bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraviolet‐A Irradiation to the Eye Modulates Intestinal Mucosal Functions and Properties of Mast Cells in the Mouse
Authors: Yamate Yurika , Hiramoto Keiichi , Kasahara Emiko , Jikumaru Mika , Sato Eisuke F. , Inoue June , Inoue Masayasu 
Published: September 2010

AbstractWe previously reported that topical irradiation of the eye by ultraviolet‐B (UVB) activated hypothalamo‐pituitary‐adrenal axis (HPA‐A) of the mouse to increase 3, 4‐dihydroxyphenylalanine (DOPA)‐positive melanocytes in the skin by an inducible nitric oxide synthase (iNOS)‐dependent mechanism. This work demonstrates that irradiation of the eye by ultraviolet‐A (UVA) specifically increased DOPA‐positive cells in the mucosa of the jejunum and colon of C57BL/6J mice by some HPA‐ and iNOS‐independent mechanism. UVA‐induced increase in DOPA‐positive cells in the intestine was inhibited by the administration of hexamethonium or prazosin plus propranolol, blockers for the sympathetic nervous system. UVA irradiation of the eye increased DOPA‐ and histidine decarboxylase (HDC)‐positive cells in the intestinal mucosa of both C57BL/6J and WBB6F1/J mice but not in the mutant strain W/Wv of the latter that lack mast cells. UVA irradiation of the eye suppressed the intestinal peristalsis of control, hypophysectomized or iNOS−/− C57BL/6J mice by the mechanism that was inhibited by hexamethonium or prazosin plus propranolol. These observations suggest that UVA irradiation of the eye stimulated the sympathetic nervous system to increase the mucosal DOPA‐ and HDC‐positive mast cells and suppressed the peristalsis of the small intestine of the mouse.
Effect of cytotoxic T lymphocyte‐associated molecule 4 1661 gene polymorphism on its expression and transcription in ulcerative colitis
Authors: JIANG Ting , GE Liu Qing , CHEN Zhi Tao , LI Chun , ZHOU Feng , LUO Yan , XIA Bing 
Published: September 2010

OBJECTIVE:  Our aim was to investigate the expression of cytotoxic T lymphocyte‐associated molecule 4 (CTLA‐4) in ulcerative colitis (UC) and to evaluate the effect of CTLA‐4 gene ‐1661A/G polymorphism on CTLA‐4 expression and transcription.METHODS:  A total of 20 UC patients and 22 healthy controls matched by age and sex were enrolled at Zhongnan Hospital of Wuhan University in central China. The CTLA‐4 ‐1661A/G polymorphism was genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. A Western blot analysis was performed to determine the full length CTLA‐4 (flCTLA‐4) protein expression in the peripheral blood of the UC patients. Serum‐soluble CTLA‐4 (sCTLA‐4) levels were measured by enzyme‐linked immunosorbent assay. CTLA‐4‐1661G mutant promoter transcription function was analyzed by site‐directed PCR‐based mutagenesis.RESULTS:  CTLA‐4 protein expression on CD4+ T cells in UC patients was lower than that in the healthy controls (P < 0.001) while serum sCTLA‐4 in the UC patients was significantly higher than that in the healthy controls (P < 0.001). No correlation was found between flCTLA‐4 and sCTLA‐4 expression levels and the ‐1661 A/G polymorphism of the CTLA‐4 gene. Meanwhile, CTLA‐4 ‐1661 allele A had no significant impact on the promoter activity compared with allele G (P > 0.05).CONCLUSION:  CTLA‐4 expressions were aberrant in UC patients compared with the healthy controls. CTLA‐4 ‐1661A/G polymorphism had no significant impact on CTLA‐4 expression and transcription in the peripheral CD4 T cells of UC patients.
Quantitative expression profiling of G‐protein‐coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target
Authors: Qin Y. , Verdegaal E. M. E. , Siderius M. , Bebelman J. P. , Smit M. J. , Leurs R. , Willemze R. , Tensen C. P. , Osanto S. 
Published: September 2010

SummaryG‐protein‐coupled receptors (GPCRs) have been implicated in the tumorigenesis and metastasis of human cancers and are considered amongst the most desirable targets for drug development. Utilizing a robust quantitative PCR array, we quantified expression of 94 human GPCRs, including 75 orphan GPCRs and 19 chemokine receptors, and 36 chemokine ligands, in 40 melanoma metastases from different individuals and benign nevi. Inter‐metastatic site comparison revealed that orphan GPR174 and CCL28 are statistically significantly overexpressed in subcutaneous metastases, while P2RY5 is overexpressed in brain metastases. Comparison between metastases (all three metastatic sites) and benign nevi revealed that 16 genes, including six orphan receptors (GPR18, GPR34, GPR119, GPR160, GPR183 and P2RY10) and chemokine receptors CCR5, CXCR4, and CXCR6, were statistically significantly differentially expressed. Subsequent functional experiments in yeast and melanoma cells indicate that GPR18, the most abundantly overexpressed orphan GPCR in all melanoma metastases, is constitutively active and inhibits apoptosis, indicating an important role for GPR18 in tumor cell survival. GPR18 and five other orphan GPCRs with yet unknown biological function may be considered potential novel anticancer targets in metastatic melanoma.
High sensitivity assay using serum sample for IL28B genotyping to predict treatment response in chronic hepatitis C patients
Authors: Akkarathamrongsin Srunthron , Sugiyama Masaya , Matsuura Kentaro , Kurbanov Fuat , Poovorawan Yong , Tanaka Yasuhito , Mizokami Masashi 
Published: September 2010

Aim:  Recent human genome‐wide association studies (GWAS) revealed a strong association between IL28B gene variation and the pegylated interferon‐α with ribavirin (PEG‐IFN‐α/RBV) treatment response in chronic hepatitis C patients. Two single nucleotide polymorphisms (SNP), rs8103142 and rs11881222 located in the IL28B gene, were found in significant association with the viral clearance. The present study employed these SNPs to develop a new accessible screening method allowing identification of potential non‐responders before starting the therapy.Methods:  Primer sets were designed to amplify rs8103142 and rs11881222 fragments from genomic DNA extracted from serum samples. This method was validated using microarray typing (GWAS) and applied for genotyping of 68 hepatitis C virus‐infected patients with PEG‐IFN‐α/RBV treatment at baseline.Results:  In comparison with GWAS, the screening method showed 100% and 95.6% accuracy in typing of rs8103142 and rs11881222, respectively, indicating incomplete specificity but 100% of sensitivity in both. Genotyping by both SNP showed that 53 (77.9%), 14 (20.6%) and one (1.5%) of the patients were of major homozygous, heterozygous and minor homozygous type, respectively. The majority (85%) of homozygous patients exhibited response to therapy in contrast to heterozygous patients (29%). Among all genotyped only one case was found with the minor homozygous genotype which had late virological response to therapy before relapsing.Conclusion:  This study described a highly sensitive assay that can be useful in determining SNP genotypes as well as in predicting the response to IFN‐based treatment.
New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma
Authors: Kawamura Yusuke , Ikeda Kenji , Hirakawa Miharu , Yatsuji Hiromi , Sezaki Hitomi , Hosaka Tetsuya , Akuta Norio , Kobayashi Masahiro , Saitoh Satoshi , Suzuki Fumitaka , Suzuki Yoshiyuki , Arase Yasuji , Kumada Hiromitsu 
Published: September 2010

Aim:  The aim of this study was to elucidate whether the histopathological characteristics of hepatocellular carcinoma (HCC) can be predicted from baseline dynamic computed tomography (CT) images.Methods:  This retrospective study included 86 consecutive patients with HCC who underwent surgical resection between January 2000 and September 2008. The arterial‐ and portal‐phase dynamic CT images obtained preoperatively were classified into four enhancement patterns: Type‐1 and Type‐2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively; Type‐3, heterogeneous enhancement pattern with septum‐like structure; and Type‐4, heterogeneous enhancement pattern with irregular ring‐like structures. We also evaluated the predictive factors for poorly‐differentiated HCC, specific macroscopic type of HCC (simple nodular type with extranodular growth [SNEG] and confluent multinodular [CMN]) by univariate and multivariate analyses.Results:  The percentages of poorly‐differentiated HCC according to the enhancement pattern were three of 51 nodules (6%) of Type‐1 and ‐2, three of 24 (13%) of Type‐3, and eight of 11 (73%) of Type‐4. The percentages of SNEG/CMN according to the enhancement pattern were 12 of 51 nodules (24%) of Type‐1 and ‐2, 13 of 24 (54%) of Type‐3, and five of 11 (45%) of Type‐4. Multivariate analysis identified Type‐4 pattern as a significant and independent predictor of poorly‐differentiated HCC (P < 0.001) while Type‐3 pattern was a significant predictor of SNEG/CMN (P = 0.017).Conclusion:  Heterogeneity of dynamic CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment.
Efficacy and safety of double filtration plasmapheresis in combination with interferon therapy for chronic hepatitis C
Authors: Kaneko Shuichi , Sata Michio , Ide Tatsuya , Yamashita Tatsuya , Hige Shuhei , Tomita Eiichi , Mochida Satoshi , Yamashita Yukitaka , Inui Yoshiaki , Kim Soo Ryang , Komada Naoto , Mikami Takafumi , Satoh Shinichi , Morita Sumiharu , Takaguchi Koichi , Hirashima Noboru , Nishio Yuji , Watanabe Daisuke , Kioka Kiyohide , Fujiwara Kenji 
Published: September 2010

Aim:  Efficacy and safety of double filtration plasmapheresis (DFPP) for chronic hepatitis C were prospectively analyzed in Japanese clinical settings.Methods:  All patients who received DFPP in combination with interferon (IFN) therapy for chronic hepatitis C were serially recruited at 36 institutions between April 2008 and July 2009 in Japan.Results:  A total of 239 patients were analyzed for the safety of DFPP and 206 patients for the efficacy. Of the 206 patients, 181 patients were treated with DFPP in combination with pegylated interferon plus ribavirin (PEG‐IFN/RBV + DFPP). Among the 181 patients, 60 patients (33.1%) were treatment‐naïves, 35 (19.3%) relapsers and 62 (34.3%) non‐responders. Complete early virological response (cEVR) in patients treated with PEG‐IFN/RBV + DFPP was achieved in 57.5% overall, 70.0% in treatment‐naïves, 57.1% in relapsers and 41.9% in non‐responders. In patients with previous PEG‐IFN/RBV therapy, cEVR were found in 63.0% of relapsers and 18.9 % of non‐responders, and cEVR in patients with other than PEG‐IFN/RBV therapy as previous IFN therapy, relapsers and non‐responders was 37.5% and 76.0%, respectively. Adverse events were found in 55 patients (23.0%). Serious adverse events were found in four patients (1.7%) who showed puncture‐site injury. Adverse events were related to female sex, but not related to age, and DFPP could be performed safely.Conclusion:  The cEVR results in this study suggest that high rates of sustained virological response can be achieved in retreated and treatment‐naïve patients using DFPP in combination with PEG‐IFN/RBV therapy. Results indicate that this therapy could be safely conducted, even in elderly patients.
Radiofrequency ablation of hepatocellular carcinoma: The feasibility of magnetic resonance imaging with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid for evaluating the ablative margin
Authors: Okubo Hironao , Kokubu Shigehiro , Komiyama Masae , Yamagata Hisafumi , Uchiyama Akira , Miyazaki Akihisa , Watanabe Sumio 
Published: September 2010

Aim:  The aim of this study was to evaluate the feasibility of gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd‐EOB‐DTPA) in magnetic resonance imaging (MRI) to assess the ablative margin of radiofrequency (RF) ablation to hepatocellular carcinoma (HCC).Methods:  RF ablation was performed in the livers of six pigs after the i.v. administration of Gd‐EOB‐DTPA 20 min before ablation. Three pigs were killed 2 h after administration (group A), and the other pigs were killed 7 days after ablation (group B). Thereafter, correlation between pathological findings and MRI was investigated. Moreover, the Gd concentrations were examined in ablated and non‐ablated regions. An initial clinical evaluation was conducted for 28 HCC nodules. Percutaneous RF ablation was performed 20 min after administration, and T1‐weighted images were taken 2, 24 and 72 h post‐treatment.Results:  On T1‐weighted images of the porcine liver, the RF ablated lesions showed hyperintense regions with hypointense rims, which histopathologically corresponded to sinusoidal congestion. The Gd concentrations in ablated regions in group A were significantly higher than those in non‐ablated regions, while the concentrations in both regions in group B fell to nearly undetectable levels. In 27 of the 28 HCC nodules, the treated area consisted of a hypointense region, indicative of the tumor, and a surrounding hyperintense rim 2 h after ablation. Subsequently, a thin hypointense region was observed in the outermost layer 24 and 72 h after ablation.Conclusion:  Administration of Gd‐EOB‐DTPA in conjunction with RF ablation of HCC may be feasible for the assessment of an accurate ablative margin.
Scintigraphic evaluation of intrapulmonary shunt in normoxemic cirrhotic patients and effects of terlipressin
Authors: Kalambokis George , Baltayiannis Gerasimos , Tsiouris Spyridon , Pappas Konstantinos , Kokkinou Panorea , Fotopoulos Andreas , Tsianos Epameinondas V. 
Published: September 2010

Aim:  The magnitude of intrapulmonary shunt (IPS) in cirrhotic patients without hypoxemia remains undefined. We evaluated the severity and clinical correlations of IPS in normoxemic cirrhotics, and possible IPS alterations after terlipressin treatment.Methods:  Fifteen patients with alcoholic cirrhosis without hypoxemia were studied at baseline and after the administration of 2 mg of terlipressin. The IPS fraction was evaluated by lung perfusion scan after the i.v. injection of technetium‐99m‐labeled macroaggregated albumin (99mTc‐MAA) and calculation of brain uptake (positive value ≥6%). Cardiac output (CO), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were evaluated by Doppler echocardiography. Mean arterial pressure (MAP) was measured and the ratio MAP/CO was calculated as an index of systemic vascular resistance (SVR). Portal vein velocity (PVV) and portal venous flow (PVF) were also assessed by Doppler ultrasonography.Results:  Three patients (20%) had an IPS fraction of more than 6%. A significant inverse correlation with platelet count (P = 0.001) and a direct correlation with Child–Pugh score (P = 0.06), PVV (P = 0.07) and PVF (P = 0.07) were noted. IPS fractions decreased significantly after terlipressin administration (P = 0.00001); the IPS fraction fell below 6% in all three patients with positive baseline values. Terlipressin treatment induced a significant decrease in CO (P = 0.003) and significant increases in MAP (P = 0.0003), SVR (P = 0.0003), SPAP (P = 0.001) and PVR (P = 0.01).Conclusion:  IPS fractions detected by 99mTc‐MAA lung scan were inversely correlated with platelet count and directly with liver disease severity, and found abnormal in 20% of normoxemic cirrhotic patients. Terlipressin reduced significantly the magnitude of the shunt.
Clinical and histopathological study of “follicular cholangitis”: Sclerosing cholangitis with prominent lymphocytic infiltration masquerading as hilar cholangiocarcinoma
Authors: Fujita Takeo , Kojima Motohiro , Kato Yuichiro , Gotohda Naoto , Takahashi Shinichiro , Konishi Masaru , Kinoshita Taira 
Published: September 2010

Aim:  Sclerosing cholangitis which mimic hilar biliary carcinoma have not been fully categorized. In this study, we investigated the clinicopathological features of sclerosing cholangitis of unknown origin, so‐called “follicular cholangitis”.Methods:  Patients who had undergone surgery of the proximal bile duct from 1993–2008 on suspicion of proximal bile carcinoma were evaluated. Of these, we investigated the cases compatible with follicular cholangitis. Then, we reviewed the previous reports of follicular cholangitis showing similar clinicopathological findings.Results:  Among 176 patients, two who were diagnosed with benign sclerosing cholangitis of unknown origin shared the common histopathological findings compatible with follicular cholangitis. Histopathological findings showed dense fibrosis with prominent lymph follicles and germinal centers, being appropriate for neither primary sclerosing cholangitis nor immunoglobulin G4‐related sclerosing cholangitis. Review of previous published work revealed two other cases diagnosed with follicular cholangitis and showing histopathological findings similar to ours. All these cases were middle‐aged patients with no history of autoimmune disease with focal strictures mainly involved in the hilar bile duct, mimicking hilar cholangiocarcinoma.Conclusion:  Benign sclerosing cholangitis has not been fully categorized, yet. Follicular cholangitis shows unique histopathological features and can be categorized as an independent entity.
Iron state in association with retinoid metabolism in non‐alcoholic fatty liver disease
Authors: Tsuchiya Hiroyuki , Ashla An Afida , Hoshikawa Yoshiko , Matsumi Yoshiaki , Kanki Keita , Enjoji Munechika , Momosaki Seiya , Nakamuta Makoto , Taketomi Akinobu , Maehara Yoshihiko , Shomori Kohei , Kurimasa Akihiro , Hisatome Ichiro , Ito Hisao , Shiota Goshi 
Published: September 2010

Aim:  We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non‐alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders.Methods:  Thirty‐six persons, comprising 17 patients with simple steatosis (SS), 11 with NASH, and 8 normal controls (N), were examined on hepatic expression of iron metabolism‐related genes including hemojuvelin (HJV), hepcidin (HEPC), transferrin receptor 1 and 2 (TfR1, TfR2), ferroportin (FPN), neogenin (NEO) and ferritin heavy chain (FtH) and hepatic iron contents in addition to expression 51 genes which is involved in retinoid metabolism and antioxidative action.Results:  In patients with NAFLD, expression of HJV, TfR2, FPN, TfR1, FtH, SOD and catalase was increased, compared with that in N. In addition, hepatic iron content, which was increased in NASH, was correlated with expression level of TfR2. Expression of cellular retinoid binding protein (CRBP1), alcohol dehydrogenase 1 (ADH1) and cytochrome P450 26A1(CYP26A1) was significantly correlated with that of HJV, TfR2 and FPN, respectively.Conclusion:  The results of the present study suggest that the reasons responsible for iron accumulation in NASH in the present study may partly be due to enhanced expression of TfRs, especially TfR2, and hyperdynamic state of retinoid metabolism is closely related to iron metabolism in the disease.
Cyclooxygenase‐2 gene promoter polymorphisms affect susceptibility to hepatitis C virus infection and disease progression
Authors: Sakaki Masashi , Makino Reiko , Hiroishi Kazumasa , Ueda Kumiko , Eguchi Junichi , Hiraide Ayako , Doi Hiroyoshi , Omori Risa , Imawari Michio 
Published: September 2010

Aim:  Because polymorphisms of cyclooxygenase‐2 (COX‐2) and osteopontin (OPN) promoter regions and a promoter/enhancer region of forkhead box protein 3 (FOXP3) gene are known to affect immune responses, we examined whether these polymorphisms can influence susceptibility to hepatitis C virus (HCV) infection and progression of liver disease.Methods:  Peripheral blood samples were obtained from 104 Japanese patients with chronic HCV infection and 74 healthy Japanese donors. Polymerase chain reaction single‐stranded conformational polymorphism analysis of genomic DNA was performed to determine the polymorphisms.Results:  The risk of persistent HCV infection was decreased in subjects with –1195GG genotype of the COX‐2 promoter region. However, in patients with chronic HCV infection, the –1195GG genotype was associated with advanced‐stage liver disease. A luciferase reporter assay performed to analyze the effect of single nucleotide polymorphisms (SNP) (–1195A or –1195G) in COX‐2 gene on transcriptional activity using the HepG2, Huh7 and HeLa cell lines indicated that the –1195G genotype showed higher transcriptional activity than the –1195A genotype. SNP of OPN and FOXP3 did not differ between patients with chronic HCV infection and controls. However, the –443TT genotype of the OPN promoter region was associated with increased inflammatory activity of the liver.Conclusion:  These results suggest that the –1195GG genotype of the COX‐2 promoter region protects against HCV infection in the Japanese. However, once chronic infection is established, the –443TT genotype of the OPN promoter region and the –1195GG genotype of the COX‐2 promoter are thought to promote inflammation and contribute to the progression of liver disease.
An Iterative Learning Control of Nonlinear Systems Using Neural Network Design
Authors: Chien Chiang‐Ju , Fu Li‐Chen 
Published: September 2010

ABSTRACTIn this paper, a feedforward neural network with sigmoid hidden units is used to design a neural network based iterative learning controller for nonlinear systems with state dependent input gains. No prior offline training phase is necessary, and only a single neural network is employed. All the weights of the neurons are tuned during the iteration process in order to achieve the desired learning performance. The adaptive laws for the weights of neurons and the analysis of learning performance are determined via Lyapunov‐like analysis. A projection learning algorithm is used to prevent drifting of weights. It is shown that the tracking error vector will asymptotically converges to zero as the iteration goes to infinity, and the all adjustable parameters as well as internal signals remain bounded.
Kit for detection of fungal endophytes of grasses yields inconsistent results
Authors: Jensen John Beck , González Victoria T. , Guevara Diego Urrutia , Bhuvaneswari T. V. , Wäli Piippa R. , Tejesvi Mysore V. , Pirttilä Anna Maria , Bazely Dawn , Vicari Mark , Bråthen Kari Anne 
Published: September 2010

Summary1. The Agrinostics field immunoblot assay is a colour‐imprint assay originally developed for routinely and rapid detection of mycotoxin‐producing fungi Neotyphodium spp./Epichloë spp. from samples of pasture, turf, cereals and seeds of agricultural grasses.2. In addition the Agrinostics immunoblot assay has been used and recommended for exploring the presence and ecological role of Neotyphodium and the closely related Epichloë in several cool season grasses.3. Here we demonstrate that this method is not limited to detection of only these two species, as several other fungal endophyte genera or species also yielded positive results when mycelia were loaded onto cards. Moreover, other closely related endophyte genera or species were found to yield negative result. Thus, the assay is neither specific to isolates of Neotyphodium/Epichloë nor is it universal for fungal endophyte detection.4. Our study underscore the fact that the Agrinostics field immunoblot assay should not be used on its own for field research into the broader ecological significance of Neotyphodium/Epichloë.5. We suggest that the assay may be best suited for use in agricultural fields or in controlled greenhouse experiments for hyphal load estimates, and should always be accompanied by other methods (e.g. microscopic visualization, DNA‐sequencing) to confirm infection frequencies and certify that the endophyte present actually is Neotyphodium/Epichloë.