bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan
Authors: Khan Anis , Tanaka Yasuhito , Azam Zahid , Abbas Zaigham , Kurbanov Fuat , Saleem Uzma , Hamid Saeed , Jafri Wasim , Mizokami Masashi 
Published: May 2009

AbstractStudies conducted in different populations worldwide revealed an association between HCV genotype 1 and the development of hepatocellular carcinoma (HCC) than in infection with other HCV genotypes. There are reports which reveal the association of HCV genotype 3a (HCV‐3a) with hepatic steatosis and fibrosis but its relation with the development of HCC has not been investigated. In Pakistan, where the incidence of HCC is increasing, 189 patients with chronic liver disease including 82 with HCC were enrolled. HCV genotypes were determined by phylogeny in the NS5B region and the epidemic history of HCV‐3a was examined using coalescent theory based methods. HCV‐3a was the predominant genotype (81.4%) in the cohort studied, followed by 3b (9.3%), 3k (2.3%), 1a (1.5%), 1c (1.5%), 1b (0.8%), and 2a (0.8%) where 76% of HCC and 86% of non‐HCC were infected with HCV‐3a. The significant factors associated with HCC were older age (mean ± SD) 55.8 (±9.9) (P < 0.0001), and male gender (P < 0.001). HCV RNA was significantly higher in patients with HCC and chronic hepatitis than in liver cirrhosis (P < 0.0001). Molecular evolutionary analysis revealed a distinct phylogenetic cluster of HCV‐3a in Pakistan and an estimation of the effective number of HCV infections indicated the appearance of HCV‐3a in this region around 1920s and a rapid exponential growth in the 1950s. This indicates that the epidemic spread of HCV‐3a occurred earlier in Pakistan than in other countries in which this genotype has been reported. HCV‐3a which spread earlier in Pakistan may be associated with an increasing incidence of HCC. J. Med. Virol. 81:1189–1197, 2009. © 2009 Wiley‐Liss, Inc.
Hepatitis C virus infection in the family setting of patients with occult hepatitis C
Authors: Castillo Inmaculada , Bartolomé Javier , Quiroga Juan Antonio , Barril Guillermina , Carreño Vicente 
Published: May 2009

AbstractFamily members of patients with chronic hepatitis C virus (HCV) infection are at increased risk of HCV infection but the prevalence of HCV among family members of patients with occult HCV infection is not known. Anti‐HCV, serum HCV RNA and levels of liver enzymes were determined in 102 family members of 50 index patients with occult HCV infection and in 118 family members of 59 chronic hepatitis C index patients. HCV RNA and/or anti‐HCV were detected in 10/102 (9.8%) relatives of patients with occult HCV infection and in 4/118 (3.4%) of patients with chronic hepatitis C. Fourteen additional family members (seven were relatives of index patients with occult HCV infection) had abnormal values of liver enzymes without serological markers of HCV infection. Two of these patients (who were relatives of two index patients with occult HCV infection) underwent a liver biopsy and were diagnosed with an occult HCV infection because HCV RNA was detected in the liver cells in the absence of serological HCV markers. In conclusion, the prevalence of HCV infection among family members of patients with occult HCV infection was similar to that found among family members of patients with chronic hepatitis C. This stresses the need to adopt strategies to prevent the transmission of HCV in the family setting of patients with occult HCV infection. J. Med. Virol. 81:1198–1203, 2009. © 2009 Wiley‐Liss, Inc.
TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C
Authors: Askar Eva , Bregadze Rusudan , Mertens Jasmin , Schweyer Stefan , Rosenberger Albert , Ramadori Giuliano , Mihm Sabine 
Published: May 2009

AbstractPhenotypes of liver disease due to chronic hepatitis C virus (HCV) infection show a wide range of variations in terms of histological manifestations and the clinical outcome. Sensing of viral double‐stranded RNA (dsRNA) by Toll‐like receptor 3 (TLR3) is likely involved in early pathogen detection and the host response to viral infection. This study analyzed epidemiological and clinical data from a total of 137 patients with chronic HCV infection with regard to two polymorphic positions within the TLR3 gene: rs5743305 (T/A) is located within the promoter region and might affect transcriptional activity, rs3775291 (C/T) is a non‐synonymous single nucleotide polymorphism (SNP) located within exon 4 and the variant receptor has been shown to be functionally impaired. TLR3 promoter and the exon 4 variations were not found to be associated with TLR3 gene expression in peripheral blood mononuclear cells (PBMCs). In the liver, however, a tendency of higher TLR3 gene expression was found for exon 4 TT genotypes. Both variations were not found to be associated with clinical parameters of chronic disease. On the other hand, an analysis of the TLR3 exon 4 genotype distribution with respect to HCV subtype revealed an absence of TT genotype among HCV subtype 1a infected individuals. This study thus failed to reveal any association of the two SNPs under investigation with clinical parameters of chronic hepatitis C. However, data argue for a functional relevance of the exon 4 SNP in terms of conferring a different susceptibility towards HCV subtype infection. J. Med. Virol. 81:1204–1211, 2009. © 2009 Wiley‐Liss, Inc.
Investigation of pre‐diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus‐infected patients
Authors: Grabowski Mary K. , Viscidi Raphael P. , Margolick Joseph B. , Jacobson Lisa P. , Shah Keerti V. 
Published: May 2009

AbstractProgressive multifocal leukoencephalopathy (PML) is a severe neurological disorder due to JC virus (JCV) infection. Pre‐diagnostic biological markers and risk factors for PML are not well understood. We conducted a case–control study nested within the Multicenter AIDS Cohort Study to examine the association between JCV viruria and viremia and serum antibody to JCV capsids, in relation to subsequent PML diagnoses, 5 months to 12 years later. Other demographic and immunologic factors were also examined. The study population included 28 incident cases of PML, 26 matched HIV‐positive controls, and 50 HIV‐negative controls. Prevalence of JCV viruria was 37% in cases, 42% in HIV‐positive controls, and 28% in HIV‐negative controls (P = 0.43). Among persons with JCV viruria, persistent viruria was more common in cases (89%) than in HIV‐positive controls (33%) (P = 0.02). Presence of JCV viruria was not related to the time to PML diagnosis (OR: 1.03, 95% CI: 0.8–1.4); however, the urinary concentration of JCV DNA increased with proximity to the date of PML diagnosis in cases. JCV seropositivity did not differ between cases or controls (P = 0.42). Four cases tested JCV seronegative, including one case only 5 months prior to diagnosis with PML. JCV DNA was detected in the serum of one HIV‐positive control. Smoking was the only demographic variable analyzed associated with an increased risk for PML (MOR: 9.0, 95% CI: 1.2–394.5). The results suggest that persistent JCV viruria and increasing urinary concentration of JCV DNA may be predictive of PML for some patients. J. Med. Virol. 81:1140–1150, 2009. © 2009 Wiley‐Liss, Inc.
Molecular analysis of HPV 16 E6I/E6II spliced mRNAs and correlation with the viral physical state and the grade of the cervical lesion
Authors: Cricca Monica , Venturoli Simona , Leo Elisa , Costa Silvano , Musiani Monica , Zerbini Marialuisa 
Published: May 2009

AbstractThe presence of HPV 16 E6*I/E6*II spliced transcripts, in cervical lesions of different grade, was analyzed to characterize the transcription pattern. The presence and amount of spliced transcripts were correlated with DNA viral markers such as E2/E6 ratio and physical state. The detection of HPV 16 E6*I/E6*II mRNAs was set up by an SYBR Green real‐time reverse transcriptase PCR assay with an optimal dynamic range and sensitivity. The assay was applied to the analysis of 71 specimens, positive to HPV 16 as a sole infection, from women with abnormal cervical smears, precisely 31 low‐grade squamous intraepithelial lesions and 40 high‐grade lesions. Samples negative to both transcripts were found only in low‐grade cervical lesions. Three different transcription profiles were found in the low‐ and high‐grade lesions analyzed: in low‐grade lesions samples positive only to E6*II and in high‐grade lesions samples positive only to E6*I were detected. In low‐ and high‐grade lesions, samples positive to both E6*I and E6*II were found. In the samples positive for both transcripts, the E6*I/E6*II ratio was higher than that in the majority of high‐grade lesions and lower than that in all the low‐grade lesions. Analyzing the transcription pattern in relation to E2/E6 ratio and to the DNA physical state, the presence of high values of E6*I was associated mainly with low values of E2/E6 ratio and of mixed DNA forms. The detection of HPV 16 E6*I/E6*II mRNAs may serve to identify transcription patterns indicative of cervical disease progression and help physicians to decide clinical management. J. Med. Virol. 81:1276–1282, 2009. © 2009 Wiley‐Liss, Inc.
Enterovirus 71‐induced autophagy detected in vitro and in vivo promotes viral replication
Authors: Huang Shu‐Chen , Chang Chia‐Lun , Wang Po‐Shun , Tsai Yu , Liu Hsiao‐Sheng 
Published: May 2009

AbstractEnterovirus 71 (EV71) is an important pathogen causing death in children under 5 years old worldwide. However, the underlying pathogenesis remains unclear. This study reveals that EV71 infection in rhabdomyosarcoma (RD) and neuroblastoma (SK‐N‐SH) cells stimulated the autophagic process, which was demonstrated by an increase of punctate GFP‐microtubule‐associated protein 1 light chain 3 (GFP‐LC3), the level of autophagosome‐bound LC3‐II protein and double‐membrane autophagosome formation. EV71‐induced autophagy benefited EV71 replication, which was confirmed by the autophagic inducer rapamycin and the inhibitor 3‐methyladenine. Signaling pathway investigation revealed that the decreased expression of phosphorylated mTOR and phosphorylated p70S6K is involved in EV71‐induced autophagy in a cell‐specific manner. The expression of phosphorylated extracellular signal‐regulated kinase (Erk) was suppressed consistently in EV71‐infected cells. However it did not participate in the autophagic response of the cell. Other signaling pathway molecules, such as Erk, PI3K/Akt, Bcl‐2, BNIP3, and Beclin‐1 were not affected by infection with EV71. Electron microscopy showed co‐localization of autophagosome‐like vesicles with either EV71‐VP1 or LC3 protein in neurons of the cervical spinal cord in ICR mice infected with EV71. In conclusion, EV71 infection triggered autophagic flux and induced autophagosome formation both in vitro and in vivo. Autophagy induced by EV71 is beneficial for viral replication. Understanding the role of autophagy induced by EV71 in vitro and the formation of autophagosome‐like vesicle in vivo provide new insights into the pathogenesis of EV71 infection. J. Med. Virol. 81:1241–1252, 2009. © 2009 Wiley‐Liss, Inc.
The dominance of China 1 in the spectrum of Epstein–Barr virus strains from Cantonese patients with nasopharyngeal carcinoma
Authors: Li Da‐Jiang , Bei Jin‐Xin , Mai Shi‐Juan , Xu Jin‐Fen , Chen Li‐Zhen , Zhang Ru‐Hua , Yu Xing‐Juan , Hong Ming‐Huang , Zeng Yi‐Xin , Kang Tiebang 
Published: May 2009

AbstractNasopharyngeal carcinoma is a disease with a remarkable geographic and ethnic distribution, and has a high incidence in southern China. Infection with Epstein–Barr virus (EBV) is an important contributing factor. The profile of EBV strains in Cantonese patients from Guangdong, the nasopharyngeal carcinoma endemic region in southern China, is described on the sequence variations in latent membrane protein 1 carboxyl‐terminus. The results show that China 1 was the dominant EBV strain detected in both the tumor biopsies and samples of throat washings, whereas multiple strains, including China 1, China 2, B95‐8, and Med, were detected in blood samples. In addition, a new strain named China 4 was found in blood samples. These findings suggest that the host population is susceptible to the predominant China 1 strain in the nasopharyngeal carcinoma endemic region of China, but its relationship with the host remains to be characterized further. J. Med. Virol. 81:1253–1260, 2009. © 2009 Wiley‐Liss, Inc.
Effect of HIV co‐infection on mutation patterns of HBV in patients with lamivudine‐resistant chronic hepatitis B
Authors: Iacomi Fabio , Vincenti Donatella , Vairo Francesco , Solmone Mariacarmela , Mariano Andrea , Piselli Pierluca , Puro Vincenzo , Capobianchi Maria Rosaria , Antonucci Giorgio 
Published: May 2009

AbstractA retrospective review was performed comparing lamivudine‐resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co‐infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti‐HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125–213 aa. Eighty‐nine patients infected with HBV (29 co‐infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co‐infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co‐infection (adjusted OR 11.2, 95% CI 2.0–61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5–34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co‐infection were more likely to harbor the rtM204V mutation. Patients co‐infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co‐infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat. J. Med. Virol. 81:1151–1156, 2009. © 2009 Wiley‐Liss, Inc.
Sequence and structural analysis of the 5′ noncoding region of hepatitis C virus in patients with chronic infection
Authors: Araújo Flávio Marcos Gomes , Machado‐Lima Ariane , Durham Alan Mitchell , Teixeira Rosangela , Oliveira Guilherme 
Published: May 2009

AbstractHepatitis C virus (HCV), exhibits considerable genetic diversity, but presents a relatively well conserved 5′ noncoding region (5′ NCR) among all genotypes. In this study, the structural features and translational efficiency of the HCV 5′ NCR sequences were analyzed using the programs RNAfold, RNAshapes and RNApdist and with a bicistronic dual luciferase expression system, respectively. RNA structure prediction software indicated that base substitutions will alter potentially the 5′ NCR structure. The heterogeneous sequence observed on 5′ NCR led to important changes in their translation efficiency in different cell culture lines. Interactions of the viral RNA with cellular transacting factors may vary according to the cell type and viral genome polymorphisms that may result in the translational efficiency observed. J. Med. Virol. 81:1212–1219, 2009. © 2009 Wiley‐Liss, Inc.
A neuropsychological study comparing patients infected with HCV and HBV without psychiatric comorbidities
Authors: Quarantini Lucas C. , Miranda‐Scippa Angela , Batista‐Neves Susana , Powell Vania B. , Abreu Neander , Abreu Katiusha C. , Moura Ilka , Crane Jacquelyn , Sampaio Aline S. , Netto Liana R. , deOliveira Irismar R. , Paraná Raymundo , Bressan Rodrigo A. , Lacerda Acioly L.T. 
Published: May 2009

AbstractHepatitis C is one of the most common chronic infectious diseases worldwide, with well‐documented extra‐hepatic manifestations, such as a broad number of cognitive deficits. These impairments may be explained by psychiatric comorbidities, which have not been investigated properly in the literature. In order to elucidate a specific hepatitis C virus (HCV) induced cognitive impairment not related to mental disorders, neuropsychological performance of patients infected with HCV was compared with that of patients infected with hepatitis B virus cognitive impairment, especially psychiatric comorbidities. A total of 33 patients infected with HCV and 22 patients infected with HBV were included in the study. There were no significant differences between the two groups with regard to age or years of education. The group of patients infected with HCV performed significantly worse on visuo‐spatial memory tasks after adjusting for years of education and age. There were no significant differences between patients infected with HCV and patients infected with HBV with regards to other neuropsychological functions. The data indicate that patients infected with HCV patients have poorer visuo‐spacial memory performance than patients infected with HBV, suggesting that the cognitive deficit may be specific to HCV infection and not to secondary comorbid psychiatric disorders. J. Med. Virol. 81:1184–1188, 2009. © 2009 Wiley‐Liss, Inc.
Tracking the transmission routes of genogroup II noroviruses in suspected food‐borne or environmental outbreaks of gastroenteritis through sequence analysis of the P2 domain
Authors: Xerry Jacqueline , Gallimore Chris I. , Iturriza‐Gómara Miren , Gray Jim J. 
Published: May 2009

AbstractThe aim of this study was to apply sequence analysis of a hyper variable region of the norovirus (NoV) genome in order to identify point source outbreaks associated with suspect food or water. The hyper‐variable region of the gene encoding the P2 domain was chosen as small differences in sequence are likely to indicate virus from different sources whereas identical sequence may reveal transmission routes and the source of contamination. Strains with 100% similarity were considered as originating from a common source, whereas, strains with one or more mutations in the hyper variable region sequenced were regarded as representing unrelated transmission events. This study was able to identify a point source outbreak of a dominant strain, GII‐4, on a cruise ship but also of a less common strain, GII‐2, between two schools. Also identical GII‐3 strains were demonstrated in food handlers amongst the same outbreak; however epidemiologically related outbreaks showed different GII‐3 strains indicating multiple sources of contamination. J. Med. Virol. 81:1298–1304, 2009. © 2009 Wiley‐Liss, Inc.
Hepatitis C virus screening and clinical monitoring of biomarkers in patients undergoing hemodialysis
Authors: Maia Laura Patrícia Viana , Martins‐Filho Olindo Assis , Teixeira‐Carvalho Andréa , Speziali Elaine , Vermhren Rolandro , Lira Edson Fonseca , Lima Tatiane Amabile , Braga Wornei Silva , Torres Kátia Luz , Malheiro Adriana 
Published: May 2009

AbstractIn this study, 395 volunteers were enrolled to investigate the seroprevalence of hepatitis C virus, the immunological and the alanine aminotransferase (ALT) biomarkers amongst hemodialysis patients, living in Manaus, Brazil. An overall seroprevalence of 13.9% was found in the hemodialysis patients. Analysis of seroconversion patterns demonstrated that most patients with HCV seroconverted up to 10 years following the first hemodialysis session. Anti‐NS5 antibody was detectable in 60.4% of patients with HCV. A lower percentage of circulating CD3+ and CD4+ T‐cells was found in patients seronegative for HCV, whereas a higher frequency of CD8+ T‐cells was the hallmark of patients with HCV. An overall low activation state of monocytes and eosinophils were observed in hemodialysis patients. In contrast, a higher frequency of activated neutrophils was observed in patients with HCV, selectively in the NS5+ subgroup. All hemodialysis patients had a higher percentage of activated lymphocytes, with the higher activation state in patients with NS5− reactivity. Higher ALT levels were observed in patients with HCV, especially in the NS5+ subgroup. Interestingly, the ALT levels were correlated negatively with the lymphocyte activation state, selectively in the NS5− subgroup, suggesting a protective role of these activated lymphocytes in patients with HCV. These findings reinforce the importance of the transmission of HCV among hemodialysis patients, suggesting that apart from the HCV screening, the serological and ALT biomarkers may represent important predictors of morbidity and/or mortality among patients undergoing hemodialysis. J. Med. Virol. 81:1220–1231, 2009. © 2009 Wiley‐Liss, Inc.
Aberrant expression of synaptic plasticity‐related genes in the NF1+/− mouse hippocampus
Authors: Park Chang Sin , Zhong Ling , Tang Shao‐Jun 
Published: May 2009

AbstractNeurofibromatosis 1 (NF1) is a common single‐gene disorder that causes learning impairments in patients. Neurofibromin encoded by the NF1 causal gene regulates Ras/MAPK and cAMP signaling pathways. These signaling pathways play critical roles in controlling gene transcription during synaptic plasticity and memory formation. We hypothesized that NF1 mutations disturb the expression of genes important for memory formation. To test this hypothesis, we performed DNA microarray analysis on the hippocampus of NF1+/− mice, the mouse model for NF1 learning disabilities. Our results indicated that genes involved in a wide spectrum of biological processes are dysregulated in the NF1+/− hippocampus. Many of the NF1‐affected genes play critical roles in synaptic plasticity, such as Rabs, synaptotagmins, NMDAR1, CaMKII, and CREB1. Because NF1‐associated learning disabilities can be reversed by lovastatin, we also determined the effect of lovastatin treatment on genome‐wide expression patterns of the NF1+/− hippocampus. We found that lovastatin altered the expression of a large number of genes, including those disturbed by NF1 mutations. Our results reveal a genome‐wide overview of the molecular abnormalities in the NF1+/− hippocampus and should be useful for further identifying the novel molecular pathways that cause NF1 learning deficits. © 2009 Wiley‐Liss, Inc.