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Biomedical subjects

H W Doerr

Publications and source records attributed to H W Doerr.

At least 91 records · Page 5Linked to original sources
PubMed1998

Quantification of viral load: clinical relevance for human immunodeficiency virus, hepatitis B virus and hepatitis C virus infection.

Quantitative determination of viral load using nucleic acid amplification techniques represents the most accurate prognostic marker for human immunodeficiency virus type 1 (HIV-1) infection, independently of CD4+ cell count. Overall, the different methods for HIV-1 RNA determination (RT-PCR, nucleic acid sequence-based amplification, branched DNA) show a good reproducibility (0.5 log), however for low copy numbers and in HIV-1-infected children the variability may exceed 0.7 log. In non-HIV-1 subtype B infections the copy number is underestimated. While serology permits an accurate follow-up of hepatitis B virus (HBV) infection, HBV DNA quantification is used for monitoring of antiviral therapy, determination of infectiosity and in combination with serological markers for the resolution of unusual profiles, i.e. isolated anti-HBc reactivity. The prognostic relevance of hepatitis C virus (HCV) RNA determination is of limited value for the long-term prognosis of chronic hepatitis C, however the viral load may predict the outcome of antiviral therapy. Genetic diversity represents a challenge for HCV RNA quantification.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Improvement of the specificity of enzyme immunoassays for the detection of rotavirus and adenovirus in fecal specimens.

A variable rate of false-positive results may be observed with commercial enzyme immunoassays (EIAs) for the detection of rotavirus and adenovirus antigen in stool specimens, depending on the quality of the reagents and the presence of potentially interfering substances in stool samples. The present study was performed in an attempt to improve the specificity of current commercial rotavirus and adenovirus EIAs without significant loss of sensitivity by optimizing the cut-off value. A collective of 174 stool samples obtained from children suffering from acute gastroenteritis was tested. Electron microscopy (EM) and PAGE were used as reference methods for rotavirus detection. For the evaluation of the adenovirus kits, virus isolation in cell culture and the polymerase chain reaction served as reference standards. The highest sensitivity for rotavirus and adenovirus detection was achieved by the Ridascreen(R) Rotavirus and Ridascreen Adenovirus. However, the Ridascreen(R) Rotavirus and Ridascreen Adenovirus produced the highest number of false-positive results (n = 9) for each rotavirus and adenovirus detection. Cross-reactivities to coronaviruses and reoviruses were observed with the rotavirus antigen EIAs. For Rotazyme II, Ridascreen Rotavirus and Ridascreen Adenovirus, the specificity could be markedly increased without loss of sensitivity by doubling the cut-off value. For the alternative immunoassays, which were overall more specific, it was not possible to significantly decrease the rate of false-positive results without impairment of sensitivity by raising the cut-off value. In conclusion, at least for some rotavirus and adenovirus antigen EIAs, the cut-off value set by the manufacturer may not permit an optimal differentiation between true-positive and -negative samples. By raising the cut-off value from 50 to 100%, the specificity of two rotavirus antigen and one adenovirus antigen EIA can be improved markedly without significant loss of sensitivity.

Adenoviridae Infections↗
PubMed1998

Human immunodeficiency virus and hepatitis B virus infection in pregnancy: diagnostic potential of viral genome detection.

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) account for millions of cases of vertical infections worldwide. Laboratory diagnosis is essential for the detection of potentially infectious carriers. HBeAg represents the best serological marker for HBV replication. Since 10% of HBeAg-negative carriers transmit the virus to their children, determination of viral DNA is more reliable for the assessment of the risk to vertical infection. Risk assessment of vertical HIV transmission and monitoring AZT therapy during pregnancy are achieved by determination of HIV-1 viral load and CD4+ cell count. HIV-1 RNA or cDNA detection permits a nearly 100% sensitive diagnosis of congenital HIV infection already 2 weeks after birth. While qualitative HBV DNA determination should be limited only to anti-HBe carriers in order to assess infectiosity, HIV-1 RNA measurement represents in combination with the CD4+ cell count the best prognostic marker for vertical HIV infection and for the follow-up of infected children.

Female↗
PubMed1998

Azidothymidine resistance of H9 human T-cell lymphoma cells is associated with decreased sensitivity to antitumor agents and inhibition of apoptosis.

Biology of HIV-1 associated neoplasias is modulated by viral and host factors. In addition the development of tumors and their response to therapy may be further influenced by long-term treatment of HIV-1 patients with nucleoside analogs such as AZT (3'-azido-3'deoxythymidine), ddI (2',3'-dideoxyinosine), ddC (2',3'-dideoxycytidine), d4T (2',3'-didehydro-2'3'-dideoxythymidine), and 3TC [(-)-beta-L-2',3'-dideoxy-3'-thiacytidine] alone or in combination. As these compounds can trigger mechanisms involved in chemoresistance, we tested whether prolonged in vitro treatment of H9 cells (T-cell lymphoma) with AZT alters sensitivity of lymphoma cells to antitumor agents used for AIDS-associated malignancies. H9 cells grown for more than two years in medium containing 250 microM AZT developed resistance to the toxic effects of AZT while retaining sensitivity for other nucleoside analogs including ddC or cytosine arabinoside (ARA-C). These cells designated H9rAZT250 were 2 to 10-fold less sensitive to the toxic effects of antitumor agents, including cisplatin (CDDP), vincristine (VCR), doxorubicin (DOX) and etoposide (VP-16), when compared with parental H9 cells. The resistance of H9rAZT250 cells to antitumor agents was associated with inhibition of apoptosis as demonstrated by ultrastructural investigations and DNA-fragmentation assay (ELISA). The expression of the antiapoptotic gene bcl-2 was increased in H9rAZT250 cells while expression of other genes involved in the regulation of apoptosis such as c-myc, p53 and Fas was not changed. These results demonstrate that prolonged in vitro treatment of H9 lymphoma cells with AZT results in the development of resistance to antitumor agents in association with inhibition of apoptosis and increased expression of bcl-2. Therefore AZT long-term treatment of some HIV-1 patients with malignancies may have affected behavior of tumor cells including response to therapy.

Anti-HIV Agents↗
PubMed1997

Detection of human immunodeficiency virus type 1 and type 2 antibodies by a new automated microparticle immunoassay AxSYM HIV-1/HIV-2.

A new automated microparticle enzyme immunoassay (MEIA) for the AxSYM instrument developed recently by Abbott Laboratories was compared with two established assays, i.e. HIV-1/HIV-2 3rd Gen. Plus EIA (Abbott, Delkenheim, FRG) and Wellcozyme HIV 1 + 2 (Murex Diagnostics, Dartford, England) devised for the detection of human immunodeficiency virus type 1 (HIV-1) and HIV-2 antibodies. A total of 7293 serum samples were tested by the AxSYM HIV-1/HIV-2. The test panel included seroconversions (n = 22), samples from HIV-1 and HIV-2 positive individuals, hospitalized patients, blood donors, high risk individuals. To challenge further the specificity of the assays, large numbers of EIA repeatedly reactive but Western blot negative samples, potentially cross-reactive sera, Western blot indeterminate specimens and samples from pregnant women were tested. In four seroconversion panels, HIV-1 infection was detected one bleed earlier with the AxSYM HIV-1/HIV-2 than with the Abbott HIV-1/HIV-2 3rd Gen. Plus EIA. Although the AxSYM HIV-1/HIV-2 was tested with a higher number of challenging sera than the alternative assays, the specificity was very high (99.4%). The highest number of false positive results was obtained with serum samples that were repeatedly reactive in EIAs different from those compared in the present study. The automated AxSYM system permits the testing of a large sample number in a rapid turn-around time and by random access urgent tests can be carried out even when an assay is in progress.

Automation↗
PubMed1997

Antiviral effects of 6-diazo-5-oxo-L-norleucin on replication of herpes simplex virus type 1.

An L-glutamine antagonist, 6-diazo-5-oxo-L-norleucin (L-DON), inhibits replication of vesicular stomatitis virus, poliovirus and paramyxoviruses in cultured cells. We tested the antiviral activity of L-DON against different strains of herpes simplex virus type 1 (HSV-1) in Vero cells. In the presence of a physiological plasma concentration of L-glutamine (0.5mM) L-Don inhibited 50% production of virus plaques at concentrations ranging from 7.9 to 16 microM. At concentrations of 40 microM L-Don inhibited infectious virus yield by 99%. The antiviral activity of L-DON decreased with increasing L-glutamine concentrations. A concentration of 5000 microM of L-Don had no significant effects on the viability of Vero cells. Transmission electron microscopical investigations showed that L-DON prevented mainly envelopment of viral nucleocapsids in the cytoplasm. The immunoprecipitation experiments demonstrated selective inhibition of synthesis of HSV-1 glycoproteins in L-DON treated cells. The results showed that L-DON inhibits HSV-1 replication at a late stage in the virus replication cycle, probably the cytoplasmic maturation of virions and subsequent virion egress from the cells.

Animals↗
PubMed1997

Emerging viral pathogens in long-term expatriates (II): Dengue virus.

Dengue virus infections have been well known for many years; still dengue virus is regarded as an 'emerging' pathogen, as the disease profile is changing. Its geographical range and overall incidence, and the incidence of the associated complications, dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), are on the increase. Modern-day travel and increasing urbanization seem to be the main contributing factors. In order to estimate the risk of infection during long-term stays in dengue-endemic countries, we tested sera obtained from 323 development aid workers and their family members who had spent on average 9.8 years in dengue-endemic regions for the presence of dengue virus antibodies. Dengue virus antibody screening was done by a commercially available immunofluorescence test (IF). Reactive samples were re-tested by an in-house IF and also tested for cross-reactivity to yellow fever virus using yellow fever IF and neutralization test (NT). Evaluation of the results revealed that the screening test has a specificity of at least 63.2%. In 12 of 19 initially positive cases crossreacting antibodies against yellow fever virus could be ruled out. Three cases remained indeterminable, whereas four of the reactive and 10 (out of 12) of the borderline reactive cases showed crossreactivity with yellow fever virus, probably due to previous vaccination. We found seroprevalence rates of 4.3% with no significant differences related to gender or area of upbringing. Seroprevalence rates were evaluated according to region of suspected or confirmed infection. In two cases the dengue infection had taken a classical clinical course; in another three cases an extraordinary febrile illness was reported in the history. None of the other seropositive individuals had a history of an illness possibly attributable to dengue virus infection. Our results show that there definitely is a risk for long-term expatriates to acquire (mostly non- or oligo-symptomatic) dengue infection, which might be important especially in the light of the supposed aetiology of DHF or DSS as a secondary infection with another dengue virus serotype.

Adolescent↗
PubMed1997

Emerging viral pathogens in long-term expatriates (I): Hepatitis E virus.

Hepatitis E virus (HEV) is one of the so-called 'emerging' viral pathogens, whose role is increasingly being recognized. To estimate the risk of HEV infection during long-term stays in HEV-endemic countries, 500 serum samples obtained from development aid workers and their family members who had spent on average 9 years in HEV-endemic regions were tested for antibodies against HEV by ELISA and Immunoblot. We found seroprevalence rates of 5-6% with no significant differences related to gender or area of upbringing (raised in an HEV-endemic vs. nonendemic region). Seroprevalence rates did not increase with increasing number of stays or number of expatriate years. None of 77 children and adolescents tested was positive for anti-HEV. The Indian subcontinent showed the highest seropositive rate with 10%. In subjects returning from West and Central Africa, East Africa, South-east Asia and Latin America seroprevalence rates were around 7%. We found a comparatively low seroprevalence rate of 2.1% for the Arab countries and the Middle East. Our results show that there definitely is a risk for long-term expatriates to acquire HEV infection; however, in most of our cases infection seems to have been non- or oligo-symptomatic.

Adolescent↗
PubMed1997

Expression of human leukocyte antigens class I and class II on cultured biliary epithelial cells after cytomegalovirus infection.

The influence of cytomegalovirus (CMV) infection on the HLA expression on cultured biliary epithelial cells (BEC) was investigated. CMV-infection augmented expression of HLA class I but not of HLA class II. CMV reduced the IFN-gamma-mediated induction of the de novo expression of HLA class II while the stimulated expression of HLA class I was not impaired. Autologous but not allogeneic PBL responded to CMV-infected BEC. This response resulted in upregulation of HLA class I on BEC which was significantly higher compared with the expression on infected BEC alone or on uninfected BEC cocultured with autologous PBL. The results suggest that CMV modulates the immunogenic potential of BEC, which is important for the HLA and CMV-mediated pathomechanisms in vivo.

Cells, Cultured↗
PubMed1997

Rapid diagnosis of enterovirus infection by a new one-step reverse transcription-PCR assay.

The AMPLICOR Enterovirus Test was evaluated with 103 cerebrospinal fluid (CSF) specimens. Twenty-seven CSF specimens were culture positive. With the AMPLICOR test, enterovirus RNA was detected in 34 specimens. Compared with culture, the AMPLICOR test gave a sensitivity of 96.3% and a specificity of 100%. The sensitivity of culture was 79.4% in comparison with the AMPLICOR test.

Enterovirus↗
PubMed1997

Increased serum and mRNA levels of RANTES associated with elevated levels of activated CD8+CD38+ T cells in HIV-1 infected individuals.

The serum levels of the beta-chemokine RANTES and, albeit less, MIP-1 beta were found to be increased in 37 HIV-1 infected compared to seronegative individuals. In contrast the serum levels of IL-16 were only sporadically elevated in seropositives as well as in seronegatives. Concomitantly, the RANTES gene expression increased about tenfold in seropositives, whereas the MIP-1 beta and IL-16 mRNA levels were not elevated. No correlation between the increase of the MIP-1 beta and RANTES serum concentrations and the plasma virus load, the number of the peripheral CD4+ T cells or the therapy status of the patients was found. However, the increased proportion of activated CD8+CD38+ T cells in the peripheral blood of all seropositives paralleled the increased RANTES serum levels detected indicating that immune activation in HIV-1-infected individuals may contribute to increased RANTES serum levels.

ADP-ribosyl Cyclase↗
PubMed1997

Increased efficacy of aphidicolin killing of human neuroblastoma cells in vitro by encapsulation in liposomes.

Aphidicolin is a tetracyclic diterpene antibiotic which kills human neuroblastoma cells (NB) in vitro while it has no significant effect on the viability of different human cell types including normal embryonal cells. In the present study, we tested whether aphidicolin encapsulated in liposomes kills NB cells with the efficacy superior to that of unencapsulated aphidicolin. The drug was entrapped in vesicles composed of phosphatidylcholine, phosphatidylserine and cholesterol in a molar ratio of 83:5:12. The treatment with encapsulated aphidicolin at a concentration of 200 nmol for 5 days killed all cells of three human NB cell lines. In contrast, at least 30% of the cells survived 5 days of treatment with 200 nmol unencapsulated aphidicolin. The results showed that aphidicolin killing of human NB cells may be increased by encapsulation in liposomes.

Aphidicolin↗
PubMed1997

Follow-up of four HIV-infected individuals after administration of hepatitis C virus and GBV-C/hepatitis G virus contaminated intravenous immunoglobulin: evidence for HCV but not for GBV-C/HGV transmission.

In 1994, hepatitis C virus (HCV) infection was transmitted to four HIV seropositive patients attending the Department of Angiology, University Clinics, Frankfurt am Main, by the administration of Gammagard. The patients were suffering from thrombocytopenia and received betweeen 20 and 30 g of the contaminated lot 93F21AB11. GBV-C/HGV RNA could be amplified from the Gammagard lot 93F21AB11 using 5'NCR and NS5 primer pairs. All the four patients were negative in the GBV-C/HGV RT-PCR prior to therapy and until the end of the follow-up period. GBV-C/HGV IgG antibodies to the putative envelope (E2) were detected using the E2 HGV-env kit (Boehringer-Mannheim, Germany) in Gammagard lot 93F21AB11 and in one patient before donation of immunoglobulin. Anti-E2 seroconversion was observed in one recipient, the other two patients remained anti-E2 seronegative until the end of the observation period. It is concluded that there is no direct evidence for transmission of GBV-C/HGV by contaminated intravenous immunoglobulin since GBV-C/HGV RNA was not detected in the recipients up to 1 year after administration.

Adult↗
PubMed1997

[Viral exanthematic childhood diseases].

Exanthem is defined as multiple, inflammatory skin alteration with a hematogenic, lymphogenic or neurogenic origin. Typically, so called exanthematic children's diseases are measles, mumps, rubella, varicella, erythema infectiosum (fifth disease) and in the past small pox. The pathogenesis of the viral-caused diseases primarily occurs in the vascular connective tissue. The cytopathogenetic effects result in inflammatory tissue reactions with activation of defence mechanism and producing of immune complexes. First symptoms are hyperemia, edema and inflammatory infiltrates with itchy swellings. Virological laboratory diagnosis are necessary especially for the progress of atypical infectious diseases, for persons with immunological or chronical illness and under chemotherapeutical or immunosuppressival treatment.

Age Factors↗
PubMed1997

Application of automated thermal disinfection instead of sterilisation procedures for treatment of rotating dental instruments: efficacy against viruses?

In dentistry it is of primary importance to take into consideration microbial transfer due to the nature of the construction of rotating dental instruments. This aspect was the starting point for our research with the question whether or not sterilisation is fundamentally necessary for slow and high speed hand pieces to make them "safe" out of a virological point of view, or whether a thermal disinfection could also possibly be adequate for this purpose. In this context, we tested the efficiency of the cleaning and disinfection capacity of an automated steam disinfection and sterilisation unit (Sirona Hygiene Center, Siemens, AG, Bensheim) intended to the hygienic treatment of dental instruments with respect to viruses. In model tests the corresponding instruments were experimentally infected with herpes simplex virus type 1 (HSV) and simian vacuoling virus (SV40). As indicator systems we used for both cell cultures (measurement of the degree of infectiosity) and (for HSV) polymerase chain reactions (PCR; determination of viral nucleic acids). In the tests for (residual) infectiosity after thermal disinfection (as an isolated step of the Hygienic Centre) and also for a combination of cleaning and subsequent thermal disinfection (also after protein application), no infectious virus could be found in the interior of the slow handpieces and turbines tested. In opposite to this, infectious HSV and SV40 could be found after completion of every isolated cleaning program in the turbine (in all three ducts) and in the slow handpiece (only in the gearbox duct in the case of HSV, and in the case of SV40 also in the water and air ducts in very small amounts). The PCR analyses showed that no nucleic acids could be found in both instruments (in the air and water ducts) following a practice-relevant combination of cleaning and disinfection, but that PCR-positive signals were obtained for the larger-volume gearbox and drive and return air ducts in 1 or 2 of 3 test samples. The detection of viral nucleic acid proves that it is not a matter of complete removal of the infectious agents from the instruments, but rather that they are simply inactivated. Since the test samples did not show similar amounts of viral nucleic acid, it demonstrates the strong influence of the basic parameters (efficiency of the virus contamination, flushing conditions and the like). Our experimental model demonstrate that thermal disinfection may be adequate to prevent virus contamination of rotating dental instruments, while compulsory sterilisation is not mandatory. Further studies are necessary to demonstrate whether the present data are applicable for rotating dental instruments from other manufactures.

Automation↗