Induction of hepatocyte growth factor activator gene expression under hypoxia activates the hepatocyte growth factor/c-Met system via hypoxia inducible factor-1 in pancreatic cancer.

Hepatocyte growth facor activator (HGFA) is a serine protease that converts hepatocyte growth factor (HGF) into its active form. Our previous study demonstrated that tumor-stromal interaction under hypoxia augments the aggressive invasive features of pancreatic cancer line PK8 through activated HGF/c-Met signaling. The present study investigated whether or not hypoxia increases HGFA expression in PK8 cells and promotes the processing of HGF, and leads to c-Met activation.

Waist circumference correlates with hepatic fat accumulation in male Japanese patients with non-alcoholic fatty liver disease, but not in females.

Background And Aim: Abdominal obesity, a component of metabolic syndrome, is a major risk factor for non-alcoholic fatty liver disease (NAFLD). In recent worldwide definitions of metabolic syndrome, waist measurement has been proposed as a simple and useful estimate of abdominal obesity, taking into account gender differences in waist circumference. The present cross-sectional study investigated the correlation of hepatic fat accumulation and waist circumference in Japanese NAFLD patients to determine if there are gender differences in this relationship.

P120-catenin is a novel desmoglein 3 interacting partner: identification of the p120-catenin association site of desmoglein 3.

P120-catenin (p120ctn) is an armadillo-repeat protein that directly binds to the intracytoplasmic domains of classical cadherins. p120ctn binding promotes the stabilization of cadherin complexes on the plasma membrane and thus positively regulates the adhesive activity of cadherins. Using co-immunoprecipitation, we show here that p120ctn associates to desmogleins (Dsg) 1 and 3.

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus.

Our scientific knowledge of pemphigus has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in pemphigus. A major obstacle in comparing therapeutic outcomes between centers is the lack of generally accepted definitions and measurements for the clinical evaluation of patients with pemphigus.

Helicobacter pylori infection is an independent risk factor for Runx3 methylation in gastric cancer.

Runx3, a member of the human runt-related transcription factor family, is known as a possible tumor suppressor gene for gastric cancer. Runx 3 expression is frequently suppressed by the promoter hypermethylation in gastric cancer cell lines and tissues. However, the precise mechanism of the induction of Runx3 methylation, which is considered to be a critical step in gastric carcinogenesis, remains to be elucidated.

A perspective of pemphigus from bedside and laboratory-bench.

Pemphigus represents a distinct organ-specific acquired autoimmune disease characterized by intra-epidermal blistering, which is induced by autoantibodies against desmosomal cadherins, desmoglein 1 (Dsg1), and Dsg3. Pemphigus is currently divided into three distinct varieties, i.e.

Rupture of hepatic aneurysm complicating hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) for which hepatic arterial coil embolization was effective.

A 74-year-old woman was transferred to our hospital for further examinations because of abdominal fullness and abnormal levels of serum liver/biliary enzyme persisting for 3 weeks. She had anemia and dilatation of many capillary vessels in her fingers, palms, and tongue in addition to reporting frequent incidences of nasal bleeding in herself and her family. Abdominal ultrasonography detected a cystic lesion in the right hepatic lobe, connected to a dilated tortuous hepatic artery.

Aberrant methylation of p16 predicts candidates for 5-fluorouracil-based adjuvant therapy in gastric cancer patients.

Background: Aberrant methylation of some cancer-related genes has been reported to correlate with sensitivity to chemotherapeutic agents. The present study was designed to determine whether DNA methylation in six cancer-related genes affects recurrence of gastric cancer in patients who received 5-fluorouracil-based adjuvant chemotherapy.

Methods: The methylation status of six genes, MGMT, CHFR, hMLH1, p16INK4a, E-cadherin, and Runx3, was analyzed in 56 surgically resected gastric cancer tissue specimens by methylation-specific polymerase chain reaction.

Different roles of tumor marker monitoring after curative resections of gastric and colorectal cancers.

We previously demonstrated that false-positive findings for tumor markers are frequently observed, and that the sensitivity of marker monitoring for early detection of the recurrence is low after curative resection of gastric cancer. The aim of this study was to investigate whether such characters are specific to gastric cancer. Serum carcinoembryonic antigen and/or carbohydrate antigen 19-9 were periodically assessed in 258 patients who underwent curative gastrectomy for gastric cancer (n = 161) or curative resection for colorectal cancer (n = 97).

Nail discoloration occurring after 8 weeks of minocycline therapy.

Minocycline-induced nail pigmentation is an uncommon side-effect. It usually develops after years of the therapy, and coincides with other pigmented sites. We report a 73-year-old male and a 33-year-old female developing nail discoloration after 8 weeks of therapy of 100 mg minocycline twice daily.

Quantitative double-fluorescence immunohistochemistry (qDFIHC), a novel technology to assess protein expression: a pilot study analyzing 5-FU sensitive markers thymidylate synthase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferases in gastric cancer tissue specimens.

To evaluate the protein expression level in formalin-fixed cancer tissue specimens, the authors devised quantitative double-fluorescence immunohistochemistry (qDFIHC). Using this method, the 17 gastric cancer biopsy specimens, before undergoing S-1 based neoadjuvant chemotherapy, were assessed in order to determine the expression levels of the thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT) and dihydropyrimidine dehydrogenase (DPD) which determines S-1 efficacy. The ratios of OPRT/TS, OPRT/DPD and OPRT/(DPD+TS) which have been proposed to show a good correlation with S-1 efficacy, were calculated and compared with the clinical response.

Herpes gestationis in a mother and newborn: immunoclinical perspectives based on a weekly follow-up of the enzyme-linked immunosorbent assay index of a bullous pemphigoid antigen noncollagenous domain.

Background: Herpes gestationis (HG) is a rare, autoimmune, bullous disease that occurs during the second or third trimester and usually resolves over weeks or months after delivery. Neonates with HG are rare (estimated at 1 per 100,000 cases). Although anti-180-kDa bullous pemphigoid (BP180) autoantibody and transfer of this autoantibody are known as the cause, to our knowledge, no coordinated analysis of clinical symptoms and anti-BP180 antibody enzyme-linked immunosorbent assay titers has been reported in a mother and neonate with HG.

Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population.

Recent studies indicate that insulin resistance resulting from altered post-receptor signaling is associated with polycystic ovary syndrome (PCOS). We hypothesized that insulin receptor substrate-1 (IRS-1) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Lys121Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 380 healthy Japanese controls.

Inhibitory effect of trimidox on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages.

We examined the effect of trimidox (3,4,5-trihydroxybenzamidoxime) on the production of nitric oxide (NO) by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages. Trimidox (50 - 300 microM) concentration-dependently inhibited NO production by LPS (0.

Usefulness of transpapillary bile duct brushing cytology and forceps biopsy for improved diagnosis in patients with biliary strictures.

Background And Aim: Transpapillary bile duct brushing cytology and/or forceps biopsy was performed in the presence of an indwelling guidewire in patients with biliary stricture, and the treatment time, overall diagnosis rate, diagnosis rate of each disease, complications, and influences on subsequent biliary drainage were investigated.

Methods: After endoscopic retrograde cholangiography, brushing cytology was performed, followed by forceps biopsy. In patients with obstructive jaundice, endoscopic biliary drainage (EBD) was subsequently performed.

Community validation of the U.K. diagnostic criteria for atopic dermatitis in Japanese elementary schoolchildren.

Background: A simple list of diagnostic criteria for atopic dermatitis for use in epidemiological studies was developed by a U.K. working party.

The hypoxic environment in tumor-stromal cells accelerates pancreatic cancer progression via the activation of paracrine hepatocyte growth factor/c-Met signaling.

Background: Pancreatic cancer is one of the representative solid tumors, in which the hypoxic microenvironment plays a crucial role in malignant progression. We previously demonstrated that tumor-stromal interaction under hypoxia enhances the invasiveness of pancreatic cancer cells through hepatocyte growth factor (HGF)/c-Met signaling.

Methods: We investigated the immunohistochemical expression of hypoxia inducible factor-1alpha (HIF-1alpha) c-Met, and HGF in both cancer and stromal cells using 41 pancreatic cancer tissue specimens, and tried to identify any correlations with the clinical features and survival.

No activation of urokinase plasminogen activator by anti-desmoglein 3 monoclonal IgG antibodies in cultured human keratinocytes.

Background: Although pemphigus vulgaris (PV)-IgG has been shown to activate urokinase plasminogen activator (uPA) in cultured keratinocytes, activation of uPA is thought to have no primary role in PV-acantholysis, because PV-IgG is still pathogenic in uPA- and tissue-PA-knockout mice.

Objective: To determine if PV-IgG-induced uPA activation is due to specific antibody against Dsg3, we examined whether or not pathogenic monoclonal anti-Dsg3 antibody can activate uPA, because PV-IgG is thought to contain antibodies against unknown antigens besides Dsg3.

Methods: We stimulated cultured normal human and DJM-1 keratinocytes with monoclonal anti-Dsg3 IgG1 antibodies (pathogenic AK23, AK19 and nonpathogenic AK18, AK20), negative control monoclonal mouse IgG1 and positive control PV-IgG.

False-positive findings for tumor markers after curative gastrectomy for gastric cancer.

The objective of this study was to assess the frequency and characteristics of false-positive results for tumor markers after curative gastrectomy for gastric cancer. Carcinoembryonic antigen and/or carbohydrate antigen 19-9 were periodically assessed for 168 patients who underwent curative gastrectomy. Cancer recurrence was observed for 17 (10.

Preventive effect of trimidox on oxidative stress in U937 cell line.

Trimidox (3,4,5-trihydroxybenzamidoxime) is one of the most potent ribonucleotide reductase inhibitors, revealing an antitumor effect in several experimental studies. We have examined the effect of trimidox on the induction of cytotoxicity and apoptosis via oxidative stress by typical free radical inducers, hydrogen peroxide (H(2)O(2)), tert-butylhydroperoxide (tBuOOH) or ultraviolet (UV) irradiation in a human diffuse histiocytic lymphoma U937 cell line. Trimidox showed strong radical scavenging activity by the DPPH reduction assay.

CPT-11 (SN-38) chemotherapy may be selectively applicable to biliary tract cancer with low hMLH1 expression.

Biliary tract cancer is of highly malignancy with a poor 5-year survival. However, established chemotherapeutic regimens have not yet been established. Previously, we have reported that hMLH1, a mismatch repair (MMR) gene was frequently (57%) found to be lacking in surgically resected biliary tract carcinomas and the patients lacking the expression of hMLH1 revealed a poorer prognosis than those patients who possessed it.