Two cases of hepatic helminthiasis in Marmota monax with hepatitis virus(WHV) infection]

OBJECTIVE: To assess the spontaneous fertility in couples with severe seminal conditions while waiting for artificial insemination donor. STUDY DESIGN: Prospective follow-up during a period of 24 months. SETTING: University Medical School. PARTICIPANTS: There were 285 couples in which the male had a very severe seminal pathology: 166 azoospermia, 86 oligozoospermia and 33 severe asthenozoospermia. OUTCOME MEASURES: Pregnancy rates after being included on waiting list. RESULTS: The spontaneous pregnancy rate was 3.2% (9/285), per month spontaneous pregnancy rate being 0.13%. Spontaneous pregnancy rate was 0% in azoospermia (0/166). versus 7.6% (9/119) in non-azoospermia cases. Spontaneous pregnancy rate was 8.5% (4/47) in the group with less than 0.1 million motile sperm/cc, 6.5% (3/46) in the group between 0.1 and 1 million/cc and 7.7% (2/26) in the group with 1-2 million/cc. CONCLUSION: In a 2-year follow-up, pregnancy rate among non-azoospermic couples before undergoing artificial insemination was 7.6%. Extramatrimonial pregnancy (based on anamnesis and sperm analysis) seemed to be uncommon. Even in cases with less than 0.1 million of motile sperm/cc there was not a negligible spontaneous pregnancy rate.     

Antiviral activity and toxicity of fialuridine in the woodchuck model of hepatitis B virus infection

The crystal structure of the mouse major histocompatibility complex (MHC) class I molecule H-2Dd with an immunodominant peptide, designated P18-I10 (RGPGRAFVTI), from human immunodeficiency virus envelope glycoprotein 120 was determined at 3.2 A resolution. A novel orientation of the alpha3 domain of Dd relative to the alpha1/alpha2 domains results in significantly fewer contacts between alpha3 and beta2-microglobulin compared with other MHC class I proteins. Four out of ten peptide residues (P2 Gly, P3 Pro, P5 Arg and P10 Ile) are nearly completely buried in the Dd binding groove. This is consistent with previous findings that Dd exploits a four-residue binding motif comprising a glycine at P2, a proline at P3, a positively charged residue at P5, and a C-terminal hydrophobic residue at P9 or P10. The side-chain of P5 Arg is directed toward the floor of the predominantly hydrophobic binding groove where it forms two salt bridges and one hydrogen bond with Dd residue Asp77. The selection of glycine at P2 appears to be due to a narrowing of the B pocket, relative to that of other class I molecules, caused by Arg66 whose side-chain folds down into the binding cleft. Residue P3 Pro of P18-I10 occupies part of pocket D, which in Dd is partially split by a prominent hydrophobic ridge in the floor of the binding groove formed by Trp97 and Trp114. Residues P6 through P9 form a solvent-exposed bulge, with P7 Phe protruding the most from the binding groove and thereby probably constituting a major site of interaction with T cell receptors. A comparison of H-2Dd/P18-I10 with other MHC class I/peptide complexes of known structure provides insights into the possible basis for the specificity of the natural killer cell receptor Ly-49A for several related class I molecules.     

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.     

Distinguishing between acute and symptomatic chronic hepatitis B virus infection

BACKGROUND/AIMS: Differentiating between an acute hepatitis B (AH-B) infection and an acute exacerbation of a chronic hepatitis B (CH-B) infection can present a problem for the clinician. The only current serological method of distinguishing between acute and symptomatic chronic hepatitis B virus (HBV) infection is the immunoglobulin M antibody to hepatitis B core antigen (anti-HBc) assay, which can be problematic. Therefore, in an attempt to better distinguish between acute and chronic HBV infection, sera from 26 patients with AH-B and 53 patients with CH-B were compared in a variety of experimental immunoassays. METHODS: Experimental assays have been designed to detect free antibody to hepatitis B e antigen (anti-HBe), hepatitis B e antigen (HBeAg)/anti-HBe immune complexes (ICs), and hepatitis B surface antigens (HBsAg)/antibody to hepatitis B surface antigen (anti-HBs) in the presence of excess antigen. An additional assay was developed to detect a novel anti-HBc specificity, designated antibody to woodchuck hepatitis virus (anti-HBcW), which cross-reacts with the core antigen of the woodchuck hepatitis virus. RESULTS: Sera from patients with CH-B showed significantly higher levels of free anti-HBe, HBeAg/anti-HBe ICs, and HBsAg/anti-HBs ICs compared with AH-B patient sera. Furthermore, patients with CH-B consistently produced high titer anti-HBcW, whereas patients with AH-B produced little or no anti-HBcW antibody. CONCLUSIONS: The serology of AH-B infection and symptomatic CH-B infection can be distinguished using a variety of experimental immunoassays in addition to the immunoglobulin M anti-HBc assay.     

T-lymphocyte response to hepatitis C virus in different clinical courses of infection

BACKGROUND: To assess the role played by the immune response in the outcome of hepatitis C virus infection, the CD4+ T-lymphocyte response to viral antigens was studied in infected individuals with different clinical courses. METHODS: Using six recombinant proteins of hepatitis C virus, the study assessed the proliferative responses of peripheral blood mononuclear cells from 41 patients with chronic hepatitis C, 11 patients whose chronic hepatitis was successfully treated with interferon alfa and 11 healthy HCV seropositive individuals. RESULTS: (1) Sixty-five percent of hepatitis C virus-seropositive individuals had CD4+ T-cell responses to viral proteins. (2) All viral proteins were immunogenic for T cells, although NS4 was the most immunogenic. (3) There was a significant correlation between the presence of CD4+ T cell responses to Core and a benign course of infection in healthy seropositives, most of whom were viremic. CONCLUSIONS: CD4+ T-cell responses to Core, although they do not coincide with virus clearance, are associated with a benign course of infection and may be required to maintain humoral and cellular responses protective against the disease.     

Secretory immune response to membrane antigens during Giardia lamblia infection in humans

The secretory immune response in humans infected with Giardia lamblia was studied by using saliva samples and a membrane-rich protein fraction. The membrane fraction, studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed 24 antigen bands, ranging from 170 to 14 kDa. Saliva samples from giardiasis patients showed a heterogeneous response against the membrane fraction when they were assayed by immunoblotting. Among the antigens recognized by patient saliva samples, those of 170, 105, 92, 66, 32, 29, and 14 kDa stood out. These antigens were not recognized by saliva samples from healthy individuals. They may be of importance in future studies of protection from or diagnosis of G. lamblia infections.     

T-lymphocyte downregulation after acute viral infection is not dependent on CD95 (Fas) receptor-ligand interactions

Infection of mice with lymphocytic choriomeningitis virus (LCMV) causes a major expansion of CD8+ T cells followed by a period of immune downregulation that coincides with the induction of lymphocyte apoptosis in the mouse spleen. CD95 (Fas) and its ligand are important for regulating peripheral T-lymphocyte numbers and can mediate apoptosis of mature T lymphocytes. We infected CD95- and CD95L-deficient mice (lpr and gld, respectively) with LCMV to determine if the immune downregulation that occurred following resolution of the LCMV infection was due to a CD95-dependent apoptotic mechanism. Lymphocytes from LCMV-infected lpr and gld mice were capable of normal T-cell expansion and cytolytic function but were, in contrast to activated cells from normal virus-infected mice, relatively more resistant to T-cell receptor-induced apoptosis in vitro. However, in vivo there were significant numbers of apoptotic cells in the spleens of lpr and gld mice recovering from the infection, and the T-cell number and cytolytic activity decreased to normal postinfection levels. Thus, CD95 is not required for the immune downregulation of the CD8+-T-lymphocyte response following acute LCMV infection.     

Prevalence of hepatitis C virus (HCV) infection in Mumbai

A study was carried out to determine the prevalence of Hepatitis C virus (HCV) in Mumbai among certain high risk groups such as renal transplant recipients, multitransfused and haemodialysis patients; professional and voluntary blood donors and viral hepatitis cases for comparison. Repeated testing of 602 subjects for antibodies to HCV using a second generation ELISA assay (Abbott, USA) showed an overall prevalence of 16.9%. We found 36.4% of multitransfused patients, 27.8% of renal failure cases and 26.2% of renal transplant recipients to be seropositive. Voluntary blood donors in our series showed a surprisingly high prevalence of 15.9%, and this group needs further investigation. Fifty-six of these sera (of which 45 were anti-HCV positive) were tested for HCV RNA by PCR and 14(31.1%) of the seropositive samples were also HCV RNA positive. The present investigation not only shows a high prevalence of HCV in the study groups but also proves the presence of HCV genomes in a significant proportion.     

Prevalence of cryoglobulinemia in chronic hepatitis C virus infection and response to treatment with interferon-alpha

A recombinant Schistosoma mansoni protein has been identified as a useful antigen for the detection of S. mansoni and Schistosoma haematobium antibodies. The purified recombinant protein, Sm22.3, was assayed using an enzyme-linked immunosorbent assay format against a battery of 491 well defined sera, including S. mansoni, S. haematobium, and Schistosoma japonicum infection sera, normal human sera, sera from 9 other parasitic infections, and sera from 2 additional infections. The sensitivity for detecting S. mansoni and S. haematobium infections with this single recombinant protein is 80.1%. The specificity is 94.8%. However, 15 of the 16 cross-reactive sera are malaria infection sera, and we have data suggesting that these malaria sera are actually recognizing an epitope on the vector-derived 6Xhistidine tag of recombinant Sm22.3. If this is the case, then, the actual specificity of the assay is 99.6%.     

Increased transmission of vertical hepatitis C virus (HCV) infection to human immunodeficiency virus (HIV)-infected infants of HIV- and HCV-coinfected women

The transmission of perinatal hepatitis C virus (HCV) infection was studied retrospectively in 62 infants born to 54 HCV- and human immunodeficiency virus (HIV)-coinfected women enrolled in a prospective natural history study of HIV transmission. Infant HCV infection was assessed by nested RNA polymerase chain reaction. The overall rate of vertical HCV transmission was 16.4% (9/62). Most HCV-infected children did not develop antibodies to HCV. The rate of HCV infection was higher among HIV-infected infants (40%) than among HIV-uninfected infants (7.5%; odds ratio, 8.2; P = .009). This difference in transmission was not related to differences in maternal HCV load, as measured by branched DNA assay, or mode of delivery. Why HIV-infected infants of HCV- and HIV-coinfected women have significantly higher rates of perinatal HCV transmission remains to be elucidated. The rate of HCV transmission in HIV-uninfected infants of HCV- and HIV-coinfected women is similar to that reported for infants born to HIV-seronegative mothers.     

Hepatitis in used syringes: the limits of sensitivity of techniques to detect hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA, and antibodies to HBV core and HCV antigens

Hepatitis virus infections are common among injecting drug users. Syringes containing hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were identified by polymerase chain reaction (PCR); syringes containing antibodies to HBV core antigen and HCV were identified by EIA. Syringe use was simulated to determine the sensitivity of these assays. The mean limits for PCR were 0.082 microliter of blood for HBV and 0.185 microliter for HCV; the mean limits for EIA were 0.185 microliter for HBV and 0.023 microliter for HCV. HBV PCR testing of 681 syringes returned to the needle exchange program in New Haven, Connecticut, revealed a decline from 7.8% HBV-positive at the program's outset to 2.6%. HCV antibodies were found in 12.1% of 207 syringes tested. Syringe testing can help estimate the prevalence and incidence of hepatitis virus infections when standard seroepidemiologic analyses cannot be applied.     

New mechanisms of viral persistence in primary human immunodeficiency virus (HIV) infection

Viruses, including the Human Immunodeficiency Virus (HIV), have evolved multiple strategies to overcome host immune defenses, allowing them to persist in the host. Molecular and cellular approaches were simultaneously used to provide sensitive and unbiased delineation of the diversity and dynamics of the immune response, and to study the relative compartimentalization of HIV-specific CTL clones in patients undergoing primary HIV infection. This approach revealed that some HIV-specific CTL clones can be deleted in presence of high levels of antigen, a phenomenon analogous to high-dose tolerance or clonal exhaustion described in murine models of persistent viral infections. Also, HIV-specific CTL clones were found to accumulate preferentially in peripheral blood as compared to lymph nodes, even though the large majority of viral replication during primary HIV infection takes place within lymph nodes. These two mechanisms may decrease the effectiveness of the host cell-mediated immune responses, and favor the establishment of virus persistence during primary HIV infection.     

Impact of hepatitis G virus co-infection on the course of hepatitis C virus infection before and after liver transplantation

Large-scale DNA sequencing is creating a sequence infrastructure of great benefit to protein biochemistry. Concurrent with the application of large-scale DNA sequencing to whole genome analysis, mass spectrometry has attained the capability to rapidly, and with remarkable sensitivity, determine weights and amino acid sequences of peptides. Computer algorithms have been developed to use the two different types of data generated by mass spectrometers to search sequence databases. When a protein is digested with a site-specific protease, the molecular weights of the resulting collection of peptides, the mass map or fingerprint, can be determined using mass spectrometry. The molecular weights of the set of peptides derived from the digestion of a protein can then be used to identify the protein. Several different approaches have been developed. Protein identification using peptide mass mapping is an effective technique when studying organisms with completed genomes. A second method is based on the use of data created by tandem mass spectrometers. Tandem mass spectra contain highly specific information in the fragmentation pattern as well as sequence information. This information has been used to search databases of translated protein sequences as well as nucleotide databases such as expressed sequence tag (EST) sequences. The ability to search nucleotide databases is an advantage when analyzing data obtained from organisms whose genomes are not yet completed, but a large amount of expressed gene sequence is available (e.g., human and mouse). Furthermore, a strength of using tandem mass spectra to search databases is the ability to identify proteins present in fairly complex mixtures.     

High prevalence of hepatitis G virus (HGV) infection in renal transplantation

INTRODUCTION: The newly discovered (1995) hepatitis G virus (HGV) is an RNA virus from the Flaviviridae family with 85% genomic homology to GB virus C (GBV-C). We studied the prevalence of HGV infection among a cohort of 398 renal transplant recipients (RTR), all of whom had previously received blood transfusions, been grafted between August 1984 and December 1991, and been treated by cyclosporin A (CsA) as the main immunosuppressant. SUBJECTS AND METHODS: According to hepatitis C virus (HCV) antibody status, and after exclusion of 28 HBs antigen-positive recipients, this cohort had previously been divided into an HCV +ve subgroup (106 RTR; 62 M vs 44 F; 29 French vs 77 non-French) and an HCV -ve subgroup (264 RTR; 181 M vs 83 F, 196 French vs 68 non-French). We randomly selected 27 RTR in the HCV+/HBV- subgroup (14 M vs 13 F, 10 French vs 17 Italians) and 27 RTR in the HCV-/HBV- subgroup (19 M vs 8 F, 18 French vs 9 Italians) for HGV screening. The detection of HGV RNA sequences in serum (viraemia) was done by double nested RT-PCR using specific primers chosen in the 5' non-coding genomic region. The serum detection of specific antibodies (anti E2) was done by ELISA test. All sera (at time of liver biopsy or at last follow-up) were tested in duplicate. RESULTS: The prevalence of HGV viraemia was 26% (14/54) in the whole group and in both HCV +ve and -ve subgroups (7/27). The prevalence of HGV infection (viraemia + and/or anti E2 antibodies +) was 44% (24/54) in the whole group and in both HCV +ve and -ve subgroups (12/27). In addition, the prevalence was similar in males vs females and in French vs foreigners recipients (mostly Italians). In the HCV +ve subgroup, the seven HGV viraemia-positive patients who previously had liver biopsies disclosed chronic active hepatitis in four (mean Knodell score 5.75) and normal livers in three, with only one case of elevated ALT (CAH 5). In the HCV- subgroup, none of the seven HGV+ viraemic patients had elevated ALT and liver biopsy was not performed. CONCLUSION: HGV infection prevalence is high (44%) in RTR, but clearly independent of HCV status and/or the geographical origin of the recipients. This data indicates a different epidemiology as compared to our HCVs previous experience.     

Viral hepatitis infection and response to the hepatitis B vaccine in hemodialyzed patients

Data from 219 hemodyalized patients receiving attention in our Hospital and other private centers in our city are shown. Mean age was 46.9 (range: 14-85), and 132 were male; mean time under dialysis was 20 months, and subjects received an average of 5 transfusions per patient year. Serological reactivity to HBs Ag, Anti HBs and IgG anti HBc by ELISA were investigated in all of them, and anti HCV by second generation enzimo-immunoassay (EIA II) in 73 HBe Ag/anti HBe system were determined in HBs Ag positive patients and those reactive to anti HCV (EIA II) were confirmed by LIA (immunoblotting of synthetic peptides LIA-TEK Organos Teknica). Recombinant anti HBV vaccine 40 mcg at 0-1 and six month were received by 81 cases without HBV markers in their sera and a protective response was considered when anti HBs titration of 10 mU/ml or more were obtained two months later. Prevalence for anti HBc and anti HBs were 38.8% respectively and that for HBs Ag was 21% with 78% of them reactive for HBs Ag. True reactivity for anti HCV (confirmed by LIA) was present in 35.6%, but it was 9.7% in our Hospital and 54.8% in private units (p < 0.0002). Anti HBs titration was done in 69/81 patients who received anti HBV vaccine, and a protective response in 49% were obtained; the other 12 patients underwent acute hepatitis B during the vaccination period.(ABSTRACT TRUNCATED AT 250 WORDS)