bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of hepatitis C and B viruses infection on the development of hepatocellular carcinoma
Authors: Tsai Jung‐Fa , Chang Wen‐Yu , Jeng Jen‐Eing , Ho Mei‐Shang , Lin Zu‐Yau , Tsai Juei‐Hsiung
Published: March 2007

A case control study consisting of 102 patients with HCC, 102 sex‐matched and age‐matched patients with nonhepatic disease, and 204 matched healthy controls was carried out to investigate the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC). The prevalence of antibody to HCV (anti‐HCV) in HCC (34.3%) was higher than in nonhepatic disease (10.7%, P< 0.001) or in healthy controls (2.4%, P< 0.001). The prevalence of hepatitis B surface antigen (HBsAg) in HCC (77.4%) was higher than in nonhepatic disease (16.6%, P< 0.001) or in healthy controls (19.6%, P< 0.001). Anti‐HCV positivity in nonhepatic disease was higher than in healthy controls (P<0.01). Using patients with nonhepatic disease as controls, stepwise logistic regression analysis indicated that both anti‐HCV (odds ratio, 3.4; 95% confidence interval, 2.1‐5.6) and HBsAg (odds ratio, 5.6; 95% confidence interval, 3.6–8.5) are independent risk factors for HCC. Using healthy controls, the development of HCC was also strongly associated with anti‐HCV (odds ratio, 8.0; 95% confidence interval, 4.3–14.6) and HBsAg (odds ratio, 5.5; 95% confidence interval, 3.7–8.2). Calculation of incremental odds ratio indicated that there is no interaction between HBV and HCV. In conclusion, HBV and HCV are risk factors of HCC. They act independently and without interaction. © 1994 Wiley‐Liss, Inc.
Differences in the entire nucleotide sequence between hepatitis B virus genomes from carriers positive for antibody to hepatitis B e antigen with and without active disease
Authors: Horikita Minoru , Itoh Susumu , Yamamoto Kayoko , Shibayama Takao , Tsuda Fumio , Okamoto Hiroaki
Published: March 2007

The entire nucleotide sequence was determined for eight hepatitis B virus (HBV) genomes from three symptom‐free carriers, two patients with chronic persistent hepatitis and one patient with chronic active hepatitis, who were positive for antibody to hepatitis B e antigen (HBeAg). The two patients with chronic persistent hepatitis were tested again after they developed chronic active or fulminant hepatitis, making a total of eight samples. Six had a point mutation in the preC region prohibiting the encoding of HBeAg precursor, while the remaining two had a deletion of 8 or 21 nucleotides within the X gene upstream of the preC transcription initiation sites which would affect the X gene and the putative preC/C promoter. Most genomes from the three symptom‐free carriers and the two patients with chronic persistent hepatitis, with HBV DNA levels of 102–103/ml, had deletion, frameshift mutation, initiation failure or a premature stop codon, rendering them replication‐incompetent. In contrast, such mutations were rarely seen in HBV genomes from the two patients with chronic persistent hepatitis after they had developed active or fulminant hepatitis and from the patient with chronic active hepatitis, all of whom had vigorous HBV replication with serum HBV DNA from 106 to 109/ml. Unique mutations for amino acid changes were more frequent in HBV genomes with a higher replicative activity. These results indicate two kinds of HBV genomes with an HBeAg‐minus phenotype, one with defects seriously affecting viral replication and the other without such defects, which would account for different clinical profiles in carriers with antibody to HBeAg. © 1994 Wiley‐Liss, Inc.
Detection of hepatitis B virus DNA in the serum of Canadian hepatitis B surface antigen negative, anti‐HBc positive individuals, using the polymerase chain reaction
Authors: Scully Linda J. , Sung Howard , Pennie Ross , Gill Peter
Published: March 2007

Continuing hepatitis B virus (HBV) infection is normally associated with the presence of hepatitis B surface antigen (HBsAg) in the serum. In spite of sensitive screening assays for HBsAg, rare cases of post‐transfusion HBV infection are still observed. Antibody to hepatitis B core antigen (anti‐HBc) often indicates remote HBV infection but DNA hybridisation and more sensitive polymerase chain reaction (PCR) assays have demonstrated that some HBsAg negative individuals, positive for anti‐HBc, have continuing HBV replication. To determine the incidence of ongoing HBV infection in a Canadian HBsAg negative, anti‐HBc positive population we studied three groups with this combination of HBV markers: Group A, 36 patients referred for investigation of raised serum aminotransferases; Group B, 21 Canadian Red Cross blood donors; Group C, seven vaccinees in an Ottawa Health Care Student hepatitis B vaccination programme. The PCR was carried out using a nested PCR reaction with primers specific for the pre‐core region of HBV.

Seven of 36 (19%) patients in Group A had detectable HBV DNA whereas none of Group B or C were positive. This data indicates that in some HBsAg negative patients with ongoing hepatic inflammation, continuing HBV replication may persist. This was not observed in any healthy blood donors or health care students investigated. Larger studies are required, but this data would suggest that, in Canada, the addition of anti‐HBc testing for all blood donors for detection of low level HBV replication would not be indicated. © 1994 Wiley‐Liss, Inc.
Polymerase chain reaction and sequencing for typing rhinovirus RNA
Authors: Mori Julie , Clewley Jonathan P.
Published: March 2007

Primers were designed and tested for their ability to distinguish rhinoviruses from enterovi‐ruses. A primer set derived from the 5′‐UTR/VP coding region junction was able to amplify all the rhinovirus serotypes tested. Enteroviruses were either not amplified by these primer pairs or produced a band of larger size that could easily be discriminated from the rhinovirus‐specific product. In contrast, primers embedded in the 5′‐UTR region alone were able to amplify both rhinovirus and enterovirus RNA. It is shown that rhino‐viruses could be specifically typed by sequencing the amplicon derived from this 5′‐UTR set. The sequences of the 5′‐UTR region often previously unsequenced rhinoviruses were derived. The sequences obtained cluster into two groups: 18,41, 15, 30, 63, 31,56, and 44; and 17, 69, and 70. Ampliconsfrom serotypes 17, 69, and 70 also group by sequence with the equivalent region of HRV14 from the genetic database, while the others group with 2 and 89. © 1994 Wiley‐Liss, inc.
Long‐term follow‐up of hepatitis B virus carrier infants
Authors: Chan Cho‐Yu , Lee Shou‐Dong , Yu May‐Ing , Wang Yuan‐Jen , Tsai Yang‐Te , Lo Kwang‐Juei
Published: March 2007

One hundred twenty‐two hepatitis B surface antigen (HBsAg) carrier infants were followed‐up for 8–10 years. One hundred eleven had antibody to hepatitis B core antigen (anti‐HBc; 83 had been vaccinated) and the remaining 11 were without anti‐HBc (7 had been vaccinated). During the follow‐up period, 29 (26.1%) carrier infants with anti‐HBc had one or more episodes of ala‐nine aminotransferase (ALT) elevation and up to 32.8% (21/64) of the carriers in this group lost their hepatitis B e antigen (HBeAg) before the age of 10. In addition, 2 (1.8%) carriers lost their HBsAg at the age of 3 and 8, respectively. No significant symptom or sign was noted during HBeAg seroconversion. In contrast, all the carrier infants without anti‐HBc were still positive for both HBeAg and hepatitis B virus (HBV) DMA and none displayed abnormal ALT levels or any symptom related to liver disease. One became anti‐HBc positive at the age of 9, and 5 other carriers had inconsistent borderline or weakly positive titers of anti‐HBc. The episodes of ALT elevation and the prevalence of HBeAg seroconversion were not significantly different between immunized carrier infants. In conclusion, HBeAg seroconversion may occur in about one third of the anti‐HBc‐positive carrier infants during the first decade. On the other hand, the anti‐HBc‐negative HBsAg carrier infants' immune incompetence to the HBV antigens could persist for more than 10 years. Hepatitis B immunization did not have significant effect on the clinical course in carriers. © 1994 Wiley‐Liss, Inc.
Complete nucleotide sequence of a strain of coxsackie B4 virus of human origin that induces diabetes in mice and its comparison with nondiabetogenic coxsackie B4 JBV strain
Authors: Kang Yup , Chatterjee Nando K. , Nodwell Michael J. , Yoon Ji‐Won
Published: March 2007

The E2 strain of coxsackie B4 virus (CB4), which is of human origin, can induce a diabetes‐like syndrome in mice. The cDNA of the genome of the E2 strain was cloned and sequenced. The E2 viral genome was found to comprise 7,396 bases, which appear to encode a polyprotein of 2,183 amino acids with an overall similarity of 94.91% to nondiabetogenic CB4 prototype JBV strain. The E2 genome is organized like other enteroviruses. It has a 5′ noncoding region of 744 nucleotides, a single long open translational reading frame starting at nucleotide 745 and extending to nucleotide 7293, a 3′ noncoding region of 100 nucleotides, and a poly (A) tract. Ge‐nomic sequence comparison of the E2 and JBV strains showed 1,369 nucleotide substitutions in the genome of the E2 strain, most of which are single and silent. There were 111 resultant amino acid changes arising from some of these substitutions, including 82 amino acid changes in the noncapsid proteins, and 29 amino acid changes in the capsid proteins VP1, VP2, VP3, and VP4, which showed 11, 13, 4, and 1 substitution(s), respectively. Noncapsid protein P2‐C showed eight amino acid substitutions. On the basis of the sequence comparison of E2 and JBV strains of CB4, we suggest that some of the amino acid changes in the capsid and noncapsid proteins of the E2 strain may be involved in the determination of its diabetogenicity. © 1994 Wiley‐Liss, Inc.
Hepatitis E seroprevalence in selected individuals in South Africa
Authors: Grabow W. O. K. , Favorov M. O. , Khudyakova N. S. , Taylor M. B. , Fields H. A.
Published: March 2007

Antibodies to the hepatitis E virus (HEV) were detected by an enzyme immunoassay using synthetic HEV peptides. Positive anti‐HEV results were confirmed by a neutralization assay and Western blot analysis. Anti‐HEV was detected in 10 of 555 canoeists (1.8%) with regular exposure to sewage‐polluted water and in 6 of 227 (2.6%) medical students with minimal exposure. The overall prevalence of 16 per 782 individuals (2.05%) suggests that HEV may be endemic in South Africa. This is confirmed by indications of infection earlier than the third decade of life, and by individuals with anti‐HEV who had rarely or never been out of the country. The prevalence data suggest that regular exposure to sewage‐polluted water was not a particular risk factor. None of the individuals with anti‐HEV had a history of clinical hepatitis E, suggesting sporadic low level subclinical cases of infection. This is in agreement with the absence of reports on clinical cases or outbreaks of hepatitis E in South Africa. © 1994 Wiley‐Liss, Inc.
Monitoring of renal allograft recipients by quantisation of human cytomegalovirus genomes in peripheral blood leukocytes
Authors: Kühn J. E. , Wendland T. , Schäfer P. , Möhring K. , Wieland U. , Elgas M. , Eggers H. J.
Published: March 2007

The ratio of human cytomegalovirus (HCMV) genomes per cellular genomes in serial peripheral blood leukocyte (PEL) extracts of renal allograft recipients was quantitated by competitive nested polymerase chain reaction (PCR). Patients were also monitored for the development of acute HCMV infection by detection of HCMV pp65 antigenemia, HCMV IgM antibodies, and viruria. Compared to qualitative nested HCMV PCR, the frequency of positive PCR results in renal allograft recipients without further evidence of acute HCMV infection was significantly reduced by quantitative HCMV PCR. HCMV DMA levels ≥1,000 copies HCMV/106 copies β‐globin were found to be highly indicative for the development of a clinically symptomatic HCMV infection following renal allograft transplantation. In patients treated with ganciclovir, quantitation of HCMV target sequences allowed the assessment of the efficacy of antiviral therapy. © 1994 Wiley‐Liss, Inc.
Immunogenicity and safety in adults of hepatitis A virus vaccine administered as a single dose with a booster 6 months later
Authors: Briem H. , Safary A.
Published: March 2007

An inactivated vaccine against hepatitis A was administered as a single 1,440 enzyme‐linked immunosorbent assay (ELISA) units dose at month 0 with a booster at month 6 to 200 subjects divided into two age groups: group 1, 20–39 years (n = 134) and group II, 40–62 years (n = 66). At day 15, the seropositivity rates were 90% and 77% in groups I and II, respectively. At month 1 the seropositivity rate was 97% in both groups. At month 6 the seropositivity rates were 94% and 88% in groups I and II, respectively. One month after the booster, at month 7, 100% in both groups had become seropositive. The vaccine was well tolerated and did not cause any severe reactions. The results indicate that a single high vaccine dose offers protection against hepatitis A virus (HAV) for at least 6 months in the majority of cases where rapid vaccination is required even in travellers of older age. A booster dose will ensure long‐term protection. © 1994 Wiley‐Liss, Inc.
Inactivated hepatitis A vaccine: Reactogenicity, immunogenicity, and long‐term antibody persistence
Authors: van Damme P. , Thoelen S. , Cramm M. , de Groote K. , Safary A. , Meheus A.
Published: March 2007

This trial evaluated the reactogenicity, kinetics of antibody induction, and long‐term immunogenicity of a 720 enzyme‐linked immunosorbent assay units (EL. U.) antigen dose of an inactivated hepatitis A vaccine (Havrix(tm), SmithKline Beecham Biologicals, Rixensart, Belgium). One hundred six healthy adult volunteers were enrolled to receive vaccine intramuscularly according to a 0, 1, and 6‐month schedule. The vaccine was well tolerated. The most frequently reported local symptom was soreness, observed following 37.1% of all doses. Headache was the most frequently reported general symptom observed following 12.9% of documented vaccine doses. The administration of one vaccine dose induced seropositivity (anti‐hepatitis A virus [HAV] ≥ 20 mlU/ml) in 91% of all vaccinees 1 month later. The second vaccine dose resulted in seropositivity of the remaining vaccinees at month 2. All subjects remained seropositive for HAV antibodies at month 6, at which time the booster vaccine dose was given. At month 7, all vaccinees had anti‐HAV titres > 200 mlU/ml.

Serological results obtained at months 12, 18, 24, and 36 showed that antibodies against HAV induced by the vaccine booster dose persist for at least 30 months following its administration. All 49 subjects followed up until month 36 had antibody titres ≥ 20 mlU/ml. The geometric mean titre (GMT) decreased by 60% from month 7 to month 12; between month 12 and 36, the GMT decreased by approximately 14% per period of 12 months. According to the vaccine‐induced antibody kinetics and the magnitude of antibody level decrease overtime, the predicted duration of antibody persistence is estimated to be at least 20 years. © 1994 Wiley‐Liss, Inc.
A rapid and sensitive method of identification of HTLV‐II subtypes
Authors: Dube Syamalima , Spicer Timothy , Bryz‐Gornia Virginia , Jones Barbara , Dean Therese , Love Jayne , Dube Dipak K. , Poiesz Bernard J. , Ferrer Jorge , Esteban Nestor , Harrington William , Glaser Jordan , Williams Allan , Dosik Harvy , Siegal Frederick
Published: March 2007

There are 2 subtypes of human T‐cell lymphoma/ leukemia virus type II (HTLV‐II), A and B. HTLV‐II is increasingly associated with rare forms of lymphocytic neoplasia and a neurodegenerative disorder, characterized by hyperspasticity and ataxia. We have used PCR to amplify, clone and sequence 140 bp of the pol gene from many isolates of HTLV‐IIA and HTLV‐IIB from around the world. Analysis of these and other published sequences established that all HTLV‐IIA sequences contained a unique Hinf I site and all HTLV‐IIB sequences a unique Mse I site. A rapid and specific oligomer restriction (OR) assay was developed utilizing the primer pair SK110/SK111 and subsequent digestion with these enzymes. Concordance between sequenced and OR‐based subtyping of DNA amplified by PCR was absolute among 22 HTLV‐II isolates tested.

Further OR or sequence analyses on an additional 30 other isolates indicated that the majority of North American non‐indian HTLV‐II isolates were subtype A, while all Paleo‐Amerindian samples, including those from the Seminole of Florida; the Guaymi from Panama; and the Toba, Chorote, Wichi, and Chulupe of Argentina, belonged to subtype B. The SK110/SK111 PCR‐OR format should facilitate molecular epidemiology studies of HTLV‐II infection and allow for subtype stratification in assessing the sensitivity and specificity of HTLV detection formats and HTLV‐II disease association. © 1995 Wiley‐Liss, inc.
Clinical recurrence of hepatitis A following liver transplantation for acute liver failure
Authors: Gane Edward , Sallie Richard , Saleh Mohammed , Portmann Bernard , Williams Roger
Published: March 2007

This paper documents clinically significant recurrence of hepatitis A virus (HAV) infection in a 63‐year‐old man transplanted for HAV‐related acute liver failure. HAV RNA was documented in the explant and, following early clearance from the blood and graft, was again detected in postoperative biopsies at the time of an acute hepatic illness. Although the clinical and biochemical abnormalities resolved completely, the patient had a second episode of graft dysfunction 6 months later and investigations revealed hepatitis C virus (HCV)‐related chronic active hepatitis consistent with acquired HCV infection at the time of transplantation. The possible interaction with hepatitis A may have delayed the appearance of hepatitis C. Administration of HAV immunoglobulin at the time of transplantation should be considered in all cases of HAV‐related fulminant hepatic failure. © 1995 Wiley‐Liss, Inc.
Enteric prevalence of adenovirus in human immunodeficiency virus seropositive patients
Authors: Durepaire Nathalie , Ranger‐Rogez Sylvie , Denis Francois , Gandji Jean Alain , Weinbreck Pierre , Rogez Jean Philippe
Published: March 2007

To evaluate the prevalence of adenovirus strains in human immunodeficiency virus (HlV)‐positive patients and to investigate their possible role in the onset of diarrhea, a total of 103 stools from HIV‐seropositive patients at various stages of infection and 200 stools from sex and age cross‐matched control subjects were examined. Adenovirus prevalence was measured by ELISA as well as conventional and rapid cell culture techniques. Results were compared between patients suffering from diarrhea and those without diarrhea. Adenovirus prevalence was statistically greater in HIV‐seropositive cases than controls (8.7%, 2.5%, respectively). No significant difference was found between HIV‐positive patients with diarrhea and those without gastrointestinal complications (P > 0.05). However, a significant difference in adenovirus prevalence was found between HIV‐positive patients with diarrhea and control subjects with diarrhea (P = 0.02). Although viral prevalence varied with the different stages of HIV infection, differences were not statistically significant. In conclusion, although current opinion considers adenovi‐ruses to be no more than opportunistic pathogens, the results of this large‐scale study do not exclude a potential reactivation of latent adenovirus in HIV infection and suggest that further effort should be directed to elucidating such a mechanism if it exists as well as investigating the specific role of certain adenovirus serotypes in provoking diarrhea during later stages of HIV infection. © 1995 Wiley‐Liss, Inc.
Adenovirus genome types isolated from stools of children with gastroenteritis in São Paulo, Brazil
Authors: Hársi Charlotte M. , Rolim Danielle P. , Stewien Klaus E. , Candeias José Alberto N. , Gomes Selma A. , Gilio Alfredo E. , Baldacci Evandro R.
Published: March 2007

In a prospective one‐year study of acute gastroenteritis in hospitalized children less than 2 years of age, in São Paulo (Brazil), adenoviruses were detected by specific enzyme immunoassay (El‐ARA) in 7 of 67 (10%) ill children and in 9 of 79 (11.4%) controls. They were the sole recognizable agent of diarrhea in 6 ill children. In another child these viruses were detected in a dual infection with astrovirus. Enteric adenoviruses (Ad40/41) were the most common serotypes detected in children with diarrhea (3/7) and Ad7 the sero‐type most detected in the controls (5/9), associated with lower respiratory tract infection. Thirteen adenovirus strains, isolated in HEp2 or HEK‐293 cells, were characterized by seroneutralization and restriction enzyme analysis. The established adenoviruses were typed as AV‐7‐D5 (five associated to lower respiratory tract infection and one to diarrhea), AV‐1‐D10 (one diarrhea case), AV‐31‐D2 (two controls with respiratory infection), and two isolates as AV‐12‐D7, a new genome type. One subgenus D isolate, sero‐type 28, with restriction patterns different from those of the prototype, remained untyped. Only one enteric adenovirus could be typed. The restriction patterns of this isolated were similar to those of the prototype AV‐41‐D1. The genome type of the other three enteric adenoviruses could not be determined. © 1995 wiley‐Liss, inc.
Single‐step nested polymerase chain reaction for detection of different genotypes of hepatitis C virus
Authors: Li Ji‐Su , Tong Shu‐Ping , Vitvitski Ludmila , Trépo Christian
Published: March 2007

Hepatitis C virus (HCV) exhibits considerable sequence variability and circulates in the blood at extremely low levels. Current methods for detecting HCV RNA are based mostly on nested polymerase chain reaction (PCR), in which part of the first amplification product is reamplified in the second tube by an internal primer pair. A novel nested PCR method was developed in which the two successive amplification processes are carried out in the same tube with a single step of physical manipulation. Careful selection of highly conserved sequences of the 5′ noncoding region as primers enabled successful detection of all three major genotypes circulating in France, including the one with variation in this region. Retaining high sensitivity of the conventional nested PCR, the novel method reduced greatly the risk of carry‐over contaminations. It was also cost‐ and time‐saving. The one‐step nested PCR method is especially suitable for routine diagnosis of HCV infection in clinical laboratories. © 1995 Wiley‐Liss, Inc.
Detection of acute measles infections by indirect and μ‐capture enzyme immunoassays for immunoglobulin M antibodies and measles immunoglobulin G antibody avidity enzyme immunoassay
Authors: Tuokko Hanna
Published: March 2007

An avidity test for measles IgG was developed and applied to the study of IgG immunoglobulin maturation kinetics in follow‐up sera from 12 patients with known acute primary and convalescent measles and sera from blood donors. The avidity of the IgG anti‐measles responses was measured using the 8 M urea elution technique, the results being expressed as the percentage ratio between the test readings for eluted and noneluted samples. The IgG avidity results were compared with those of indirect and μ‐capture IgM enzyme immunoassays. This test was capable of detecting low‐avidity antibodies at the acute phase of measles up to 7 weeks, and increasing avidity through immunosaturation during the convalescent phase. The avidity in these samples did not reach the level found in the samples of the blood donors under the follow‐up time. Although a limited number of serum samples was examined, the results suggest that the measles IgG avidity test is a powerful tool for differentiating primary measles infection from the convalescent phase. © 1995 Wiley‐Liss, inc.
Hepatitis B vaccination in infants of mothers infected with human immunodeficiency virus
Authors: Arrazola M. P. , De Juanes J. R. , Aragón A. J. , de Codes A. Garcia , Ramos J. T.
Published: March 2007

A study was conducted to investigate the immunogenicity of a recombinant DNA hepatitis B vaccine in neonates and children of HIV‐infected women. Immunization against hepatitis B consisted of three 10 μg doses of the vaccine administered on a 0‐, 1‐ and 6‐month schedule. The children were followed up for an average of 11 months. Of the 118 HIV‐positive neonates who participated in the study, 95 lost their HIV antibodies during the follow‐up period. Most (94.2%) of the latter who completed the study responded to the vaccine. Of the 23 who remained HIV‐positive, 17 completed the study and 7 produced hepatitis B antibodies. © 1995 Wiley‐Liss, inc.
Follow‐up of antibody responses to human papillomavirus type 16 E7 in patients treated for cervical carcinoma
Authors: Baay Marc F. D. , Herbrink Paul , Stolz Ernst , Duk Jitze M. , Burger Matthé P. M. , De Bruijn Henk W. A.
Published: March 2007

A synthetic peptide comprising amino acids 6‐35 of HPV‐16 E7 was used in an ELISA to screen sera taken from 31 cervical carcinoma patients. Sera obtained before and during treatment, and in follow‐up, were tested for the presence of antibodies to this peptide. Sixteen patients with negative pretreatment serum determination remained negative during treatment and follow‐up. Of the 15 patients with positive pretreatment sera, 12 showed a decrease in anti‐E7 6–35 antibody level during treatment. During follow‐up an increase in anti‐E76–35 antibody level was observed in 6 out of 7 patients with progressive or recurrent disease, whereas all patients who remained in complete remission showed stable or further decreasing antibody levels. During the course of disease of the 15 seropositive patients, serum anti‐E76–35 antibody levels were compared with serum squamous cell carcinoma antigen (SCC‐Ag) profiles, a clinically useful tumor marker in the management of cervical cancer patients. Similar patterns were observed in 10 out of 15 patients. The results of this study suggest that in a subset of cervical cancer patients, anti‐E76–35 antibody response against HPV‐16 E7 at least partially depends on the presence of viable tumor lesions, and that to some extent the anti‐E7 profile reflects the course of disease. © 1995 Wiley‐Liss, inc.
Epidemiologic survey and genetic analysis of endemic hepatitis C virus infection in a Japanese town with a high prevalence of hepatitis B virus carriers
Authors: Tawaraya Hironobu , Ohkoshi Showgo , Kuwana Kenji , Watanabe Masashi , And Tomoteru Kamimura , Asakura Hitoshi
Published: March 2007

Mass screening for hepatitis C virus antibody was carried out in 875 inhabitants (313 men and 562 women) of a town in Japan with a high rate of hepatitis B virus infection. The overall rate of positivity for anti‐HCV was 8.8% (6.4% in men and 10,1% in women). The rate of positivity for hepatitis B virus surface antigen was 11.2%. Five subjects (0.6%) were positive for both markers. HCV‐RNA was detected in 65 (88.4%) of 77 individuals who were positive for anti‐HCV and in 1 (1.5%) of 60 individuals negative for anti‐HCV. The genotype of the HCV genome was determined by PCR analysis using type‐specific primers in 60 individuals. HCV type 1b was detected in 51 subjects (85%), type 2a in 3 subjects (5%), and type 2b in 6 subjects (10%). None of the individuals was infected with more than one genotype. The nucleotide sequences of the partial nonstructural 5 region of HCV type 1b genotype obtained from 6 individuals showed at least 92.0% homology in the nucleotide sequence, and 94.8% homology in the amino acid sequence. Homology among these clones was greater than their homology with previously described type 1 b sequences. The findings suggest that there was a specific local origin of HCV infection, although it was not possible to identify any single source of HCV infection. The results also indicate the presence of asymptomatic HCV carriers. © 1995 Wiley‐Liss, Inc.
Intrafamilial transmission of hepatitis C virus in hemodialysis patients
Authors: Hou Chia‐Hsiu , Chen Wan‐Yu , Kao Jia‐Horng , Chen Ding‐Shinn , Yang Yu , Chen Jyuhn‐Juh , Lee Suh‐Huoy , Wu Der‐John , Yang Shu‐Chang
Published: March 2007

The prevalence of hepatitis C virus (HCV) infection in chronic hemodialysis patients ranges from 20 to 50% and these patients may serve as a reservoir of infection for their household contacts. The aim of this study was to investigate the prevalence of anti‐HCV in hemodialysis patients and their families, and to evaluate possible routes of infection. One hundred eighty‐six family members of 84 hemodialysis patients and 529 healthy adults were enrolled. The family members consisted of 50 spouses, 96 children, 11 parents, 29 siblings, and other relatives living together with the patients. Serum samples were collected for testing anti‐HCV. Exposure to risk factors was obtained by a questionnaire and an interview. The results showed that prevalence of anti‐HCV in hemodialysis patients was 44%, whereas in family members it was 5.4%, not significantly different from that of age‐matched healthy adults (standardized morbidity rate = 1.51, P = 0.390). The anti‐HCV rate in family members tended to increase with age, and a spouse of an infected hemodialysis patient had a higher risk of HCV infection than other family members (15% vs. 2.6%, odds ratio 6.6, P = 0.058). Except for the age factor, no difference was found between seropositive and se‐ronegative family members with respect to risk factors such as blood transfusion, surgery, frequent injections, dental procedures, or acupuncture. It was concluded that, although the anti‐HCV positivity of hemodialysis patients is high, the risk of HCV infection for their family members is not higher than that of the general population. Among family members, spouses of seropositive hemodialysis patients have the highest risk of HCV infection. These data imply that long‐term intimate contact between spouses plays a key role in the intrafamilial transmission of HCV. © 1995 Wiley‐Liss, inc.
A helper T‐cell antigen enhances generation of hepatitis C virus‐specific cytotoxic T lymphocytes in vitro
Authors: Kita Hiroto , Miura Hideaki , Nakamura Ikuo , Inamori Hideaki , Kaneko Takashi , Ohnishi Shin , Yazaki Yoshio , Moriyama Takashi , Kodama Tatsuhiko , Hiroishi Kazumasa , Imawari Michio , Harase Ichiro
Published: March 2007

A T‐cell help for generation of hepatitis C virus‐specific cytotoxic T lymphocytes was studied in three patients with chronic hepatitis C. In all three, human leukocyte antigen B44‐restricted cytotoxic T lymphocytes recognizing an epitope in hepatitis C virus nucleocapsid protein residues 81–100 were generated from the peripheral blood lymphocytes by repeated stimulation with a synthetic hepatitis C virus nucleocapsid pep‐tide. The proliferative response of peripheral blood lymphocytes to hepatitis C virus nucleocapsid protein residues 1–120 was observed in one patient, and was ascribed to CD4+ T cells. The helper T cells recognized a major epitope in residues 21–40 and a minor epitope(s) in residues 81–110. They produced interferon γ, but interleukin 4 was not detectable in the T‐helper cell culture supernatants. The hepatitis C virus nucleocapsid protein residues 1–120 and the major helper T‐cell epitope enhanced generation of hepatitis C virus‐specific cytotoxic T lymphocytes in vitro, although the protein alone did not generate them. In the other two patients, the protein did not enhance generation of hepatitis C virus‐specific cytotoxic T lymphocytes in vitro. The results suggest that a hepatitis C virus‐specific helper T‐cell epitope is helpful for inducing a strong specific cytotoxic T‐lymphocyte response. © 1995 Wiley‐Liss, Inc.
Herpes simplex virus‐1 replication in histiotypic rotation‐mediated reaggregated murine brain
Authors: Fowler Sandra L. , Forbes Robert A.
Published: March 2007

Inbred mouse strains exhibit varying susceptibilities to severe herpes simplex virus (HSV)‐1 ‐related neurologic disease. HSV‐1 replication was examined in neural tissue obtained from mouse strains susceptible (A/J, SJL), moderately resistant (Balb/c), or resistant (C57BL/6) to severe HSV‐1 disease. Reaggregated brain cultures were prepared from mechanically dissociated fetal mouse brains maintained with constant rotation. The resulting aggregates each contain neurons, astrocytes, oligodendrocytes, and microglia. These were inoculated with 10−2−104 plaque‐forming units (pfu) HSV‐1 Maclntyre/aggregate. Aggregates and media were harvested at 24, 48, 72, and 96 hr post‐inoculation (p.i.) and assayed for virus production by plaque titration. Brain cultures prepared from A/J, SJL, Balb/c, and C57BL/6 mice supported HSV‐1 replication equally well: by 96 hr p.i., titers of 106 pfu/ml were produced by each strain at each inoculum. ID50s were similar for A/J and C57BL/6 cultures. There was no increased capacity for HSV‐1 replication or for permissiveness for HSV‐1 infection in histiotypic brain cultures from mouse strains susceptible to severe HSV‐1 disease. © 1995 Wiley‐Liss, Inc.
Treatment of chronic hepatitis C with cirrhosis with recombinant human granulocyte colony‐stimulating factor plus recombinant interferon‐alpha
Authors: Pardo Margarita , Castillo Inmaculada , Navas Sonia , Carreño Vicente
Published: March 2007

Interferon therapy in cirrhotic patients with hepatitis C virus infection is not efficient. In an attempt to improve the response rate, a pilot study using recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) alone, and in combination with recombinant interferon‐alpha (rIFN), was carried out. Fifteen cirrhotic patients with hepatitis C virus infection were randomly allocated into 3 groups to receive treatment: 0.5, 1, or 1.5 μg/kg of rhG‐CSF daily for 4 weeks, followed by a 4 week resting period, and by the same dose of rhG‐CSF daily, plus 6 MU of rIFN 3 times weekly for 4 weeks. They then continued to receive 6 MU of rIFN alone for 4 weeks, followed by 3 MU of rIFN for 16 weeks. After the 4 weeks of treatment with rhG‐CSF alone, no changes in ala‐nine aminotransferase (ALT) levels were observed. No changes occurred during the resting period. Three of 10 patients who ended the rhG‐CSF plus rIFN treatment period had normal ALT values. During the treatment with rIFN alone, two responders suffered a relapse. The other responder had normal ALT until the first month of follow‐up. In summary, the combination of rhG‐CSF and rIFN seems promising for the treatment of patients with chronic hepatitis C and liver cirrhosis. © 1995 Wiley‐Liss, Inc.
Hepatitis C virus type I(1a) in Northern China
Authors: Niu Junqi , Kumar Umesh , Pan Yu , Liu Yuanyuan , Zhan Qingquan , Thomas Howard , Monjardino John
Published: March 2007

Twenty‐four patients with hepatitis C virus (HCV) antibody from the Chinese North Western province of Jilin were further analysed by the immunoblot assay‐2 (RIBA‐2). reverse transcription‐polymerase chain reaction (RT‐PCR) for serum HCV RNA detection, and direct sequence‐geno‐typing. Good concordance was found between the original second generation HCV antibody ELISA, RIBA‐2, and serum HCV RNA. The occurrence of genotype I (la), a genotype not previously reported in China, is described in 5(20.8%) of 24 cases, in association with genotypes II(1b) and III(2a) which were found in 16(66.7%) and 3(12.5%) of 24 cases, respectively. Imported blood products were unlikely to be the source of infection with genotype I (1a) but could not be definitively ruled out. © 1995 Wiley‐Liss, Inc.
Distribution of varicella‐zoster virus gpI and gpII and corresponding genome sequences in the skin
Authors: Nikkels Arjen F. , Delvenne Philippe , Debrus Serge , Sadzot‐Delvaux Catherine , Piette Jacques , Rentier Bernard , Piérard Gérald E.
Published: March 2007

In the course of varicella‐zoster virus (VZV) infection, some viral capsid antigens are found in the epidermis and dermis. The aim of this study was to investigate the localisation of two major VZV glycoproteins (gpI and gpII) and of their respective genes in the skin.

The distribution of VZV gpI and II in 27 formalin fixed paraffin embedded skin biopsies from herpes zoster eruptions were compared by immunohistochemistry. Double immunostaining was carried our to identify infected cells. The presence of viral nucleic acids coding for gpI and gpII was examined by in situ hybridisation.

The distribution of gpI and gpII and their corresponding genome sequences was similar in the epidermis. gpI and gpII were also detected in dermal FXIIIa positive dendrocytes, in Mac 387 and CD68 positive macrophages, and in perineural and endothelial cells. However, the corresponding viral nucleic acids were rarely and barely detected in these cells of the dermis. It is concluded that VZV infection of epithelial cells follows a different course than in dermal cells. © 1995 Wiley‐Liss, Inc. © 1995 Wiley‐Liss, Inc.
Heterosexual activity as a risk factor for the transmission of hepatitis C virus
Authors: Utsumi Takeshi , Hashimoto Etsuo , Okumura Yusuke , Takayanagi Makiko , Nishikawa Hiroaki , Kigawa Mika , Kumakura Nobuhiro , Toyokawa Hiroyuki
Published: March 2007

Hepatitis C virus (HCV), the major causative agent of non‐A, non‐B hepatitis, is transmitted by parenteral exposure. Transmission by sexual activity, however, is controversial. Possible behavioral risk factors for HCV infection were studied retrospectively among imprisoned men (n = 201, mean age: 45 years [S.D. 13]) who visited a health service center at a Japanese correctional facility for medical examination. Seropositivity of anti‐HCV antibody was disproportionately high (49.8%) in comparison with volunteer blood donors. Among possible risk factors significant on univariate analysis, intravenous drug abuse and Tama‐Ire, a Japanese custom of sexual behavior that suggests frequent, aggressive or promiscuous heterosexual activity, proved to be independent risk factors for HCV infection (odds ratio = 7.39, 95% CI = 3.41 ‐ 16.05, P< 0.0001; odds ratio = 3.16, 95% CI = 1.16 ‐ 8.64, P = 0.026, respectively) as shown by logistic regression analysis. The data suggest that HCV may be transmitted by sexual activity. © 1995 Wiley‐Liss, Inc. © 1995 Wiley‐Liss, Inc.
Usefulness of simple assays for serum concentration of hepatitis C virus RNA and HCV genotype in predicting the response of patients with chronic hepatitis C to interferon α2a therapy
Authors: Suzuki Toshio , Tanaka Eiji , Matsumoto Akihiro , Urushihara Akihiko , Sodeyama Takeshi
Published: March 2007

The use of two new assays was evaluated for predicting the response to interferon (IFN) therapy in patients with chronic hepatitis C. The genotype of hepatitis C virus (HCV) was establishe by an enzyme‐linked immunosorbent assay based on genotype‐specific recombinant peptides of the NS4 region (genotyping ELISA). The concentration of HCV RNA was measured by a branched DNA assay (bDNA assay). Seventy‐eight patients received the same regimen of IFNα2a. Of the 74 patients assessed who completed the program, 38 (51.4%) were responders; i.e., their serum aminotransferase levels remained normal for 6 months or longer after stopping IFN, while 36 (48.6%) were nonresponders. The results of the HCV genotype determined by the genotyping ELISA and by the polymerase chain reaction (PCR) assay based on genotype specific primers were similar. The serum concentrations of HCV RNA as measured by the bDNA assay and by the competitive PCR assay correlated closely and significantly (r = 0.82, P< 0.0011. Multiple logistic regression analysis showed that the serum concentration of HCV RNA determined by the bDNA assay, the HCV genotype determined by the genotyping ELISA, and the histology activity index (HAI) of the liver were independently associated with IFN efficacy. By using these three variables in combination, a predictive rate of 82.4% was obtained. A lower level of HCV RNA, genotype 2 and a lower HAI score for liver histology were predictive of a favorable response to IFN. Thus, the genotyping ELISA and the bDNA assay appear to be useful for clinical management of patients receiving IFN therapy. © 1995 Wiiey‐Liss, Inc.
Sequential respiratory syncytial virus cytomegalovirus pneumonia following bone marrow transplantation
Authors: Kapelushnik Joseph , Engelhard Dan , Mehta Jayesh , Or Reuven , Brandstetter Yuval , Picard Elie , Cividalli Gabriel , Nagler Arnon
Published: March 2007

A 6‐month‐old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV‐ and CMV‐induced lung injury in these life‐threatening infections. © 1995 Wiley‐Liss, Inc.
Nucleotide sequence of hepatitis B virus isolated from subjects without serum anti‐hepatitis B core antibody
Authors: Gotoh Kenichiro , Mima Satoaki , Uchida Toshikazu , Shikata Toshio , Yoshizawa Kouji , Irie Mitsuru , Mizui Masaaki
Published: March 2007

The nucleotide sequences of the precore/core and X open reading frames (ORFs) of hepatitis B virus (HBV) were studied in four subjects who were serologically negative for anti‐hepatitis B core antibody. These subjects were positive for serum hepatitis B surface antigen and were considered to be asymptomatic HBV carriers. Sequencing of the precore/core ORF revealed precore wild type and 3 to 8 nucleotide substitutions (replacing 0 to 2 amino acids) in the core region compared with the sequence of subtype adr. These substitutions were not considered to have changed the epitope of the core antigen, resulting in the absence of anti‐HBc as determined by a conventional diagnostic kit. The X ORF showed 1 to 5 nucleotide substitutions (replacing 1 to 3 amino acids) and the structure of the X protein and the core promoter/enhancer II complex appeared to be conserved. These findings strongly suggest that the absence of serum anti‐HBc is not due to mutation of the HBV DNA but to an aberrant immune reaction of the host to HBV. © 1995 Wiley‐Liss, Inc.
Persistence of extrahepatic hepatitis B virus DNA in the absence of detectable hepatic replication in patients with baboon liver transplants
Authors: Lanford Robert E. , Michaels Marian G. , Chavez Deborah , Brasky Kathleen , Fung John , Starzl Thomas E.
Published: March 2007

The presence of hepatitis B virus (HBV) DNA in extrahepatic tissues has been well documented. Whether HBV DNA can persist in extrahepatic tissues for long periods of time in the absence of replication in the liver has not been determined previously. Recently, two patients with end‐stage liver disease secondary to chronic active HBV were treated with baboon liver xenotransplants as these animals are felt to be resistant to HBV infection. Multiple tissues from these two patients were examined for HBV DNA using polymerase chain reaction (PCR). HBV DNA was not detectable in four of five samples of the liver xenografts. A positive signal was observed in a single assay for one sample, but this sample was not positive in subsequent assays. HBV DNA was detected in peripheral blood lymphocytes, spleen, kidney, bone marrow, pancreas, lymph node, heart and small intestine. The level of HBV DNA in these tissues was too low for the detection of HBV DNA replicative intermediates by Southern hybridization; thus, it could not be determined whether the HBV DNA in these tissues represented actively replicating HBV in extrahepatic sites, integrated HBV sequences, HBV in infiltrating lymphocytes, or deposition of HBV immune complexes originating from the plasma. However, it is clear from this study that HBV DNA persisted in multiple tissues for 70 days after replication in the liver had ceased or at least was below the level of detection by PCR. © 1995 Wiley‐Liss, Inc.
Absence of human papillomavirus DNA from esophageal carcinoma as determined by multiple broad spectrum polymerase chain reactions
Authors: Smits Henk L. , Tjong‐A‐Hung Steven P. , Schegget Jan Ter , Nooter Kees , Kok Tjebbe
Published: March 2007

Strong evidence has implicated human papillomaviruses (HPV) in the pathogenesis of anogenital cancers and a number of other mucosal and cutaneous lesions. Data concerning the involvement of HPV in esophageal cancers are controversial. Different investigators have detected HPV types (mainly types 16 and 18) in biopsy specimens of esophageal cancers. A study was undertaken to determine whether responses to chemotherapy of advanced squamous cell carcinomas could be correlated with the HPV status. Polymerase chain reaction (PCR) amplification was used for the detection of HPV DNA in biopsies of esophageal squamous cell carcinomas treated with either surgical resection alone (n = 42) or chemotherapy followed by surgical resection (n = 21). Different general and consensus PCR primer sets, which allow the detection of most of the known as well as a number of not yet characterized HPV types, were used. HPV DNA was not detected in any of the 61 esophageal squamous cell carcinomas, suggesting that HPV infections are not likely to play a major role in the etiology of this neoplasm. © 1995 Wiley‐Liss, Inc.
Prediction of relapses after interferon‐alpha therapy by hepatitis C virus RNA in peripheral blood mononuclear cells
Authors: Kusaka Seiji , Okusa Tosifumi , Araki Akihiro , Fujiki Kazuhiko , Takashimizu Ichizen , Okayasu Isao , Yamamoto Naoki , Sato Chifumi
Published: March 2007

To investigate the predictive value of hepatitis C virus (HCV)‐RNA in peripheral blood mononuclear cells in the response to interferon therapy in patients with chronic hepatitis C, 15 patients with histologically proven chronic active hepatitis and who were positive for serum HCV‐RNA were treated with interferon‐alpha (6 million units; i.m.) every day for two weeks and then three times a week for 22 weeks. Ten of the 15 patients were responders whose alanine aminotransferase levels decreased to the normal range at the end of interferon therapy. In four of the 10 responders, HCV‐RNA was not detected by reverse transcription‐polymerase chain reaction in peripheral blood mononuclear cells nor in serum at the end of treatment. These four patients were complete responders, with alanine aminotransferase levels remaining normal for the next 24 weeks. In five of the 10 responders, HCV‐RNA was detected in peripheral blood mononuclear cells but not in serum at the end of treatment. All of these relapsed within the next 24 weeks. In the remaining responder, HCV‐RNA was detected both in peripheral blood mononuclear cells and in serum at the end of treatment. This responder also had a relapse within the next 24 weeks. Five of the 15 patients were non‐responders, in whom HCV‐RNA was detected both in peripheral blood mononuclear cells and in serum. Thus, detection of HCV‐RNA in peripheral blood mononuclear cells may be a good clinical marker to predict relapse after interferon treatment. © 1995 Wiley‐Liss, Inc.