosis.

Methods: We analyzed the expression of alpha-smooth muscle actin (alpha-SMA), collagens and other markers in primary cultured HSCs derived from wild-type and Sept4(-/-) mice.

Significance of Tei-index alterations induced by acute preload reduction with hemodialysis.

Aim: The load dependence of Tei-index, an index to estimate combined systolic and diastolic ventricular functions, remains controversial. Moreover, its significance in the setting of acute preload reduction including hemodialysis (HD) remains unknown. Therefore, we examined the significance of the Tei-index in HD patients.

A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells.

Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding soluble receptors.

Hepatitis C virus-induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity.

Unlabelled: Chronic hepatitis C is characterized by iron accumulation in the liver, and excessive iron is hepatotoxic. However, the mechanism by which hepatitis C virus (HCV) regulates iron metabolism is poorly understood. Hepcidin plays a pivotal role as a negative regulator of iron absorption.

[Efficacy and toxicity of transcatheter arterial chemoembolization with Cisplatin suspended in lipiodol for unresectable hepatocellular carcinoma].

In this study we evaluated the efficacy and toxicity of transcatheter arterial chemoembolization (TACE) with Cisplatin (CDDP)-Lipiodol (LIP) suspension in 24 patients with advanced hepatocellular carcinoma (HCC). Eligibility criteria were as follows; unresectable HCC, age <75 years, performance status (PS) 0-2, Child-Pugh A or B and adequate heart and renal function. When TACE was performed, the catheter was placed selectively in feeding arteries of the tumors, and CDDP-LIP suspension (20 mg/mL) was injected followed by gelatin sponge particles.

CHOP deficiency attenuates cholestasis-induced liver fibrosis by reduction of hepatocyte injury.

CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is a key component in endoplasmic reticulum (ER) stress-mediated apoptosis. The goal of the study was to investigate the role of CHOP in cholestatic liver injury. Acute liver injury and liver fibrosis were assessed in wild-type (WT) and CHOP-deficient mice following bile duct ligation (BDL).

Influence of coexisting cirrhosis on outcomes after partial hepatic resection for hepatocellular carcinoma fulfilling the Milan criteria: an analysis of 293 patients.

Background: For patients with liver cirrhosis and hepatocellular carcinoma (HCC) satisfying the Milan criteria (single tumor < or =5 cm or 2 or 3 tumors < or =3 cm), orthotopic liver transplantation (OLT) is an effective treatment. Nevertheless, it remains controversial whether OLT is the best treatment strategy for patients with resectable HCC.

Methods: This study included 293 HCC patients (both with and without cirrhosis) oncologically satisfying the Milan criteria who underwent primary and curative liver resection between 1990 and 2003.

Evaluation of genome-wide power of genetic association studies based on empirical data from the HapMap project.

With recent advances in high-throughput single nucleotide polymorphism (SNP) typing technologies, genome-wide association studies have become a realistic approach to identify the causative genes that are responsible for common diseases of complex genetic traits. In this strategy, a trade-off between the increased genome coverage and a chance of finding SNPs incidentally showing a large statistics becomes serious due to extreme multiple-hypothesis testing. We investigated the extent to which this trade-off limits the genome-wide power with this approach by simulating a large number of case-control panels based on the empirical data from the HapMap Project.

Prednisolone co-administered with losartan confers renoprotection in patients with IgA nephropathy.

Background: Treatment options for progressive IgA nephropathy are limited.

Methods: We performed a small, randomized controlled trial to evaluate the effects of prednisolone (PSL, 30 mg/dL, gradually tapered to 5 mg/dL over two years) plus 50 mg/day of losartan (LST, an angiotensin II receptor blocker) or PSL alone on IgA nephropathy. We separated 38 patients (age, 33 +/- 11 years; creatinine clearance, 103 +/- 31 mL/min; proteinuria, 1.

Systemic mediators induce fibrogenic effects in normal liver after partial bile duct ligation.

Background/aims: Collagen production by activated hepatic stellate cells (HSCs) is a key event in liver fibrosis, and a number of factors have been characterized that trigger HSC activation and collagen production. However, it remains unclear if these factors act locally at the site of injury or also affect HSCs distant to the site of injury.

Methods: A model of partial bile duct ligation (PBDL) in which fibrogenesis can be compared between the injured ligated lobe and the non-ligated lobe.

Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy.

Background: We are investigating whether aldosterone breakthrough negatively impacts on the antiproteinuric effects of angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB).

Methods: We examine the role of aldosterone breakthrough in 43 normotensive, proteinuric (0.7 +/- 0.

Pancreatic arteriovenous malformation with portal hypertension.

A 45-year-old man with recurrent episodes of hematemesis caused by extensive varices in the esophagus and stomach was admitted. He had a history of liver cirrhosis with hepatitis C virus infection. Computed tomography revealed a conglomeration of small strong nodular stains in the pancreatic head.

Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old.

Objective: By comparing cohorts in 2 exclusive time frames, the factors that affected the surgical outcomes of patients with hepatocellular carcinoma (HCC) are presented.

Summary Background Data: Reportedly, survival results of patients with HCC who underwent hepatectomy have improved in recent years. However, the major factors contributing to these favorable outcomes have not been fully explained.

High volume hydrodynamic injection of plasmid DNA via the hepatic artery results in a high level of gene expression in rat hepatocellular carcinoma induced by diethylnitrosamine.

Background: Hydrodynamic injection of naked plasmid DNA (pDNA) via the tail vein is a safe and effective method of gene transfer to the liver. However, successful gene transfer has yet to be shown for hepatocellular carcinoma (HCC); therefore, we investigated the feasibility and efficacy of hydrodynamic injection via the tail vein and hepatic artery in a diethylnitrosamine (DEN)-induced HCC model in rats.

Methods: HCC was induced in Sprague-Dawley rats by 100 ppm DEN in drinking water.

Renal circulatory effects of acetazolamide in patients with essential hypertension.

Background: Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension.

Prognostic index for patients with hepatocellular carcinoma combined with tumor thrombosis in the major portal vein.

Background: This study sought to analyze prognostic factors in patients with hepatocellular carcinoma and tumor thrombosis in the first branch or trunk of the portal vein, and to provide a prognostic index.

Study Design: We performed a retrospective cohort study of 78 consecutive patients with hepatocellular carcinoma and tumor thrombosis in the first branch or trunk of the portal vein who underwent liver resection. Multivariate analysis of survival used the Cox's proportional hazard model.

Complete response by a combination of 5-fluorouracil and interferon-alpha chemotherapy for lung metastasis of hepatocellular carcinoma after hepatic resection with portal and hepatic vein tumor thrombectomy.

A 75-year-old female was admitted to our hospital and diagnosed with hepatocellular carcinoma (HCC). Computed tomography (CT) revealed a liver tumor with tumor thrombi in the portal trunk and main hepatic vein, as well as small lung metastases. The patient had good liver function with no sign of hepatitis B or C infection.

Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy.

This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.

Blocking of PI3K/Akt pathway enhances apoptosis induced by SN-38, an active form of CPT-11, in human hepatoma cells.

Hepatocellular carcinoma (HCC) is a common malignancy and often resistant to chemotherapy. Many chemotherapy regimens have been tried to control advanced HCC, but have produced a low response rate and no clear impact. CPT-11, a derivative of camptothecin, works as type-I DNA topoisomerase inhibitor and showed a major objective response rate in patients with metastatic colorectal cancer.

Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy.

We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection.

Impact of novel histone deacetylase inhibitors, CHAP31 and FR901228 (FK228), on adenovirus-mediated transgene expression.

Background: Histone deacetylase inhibitors (HDIs) are known to enhance adenovirus (Ad)-mediated transgene expression. Recently, novel HDIs, including cyclic hydroxamic-acid-containing peptide 31 (CHAP31) and FR901228 (FK228), have been developed.

Methods: The effects of these two novel HDIs on Ad-transduced or endogenous gene expression were investigated.