bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of interferon α‐2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis
Authors: Kurokawa Mika , Hiramatsu Naoki , Oze Tsugiko , Mochizuki Kiyoshi , Yakushijin Takayuki , Kurashige Nao , Inoue Yuko , Igura Takumi , Imanaka Kazuho , Yamada Akira , Oshita Masahide , Hagiwara Hideki , Mita Eiji , Ito Toshifumi , Inui Yoshiaki , Hijioka Taizo , Yoshihara Harumasa , Inoue Atsuo , Imai Yasuharu , Kato Michio , Kiso Shinichi , Kanto Tatsuya , Takehara Tetsuo , Kasahara Akinori , Hayashi Norio 
Published: January 2009

Aim:  The objective of this study was to elucidate the long‐term effects of interferon (IFN)α‐2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C.Methods:  A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN‐α‐2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis.Results:  A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non‐SVR patients (P = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years (P = 0.006), advanced histological staging (P = 0.033), non‐SVR to IFN therapy (P = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of ≧ 40 IU/L after the combination therapy (P = 0.021).Conclusions:  These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.
The α‐glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice
Authors: Okada Kosuke , Yanagawa Toru , Warabi Eiji , Yamastu Keiko , Uwayama Junya , Takeda Koichi , Utsunomiya Hirotoshi , Yoshida Hiroshi , Shoda Junichi , Ishii Tetsuro 
Published: January 2009

Aim:  Sequestosome 1 (SQSTM1)/A170/p62 plays an important role in membrane‐receptor mediated signal transduction and autophagic protein degradation. Although the mechanism involved is not clear, sqstm1 gene knockout (KO) mice develop mature‐onset obesity and insulin resistance, leading to type II diabetes. KO mice show accumulation of fat in white adipose tissue and the liver when fed a standard diet. Acarbose is an α‐glucosidase inhibitor that improves insulin sensitivity and decreases postprandial hyperglycemia, and it is used to treat type 2 diabetes. We examined whether or not dietary acarbose prevented obesity and simple steatosis in KO mice.Methods:  Wild‐type (WT) and KO mice were fed a standard diet with or without acarbose (0.8% w/w) from 15–25 weeks of age. The body weight and the fat content of adipose tissue and the liver were measured, and changes of lipid metabolism in these tissues were assessed from gene expression.Results:  Acarbose treatment suppressed weight gain and the development of hepatic steatosis in KO mice. Acarbose treatment up‐regulated hepatic expression of the pparα, ucp‐2, and abca1 genes, as well as srebp1c, pparα, and pparγ in adipose tissue. In WT mice, however, acarbose treatment had little influence on weight gain and gene expression.Conclusions:  The results of this study suggest that long‐term administration of acarbose is effective for prevention of obesity and simple steatosis in SQSTM1‐KO mice.
Effectiveness of combination therapy of splenectomy and long‐term interferon in patients with hepatitis C virus‐related cirrhosis and thrombocytopenia
Authors: Morihara Daisuke , Kobayashi Masahiro , Ikeda Kenji , Kawamura Yusuke , Saneto Hiromi , Yatuji Hiromi , Hosaka Tetuya , Sezaki Hitomi , Akuta Norio , Suzuki Yoshiyuki , Suzuki Fumitaka , Kumada Hiromitu 
Published: January 2009

Aim:  To elucidate the effectiveness of combination therapy of splenectomy and long‐term interferon (IFN) on survival and hepatocarcinogenesis, we retrospectively analyzed 180 patients with hepatitis C virus (HCV)‐related cirrhosis and thrombocytopenia.Methods:  Group A consisted of 121 patients who received neither splenectomy nor IFN therapy. Group B consisted of 11 patients who underwent splenectomy only. Group C consisted of 32 patients who underwent IFN therapy only. Group D consisted of 16 patients who received the combination therapy splenectomy followed by IFN therapy.Results:  The viral response in group D estimated at least 6 months after IFN therapy showed sustained viral response in four patients, biochemical response in one and no response in six. Multivariate analysis using time‐dependent variables showed significant improvement of survival rate in patients on the combination therapy,but no effect on the appearance rate of hepatocarcinogenesis relative to the findings in group A.Conclusions:  In this study, the splenectomy did not directly improve the prognosis, but increased the ability for patients to undergo IFN. As a result, we considered that the combination therapy of splenectomy and long‐term IFN significantly improved survival rate in patients with advanced HCV‐related cirrhosis and thrombocytopenia.
Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells
Authors: Bechmann Lars P. , Zahn Denis , Gieseler Robert K. , Fingas Christian D. , Marquitan Guido , Jochum Christoph , Gerken Guido , Friedman Scott L. , Canbay Ali 
Published: January 2009

Aim:  To ascertain whether resveratrol affects the expression of free fatty acids (FFA)‐induced profibrogenic genes, death receptors, and/or apoptosis‐related molecules in human hepatic stellate cells, using the LX‐2 cell line.Methods:  Cells were cultured in the presence of FFAs (2:1 oleate : palmitate) and subsequently treated with resveratrol. Gene expression rates were determined by quantitative real‐time PCR. The 50% lethal dose (LD50) of resveratrol in the presence of FFAs was assessed with the MTT viability test.Results:  Compared to vehicle controls, incubation of LX‐2 cells with 0.5 mM FFAs induced profibrogenic genes (α‐SMA × 2.9; TGF‐β1 × 1.6; TIMP‐1 × 1.4), death receptors (CD95/Fas × 3.8; TNFR‐1 × 1.4), and anti‐apoptotic molecules (Bcl‐2 × 2.3; Mcl‐1 × 1.3). Subsequent addition of 15 µM resveratrol (LD50 = 23.2 µM) significantly (P < 0.05) upregulated further these genes (α‐SMA × 6.5; TGF‐β1 × 1.9; TIMP‐1 × 2.2; CD95/Fas × 13.1, TNFR‐1 × 2.1; Bcl‐2 × 3.6; Mcl‐1 × 1.9). Importantly, this effect was only observed in the presence of FFAs.Conclusion:  Resveratrol amplifies the profibrogenic activation of human hepatic LX‐2 stellate cells. This finding raises the possibility that in obese patients with elevated FFAs reserveratrol could provoke hepatic fibrogenesis. In‐vivo studies are necessary to further validate this conclusion.
An incidental enterocolic lymphocytic phlebitis pattern is seen commonly in the rectal stump of patients with diversion colitis superimposed on inflammatory bowel disease
Authors: Chetty R , Hafezi S , Montgomery E 
Published: January 2009

Aims:Enterocolic lymphocytic phlebitis (ELP) is an uncommon cause of bowel pathology and most frequently results in ischaemia. It is characterised by an artery-sparing, venulocentric lymphoid infiltrate that causes a phlebitis and vascular compromise. Rare cases of ELP have been encountered with lymphocytic colitis in the absence of ischaemic bowel change. The present study examined the occurrence of ELP in the setting of diversion colitis and inflammatory bowel disease, as well as in random colectomy specimens.Methods:The study cohort comprised the following: 26 completion proctectomy specimens for ulcerative colitis with superimposed diversion colitis in the rectal stump; 3 colectomy specimens for Crohn disease with diversion colitis; 6 colectomy specimens for adenocarcinoma and/or diverticular disease with diversion colitis; 34 resection specimens with ulcerative colitis only; 19 with Crohn disease only; and 100 random colon resection specimens for adenocarcinoma, adenoma, diverticular disease and ischaemia.Results:ELP was present in 18 of the 26 ulcerative colitis cases with diversion colitis, 3/3 Crohn disease cases with diversion colitis, 1/6 cases of diverticular disease with diversion colitis, 6/34 cases of ulcerative colitis without diversion, 2/19 Crohn disease cases without diversion colitis, and only 1 of 100 colectomy cases without inflammatory bowel disease or diversion colitis.Conclusion:ELP occurs most frequently in cases that have been diverted for inflammatory bowel disease. Fewer cases of ELP were noted in cases of inflammatory bowel disease in the absence of diversion colitis. It is postulated that altered bowel flora and immune dysregulation may be pivotal in the causation of this association.
Repeated respiratory hospital encounters among children with asthma and residential proximity to traffic
Authors: Chang J , Delfino R J , Gillen D , Tjoa T , Nickerson B , Cooper D 
Published: January 2009

Objective:The prevalence of adverse respiratory outcomes among children has been frequently associated with measurements of traffic-related exposures, and other data suggest asthma severity is worsened with residence near heavy traffic. We examined the association between neighbourhood traffic burden and repeated acute respiratory illnesses that required emergency department visits and/or hospitalisation for children with a primary or secondary diagnosis of asthma (89% acute bronchitis or pneumonia).Methods:This is a hospital-based longitudinal study of a southern California urban catchment area around two adjacent children’s hospitals. Subjects’ home addresses were geocoded and linked to nearby traffic data. Recurrent event proportional hazard analysis was used to estimate the hazard of repeated hospital encounters.Results:We found living within 300 metres of arterial roads or freeways increased risk of repeated hospital encounters in 3297 children age 18 years or less. At highest risk were children in the top quintile of traffic density (HR = 1.21; 95% CL 0.99 to 1.49) and those who had 750 metres or more of arterial road and freeway length within 300 metres of their residence (HR = 1.18; 95% CL 0.99 to 1.41). Associations between repeated hospital encounters and residence near heavy traffic were stronger in females than males and in children without insurance or who required government sponsored insurance than children with private insurance. The gender disparity was most notable among infants (age 0) and children ages 6–18 years.Conclusions:Results suggest exposure to traffic-related air pollution increases asthma severity as indicated by hospital utilisation. The finding in infants suggests this is an especially vulnerable population, although the validity of asthma diagnosis at this age is unknown. Females and children who do not have private insurance may also be more vulnerable to air pollution from traffic.
Mobile phone base stations and adverse health effects: phase 2 of a cross-sectional study with measured radio frequency electromagnetic fields
Authors: Berg-Beckhoff G , Blettner M , Kowall B , Breckenkamp J , Schlehofer B , Schmiedel S , Bornkessel C , Reis U , Potthoff P , Schüz J 
Published: January 2009

Objective:The aim of the cross-sectional study was to test the hypothesis that exposure to continuous low-level radio frequency electromagnetic fields (RF-EMFs) emitted from mobile phone base stations was related to various health disturbances.Methods:For the investigation people living mainly in urban regions were selected from a nationwide study in 2006. In total, 3526 persons responded to a questionnaire (response rate 85%). For the exposure assessment a dosimeter measuring different RF-EMF frequencies was used. Participants answered a postal questionnaire on how mobile phone base stations affected their health and they gave information on sleep disturbances, headaches, health complaints and mental and physical health using standardised health questionnaires. Information on stress was also collected. Multiple linear regression models were used with health outcomes as dependent variables (n = 1326).Results:For the five health scores used, no differences in their medians were observed for exposed versus non-exposed participants. People who attributed adverse health effects to mobile phone base stations reported significantly more sleep disturbances and health complaints, but they did not report more headaches or less mental and physical health. Individuals concerned about mobile phone base stations did not have different well-being scores compared with those who were not concerned.Conclusions:In this large population-based study, measured RF-EMFs emitted from mobile phone base stations were not associated with adverse health effects.
Isotopic homogeneity of breath CO2 from fasting and berry-eating polar bears: implications for tracing reliance on terrestrial foods in a changing Arctic
Authors: Hobson K. A. , Stirling I. , Andriashek D. S. 
Published: January 2009

With a changing Arctic climate, it is important to know whether polar bears ( Ursus maritimus Phipps, 1774) can supplement their stored fat reserves by intake of terrestrial berries. Although polar bears are known to consume berries while on land, it has been difficult to quantify their relative dependence on stored adipose tissue and berry carbohydrates to meet their energy needs. We sampled breath CO2 from 300 bears fasting on land in western Hudson Bay during the open-water seasons of 1997 and 1998 and analyzed this breath for stable carbon isotope (δ13C) values. We found no difference in the bear breath δ13C values for bears known to have recently fed on berries and those that had not. The distribution of δ13C values was remarkably tight with average values ranging from –24.2‰ to –24.8‰ with no effect of age, sex, or year of capture. This result was counter to our simple isotopic discrimination model that predicted bears metabolizing adipose tissue derived from seals would have breath δ13C values close to –24.7‰ and those metabolizing berries exclusively would have values close to –32.6‰. If correct, our results suggests that the bears which had fed on berries while fasting on land received an insignificant amount of energetic benefit.
Acute Chlamydia pneumoniae infection in the pathogenesis of autoimmune diseases
Authors: Fujita M , Hatachi S , Yagita M 
Published: January 2009

Autoimmune diseases have several etiologies. Acute Chlamydia pneumoniae ( C. pneumoniae) infection may be involved in the pathogenesis of several autoimmune diseases. In this study, 82 patients with several autoimmune diseases and 70 controls were enrolled, and acute C. pneumoniae infection has been evaluated by monitoring the levels of IgM antibody. Chlamydia pneumoniae IgM positive results were observed in 29% ( P < 0.05) of the patients with several autoimmune diseases and in 10% of the controls. Chlamydia pneumoniae IgM positive cases were more frequent among the patients with rheumatoid arthritis (RA; 30%, P < 0.05), systemic lupus erythematosus (SLE; 28.0%, P < 0.05), dermatomyositis/polymyositis (23%, NS), myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis (33%, NS), adult onset of Still’s disease (29%, NS) and giant cell arteritis/Takayasu arteritis (50%, NS) than among the controls. This positive frequency was statistically significant in RA and SLE. These results suggest that acute C. pneumoniae infection is probably involved in the pathogenesis of autoimmune diseases.
Development and Evaluation of a Computerized Test Battery for Alzheimer's Disease Screening in Community-based Settings
Authors: Inoue Masashi , Jinbo Daiki , Nakamura Yuka , Taniguchi Miyako , Urakami Katsuya 
Published: January 2009

Aim. To evaluate the capability of a computerized test battery for Alzheimer's disease screening which has been newly developed to provide a standardized and efficient method for widespread use in routine clinical and community-based settings. Methods. Participants were 72 individuals diagnosed with Alzheimer's disease and 102 healthy elderly individuals. Both groups were tested by the battery. Receiver operating characteristic analysis was used to examine the ability of the battery to differentiate between those with Alzheimer's disease and cognitively healthy elderly individuals. Results. On a group level, the Alzheimer's disease group performed worse than the control group on each of the 4 computerized test tasks. Receiver operating characteristic analysis yielded maximum sensitivity and specificity values of 96% and 86% for total scores, respectively. Conclusion. We believe the battery is very useful for routine clinical and community-based settings.
Expression of CD133 on leukemia-initiating cells in childhood ALL
Authors: Cox Charlotte V. , Diamanti Paraskevi , Evely Roger S. , Kearns Pamela R. , Blair Allison 
Published: January 2009

Abstract
Optimization of therapy for childhood acute lymphoblastic leukemia (ALL) requires a greater understanding of the cells that proliferate to maintain this malignancy because a significant number of cases relapse, resulting from failure to eradicate the disease. Putative ALL stem cells may be resistant to therapy and subsequent relapses may arise from these cells. We investigated expression of CD133, CD19, and CD38 in pediatric B-ALL. Cytogenetic and molecular analyses demonstrated that karyotypically aberrant cells were present in both CD133+/CD19+ and CD133+/CD19− subfractions, as were most of the antigen receptor gene rearrangements. However, ALL cells capable of long-term proliferation in vitro and in vivo were derived from the CD133+/CD19− subfraction. Moreover, these CD133+/CD19− cells could self-renew to engraft serial nonobese diabetic–severe combined immunodeficient recipients and differentiate in vivo to produce leukemias with similar immunophenotypes and karyotypes to the diagnostic samples. Furthermore, these CD133+/CD19− ALL cells were more resistant to treatment with dexamethasone and vincristine, key components in childhood ALL therapy, than the bulk leukemia population. Similar results were obtained using cells sorted for CD133 and CD38, with only the CD133+/CD38− subfraction demonstrating xenograft repopulating capacity. These data suggest that leukemia-initiating cells in childhood B-ALL have a primitive CD133+/CD19− and CD38− phenotype.
A novel regulatory event-based gene set analysis method for exploring global functional changes in heterogeneous genomic data sets
Authors: Tung Chien-Yi , Jen Chih-Hung , Hsu Ming-Ta , Wang Hsei-Wei , Lin Chi-Hung 
Published: January 2009

Abstract

Background
Analyzing gene expression data by assessing the significance of pre-defined gene sets, rather than individual genes, has become a main approach in microarray data analysis and this has promisingly derive new biological interpretations of microarray data. However, the detection power of conventional gene list or gene set-based approaches is limited on highly heterogeneous samples, such as tumors.

Results
We developed a novel method, the regulatory
e
vent-based
G
ene
S
et
A
nalysis (eGSA), which considers not only the consistently changed genes but also every gene regulation (event) of each sample to overcome the detection limit. In comparison with conventional methods, eGSA can detect functional changes in heterogeneous samples more precisely and robustly. Furthermore, by utilizing eGSA, we successfully revealed novel functional characteristics and potential mechanisms of very early hepatocellular carcinoma (HCC).

Conclusion
Our study creates a novel scheme to directly target the major cellular functional changes in heterogeneous samples. All potential regulatory routines of a functional change can be further analyzed by the regulatory event frequency. We also provide a case study on early HCCs and reveal a novel insight at the initial stage of hepatocarcinogenesis. eGSA therefore accelerates and refines the interpretation of heterogeneous genomic data sets in the absence of gene-phenotype correlations.
Molecular profiling of T-helper immune genes during dengue virus infection
Authors: Chen Jincheng , Ng Mary Mah Lee , Chu Justin Jang Hann 
Published: January 2009

Abstract
In this study, we provide a comprehensive molecular profiling of the involvement of T- helper (Th) genes during dengue virus infection of different cell types. The Th gene profiles of three human cell types (monocytes, T-cells and hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection with dengue virus. Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability. Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability. Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome.
Polymerization of actin does not regulate desensitization in human basophils
Authors: MacGlashan Donald , Vilariño Natalia 
Published: January 2009

AbstractPrevious studies have suggested that maintenance of IgE-mediated signaling results from regulation of the activity of signaling complexes by actin polymerization. This process is also hypothesized to be related to desensitization of basophils and mast cells. Recent studies demonstrated that any signaling process dependent on syk or PI-3K activity cannot be a mechanism of desensitization, and in this context, syk and PI-3K inhibitors were found to inhibit actin polymerization. Inhibitors of actin polymerization were tested for their effect on desensitization of human peripheral blood basophils. Latrunculin A, in particular, removed all resting and stimulated f-actin but did not inhibit desensitization. Cytochalasin D and latrunculin A also did not reverse the loss of syk phosphorylation that accompanies desensitization. These results demonstrate that desensitization mechanisms are not dependent on actin polymerization. In this context, it was also shown that progressive immobilization of FcεRI during aggregation was sensitive to syk or actin polymerization inhibition. Therefore, desensitization is also not dependent on receptor immobilization. These studies demonstrate that desensitization is not the result of two signaling pathways once considered relevant to down-regulation of IgE-mediated signaling.
Organellar calcium signalling mechanisms inDrosophilaepithelial function
Authors: Davies Shireen A. , Terhzaz Selim 
Published: January 2009

SUMMARYCalcium signalling and calcium homeostasis are essential for life. Studies of calcium signalling thus constitute a major proportion of research in the life sciences, although the majority of these studies are based in cell lines or isolated cells. Epithelial cells and tissues are essential in the regulation of critical physiological processes, including fluid transport; and so the modulation of such processes in vivo by cell-specific calcium signalling is thus of interest. In this review, we describe the approaches to measuring intracellular calcium in the genetically tractable fluid-transporting tissue, the Drosophila Malpighian tubule by targeting cell-specific protein-based calcium reporters to defined regions,cells and intracellular compartments of the intact Malpighian tubule. We also discuss recent findings on the roles of plasma membrane and intracellular calcium channels; and on organellar stores – including mitochondria,Golgi and peroxisomes – in Malpighian tubule function.