Effects of Helicobacter pylori eradication therapy on gastric emptying measured using the 13C-octanoic acid breath test and the acetaminophen method.

Background: The relationship between Helicobacter pylori eradication and gastric emptying has been reported; however, the effect of eradication therapy on gastric emptying is still unclear. This study evaluated the relationship between three gastric emptying techniques, the scintigraphic technique, the 13C-octanoic acid breath test, and the acetaminophen method, measured simultaneously, and the effect of H. pylori eradication therapy on gastric emptying and abdominal symptoms in patients with functional dyspepsia who were H.

Efficacy and safety of growth hormone (GH) in the treatment of adult Japanese patients with GH deficiency: a randomised, placebo-controlled study.

Objective: The aim of this study was to assess the effect of growth hormone (GH) replacement therapy on lean body mass (LBM) and other variables including body fat mass, serum lipids and quality of life measures in GH-deficient Japanese adults.

Design: This was a multicentre, double-blind, placebo-controlled, parallel group study. Following initial screening, patients were randomly assigned to GH treatment (n=37) or placebo (n=36).

MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.

Adipocytes secrete a variety of bioactive molecules that affect the insulin sensitivity of other tissues. We now show that the abundance of monocyte chemoattractant protein-1 (MCP-1) mRNA in adipose tissue and the plasma concentration of MCP-1 were increased both in genetically obese diabetic (db/db) mice and in WT mice with obesity induced by a high-fat diet. Mice engineered to express an MCP-1 transgene in adipose tissue under the control of the aP2 gene promoter exhibited insulin resistance, macrophage infiltration into adipose tissue, and increased hepatic triglyceride content.

Expression of thioredoxin and thioredoxin-binding protein-2 in the liver of patients with chronic hepatitis C as a predictor of response to interferon therapy.

Oxidative stress contributes to the pathogenesis of various hepatic injuries. Thioredoxin (TRX) is an indicator of oxidative stress, reported to be increased in the serum of patients with chronic hepatitis C with the progression of fibrosis. The aim of this study was to evaluate the clinical significance of the expression of TRX and thioredoxin-binding protein-2 (TBP-2), which is a negative regulator of TRX function, in the liver of patients with chronic hepatitis C and the relationship of this to the efficacy of interferon (IFN) treatment.

Diagnostic significance of gently sloping depression and irregular margin in superficial elevated colorectal tumors.

Introduction: Recently, superficial elevated colorectal tumors have been increasingly diagnosed after improvements in endoscopic instruments and techniques. However, their biological characteristics remain obscure and it is difficult to predict malignant potential. The aim of this study is to clarify the characteristics of superficial elevated tumors in endoscopic examination for the evaluation of malignant potential.

Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass.

The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes, possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol (PI) 3-kinase. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase.

Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic, insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice.

We have tested the hypothesis that sustained leptin action in the hypothalamus alone can engender and maintain euglycemia in wild type mice and in two monogenic diabetic models, the insulin-deficient nonobese Akita mice and the hyperinsulinemic leptin-deficient obese, ob/ob mice. A single intracerebroventricular injection of recombinant adeno-associated virus vector encoding leptin (rAAV-lep) enhanced leptin transgene expression in the hypothalamus without any evidence of leptin leakage to the peripheral circulation, and promptly reinstated euglycemia that persisted along with severe insulinopenia in all three genotypes through the 7-week period of observation. A comparative evaluation of known etiologic factors of hyperglycemia showed that this long-term benefit on glucose homeostasis was not due to diminished energy consumption, weight and adiposity, but was conferred by at least two mechanisms operating simultaneously, enhanced glucose metabolism to meet the demand for the rAAV-lep induced increased non-shivering thermogenesis mediated by brown adipose tissue and insulin hypersensitivity.

A novel mutation in the von Hippel-Lindau tumor suppressor gene identified in a Japanese family with pheochromocytoma and hepatic hemangioma.

Von Hippel-Lindau (VHL) syndrome is a neoplastic syndrome caused by a mutation in the VHL gene. There is a discrepancy between the phenotypes of human VHL syndrome and VHL gene-disrupted mouse models. A heterozygous VHL gene-disrupted model (vhl +/-) developed hepatic vascular lesions; in contrast, hepatic hemangioma is a rare manifestation of human VHL syndrome.

Role of hepatic STAT3 in brain-insulin action on hepatic glucose production.

STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver.

The threshold of bone mineral density for vertebral fracture in female patients with glucocorticoid-induced osteoporosis.

Glucocorticoid (GC)-induced osteoporosis (GIO) is a serious problem for patients taking GC therapy. GC increases risk for fracture. However, there are controversies regarding the threshold of bone mineral density (BMD) in patients with GIO.

Stat3 activation is required for cell proliferation and tumorigenesis but not for cell viability in cutaneous squamous cell carcinoma cell lines.

Signal transducer and activator of transcription 3 (Stat3), a cytoplasmic transcription factor, is constitutively activated in various types of cancer. Previous investigations have demonstrated that Stat3 plays important roles in cell growth, survival, differentiation, and transformation. The constitutive activation of Stat3 in human malignancies is an important key to maintain the characteristics of a malignant tumor, such as the rate of proliferation and/or immortalization, and inhibition of Stat3 function could be a potent therapeutic approach.

HLA-DQB1 locus and gastric cancer in Helicobacter pylori infection.

Background And Aims: It has been suggested that the incidence of digestive diseases associated with Helicobacter pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. The authors have previously reported that human leukocyte antigen (HLA)-DQB1*0401 plays an important role in the development of atrophic gastritis in H.

Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells.

PTH, via the PTH/PTH-related protein receptor type 1 that couples to both protein kinase A (PKA) and protein kinase C (PKC) pathways, and the canonical Wnt-beta-catenin signaling pathway play important roles in bone formation. In the present study we have examined the interaction between the PTH and Wnt signaling pathways in mouse osteoblastic MC3T3-E1 cells. PTH dose- and time-dependently increased the concentrations of beta-catenin.

Cellular aspects of photocarcinogenesis.

Many aspects are involved in photocarcinogenesis. Historically, genetic change caused by UV-B-induced pyrimidine photoproducts have been paid much attention. Indeed they are very important factors.

MDR1 C3435T polymorphism is predictive of later onset of ulcerative colitis in Japanese.

Recently, a silent polymorphism of C3435T of the MDR1 gene, encoding the multidrug resistant transporter MDR1/P-glycoprotein, has been found to be associated with susceptibility to ulcerative colitis (UC), but this remains controversial. This study was conducted to find a possible reason for the discrepancies, and it was suggested that the age of onset was important for the association, namely, C3435T was predictive of susceptibility to later onset UC, but not for early onset UC. Linkage disequilibrium of C3435T with T-129C, C1236T and G2677A, T was suggested to be altered in UC, but the analysis of their haplotype provided no advantage in terms of prediction over that with only C3435T.

Engagement of CD47 inhibits the contact hypersensitivity response via the suppression of motility and B7 expression by Langerhans cells.

CD47 is a membrane-associated glycoprotein that suppresses the function of immune cells. We previously reported that Langerhans cells (LCs) express Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for CD47, which plays an important role in the regulation of their motility. In this study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1-Fc fusion protein in vivo diminishes the development of the contact hypersensitivity response.

Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) (formerly known as hepatic veno-occlusive disease (VOD)) is a life-threatening complication subsequent to hematopoietic stem cell transplantation. However, no completely satisfactory strategies for the treatment of SOS have been established yet. Defibrotide is a single-stranded polydeoxyribonucleotide with anti-thrombotic, anti-ischemic, anti-inflammatory and thrombolytic properties, but without systemic anticoagulant effects, and some encouraging results have been reported in western countries.

Body composition and vertebral fracture risk in female patients treated with glucocorticoid.

Introduction: Glucocorticoid (GC) causes bone loss and an increase in bone fragility. However, fracture risk was found to be only partly explained by bone mineral density in GC-treated patients (GC patients). Although GC causes a change in the distribution of fat in the body, the relationship between body composition and fracture risk in GC patients remains unknown.

Gene expression profile in the heart of spontaneous dwarf rat: in vivo effects of growth hormone.

Excess and deficit of growth hormone (GH) both affect cardiac architecture as well as its function. To date, experimental and clinical studies have reported that GH has an inotropic effect on animal and human heart, however, it remains controversial whether GH is applicable to the treatment for the patients with chronic heart failure. Also, the mechanism by which GH exerts these biological effects on the heart is not well understood.

Effects of age, grip strength and smoking on forearm volumetric bone mineral density and bone geometry by peripheral quantitative computed tomography: comparisons between female and male.

Peripheral quantitative computed tomography (pQCT) is useful to measure volumetric bone mineral density (vBMD) distinguishing trabecular from cortical bones as well as quantity of bone geometry. In the present study, we examined the effects of age, grip strength and smoking on vBMD, bone geometry and bone strength index (polar strength strain index (SSIp)), and then compared with the differences between female and male by employing pQCT in Japanese 252 female and 230 male subjects. Age was negatively correlated with vBMD, cortical area (Ct.

Association of the -112A>C polymorphism of the uncoupling protein 1 gene with insulin resistance in Japanese individuals with type 2 diabetes.

The -112A>C polymorphism (rs10011540) of the gene for uncoupling protein 1 (UCP1) has been associated with type 2 diabetes mellitus in Japanese individuals. The aim of the present study was to investigate the effects of this polymorphism, as well as the well-known -3826A>G polymorphism (rs1800592), on clinical characteristics of type 2 diabetes. We determined the genotypes of the two polymorphisms in 93 Japanese patients with type 2 diabetes.

N-retinoyl-D-glucosamine, a new retinoic acid agonist, mediates topical retinoid efficacy with no irritation on photoaged skin.

Background: Chronic ultraviolet (UV) radiation from sunlight induces wrinkle formation. Retinoic acid (RA) can markedly improve wrinkles, although RA does have some side-effects, such as skin irritation. As the efficacy and cytotoxicity of RA has been traced to its free carboxylic acid, we synthesized a new molecule, N-retinoyl-D-glucosamine (GRA), in which a glucosamine has been attached to the polar end group of all-trans retinoic acid.