bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations of the interferon sensitivity‐determining region (ISDR) correlate with the complexity of hypervariable region (HVR)‐1 in the Japanese variant of hepatitis C virus (HCV) type 1b
Authors: Nakano Isao , Fukuda Yoshihide , Katano Yoshiaki , Toyoda Hidenori , Hayashi Kazuhiko , Kumada Takashi , Nakano Satoshi 
Published: July 2004

AbstractHepatitis C virus (HCV) genotype 1b comprises mainly two subtypes in Japan, each named for its geographic prevalence (Japan‐specific, J type; worldwide, W type). Because the newly identified subtypes have not been fully characterized, the present study directed this issue from virological viewpoints such as hypervariable region (HVR)‐1 as well as interferon (IFN) sensitivity‐determining region (ISDR). Fifty chronic hepatitis patients with HCV 1b (31 men and 19 women; mean age 50.5 years) were enrolled, and J/W type was determined according to envelope 1 (E1) sequence as described previously (23 J type and 27 W type). Correlations between age, number of HVR‐1 clones, HVR‐1 diversity, and ISDR mutations were analyzed in J and W type patients independently. In addition, the sequences of the three HCV regions obtained for the determination of the above genetic factors were studied phylogenetically. The number of HVR‐1 clones was significantly higher for J type in comparison with W type (P = 0.044). In the J type‐infected patients, the ISDR mutation number was correlated inversely with HVR‐1 clone number (P = 0.0001, r = −0.734) and HVR‐1 diversity (P = 0.0001, r = −0.722). However, this correlation was not observed in the W type patients. W type patients showed a significant correlation between age and HVR‐1 clone number (P = 0.015, r = 0.462). Phylogenetic study revealed that the nonstructural (NS) 5A sequence, which is obtained for ISDR type determination, can distinguish between J and W types. The inverse correlation in J type patients between ISDR mutations and HVR‐1 complexity may explain the usefulness of the ISDR for prediction of IFN response only in Japanese patients. This suggests that the ISDR is not directly related to IFN responsiveness, but the degree of HVR‐1 complexity may be more important. J. Med. Virol. 74:54–61, 2004. © 2004 Wiley‐Liss, Inc.
Hepatitis C virus among self declared non‐injecting sexual partners of injecting drug users
Authors: Roy K.M. , Goldberg D.J. , Hutchinson S. , Cameron S.O. , Wilson K. , MacDonald L. 
Published: July 2004

AbstractWhile much is known about hepatitis C virus (HCV) among injecting drug users (IDUs), there is scant information about the risk of HCV infection to non‐injecting sexual partners of injecting drug users; it is possible that such individuals may have a greater risk of acquiring HCV than any other group barring injecting drug users. This study examines the prevalence of HCV among a population of non‐injecting sexual partners of injecting drug users. Unlinked anonymous testing for anti‐HCV of residual sera stored following the named HIV testing of specimens originally from persons who had indicated to their attending clinicians that they were non‐injecting sexual partners of injecting drug users. The prevalence of anti‐HCV among the sexual partners was 4.1% (25/611) overall, 6.4% (13/202) among heterosexual male and 3.0% (12/397) among the heterosexual female partners. None of the homosexual/bisexual partners were HCV antibody positive (0/12). Although we cannot be sure how non‐injecting partners of injecting drug users acquire their HCV infection, having a relationship with someone who injects drugs may place an individual at appreciable risk of being infected; such individuals should consider being tested for HCV. J. Med. Virol. 74:62–66, 2004. © 2004 Wiley‐Liss, Inc.
One‐year survey of astrovirus infection in children with gastroenteritis in a large hospital in Hungary: Occurrence and genetic analysis of astroviruses
Authors: Jakab Ferenc , Meleg Edina , Bányai Krisztián , Melegh Béla , Tímár László , Péterfai János , Szűcs György 
Published: July 2004

AbstractHuman astroviruses (HAstV) are the causative agents of viral gastroenteritis mainly in children worldwide. This study investigated the epidemiology and genotype diversity of HAstVs detected in children admitted to hospital with gastroenteritis in Hungary. Stool samples were collected from children with diarrhea at the Municipal “Szent László” Hospital, Budapest, Hungary, between January 2002 and December 2002. Of 2,758 samples, 607 were negative for both rotaviruses and bacterial pathogens and were tested for astroviruses using a reverse transcriptase‐polymerase chain reaction (RT‐PCR) targeting the open reading frame (ORF2), capsid region. Astrovirus was detected in 10 samples (1.6%) by RT‐PCR. Astrovirus infection was more frequent among children 49 to 60 months of age. Genotyping of positive samples was performed by type‐specific RT‐PCR and confirmed by sequence analysis. Phylogenetic analysis was performed using a 203 nucleotide consensus length of the 3′‐end of the capsid gene. Type‐specific RT‐PCR and sequence analysis detected genotypes 1 (50%), 4 (30%), 3 (10%), and 8 (10%) among the children admitted to hospital. Genotype 1 was the predominant genotype, but genotypes 3, 4, and 8 were also present indicating the importance of emerging genotype 8 infections. Two distinct genotype 4 variants were observed during this study. Sequence analysis confirmed type‐specific RT‐PCR results in the capsid region. This is the first comprehensive report on the occurrence of HAstV infections in Central/Eastern Europe. J. Med. Virol. 74:71–77, 2004. © 2004 Wiley‐Liss, Inc.
Cytomegalovirus antiviral resistance associated with treatment induced UL97 (protein kinase) and UL54 (DNA polymerase) mutations
Authors: Scott G.M. , Isaacs M.A. , Zeng F. , Kesson A.M. , Rawlinson W.D. 
Published: July 2004

AbstractHCMV‐related illness due to infections with antiviral resistant virus was verified by phenotypic and genotypic assays in 17% (8/47) of high‐risk immunocompromised Australian patients. Selective PCR‐sequencing of UL97 (protein kinase; PK) and UL54 (DNA polymerase; DNApol) regions important for antiviral sensitivity, identified the majority (6/8) of resistant strains through detection of mutations known to confer antiviral resistance. Additionally, eight UL54 (DNApol) mutations (N408K, T691S, A692V, S695T, L737M, A834P, V955I, and A972V) of unknown phenotype were identified in six specimens from patients with clinical evidence of antiviral resistant infections. One isolate was resistant to ganciclovir (GCV) and another resistant to PFA on phenotypic testing where mutations in UL97 (PK) or UL54 (DNApol) were not detected, suggesting a loss of correlation between phenotype and genotype. Selective PCR‐sequencing of UL97 (PK) and UL54 (DNApol) provided rapid and comprehensive results, but missed some resistance detected by phenotypic assays. A combination of phenotypic and genotypic assays is recommended for complete analysis of CMV antiviral resistance, as well as further definition of the clinical relationship between novel UL54 (DNApol) mutations and antiviral resistance. J. Med. Virol. 74:85–93, 2004. © 2004 Wiley‐Liss, Inc.
Detection of high‐risk human papillomavirus E6 and E7 oncogene transcripts in cervical scrapes by nested RT‐polymerase chain reaction
Authors: Sotlar Karl , Stubner Annette , Diemer David , Menton Susanne , Menton Michael , Dietz Klaus , Wallwiener Diethelm , Kandolf Reinhard , Bültmann Burkhard 
Published: July 2004

AbstractThe oncogenic potential of the high‐risk human papillomavirus (HPV) genotypes (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) depends on the expression of the two viral oncogenes E6 and E7. Thus, the detection of HPV E6/E7 oncogene transcripts could serve as a factor in the evaluation of a risk of development of cervical intraepithelial neoplasia (CIN) and its progression to cervical cancer. A nested RT‐PCR assay for the detection of E6/E7 oncogene transcripts of all known high‐risk HPV genotypes was established. In the study described, 779 high‐risk HPV‐DNA‐positive cervical scrapes exhibiting all grades of CIN, including non‐dysplastic cervical mucosa (CIN 0), were examined. Spliced E6/E7 oncogene transcripts of all the high‐risk HPVs were detected in numerous samples, with an overall detection rate of 47%. In 227 cases with agreement between the cytologic and histologic findings, the prevalence increased with lesion severity: CIN 0, 18%; CIN I, 58%; CIN II, 77%; CIN III, 84%. Multiple transcriptionally active high‐risk HPVs were detected in 12% (33/279) of patients with multiple high‐risk HPV infections. This work sets the stage for a prospective follow‐up study currently being undertaken to evaluate the prognostic relevance of the detection of high‐risk HPV E6/E7 oncogene transcripts for the persistence of a high risk HPV infection, and the possible evolution and further development of a CIN. Future applications of the assay described may include the monitoring of women in studies investigating antiviral treatment or vaccination. J. Med. Virol. 74:107–116, 2004. © 2004 Wiley‐Liss, Inc.
Analysis of human papillomavirus type‐16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer
Authors: Tornesello Maria Lina , Duraturo Maria Luisa , Salatiello Immacolata , Buonaguro Luigi , Losito Simona , Botti Gerardo , Stellato Giovanni , Greggi Stefano , Piccoli Roberto , Pilotti Silvana , Stefanon Bernardina , De Palo Giuseppe , Franceschi Silvia , Buonaguro Franco M. 
Published: July 2004

AbstractHuman papillomavirus type 16 (HPV‐16) classes (E, AA, As, Af1, Af2) and their variants have different geographic distribution and different degrees of association with cervical lesions. This study was designed to examine HPV‐16 variants among Italian women and their prevalence in case patients (affected by invasive cervical carcinoma or cervical intraepithelial neoplasia grade 2–3 and cervical intraepithelial neoplasia grade 1), versus control subjects with normal cervical epithelium (controls). A total of 90 HPV‐16 positive cervical samples from women of Italian Caucasian descent have been tested, including 36 invasive cervical carcinomas, 21 with cervical intraepithelial neoplasias grade 2–3, 17 with cervical intraepithelial neoplasia grade 1 and 16 controls. HPV‐16 was detected with an E6/E7 gene‐specific polymerase chain reaction, and variant HPV‐16 classes and subclasses were identified by direct nucleotide sequencing of the region coding for the E6 and the E7 oncoproteins, the MY09/11‐amplified highly conserved L1 region, and the long control region (LCR). Among the 90 HPV‐16 samples, nine viral variants have been identified belonging to the European (Ep‐T350 and E‐G350) and non‐European (AA and Af‐1) branches. The E‐G350 is the prevalent variant in all analyzed different disease stages being present in 55.5% of ICC, 52.4% of cervical intraepithelial neoplasias 2–3, 47.1% of cervical intraepithelial neoplasia grade 1, and 50.0% of control samples. The non‐European variants AA and Af1, rarely detected in control samples, represent 33.3% of all HPV‐16 infections in invasive cervical carcinoma (with a peak of 19.4% and 13.9%, respectively), showing a statistically significant increase in frequency in more advanced lesions (χ2 trend = 7.2; P < 0.05). The prevalence of HPV‐16 Ep‐T350, however, is higher in controls (43.7%) and in of cervical intraepithelial neoplasia grade 1 (41.2%) than in cervical intraepithelial neoplasia grade 2–3 (28.6%) and in invasive cervical carcinoma (11.1%) cases strongly suggesting lack of progression for pre‐neoplastic lesions associated with such variant. The increased frequency of non‐European variants in invasive lesions suggests that they are more oncogenic than European variants. This could have implications for future diagnostic and therapeutic strategies. J. Med. Virol. 74:117–126, 2004. © 2004 Wiley‐Liss, Inc.
Virus diversity and an outbreak of group C rotavirus among infants and children with diarrhea in Maizuru city, Japan during 2002–2003
Authors: Phan Tung Gia , Nishimura Shuichi , Okame Michio , Nguyen Tuan Anh , Khamrin Pattara , Okitsu Shoko , Maneekarn Niwat , Ushijima Hiroshi 
Published: July 2004

AbstractA total of 236 fecal specimens collected from infants and children with gastroenteritis in Maizuru city, Japan from July 2002 to June 2003, were tested for the presence of rotaviruses, noroviruses, sapoviruses, astroviruses, and adenoviruses by RT‐PCR, PAGE, RPHA, and latex agglutination methods. Among diarrheal viruses detected, group A rotavirus was the most prevalent (32.2%; 76 of 236) followed by norovirus GII (21.2%; 50 of 236), group C rotavirus (10.2%; 24 of 236), adenovirus (3.8%; 9 of 236), sapovirus (2.5%; 6 of 236), astrovirus (1.3%; 3 of 236), and norovirus GI (0.8%; 2 of 236), respectively. It is noteworthy that group C rotavirus infection was apparently confined only within the period of 5 months (December 2002 through April 2003). This pattern of infection implied that the outbreak of group C rotavirus in these patients, which was the first outbreak of gastroenteritis attributed to group C rotavirus in Maizuru city. Moreover, about half (12 of 24) of group C rotavirus infected cases were confined to infants and young children less than 3 years old. Another interesting feature of the study was the demonstration of the mixed infections with group C rotavirus and group A rotavirus, as well as group C rotavirus and norovirus GII in 20.8% (5 of 24) and 8.3% (2 of 24), respectively. This is the first report of gastroenteritis associated with the mixed infections with group C rotavirus and other viral enteropathogens such as norovirus. The results indicate that group C rotavirus could infect not only older children and adults but also infants and young children under 3 years old. J. Med. Virol. 74:173–179, 2004. © 2004 Wiley‐Liss, Inc.
High‐resolution magic angle spinning and 1H magnetic resonance spectroscopy reveal significantly altered neuronal metabolite profiles in CLN1 but not in CLN3
Authors: Sitter Beathe , Autti Taina , Tyynelä Jaana , Sonnewald Ursula , Bathen Tone F. , Puranen Johanna , Santavuori Pirkko , Haltia Matti J. , Paetau Anders , Polvikoski Tuomo , Gribbestad Ingrid S. , Häkkinen Anna‐Maija 
Published: July 2004

AbstractThe neuronal ceroid lipofuscinoses (NCLs) are among the most severe inherited progressive neurodegenerative disorders of children. The purpose of this study was to compare the in vivo 1.5‐T 1H magnetic resonance (MR) and ex vivo 14.3‐T high‐resolution (HR) magic angle spinning (MAS) 1H MR brain spectra of patients with infantile (CLN1) and juvenile (CLN3) types of NCL, to obtain detailed information about the alterations in the neuronal metabolite profiles in these diseases and to test the suitability of the ex vivo HR MAS 1H MRS technique in analysis of autopsy brain tissue. Ex vivo spectra from CLN1 autopsy brain tissue (n = 9) significantly differed from those of the control (n = 9) and CLN3 (n = 5) groups, although no differences were found between the CLN3 and the control groups. Principal component analysis of ex vivo data showed that decreased levels of N‐acetylaspartate (NAA), γ‐aminobutyric acid (GABA), glutamine, and glutamate as well as increased levels of inositols characterized the CLN1 spectra. Also, the intensity ratio of lipid methylene/methyl protons was decreased in spectra of CLN1 brain tissue compared with CLN3 and control brain tissue. In concordance with the ex vivo data, the in vivo spectra of late‐stage patients with CLN1 (n = 3) revealed a dramatic decrease of NAA and a proportional increase of myo‐inositol and lipids compared with control subjects. Again, the spectra of patients with CLN3 (n = 13) did not differ from those of controls (n = 15). In conclusion, the ex vivo and in vivo spectroscopic findings were in good agreement within all analyzed groups and revealed significant alterations in metabolite profiles in CLN1 brain tissue but not in CLN3 compared with controls. Furthermore, HR MAS 1H MR spectra facilitated refined detection of neuronal metabolites, including GABA, and composition of lipids in the autopsy brain tissue of NCL patients. © 2004 Wiley‐Liss, Inc.
Proteomic analysis of phosphotyrosyl proteins in the rat brain: Effect of butorphanol dependence
Authors: Kim Seong‐Youl , Chudapongse Nuannoi , Lee Sang‐Min , Levin Michael C. , Oh Jae‐Taek , Park Hae‐Joon , Ho Ing K. 
Published: July 2004

AbstractButorphanol (17‐cyclobutylmethyl‐3,14‐dihydroxymorphinan) tartrate (Stadol) is a mixed agonist‐antagonist opioid analgesic agent that is about five to seven times as potent as morphine in analgesic effects. The chronic use of butorphanol produces physical dependence in humans and animals. Phosphorylation plays a very important role in developing butorphanol dependence; however, global phosphorylation events induced by chronic butorphanol administration have not been reported. The aim of this study is to determine the alteration of tyrosine phosphorylation of brain frontal cortical proteins in butorphanol‐dependent rats using a proteomic approach. Dependence was produced by continuous intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/μl/hr) for 72 hr via osmotic minipump in rats. Similar patterns of protein expression were detected by two‐dimensional electrophoresis (2‐DE) in brain frontal cortex of butorphanol‐dependent and saline‐treated control rats. All 65 phosphotyrosyl (p‐Tyr) protein spots detected in pH 3–10 phosphotyrosine 2‐DE of control rat brains were detected in butorphanol‐dependent rat brains. The densities of most p‐Tyr protein spots were increased in butorphanol‐dependent rat brains compared to saline‐treated control samples. Eighteen additional p‐Tyr protein spots were detected in pH 3–10 2‐DE images of butorphanol‐dependent rat brains. Immobilized pH strips with three different narrow pH ranges were examined to improve the resolution of p‐Tyr proteins in 2‐DE gels. Fifty‐three p‐Tyr protein spots were identified as known proteins involved in cell cytoskeleton, cell metabolism, and cell signaling. This proteomic approach can provide useful information for understanding the complex mechanism of butorphanol dependence in vivo. © 2004 Wiley‐Liss, Inc.
Differential roles of fibroblast growth factor‐2 during development and maintenance of auditory sensory epithelia
Authors: Carnicero Estela , Zelarayan Laura Cecilia , Rüttiger Lukas , Knipper Marlies , Alvarez Yolanda , Alonso Maria Teresa , Schimmang Thomas 
Published: July 2004

AbstractFibroblast growth factor‐2 (FGF2) has been postulated to be a key regulator involved in the proliferation, differentiation, and regeneration of sensory hair cells. Here we have addressed the potential functions of FGF2 during the formation and regeneration of the auditory epithelium in chicken and mice. By using viral gene transfer, based on herpes simplex type 1 virus (HSV‐1), we show that ectopically applied FGF2 drastically increases the number of cells expressing early hair cell markers during embryonic development in avians. Intriguingly, FGF2 does not stimulate cell division during this process. These data suggest that FGF2 plays a role during differentiation of sensory hair cells in avians. To address the potential functions of FGF2 during murine inner ear development, we analyzed FGF2 mouse mutants. Mice lacking FGF2 showed normal formation of the inner ear, and no abnormalities were observed at the adult stage. Moreover, FGF2 mouse mutants showed similar hearing thresholds compared with those observed in control mice before and after noise damage. Therefore, endogenous FGF2 appears not to be essential for the development or functional maintenance of the auditory organ in mammals. In light of these results, the differential roles of FGF2 in the vertebrate inner ear are discussed with respect to its previously postulated functions. © 2004 Wiley‐Liss, Inc.
γ‐aminobutyric acidergic interneuron vulnerability to aging in canine prefrontal cortex
Authors: Pugliese M. , Carrasco J.L. , Geloso M.C. , Mascort J. , Michetti F. , Mahy N. 
Published: July 2004

AbstractThe aged dog is considered a promising model for examining molecular and cellular processes involved in a variety of human neurological disorders. By using the canine counterpart of senile dementia of the Alzheimer's type (ccSDAT), we investigated the specific vulnerability of the γ‐aminobutyric acid (GABA) cortical subset of interneurons, characterized by their calcium‐binding protein content, to neuronal death. Dogs representing a large variety of breeds were classified into three groups: young control, aged control, and ccSDAT. In all dogs, the general distribution and cell typology of parvalbumin‐, calretinin‐, and calbindin‐positive neurons were found to be similar to those in the human. As in Alzheimer's disease patients, neurons displaying parvalbumin or calretinin immunoreactivity were resistant and the calbindin‐positive ones depleted. Together with aging, amyloid deposition in its early phase (stage II) participates in this specific neuronal death, but with a lower potency. In conclusion, our data provide evidence that preservation of GABAergic cortical interneurons has to be focused on the early stage of β‐amyloid deposition. We also demonstrate the usefulness of dogs of all breeds for investigating the early phases of human brain aging and Alzheimer's disease. © 2004 Wiley‐Liss, Inc.
Acute and persistent protein synthesis inhibition following cerebral reperfusion
Authors: DeGracia Donald J. 
Published: July 2004

AbstractLack of recovery from protein synthesis inhibition (PSI) closely correlates with neuronal death following brain ischemia and reperfusion. It has therefore been suggested that understanding the mechanisms of PSI will shed light on the mechanisms of selective neuronal death following ischemia and reperfusion. It is now known that the PKR‐like ER kinase (PERK)‐mediated phosphorylation of eukaryotic initiation factor 2α (eIF2α) causes translation inhibition at initial reperfusion. Activation of PERK, in turn, indicates endoplasmic reticulum stress and activation of the unfolded protein response. However, phosphorylation of eIF2α is a transient event and can account for PSI only in the initial hours of reperfusion. Although a number of other regulators of protein synthesis, such as eIF4F, 4EBP‐1, eEF‐2, and S6 kinase, have been assessed following cerebral ischemia and reperfusion, the causes of prolonged PSI have yet to be fully elucidated. The purpose of the present article is to bring together the evidence indicating that, at minimum, postischemic PSI should be conceptualized as consisting of two components: an acute, transient component mediated by unfolded protein response‐induced eIF2α phosphorylation and a longer term component that correlates with neuronal death. Ischemic tolerance appears to separate the acute and persistent components of reperfusion‐induced translation inhibition. Specific models of the relationship among acute PSI, persistent PSI, and neuronal death are presented to clarify issues that have emerged from ongoing work in this area. © 2004 Wiley‐Liss, Inc.