Epidemiology of Hepatitis B Virus in Japan, especially in Nagasaki

We have studied about epidemiology of hepatitis B virus (HBV) in Japan, especially in Nagasaki these ten years. Chronological changes of HBV infection were observed and are reported here

Iteration Method to Derive Exact Rotation Curves from Position-Velocity Diagrams of Spiral Galaxies

We present an iteration method to derive exact rotation curves (RC) of spiral galaxies from observed position-velocity diagrams (PVD), which comprises the following procedure. An initial rotation curve, RC0, is adopted from an observed PV diagram (PV0), obtained by any simple method such as the peak-intensity method. Using this rotation curve and an observed radial distribution of intensity (emissivity), we construct a simulated PV diagram (PV1). The difference between a rotation curve obtained from this PV1 and the original RC (e.g., difference between peak-intensity velocities) is used to correct the initial RC to obtain a corrected rotation curve, RC1. This RC1 is used to calculated another PVD (PV2) using the observed intensity distribution, and to obtain the second iterated RC (RC2). This iteration is repeated until PV$i$ converges to PV0, so that the differences between PV$i$ and PV0 becomes minimum. Finally RC$i$ is adopted as the most reliable rotation curve. We apply this method to some observed PVDs of nearby galaxies, and show that the iteration successfully converges to give reliable rotation curves. We show that the method is powerful to detect central massive objects.Comment: To appear in ApJ.Letters, 5 pages Latex with 4 figure

Disposition Kinetics of Taxanes in Peritoneal Dissemination

Treatment of cancers in the abdominal cavity, such as peritoneal dissemination, is difficult, but in principle intraperitoneal administration of anticancer drugs is expected to be preferable to systemic administration. Taxane anticancer drugs are used to treat gastric cancer patients with peritoneal dissemination. They are administered as micellar preparations, Taxol and Taxotere, which consist of paclitaxel in Cremophor EL (crEL) and docetaxel in Polysorbate-80 (PS-80), respectively. In this paper we review the disposition kinetics of taxane anticancer drugs after intraperitoneal administration in peritoneal dissemination patients and animal models and also discuss the effect of the surfactant vehicle on the behavior of taxanes

Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma

Background: We previously reported the overexpression of lipocalin2 (LCN2), a 25 kDa secretory protein involved in iron-transportation, in endometrial carcinoma and its possible contribution to endometrial carcinogenesis. Recently, a specific receptor for LCN2, solute carrier family 22 member 17 (SLC22A17), was identified. The present study was undertaken to investigate the expression of SLC22A17 in endometrial carcinoma. Methods: The expression of the SLC22A17 and LCN2 proteins was examined immunohistochemically using 69 cases of endometrial carcinoma and adjacent normal endometrial tissues. Immunoreactivity was evaluated according to the percentage of positive cells and described as a positivity index (PI, full score 100). Results: The expression of SLC22A17 was negligible in normal endometria, but positive staining for SLC22A17 (PI 1) was observed in 35 cases of endometrial carcinoma. The PI for SLC22A17 was significantly higher in cases with histological grade 3 (P < 0.0005), advanced FIGO stage (P=0.002), deep myometrial invasion (P=0.029), positive lymph-vascular space invasion (P = 0.029), positive intraperitoneal cytology (P = 0.020) and adnexal metastasis (P= 0.029). The expression of SLC22A17 and LCN2 was positively correlated with a significant difference (P= 0.002), and the patients who overexpressed both SLC22A17 and LCN2 showed poorer survival than those without the expression of SLC22A17 or LCN2 (P= 0.002). Moreover, the overexpression of both SLC22A17 and LCN2 was indicated to be an independent prognostic factor by multivariable analysis. Conclusions: These results suggested that SLC22A17, in cooperation with LCN2, to be involved in the acquisition of aggressive behavior among endometrial carcinoma cells.ArticleEXPERIMENTAL AND MOLECULAR PATHOLOGY. 91(2):563-568 (2011)journal articl

Immunohistochemical expression of keratan sulfate: a possible diagnostic marker for carcinomas of the female genital tract

Aims The authors previously reported the expression of keratan sulfate (KS), a glycosaminoglycan, in the epithelium of normal and neoplastic endometria. The aim of this study was to evaluate its potential use as a diagnostic marker, and the expression of KS was investigated in other human epithelial tissues. Methods Expression was examined immunohistochemically using 102 samples of normal epithelia and 110 samples of carcinomas from the female genital tract (FGT; cervix, endometrium, ovary, fallopian tube), digestive organs (gastrointestinal tract, pancreas, liver), urinary tract, lung, mammary gland, thyroid and mesothelium. Results In normal tissues, KS was consistently detected in the FGT and ectopic endometrium (25/26), but was not found in the digestive organs (1/42) and urinary tract (0/6), and was only partly detected in the lung (7/10), mammary gland (3/9) and thyroid (4/4). In malignant tissues, KS was consistently observed in carcinomas of the endometrium, ovary and fallopian tube (29/32), and was partly detected in carcinomas of the lung, mammary gland, thyroid, pancreas and mesothelium, but was absent in carcinomas of the gastrointestinal tract (0/17), liver (0/5) and urinary tract (0/11). Among carcinomas of the FGT, digestive organs and urinary tract, KS positivity suggested the possibility of FGT carcinomas, with 79.5% (31/39) sensitivity and 92.9% (39/42) specificity. Conclusions KS is a potentially useful marker for the supportive diagnosis of the primary site of metastatic carcinomas or unknown primary carcinomas, especially in the abdominal cavity.ArticleJOURNAL OF CLINICAL PATHOLOGY. 64(12):1058-1063 (2011)journal articl

Laser-captured microdissection-microarray analysis of the genes involved in endometrial carcinogenesis: stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance

Endometrial carcinoma often arises from normal endometrial glandular cells via a precursor, atypical endometrial hyperplasia. However, the genetic changes involved in this carcinogenetic process are not fully understood. Differentially expressed genes were selected from glandular cells of normal proliferative-phase endometria, atypical endometrial hyperplasia, and endometrial carcinoma using laser-captured microdissection and microarray. The microarray analysis revealed a total of 51 genes to be up-regulated and 23 genes to be down-regulated in neoplastic endometrial epithelia. We focused on lipocalin2 (LCN2), which showed the largest magnitude of up-regulation. Immunostaining for lipocalin2 confirmed a stepwise increase in its expression in endometrial hyperplasia and carcinoma. In addition, elevated expression of lipocalin2 was correlated with the poor outcome of endometrial carcinoma patients. The subcellular distribution of lipocalin2 was both cytoplasmic and nuclear, despite reports that lipocalin2 is a secretory protein. Treatment of endometrial carcinoma cells with 5-azacytidine increased the expression of lipocalin2, suggesting the expression to be controlled by methylation of the promoter. The forced expression of lipocalin2 resulted in the enhanced cell proliferation and invasion in vitro. The expression of lipocalin2 increased with the endometrial carcinogenesis, and accumulation of the protein conferred biological aggressiveness to endometrial carcinoma cells. These results suggest lipocalin2 to be a novel target in the treatment of endometrial carcinoma.ArticleHUMAN PATHOLOGY. 42(9):1265-1274 (2011)journal articl

Tissue damage in the canine normal esophagus by photoactivation with talaporfin sodium (laserphyrin): a preclinical study.

[Background] Treatment failure at the primary site after chemoradiotherapy is a major problem in achieving a complete response. Photodynamic therapy (PDT) with porfimer sodium (Photofrin®) has some problems such as the requirement for shielding from light for several weeks and a high incidence of skin phototoxicity. PDT with talaporfin sodium (Laserphyrin) is less toxic and is expected to have a better effect compared with Photofrin PDT. However, Laserphyrin PDT is not approved for use in the esophagus. In this preclinical study, we investigated tissue damage of the canine normal esophagus caused by photoactivation with Laserphyrin. [Methodology/Principal Findings] Diode laser irradiation was performed at 60 min after administration. An area 5 cm oral to the esophagogastric junction was irradiated at 25 J/cm2, 50 J/cm2, and 100 J/cm2 using a three-step escalation. The irradiated areas were evaluated endoscopically on postirradiation days 1 and 7, and were subjected to histological examination after autopsy. The areas injured by photoactivation were 52 mm2, 498 mm2, and 831 mm2 after irradiation at 25 J/cm2, 50 J/cm2, and 100 J/cm2, respectively. Tissue injury was observed in the muscle layer or even deeper at any irradiation level and became more severe as the irradiation dose increased. At 100 J/cm2 both inflammatory changes and necrosis were seen histologically in extra-adventitial tissue. [Conclusions/Significance]To minimize injury of the normal esophagus by photoactivation with Laserphyrin, diode laser irradiation at 25 J/cm2 appears to be safe. For human application, it would be desirable to investigate the optimal laser dose starting from this level

Obesity-induced increase of CYP2E1 activity and its effect on disposition kinetics of chlorzoxazone in Zucker rats

金沢大学医学部附属病院薬剤部This study was designed to investigate the induction of CYP2E1 in obese Zucker rats and its effect on the disposition kinetics of chlorzoxazone (CZX). CZX 20 mg/kg was administered to three groups of rats: normal Zucker rats fed a normal diet (ND), normal Zucker rats fed a high-fat diet (HF), and genetically obese Zucker rats fed a normal diet (OB). The values of the area under the plasma concentration–time curve from 0 to 1 (AUC1) of CZX were in the order of ND > HF > OB rats. The AUC1 values of total 6-hydroxychlorzoxazone (6OHCZX-T), which is considered to be a CYP2E1 metabolic marker, were in the opposite order. The values of the AUC1 ratio (6OHCZX–T/CZX) in ND, HF and OB rats were approximately 0.2, 0.3 and 0.4, respectively. The CZX concentration in fat was much higher than the concentrations in plasma, liver and kidney in all groups. Induction of CYP2E1 protein was greater in both liver and fat of OB rats than in those of HF rats. Microsomal activity of CYP2E1 in liver and fat was also in the order of OB > HF > NMrats. These results suggest that CYP2E1 may be induced in liver and fat of obese patients, thereby potentially altering the disposition kinetics of not only CZX, but also other lipophilic drugs metabolized by CYP2E1.©2006 Published by Elsevier Inc