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Biomedical subjects

M Roggendorf

Publications and source records attributed to M Roggendorf.

At least 73 records · Page 4Linked to original sources
PubMed1999

Detection of TT virus DNA in specimens other than blood.

BACKGROUND: Recently, a new infective agent of humans, TT virus (TTV), was identified. Very high prevalence rates of TTV in different population groups, including apparently healthy individuals, were reported for several countries. OBJECTIVES, STUDY DESIGN: In order to investigate whether or not non-parenteral transmission routes can contribute to TTV spread, we have tested saliva, urine, and stool samples from eight TT viraemic individuals for the presence of TTV DNA by polymerase chain reaction. RESULTS: TTT DNA was detected in saliva of five subjects and stools of four patients. None of the urine samples contained TTV DNA. Viral titres in saliva were close to those found in serum. In feces, TTV DNA could only be detected in low concentrations. CONCLUSIONS: Our findings on the presence of TTV DNA in saliva and stool suggest that TTV might be transmitted non-parenterally.

DNA Virus Infections↗
PubMed1999

Immunization of woodchucks with plasmids expressing woodchuck hepatitis virus (WHV) core antigen and surface antigen suppresses WHV infection.

DNA vaccination can induce humoral and cellular immune response to viral antigens and confer protection to virus infection. In woodchucks, we tested the protective efficacy of immune response to woodchuck hepatitis core antigen (WHcAg) and surface antigen (WHsAg) of woodchuck hepatitis virus (WHV) elicited by DNA-based vaccination. Plasmids pWHcIm and pWHsIm containing WHV c- or pre-s2/s genes expressed WHcAg and WHsAg in transient transfection assays. Pilot experiments in mice revealed that a single intramuscular injection of 100 microgram of plasmid pWHcIm DNA induced an anti-WHcAg titer over 1:300 that was enhanced by boost injections. However, two injections of 100 microgram of pWHcIm did not induce detectable anti-WHcAg in woodchucks. With an increase in the dose to 1 mg of pWHcIm per injection, transient anti-WHcAg response and WHcAg-specific proliferation of peripheral mononuclear blood cells (PMBCs) appeared in woodchucks after repeated immunizations. Four woodchucks vaccinated with pWHcIm were challenged with 10(4) or 10(5) of the WHV 50% infective dose. They remained negative for markers of WHV replication (WHV DNA and WHsAg) in peripheral blood and developed anti-WHs in week 5 after challenge. In contrast, woodchucks not immunized or immunized with the control vector pcDNA3 developed acute WHV infection. Two woodchucks immunized with 1 mg of pWHsIm developed WHsAg-specific proliferative response of PBMCs but no measurable anti-WHsAg response. A rapid anti-WHsAg response developed during week 2 after virus challenge. Neither woodchuck developed any signs of WHV infection. These data indicate that DNA-based vaccination with WHcAg and WHsAg can elicit immunity to WHV infection.

Amino Acid Sequence↗
PubMed1999

High prevalence of TT virus infection in Brazilian blood donors.

A recent report has described the molecular cloning and characterization of a novel, single-stranded DNA virus, named TT virus (TTV), which was present in the sera of Japanese patients with posttransfusion hepatitis of unknown etiology [Okamoto et al. (1998) Hepatology Research 10:1-16]. Using a nested polymerase chain reaction assay, sera from Brazilian patients with acute non A-C hepatitis and blood donors were examined for the presence of TTV DNA sequences. Thirty-seven of 52 (71%) patients with acute non A-C hepatitis and 45 of 72 (62%) blood donors were found to have TTV sequences in their sera. Such a high proportion in blood donors indicated that TTV infection is common in the general Brazilian population. Partial nucleotide sequences (326 bases in open reading frame 1) from seven isolates were determined. By phylogenetic analysis, four TTV strains were classified into the genomic subgroup G1a described previously. The three others belonged to subgroup G1b. Sequence homologies between strains belonging to a same subgroup were 92.9-99.1%, whereas homologies of 85.9-90.2% were calculated between isolates from different subgroups.

Adolescent↗
PubMed1998

Antibodies directed to envelope proteins of hepatitis C virus outside of hypervariable region 1.

The relatively high variability of the hepatitis C virus (HCV) envelope proteins E1 and E2 suggests that parts of these proteins other than the hypervariable region 1 (HVR1) might be involved in the induction of virus neutralizing antibodies. To test this hypothesis, two HCV proteins, pE1 and pE2 delta, were generated by in vitro translation. They represent amino acids 174-337 of E1 and 411-688 of E2, respectively, of isolate HCV-AD78; the protein pE2 delta contained no HVR1. As a control, protein pG.HVR1, which represents amino acids 384-410 of HVR1 of isolate HCV-AD78, was expressed separately. These three proteins were used in an immunoprecipitation assay to detect the presence of antiviral antibodies in sera of patients infected with the same isolate of HCV (HCV-AD78). Sera were obtained 4-8 months postinfection from patients who later resolved an acute infection or developed chronic liver disease. A high prevalence of antibodies (up to 85.7%) against pE1 and pE2 delta could be detected in both groups of patients, suggesting that these forms of the HCV envelope proteins contain B-cell epitopes. The antibody responses against proteins pE1 and pE2 delta did not differ significantly between patients with resolving or chronic infection, whereas antibodies against protein pG.HVR1 were associated with resolution of infection. Rabbit antisera raised against pE1 and pE2 delta were tested for their ability to neutralize the binding of HCV to susceptible cells in tissue cultures. The results suggested that although a few B-cell epitopes outside of HVR1 can induce virus neutralizing antibodies, these antibodies are probably not associated with the resolution of infection.

Animals↗
PubMed1998

Distinct prevalence of antibodies to the E2 protein of GB virus C/hepatitis G virus in different parts of the world.

Since the identification of the new human virus, GB virus C (GBV-C)/hepatitis G-virus (HGV), in 1995/1996, reverse transcription polymerase chain reaction remained the sole available diagnostic tool for GBV-C/HGV infection. Recently, a serologic test based on the detection of antibodies to the putative envelope protein 2 (anti-E2) has been introduced. We used this assay for a seroepidemiological survey including 3,314 healthy individuals from different parts of the world, 123 patients from Germany who were suspected to have an increased risk of acquiring GBV-C/HGV infection, 128 multiple organ donors, and 90 GBV-C/HGV RNA positive persons. In European countries, anti-E2 seropositivity ranged from 10.9% (Germany) to 15.3% (Austria). In South Africa (20.3%) and Brazil (19.5%), even higher anti-E2 prevalence rates were recorded. In Asian countries like Bhutan (3.9%), Malaysia (6.3%), and the Philippines (2.7%), anti-E2 positivity was significantly lower. GBV-C/HGV anti-E2 prevalence in potential "risk groups," i.e., patients on hemodialysis and renal transplant recipients, did not vary significantly from anti-E2 seroprevalence in German blood donors. Anti-E2 and GBV-C/HGV RNA were found to be mutually exclusive, confirming the notion that anti-E2 has to be considered as a marker of past infection.

Antibodies, Viral↗
PubMed1998

Hepatitis G virus infection in children on dialysis and after renal transplantation.

The aim of the present study was to use a combination of the reverse transcription-polymerase chain reaction and a new diagnostic test for antibodies against the viral envelope protein E2 to assess the prevalence of hepatitis G virus (GBV-C/HGV) infection in sera of Hungarian children on hemodialysis (HD) or peritoneal dialysis (CAPD), as well as in sera of renal transplant patients (RTx). The GBV-C/HGV RNA prevalence was significantly higher in the whole group of children with renal failure (18.5%) than in the control group (children with urinary tract infection, 2.5%). The difference between the GBV-C/HGV RNA prevalence in the RTx group (33.3%) and in the control group (2.5%) was significant (P = 0.007). Anti-E2, which is considered an indicator of a past GBV-C/ HGV infection, was detected in 10% (1/10) of HD patients, in 33.3% (4/12) of RTx patients, but in none of the children on CAPD. These differences were not significant. Children receiving a renal graft are at an increased risk of developing GBV-C/HGV infection, which may be attributed to the immunosuppressive drugs necessary to maintain the grafts.

Adolescent↗
PubMed1998

The "interferon sensitivity determining region" of hepatitis C virus is a stable sequence element.

BACKGROUND/AIMS: A sequence of 40 amino acids within the nonstructural protein 5A of hepatitis C virus (HCV) has been suggested to be an interferon sensitivity determining region (ISDR). The variations in the ISDR after 12-14 years of chronic infection and the correlation between ISDR and interferon response were studied in patients who were infected by the same HCV isolate. METHODS: We determined the HCV-ISDRs of 13 chronically infected patients by direct sequencing of polymerase chain reaction products. All patients were infected by isolate HCV-AD78, but differed with respect to their sensitivity to interferon. Four patients were complete responders, two patients were non-responders, and seven showed a partial response. RESULTS: The ISDR of HCV-AD78 differed from a prototypical HCV-1b sequence in one amino acid and was therefore classified as an intermediate type. Direct sequencing of the HCV-ISDRs of the patients 12-14 years after infection, but before interferon therapy, revealed a rate of 2.2x10(-3) nucleotide substitutions per site per year, resulting in only single intermediate type amino acid exchanges. All sequences ranked with the intermediate type. Moreover, during interferon treatment no selection to a wild type ISDR was observed in five partial responders. CONCLUSIONS: Within the homogeneous patient group examined here, no correlation was found between the ISDR and the interferon response. Recent studies found only a small number of mutant type ISDRs in Europe. Additionally, our results indicate that the ISDR is a stable sequence element. This provides an explanation for the divergent data relating to the importance of the ISDR in different geographical regions.

Amino Acid Sequence↗
PubMed1998

Lack of evidence for an association between TTV infection and severe liver disease.

BACKGROUND: In 1997 a new human virus, TTV, was identified. The clinical significance of the TTV infection, however, remains unknown. OBJECTIVE: Establishment of the prevalence of TTV DNA in different population groups in Germany and the assessment of the possible clinical significance of TTV infection. STUDY DESIGN: Detection of the TTV DNA by PCR in blood donors, patients with end-stage liver disease, and multiple transfused patients with haemotological disorders. RESULTS: TTV DNA was detected in 16 of 122 (13.1%) volunteer blood donors, in 34 of 77 (44.2%) patients with end-stage liver disease, and in 21 of 38 (55.3%) multiple transfused patients. There was no difference in the prevalence of the TTV DNA in end-stage liver disease patients with regard to sex, age, presence of HCV and HBV infection markers, and etiology of liver disease. Phylogenetic analysis of the amplified DNA fragments from 12 randomly selected TTV infected subjects demonstrated that in Germany at least two putative TTV genotypes and four subtypes are circulating. CONCLUSIONS: (i) TTV is widely spread in German population; (ii) one of the possible ways of its transmission is blood transfusion; (iii) TTV infection most probably does not generally lead to the development of the end-stage liver disease.

Adult↗
PubMed1998

Antibodies to the E2 protein of GB virus C/hepatitis G virus: low prevalence in Asian countries.

Epidemiological investigations of GB virus C (GBV-C)/hepatitis G virus (HGV), an infectious agent discovered in 1995/1996, are facilitated by a recently developed immunoassay for the detection of antibodies to the viral envelope 2 protein (anti-E2). We used this assay to establish GBV-C/HGV prevalence in seven European, African, and Asian countries. A total of 1579 serum samples from healthy adults lacking prior exposure to known parenteral risk factors was screened. Anti-E2 positivity ranged from 13.6% (Italy) to 7.7% (Mauritius) in the European and African countries investigated. Anti-E2 prevalence was exceedingly low in the Philippines and Sri Lanka. This observation might be attributable to socio-economical and demographic factors.

Adult↗
PubMed1998

Acute cerebellitis with near-fatal cerebellar swelling and benign outcome under conservative treatment with high dose steroids.

Acute cerebellar swelling is an emergency because of brainstem compression as well as upward or downward cerebellar herniation. Few childhood cases are on record, with fatal outcome in three out of six. We report a girl with probable Epstein-Barr virus-associated cerebellar swelling who recovered completely with steroid treatment after a stormy course. Review of the literature showed that all three patients, including our own, who recovered fully, received high-dose steroids in contrast to none of the four patients who died or survived with sequelae. Neuroimaging and evoked potential studies are useful for early diagnosis and disease monitoring. We conclude that for the time being high-dose steroid treatment is advocated in patients with acute infectious or parainfectious cerebellar swelling.

Acute Disease↗
PubMed1998

Comparison between subcutaneous and intravenous interleukin-2 treatment in HIV disease.

OBJECTIVES: Therapy of HIV-infection using intravenous interleukin-2 (IL-2) is known to be effective in terms of increasing CD4-counts but is associated with significant side-effects and hospitalization. However, the combination with protease-inhibitor therapy has not been tested yet. The aim of the present study was to investigate the safety and efficacy of intravenous vs. subcutaneous IL-2 regimes using 9 Mio I.U. of IL-2, in combination with protease-inhibitor therapy. DESIGN: All patients were treated with a combination of two reverse transcriptase inhibitors and a protease-inhibitor prior to IL-2 administration for at least 6 weeks. Ten patients were assigned to the intravenous IL-2 group (group A). 10 to the subcutaneous group (group B). RESULTS: In both treatment groups, CD4 count significantly increased shortly after the end of therapy (group A: 223% over baseline [day 7]; group B: 264% over baseline [day 7]). During the follow-up CD4 counts slowly decreased thereafter but remained above baseline 3 months following IL-2 treatment. The CD8 lymphocytes showed a similar but less pronounced pattern with a maximum at day 7 (group A: 116% over baseline, group B: 158% over baseline) and reached baseline earlier in the follow-up-period. Altogether the CD4/CD8-ratio was elevated through long periods on follow-up. Throughout follow-up, there were no apparent changes in viral load during IL-2 therapy in either groups. IL-2 therapy was administered for a mean time of 4.2+/-0.1 days in the intravenous group and of 4.8+/-0.1 days in the subcutaneous group until therapy was terminated at day 5 or due to side-effects. Only 1/10 patients completed the 5-day course of intravenous therapy in contrast to 6/10 in the subcutaneous group. CONCLUSIONS: Subcutaneous interleukin-2 using 9 Mio IU day(-1) in combination with protease-inhibitors showed equal efficacy as intravenous therapy and was associated with less side-effects.

Adult↗
PubMed1998

Sequence variability in the putative coding region of TT virus: evidence for two rather than several major types.

Recently a new human virus, TT virus (TTV) was identified in the serum of a patient with post-transfusion hepatitis of unknown aetiology. Comparative sequence analysis of a 222 nt fragment of ORF 1 of TTV was performed to assess the genomic variability of this virus. Phylogenetic analysis of the nucleotide sequences of 76 TTV isolates collected in 17 countries segregated them into two major groups: TTV 1 and TTV 2. The TTV 1 group comprised two distinct subgroups, which corresponded to previously described TTV subtypes 1a and 1b. The TTV 2 group was separated into four main branches, two of which included sequences previously provisionally attributed as TTV types 2 and 3. Bootstrap resampling, however, did not support the reliability of this grouping, suggesting that the isolates in the TTV 2 group should be considered as subtypes of a single type rather than different TTV types.

Base Sequence↗
PubMed1998

T-Cell response to woodchuck hepatitis virus (WHV) antigens during acute self-limited WHV infection and convalescence and after viral challenge.

The infection of woodchucks with woodchuck hepatitis virus (WHV) provides an experimental model to study early immune responses during hepadnavirus infection that cannot be tested in patients. The T-cell response of experimentally WHV-infected woodchucks to WHsAg, rWHcAg, and WHcAg peptides was monitored by observing 5-bromo-2'-deoxyuridine and [2-3H]adenine incorporation. The first T-cell responses were directed against WHsAg 3 weeks after infection; these were followed by responses to rWHcAg including the immunodominant T-cell epitope of WHcAg (amino acids 97 to 110). Maximal proliferative responses were detected when the animals seroconvered to anti-WHs and anti-WHc (week 6). A decrease in the T-cell response to viral antigens coincided with clearance of viral DNA. Polyclonal rWHcAg-specific T-cell lines were established 6, 12, 18, and 24 weeks postinfection, and their responses to WHcAg peptides were assessed. Five to seven peptides including the immunodominant epitope were recognized throughout the observation period (6 months). At 12 months after infection, T-cell responses to antigens and peptides were not detected. Reactivation of T-cell responses to viral antigens and peptides occurred within 7 days after challenge of animals with WHV. These results demonstrate that a fast and vigorous T-cell response to WHsAg, rWHcAg, and amino acids 97 to 110 of the WHcAg occurs within 3 weeks after WHV infection. The peak of this response was associated with viral clearance and may be crucial for recovery from infection. One year after infection, no proliferation of T cells in response to antigens was observed; however, the WHV-specific T-cell response was reactivated after challenge of woodchucks with WHV and may be responsible for protection against WHV reinfection.

Acute Disease↗
PubMed1998

Age-specific prevalence and genetic diversity of GBV-C/hepatitis G virus in Brazil.

The recently discovered GBV-C/hepatitis G virus (GBV-C/HGV) has been shown to be parenterally transmitted. The occurrence of community-acquired GBV-C/HGV infections has also been reported. In order to study the variations with age of the GBV-C/HGV prevalence, sera from 268 individuals without liver disease, aged 0-80 years, and living in the city of Rio de Janeiro, Brazil, were tested by reverse transcription-nested polymerase chain reaction for the presence of GBV-C/HGV RNA. Age-specific seroprevalence was low (2.3%) among children under the age of 10, reached a maximum of 18% in young adults (21-30 years), and declined in older age groups. Among 170 blood donors aged 18-60, the rate of individuals with antibodies against the viral envelope E2 protein increased with age, from about 6% between the ages of 18 and 24 to about 35% for individuals from the age of 43 to 60. The results suggest that sexual transmission of GBV-C/HGV might occur and that the virus could be eliminated after a long period of infection. The nucleotide sequences of GBV-C/HGV genome fragments, 422 base pairs (bp) in the E2 region and 354 bp in the nonstructural 5 region, were determined for 11 and 31 isolates, respectively. Phylogenetic tree based on concatenated E2 + NS5 sequences showed that Brazilian strains belonged to three clusters, two of which were previously characterized as genotypes 1 and 2.

Adolescent↗
PubMed1997

Early antibody response against hypervariable region 1 is associated with acute self-limiting infections of hepatitis C virus.

Antibodies directed to hypervariable region 1 (HVR1) of hepatitis C virus (HCV) have recently been shown to neutralize the corresponding HCV isolate in vitro. We analyzed the appearance of antibodies directed to HVR1 during the course of infection in a large group of patients who have been infected by the same isolate of a HCV contaminated anti-D immunoglobulin (HCV-AD78). An enzyme-linked immunosorbent assay (ELISA) was established using a synthetic peptide to detect antibodies against the main HVR1 variant of HCV-AD78. 207 sera obtained at different time points post infection (p.i.) of 51 patients having either acute self-limiting (n = 28) or chronic infection (n = 23) were studied. Antibodies directed to HVR1 were found at least at one time point during the infection course in 15 of 28 patients (53%) having acute self-limiting infections and in 17 of 23 patients (74%) with chronic disease. The time of appearance of anti-HVR1 was significantly different between these two patient groups (P < .025) although appearance and titers of other HCV-specific antibodies were found to be similar at early time points p.i. In acute self-limiting infections 9 of 21 sera (43%) of respective patients with sera available within the first 6 months p.i. were anti-HVR1 positive. The highest prevalence of anti-HVR1 in this group of patients was within month 6 to 12 p.i. (64%). None of the sera available after 24 months p.i. had such antibodies. In contrast, only 2 of 15 sera (13%) of chronically infected patients with respective time points of sera were anti-HVR1 positive within the first 6 months p.i. and only 5 of 18 sera (28%) were positive within month 7 to 12 p.i. Seven patients with chronic HCV infections showed at least two consecutive anti-HVR1 negative early time points up to month 18 p.i. Prevalence of anti-HVR1 after 24 months p.i. was high (84%) in this group of patients and most of the patients maintained high levels of anti-HVR1 for up to 17 years p.i. Our findings suggest clearance of virus by respective neutralizing antibodies resulting in a self-limiting infection and may have implications for prognosis of the disease and also for any future vaccine development.

Adult↗