bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological recovery despite virological failure is independent of human immunodeficiency virus‐type 1 resistant mutants in children receiving highly active antiretroviral therapy
Authors: Chiappini Elena , Galli Luisa , Zazzi Maurizio , de Martino Maurizio 
Published: June 2003

AbstractRelationships between human immunodeficiency virus‐type‐1 (HIV‐1) drug‐resistant mutants and immunological recovery were investigated after 12‐week antiretroviral therapy in 43 children infected perinatally with virological failure. Twenty‐two children received highly active antiretroviral therapy (HAART) and 21 received double therapy with reverse transcriptase inhibitors. At baseline, no difference in reverse transcriptase or protease inhibitors resistant mutants was present among the groups. After 12 weeks, the two groups were similar regarding proportion of children with reverse transcriptase resistant mutants. Sixteen (73%) HAART‐treated children, but no child receiving double therapy had HIV‐1 with primary resistance mutations to protease inhibitors. Secondary protease mutations were found in all HAART‐treated and in 17/21 (81%) children receiving double therapy. The mutation numbers in reverse transcriptase or protease genes were significantly higher after HAART than after double therapy. Nevertheless, 12 (55%) of HAART‐treated children (but no child receiving double therapy) showed immunological recovery. The frequency and number of mutations were similar in HAART‐treated children with or without immunological recovery both at baseline and after 12 weeks. The findings suggest, immunological recovery notwithstanding, virological failure is independent of drug‐resistant mutations and consequent possible changes in viral fitness. J. Med. Virol. 70:506–512, 2003. © 2003 Wiley‐Liss, Inc.
Molecular epidemiology and transmission of hepatitis B virus in close family contacts of HBV‐related chronic liver disease patients
Authors: Thakur Varsha , Kazim Seyed N. , Guptan Rajkumar C. , Malhotra Veena , Sarin Shiv K. 
Published: June 2003

AbstractThere is limited data on the patterns of HBV mutation in family contacts of chronic liver disease (CLD) patients in India. DNA sequence analysis is an important tool to study this viral epidemiology. Transmission and prevalence of mutations in the S and pre‐C gene region in HBV infected close family contacts of HBV‐related CLD patients were studied. Twelve HBsAg+ index patients and their 20 HBV DNA contacts were studied in detail. The S ORF and the pre‐C region were sequenced using direct PCR products. S‐gene sequencing included 32 specimens (12 index cases and all 20 contacts). Pre‐C gene sequencing included 26 specimens (12 index cases and all the 14 HBsAg+ contacts irrespective of their HBeAg status). More than 98% sequence homology was found between the index patients and their contacts. The in‐depth study of 12 families revealed that the transmission pattern was primarily horizontal in 6 (50%) and vertical in 2 (17%) families (P < 0.05). The remaining four families had evidence of both horizontal and vertical transmission. Mutations in the S‐gene were found in 80% of HBsAg+ and 17% HBsAg− subjects (P < 0.05). A total of 22‐point mutations at different nucleotide positions were found. In these, 16 (72%) were mutation of the “a” determinant region and 14 (64%) resulted in missense mutations. The commonest S‐gene mutations were T118V and A128V, present in 44 and 38% specimens, respectively. T143M and G145R mutations in the second loop of the “a” determinant were found in 9% of the specimens. Novel mutations, C137stp and C138stp were found in only one HBsAg− subject. Mutations in the pre‐C gene were common (91%) in patients with HBeAg− phenotype. G1896A mutation was found in 7 of 11 (64%) specimens changing amino acid tryptophane (W) to stop codon. Other mutations were at codons 25 and 29. The results of the study, demonstrate (1) clustering of Pre‐C and S‐gene mutations in the families, (2) horizontal mode of transmission and a common source infection appears to be frequent as evidenced by sequence homology and detailed history, (3) T118V and A128V were the commonest mutations in the S‐gene region, while (4) M2 (G1896A) was the commonest pre‐C gene mutation, and (5) long‐term follow‐up evaluation of these mutations suggested. J. Med. Virol. 70:520–528, 2003. © 2003 Wiley‐Liss, Inc.
Genotypes and phylogenetic characterization of hepatitis B and delta viruses in Egypt
Authors: Saudy Niveen , Sugauchi Fuminaka , Tanaka Yasuhito , Suzuki Seiji , Aal Amina Abdel , Zaid Mostafa Abo , Agha Salah , Mizokami Masashi 
Published: June 2003

AbstractHepatitis B virus (HBV) and hepatitis D virus (HDV) sequences among HBV carriers from Egypt have not been evaluated sufficiently. The genotypes of HBV isolated from 105 serum samples from Egyptian carriers were determined. Four complete genomes and 11 entire preS1/S2/S genes were sequenced and evaluated. All serum samples were classified into HBV genotype D using serologic and genetic methods. The length of four complete nucleotide sequences was 3,182 bp. In all 15 samples, the common 33 nucleotides (11 amino acids) deletions in the preS1 region specific for HBV genotype D were observed. In the phylogenetic analysis based on the complete nucleotide sequences, all samples were clustered with the HBV isolates reported from previously Western and Mediterranean countries with nucleotide homology ranging from 96.0–98.0%. Of 75 HBsAg positive samples, anti‐HDV was found in 15 (20%), and HDV RNA was detected in 9 of 15 (60%). The proportion of the patients with liver disease was higher in HBV carriers of anti‐HDV positive with HDV RNA than in HBV carriers of anti‐HDV positive without HDV RNA (P < 0.05). In the phylogenetic analysis based on the sequences in nucleotide position 853–1267 of HDV, nine samples were classified into HDV genotype I with the nucleotide homology ranging from 88.3–92.1% (mean; 90.5%) and clustered with HDV strains reported previously from Ethiopia, Somalia, Egypt, and Lebanon. These results indicate that HBV genotype D and HDV genotype I are most prevalent in Egypt, and HDV co‐infection in HBV carriers is related to severity of liver disease. J. Med. Virol. 70:529–536, 2003. © 2003 Wiley‐Liss, Inc.
A case‐control study for early prediction of hepatitis B e antigen seroconversion by hepatitis B virus DNA levels and mutations in the precore region and core promoter
Authors: Yamaura Takahiro , Tanaka Eiji , Matsumoto Akihiro , Rokuhara Akinori , Orii Koji , Yoshizawa Kaname , Miyakawa Yuzo , Kiyosawa Kendo 
Published: June 2003

AbstractFactors influencing and predictive of seroconversion from hepatitis B e antigen (HBeAg) to antibody (anti‐HBe) were sought in a case‐control study of 61 patients with chronic hepatitis B who had been observed from 5 years before to 1 year after seroconversion, and 32 patients who did not seroconvert during the entire 6‐year period. Almost all of the patients (96%) were infected with HBV genotype C. HBV DNA levels began to decrease 3 years before seroconversion in the seroconverters, while they remained high in the non‐converters. The frequency of precore mutation and the loss of HBeAg (A1896) started to increase 1 year before in the converters, and became significantly higher at seroconversion (23 vs. 3%, P = 0.030) than that in the non‐converters. Double mutation in the core promoter (T1762/A1764) was more common in the seroconverters than in the non‐converters 5 years before seroconversion (48 vs. 28%), and became significantly more frequent at seroconversion (65 vs. 41%, P = 0.046). Seroconversion occurred in 75% of the patients with at least HBV DNA levels <5.5 logarithmic equivalents/mL; precore mutation in 20% or more of HBV DNA; or core promoter mutation. Seroconversion occurred in 50% of those patients within 1 year, 88% within 2 years, and 93% within 5 years. These results indicate that a decrease in HBV DNA levels and mutations in the precore region and the core promoter were associated significantly and complementarily with seroconversion, and each of them or a combination thereof was predictive of seroconversion years ahead. J. Med. Virol. 70:545–552, 2003. © 2003 Wiley‐Liss, Inc.
Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: A prospective study
Authors: Yeo Winnie , Chan Paul K.S. , Hui Pun , Ho Wing M. , Lam Kwok C. , Kwan Wing H. , Zhong Sheng , Johnson Philip J. 
Published: June 2003

AbstractBreast cancer is a rapidly increasing problem in many developing countries, and cytotoxic chemotherapy is now an integral part of its management. In several developing countries, the carriage of hepatitis B virus (HBV) in cancer patients may be as high as 12%, and such patients are at risk of developing fatal HBV reactivation during chemotherapy. HBV reactivation is well recognized in patients with hematological malignancies, but limited data are available on patients with other, more common, cancers, such as breast cancer. Recent data have suggested that increased viral replication, an indication of HBV reactivation, may precede clinical hepatitis. In the absence of serial HBV DNA monitoring, HBV reactivation during chemotherapy may have been underestimated. In this prospective study, breast cancer patients who were hepatitis B surface antigen (HBsAg) seropositive were followed up during chemotherapy. The main objectives were to determine the incidence of HBV reactivation in breast cancer patients undergoing conventional chemotherapy; to investigate whether “serial HBV DNA monitoring” improves the accuracy of diagnosing HBV reactivation when compared with previous schema that only measured HBV DNA at the time of clinical hepatitis (“conventional monitoring”); and to assess the clinical consequences as a result of developing the condition. The secondary objective was to identify risk factors associated with this condition. Over an 18‐month period, 41 patients were studied. Ten developed HBV reactivation by conventional monitoring criteria, but with serial HBV DNA monitoring, seven additional patients were diagnosed when increased HBV DNA levels were detected before, but not concomitant with, clinical hepatitis. Thus, a total of 17 patients (41%) developed HBV reactivation. Premature termination of chemotherapy or delay in treatment schedules occurred in 71% of the patients who developed viral reactivation, as compared with 33% in those who did not develop the condition (P = 0.019). No risk factors associated with the development of HBV reactivation could be identified. Serial monitoring of HBV DNA, in addition to liver function, increases the sensitivity of diagnosing of HBV reactivation, and helps explain some cases that would otherwise be labeled as “cryptogenic hepatitis,” for which concomitant HBV DNA measured at the time of hepatitis was undetectable. The present study highlights the importance of monitoring HBsAg‐seropositive patients who are receiving chemotherapy for common solid tumors such as breast cancer. J. Med. Virol. 70:553–561, 2003. © 2003 Wiley‐Liss, Inc.
Endogenous levels of mRNA for IFNs and IFN‐related genes in hepatic biopsies of chronic HCV‐infected and non‐alcoholic steatohepatitis patients
Authors: Abbate Isabella , Romano Mario , Longo Roberta , Cappiello Giuseppina , Lo Iacono Oreste , Di Marco Vito , Paparella Concetta , Spanǒ Alberto , Capobianchi Maria Rosaria 
Published: June 2003

AbstractTo investigate the intra‐hepatic activation of the IFN system in patients affected by chronic HCV‐infection in comparison with that observed in a non‐infectious liver disease such as non‐alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon‐α, interferon‐β and interferon‐γ as well as of IFN‐related genes (IFNAR‐1, STAT1α, PKR, 2‐5 AS, IRF‐1, ICE and IL‐18). In HCV‐infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty‐four chronic untreated HCV‐infected subjects and seven patients with non‐alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra‐hepatic mRNA levels of IFNs and related genes were assessed by semi‐quantitative RT‐PCR. In comparison with non‐alcoholic steatohepatitis, in HCV‐infected subjects IFN‐α and ‐β mRNA levels were significantly lower, whereas IFN‐γ, IFNAR‐1, STAT1α IRF‐1, and IL‐18 mRNA were upregulated. Moreover, IFN‐γ mRNA steady state levels were correlated positively with those of IFNAR‐1, IRF‐1, and IL‐18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL‐18‐specific mRNA, viral load was not related to liver injury. IFN‐γ and IRF‐1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN‐α and ‐β mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN‐γ system and a downregulated IFN‐α and ‐β system, probably due to a mixed effect exerted by HCV‐specific and inflammatory non‐specific factors. J. Med. Virol. 70:581–587, 2003. © 2003 Wiley‐Liss, Inc.
Production of interleukin‐18 and interleukin‐12 in patients suffering from chronic hepatitis C virus infection before antiviral therapy
Authors: Schvoerer E. , Navas M.C. , Thumann C. , Fuchs A. , Meyer N. , Habersetzer F. , Stoll‐Keller F. 
Published: June 2003

AbstractInterleukin‐12 and ‐18 (IL‐12 and IL‐18) are known to enhance the cytotoxic T‐lymphocyte response synergistically, but their precise involvement in hepatitis C virus (HCV) infection is not well known, especially for IL‐18. Enzyme‐linked immunosorbent assay (ELISA) was used to study the production of these cytokines in plasma and peripheral blood mononuclear cells (PBMCs) stimulated by lipopolysaccharide (LPS) of patients infected chronically with HCV before initiation of antiviral therapy. Fifty‐six patients and 40 healthy controls were evaluated. Patients infected with genotype 1 or with genotype other than genotype 1 HCV had significantly a high production of plasma IL‐12 compared with controls (P < 0.05). However, patients infected with genotype 1 HCV had lower levels of PBMC IL‐18 than were founded in the controls (P < 0.05); plasma IL‐18 also tended to be lower in this group of patients than in the controls, although nonsignificantly. Plasma IL‐18 was related to hepatic histological activity (P < 0.05). The data suggest a relationship between these two cytokines and some features of HCV infection, so that their respective production in relation to the outcome of the infection deserves further study. J. Med. Virol. 70:588–593, 2003. © 2003 Wiley‐Liss, Inc.
Prevalence of BK virus and JC virus in peripheral blood leukocytes and normal arterial walls in healthy individuals in China
Authors: Gu Zhi‐Yuan , Li Qi , Si Yi‐Ling , Li Xue , Hao Hao‐Jie , Song Hai‐Jing 
Published: June 2003

AbstractSeveral studies have demonstrated that BK virus (BKV) and JC virus (JCV) establish latent infection in peripheral blood leukocytes (PBLs) of healthy individuals; however, the main populations studied are European. In this study, the prevalence of BKV and JCV DNA in PBLs from healthy adult individuals and umbilical cord blood from newborn children in China was detected by semi‐nested polymerase chain reaction (snPCR) followed by restriction enzyme analysis. The results suggest that the healthy adult Chinese population harbors BKV and JCV DNA in peripheral leukocytes. Overall, the prevalence of BKV and JCV DNA in PBLs of healthy adult individuals was 42.1% and 7.8%, respectively. The overall prevalence of BKV DNA was significantly higher than that of JCV DNA. None of the umbilical cord blood samples from newborn children were positive for BKV and JCV DNA. To understand further the target tissues involved in establishment of BKV and JCV latency in healthy individuals, the presence of DNA from both viruses was detected in normal arterial wall samples from 20 young trauma victims by the same method used for leukocyte DNA. BKV DNA was detected alone in 20% of samples tested; JCV DNA was not detected alone in any of the samples. DNA from both viruses was found in 5% of samples. This is the first report to show that normal arterial walls of healthy individuals may be another target site of latency for BKV and JCV. J. Med. Virol. 70:600–605, 2003. © 2003 Wiley‐Liss, Inc.
Measurement of EBV‐IgG anti‐VCA avidity aids the early and reliable diagnosis of primary EBV infection
Authors: Robertson Peter , Beynon Sandy , Whybin Ross , Brennan Catherine , Vollmer‐Conna Uté , Hickie Ian , Lloyd Andrew 
Published: June 2003

AbstractCurrent serological methods for the diagnosis of Epstein‐Barr virus (EBV) infection still differentiate poorly between primary infection and reactivation. This is particularly true when IgG and IgM antibodies are present simultaneously and only a single serum sample is provided for analysis. The demonstration of the IgG avidity state has the potential to distinguish recent from past or reactivated infection. An analysis of the kinetics of avidity maturation of anti‐VCA antibodies in primary EBV infection was undertaken with longitudinally collected sets of sera from 28 well‐characterised EBV cases and in sera from 35 cases with previous EBV infection and recent primary infection due to HIV, CMV, or hepatitis A. Antibodies directed against the viral capsid antigen (VCA) and Epstein‐Barr nuclear antigen (EBNA‐1) were sought, using a commercial enzyme immunoassay (EIA). In parallel with standard IgG anti‐VCA detection, serum was incubated with 8 M urea to disrupt low‐avidity complexes to allow calculation of the percentage avidity. In cases with primary EBV infection, the mean avidity rose from 54% at 6 weeks to 82% by 28 weeks after the onset of symptoms, but remained lower than that of the control sera (96%). The addition of the avidity measurement improved the sensitivity of IgG and IgM anti‐VCA testing in diagnosis of primary EBV infection from 93% to 100%. The specificity of IgM anti‐VCA testing alone was poor, with 14 of 35 cases (49%) demonstrating false‐positive results, but it improved to 97% by the demonstration of high‐avidity IgG anti‐VCA. The combination of negative IgG anti‐EBNA and low‐avidity IgG anti‐VCA had a sensitivity and specificity of 100%. The routine addition of IgG anti‐VCA avidity estimation to diagnostic EBV serology is recommended. J. Med. Virol. 70:617–623, 2003. © 2003 Wiley‐Liss, Inc.
Congenital infection with human herpesvirus 6 variant B associated with neonatal seizures and poor neurological outcome
Authors: Lanari Marcello , Papa Irene , Venturi Valentina , Lazzarotto Tiziana , Faldella Giacomo , Gabrielli Liliana , Guerra Brunella , Landini Maria Paola , Salvioli Gian Paolo 
Published: June 2003

AbstractHuman herpesvirus 6 (HHV 6) has neurotropic and neuroinvasive properties. The virus has been found in the cerebrospinal fluid of many children with aseptic meningoencephalitis. Intrauterine transmission has been documented by HHV 6 DNA detection in cord blood specimens of apparently healthy newborns and in fetuses following spontaneous abortions. A patient is described with early neonatal afebrile seizures resulting from a congenital HHV 6 variant B infection disclosed by repeated detection of viral genome by polymerase chain reaction (PCR) in cerebrospinal fluid in the first days of life. At follow‐up, magnetic resonance imaging (MRI) studies disclosed hyperintensities in the periventricular white matter and basal ganglia, associated with cerebral atrophy. Further follow‐up at 18 months revealed poor neurological outcome with mild neurodevelopmental retardation, strabismus and hypertonia of legs. This report provides evidence of neurological involvement after HHV 6 vertical transmission, and the association with neurological sequelae. J. Med. Virol. 70:628–632, 2003. © 2003 Wiley‐Liss, Inc.
Enhanced mucosal and systemic immune responses following intravaginal immunization with human papillomavirus 16 L1 virus‐like particle vaccine in thermosensitive mucoadhesive delivery systems
Authors: Park Jeong‐Sook , Oh Yu‐Kyoung , Kang Min‐Jeong , Kim Chong‐Kook 
Published: June 2003

AbstractTo develop more potent and convenient mucosal human papillomavirus (HPV) vaccines, we tested the effect of thermosensitive mucoadhesive vaginal vaccine delivery systems on the local and systemic antibody responses to HPV 16 L1 virus‐like particles (VLP). HPV 16 L1 VLP expressed from recombinant baculovirus‐infected Sf21 insect cells were delivered in phosphate‐buffered saline (PBS) or thermosensitive mucoadhesive delivery systems, composed of poloxamers (Pol) and varying amounts of polyethylene oxide (PEO). Pol/PEO‐based vaginal vaccine delivery systems existed in liquid form at room temperature, but gelled at 37°C. The mucoadhesiveness of Pol/PEO‐based delivery systems increased with PEO, but the formulations with PEO higher than 1.0% were too viscous to be administered into the vagina. Vaccine vehicles affected the vaginal and salivary immune responses to HPV 16 L1 VLP intravaginally administered into mice. At 42 days after the first intravaginal immunization of HPV 16 L1 VLP with cholera toxin, vaginal and salivary IgA titers were the highest in the group given in Pol/PEO 1.0% vehicle followed by Pol/PEO 0.4% and PBS vehicles. Intravaginal coadministration of HPV 16 L1 VLP and cholera toxin in Pol/PEO 1.0% showed 31‐ and 39‐fold higher titers compared to the PBS‐based HPV 16 L1 VLP groups administered by intravaginal and intramuscular routes, respectively. Following intravaginal administration, Pol/PEO 1.0%, but not Pol/PEO 0.4%, showed significantly higher HPV 16 L1 VLP‐specific serum IgG titers as compared to the PBS vehicle. Our results indicate that the use of in situ‐gelling vaginal vaccine delivery systems with increased mucoadhesiveness would be beneficial for more effective induction of mucosal and systemic immune responses to intravaginally administered HPV 16 L1 VLP vaccines. J. Med. Virol. 70:633–641, 2003. © 2003 Wiley‐Liss, Inc.
Genetic and antigenic characterization of measles viruses that circulated in Korea during the 2000–2001 epidemic
Authors: Na Byoung‐Kuk , Shin Ju‐Mi , Lee Joo‐Yeon , Shin Gu‐Choul , Kim Yoon‐Young , Lee Jin‐Soo , Lee Jong‐Koo , Cho Hae‐Wol , Lee Hoan‐Jong , Rota Paul A. , Bellini William J. , Kim Woo‐Joo , Kang Chun 
Published: June 2003

AbstractDespite the marked reduction in the incidence of measles in Korea by the introduction of measles vaccine, a large measles epidemic occurred during 2000–2001. During the epidemic, more than 55,000 measles cases were reported and at least 7 children were dead. In this study, we analyzed the genetic and antigenic properties of 15 measles viruses that isolated during the epidemic. Sequence analyses of entire hemagglutinin (H) and nucleoprotein (N) genes of the viruses indicated that all Korean isolates had a high degree of homology (>99.8%) when compared with each other. They differed from other wild‐type viruses by as much as 6.8% in the H gene and 6.5% in the N gene at the nucleotide level. The deduced amino acid variability was up to 6.4% for the H protein and up to 6.5% for the N protein. Phylogenetic analysis of nucleotide sequences and deduced amino acid sequences of the H and N genes revealed that all Korean viruses were grouped into the genotype H1. This strongly demonstrated that single genotype of measles virus has been circulated in Korea during the 2000–2001 epidemic. Plaque reduction neutralizing antibody titers against vaccine strains, Edmonston and Schwarz, and recently isolated Korean strains were measured using sera from vaccinees and recently infected children. Although sera of recently infected children demonstrated higher neutralizing antibody titers against wild‐type strains than against vaccine strains, both sera neutralized both strains and the reciprocal geometric mean titers (GMTs) were not significantly different against both strains. J. Med. Virol. 70:649–654, 2003. © 2003 Wiley‐Liss, Inc.