PubMed Health⌕ Search

Biomedical subjects

H W Doerr

Publications and source records attributed to H W Doerr.

At least 73 records · Page 4Linked to original sources
PubMed2000

Elevated plasma levels of 90K (Mac-2 BP) immunostimulatory glycoprotein in HIV-1-infected children.

90K is a secreted serum glycoprotein with immune stimulatory activity. In this study, 90K plasma levels were determined by an enzyme-linked immunosorbent assay in 18 HIV-1-infected children and 10 uninfected control children. 90K levels in HIV-1-infected children (median, 12.5 microg/ml) were higher than in HIV-1 uninfected control group (6.3 microg/ml; P < 0.05). 90K levels of HIV-1-infected children classified as stage B and C (median, 15.0 microg/ml and 22.7 microg/ml, respectively) were higher compared to children with stage A disease (median, 7.0 microg/ml; P < 0.05). A positive correlation (r = 0.5; P < 0.05) was found between 90K levels and HIV-1 RNA levels in 137 plasma samples of 18 HIV-1-infected children collected during a period of 1 year. No correlation was found between 90K levels and CD4 cell counts. These results suggest that 90K plasma levels may represent a novel marker of disease progression in HIV-1-infected children.

Adjuvants, Immunologic↗
PubMed2000

Cytomegalovirus-infected neuroblastoma cells exhibit augmented invasiveness mediated by beta1alpha5 integrin (VLA-5).

Previously, experimental in vivo results showed that the productively and persistently human cytomegalovirus (HCMV)-infected neuroblastoma cell line UKF-NB-4AD169 exhibits a more malignant phenotype than the non-infected variant UKF-NB-4. To prove the assumption that enhanced malignancy may be due to enhanced invasive potential of the infected cells we studied interactions of both lines with monolayers of cultured endothelial cells. UKF-NB-4AD169 cells adhered to and transmigrated through endothelial monolayer to a significantly higher extent compared with UKF-NB4. Furthermore, the adhesion of UKF-NB-4AD169 but not of UKF-NB4 resulted in focal disruption of the monolayer integrity which facilitates tumor cell transmigration. Blocking antibodies directed against the beta1 integrin chain as well as beta1alpha5 on the tumor cells specifically inhibited adhesion in a concentration-dependent manner. When UKF-NB-4 were pretreated with a beta1 integrin activating antibody, focal disruption of the endothelial integrity also occurred. These findings lead us to suggest that HCMV infection activates beta1alpha5 in the host neuroblastoma cell which in turn enables these cells to tightly adhere to endothelial cells. In the presence of the protease inhibitor phenantroline, beta1alpha5-mediated adhesion was not impaired whereas UKF-NB4AD169-mediated endothelial monolayer permeabilization was dose dependently inhibited. We conclude that human cytomegalovirus infection contributes to augmented neuroblastoma invasiveness via adhesion of activated beta1alpha5 and subsequent matrix digestion by proteases.

Antibodies, Blocking↗
PubMed2000

High frequency of HCV infection in individuals with isolated antibody to hepatitis B core antigen.

Although isolated antibody to hepatitis B core antigen (anti-HBc) is frequently nonspecific or may be the only serological marker of past self-limiting hepatitis B, where antibodies against the surface antigen have disappeared, isolated anti-HBc seropositivity is frequently associated with chronic hepatitis B in HIV- and HCV-infected individuals. Of 5,520 samples that tested positive for anti-HBc (IMx and AxSYM CORE, Abbott, Delkenheim, Germany) at the Institute of Virology, University Clinic Frankfurt during the time interval from January 1994 to February 1996, 643 (11.6%) were isolated anti-HBc-reactive in the IMx and AxSYM CORE assays (inhibition values >90%). There was a statistically significant association between isolated anti-HBc seropositivity and HCV and HIV/HCV coinfection (p < 0.05). A total of 190 samples were available for further testing. Six (3.2%) of 190 isolated anti-HBc-positive samples were considered false-positive since they were only positive in the AxSYM or IMx CORE assay and a linear decrease of the measured signal could not be observed in dilution series. Of 184 serum samples tested with nested PCR using primers of the S genome region, only 6 (3.3%) were HBV DNA-positive. Anti-HBc-IgM antibody could be detected in 3 (1.6 %) of the tested samples using the IMx CORE-M. With the more sensitive VIDAS HBc IgM specific IgM antibody was detected in 15 (8.5%) of 177 samples at concentrations ranging from 10 to >200 Paul Ehrlich Institute U/ml. HIV or HCV coinfection was present in 28.1% and 37.5% of isolated anti-HBc-positive individuals, respectively. We conclude from our observations that only a limited proportion of anti-HBc-isolated individuals are potentially infectious, however anti-HBc-IgM which is detectable in any form of liver disease associated with HBV infection was present in more than 8% of the individuals. Of isolated anti-HBc-positive sera 37% were positive for anti-HCV, suggesting that anti-HCV antibody testing should be performed in isolated anti-HBc-positive individuals.

DNA, Viral↗
PubMed1999

Antiviral and immunomodulatory effects of desferrioxamine in cytomegalovirus-infected rat liver allografts with rejection.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model. METHOD: One day after liver transplantation, PVG (RT1c) into BN(RT1n), the rats were infected with rat CMV (RCMV, Maastricht strain; 10(5) plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined. RESULTS: In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-alpha and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells. CONCLUSIONS: Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.

Adjuvants, Immunologic↗
PubMed1999

Human cytomegalovirus infection decreases expression of thrombospondin-1 independent of the tumor suppressor protein p53.

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis. It has been shown that promoter sequences of the TSP-1 gene can be transactivated by the wild-type tumor suppressor protein p53. As human cytomegalovirus (HCMV) infection inactivates wild-type p53 of various cell types, we investigated whether HCMV infection is associated with reduced TSP-1 production. We found, in conjunction with accumulated p53, that TSP-1 mRNA and protein expression was significantly reduced in HCMV-infected cultured human fibroblasts. To determine whether the observed TSP-1 suppression depends on p53 inactivation, the p53-defective astrocytoma cell line U373MG was infected with HCMV. In these cells TSP-1 expression was also significantly reduced by HCMV infection whereas expression of the p53 mutant variant remained unaltered. In both cell lines the decreased expression of TSP-1 mRNA occurred early after infection (4 hours), indicating that HCMV inhibits TSP-1 transcription during the immediate-early phase of infection before HCMV DNA replication. Inhibition of HCMV DNA synthesis by ganciclovir did not influence TSP-1 reduction whereas the antisense oligonucleotide ISIS 2922, complementary to HCMV immediate-early mRNA, completely prevented the HCMV-mediated TSP-1 suppression. These findings strongly suggest a novel role for HCMV in the modulation of angiogenesis due to p53-independent down-regulation of TSP-1 expression.

Antiviral Agents↗
PubMed1999

Epidemiological analysis of immunity to poliovirus after termination of an era of vaccination with OPV in Germany. An analysis of the German Association Against Viral Diseases (DVV).

The global eradication of poliomyelitis by the year 2000 is an objective of the World Health Organization (WHO). Since 1998, after a period of 37 years of vaccination using live oral poliovirus vaccine (OPV), single use of inactivated poliovirus vaccine (IPV) has been recommended in Germany. The present epidemiological analysis shows the immunity of 3474 patients to poliovirus types 1, 2 and 3 by using a microneutralization assay. A non-age-specific evaluation of antibodies seroprevalence to poliovirus type 1 remained 81% and similarly, for poliovirus type 2 86% while the poliovirus type 3 decreased from 78% in 1990-1992 to 68% in 1997. In the important group of children aged 5-14 years, the prevalence of antibodies to type 3 decreased clearly from 74% in 1990 to 47% in 1997. The relatively favorable level of seroprevalence of antibody to type 2 in children aged 1-4 years (89%) indicates a good acceptance of vaccination programs. However, a good immunity to all 3 serotypes was not achieved by primary vaccination. The objective of a global eradication of poliomyelitis has not yet been be achieved. Great problems still exist, especially in Africa and Asia.

Adolescent↗
PubMed1999

Screening of blood donors for human cytomegalovirus (HCMV) IgG antibody with an enzyme immunoassay using recombinant antigens.

BACKGROUND: Screening of blood donors for human cytomegalovirus (HCMV) infection is usually performed by the combined detection of specific IgG and IgM antibody. However, in most of the cases of primary infection HCMV IgG seroconversion is observed concomitantly to IgM production and HCMV IgM antibody detection for blood donor screening is subject to a relatively high frequency of false positive results. OBJECTIVE: In the present study a newly established HCMV IgG ELISA based on recombinant antigens (anti-HCMV recombinant IgG ELISA, Biotest) was evaluated in terms of sensitivity and specificity for blood donor screening. STUDY DESIGN: A total of 442 serum samples including follow-up sera of five patients suffering from primary HCMV infection, selected seropositive and seronegative blood donors and routine specimens were comparatively investigated with three HCMV antibody ELISAs (anti-HCMV recombinant IgG ELISA, Biotest; Enzygnost anti-CMV/IgG + IgM, Dade Behring; and Captia CMV-TA, Centocor). RESULTS: IgG seroconversion was detected with anti-HCMV recombinant IgG ELISA as early as IgM in all five patients suffering from primary infection. The alternative ELISAs were less sensitive, detecting seroconversion one to three bleeds later in 2 (Enzygnost anti-CMV/IgG + IgM) and 4 patients (Captia CMV-TA), respectively. Anti-HCMV recombinant IgG ELISA showed a 99.1% agreement with Enzygnost anti-CMV/IgG + IgM and/or Western blot in the preselected blood donors and routine specimens. Relatively high numbers of false negative (n=20) and positive results (n=7) were obtained with Captia CMV-TA. CONCLUSIONS: Our preliminary data suggest that HCMV antibody screening of blood donors can be performed reliably by detection of specific IgG provided that a highly sensitive assay system is used.

Antibodies, Viral↗
PubMed1999

Cytomegalovirus-induced transendothelial cell migration. a closer look at intercellular communication mechanisms.

A variety of cells such as leukocytes and tumor cells may adhere to endothelial cells and subsequently transmigrate into the solid tissue by involving specific intercellular molecular pathways. One important prerequisite for transendothelial migration is the loosening of endothelial cell-to-cell contact sites, which can be triggered by extravasating cells. Cytomegalovirus (CMV) has obviously evolved the ability not only to influence host cells floating in the blood stream to adhere to endothelial cells, but also to induce the formation of intercellular gaps within the endothelium, resulting in transendothelial migration. These features allow the virus to disseminate and evade the immune system. In coculture experiments with human endothelial monolayers and human CMV (HCMV)-infected neuroblastoma cells or leukocytes, changes in the integrity of the monolayer were observed and further analyzed on the molecular level. For example, HCMV may activate the integrin beta1alpha5 (VLA-5) that triggers adhesion to endothelial cells with subsequent focal disruption of endothelial cell-to-cell connections. It is hypothesized that a Ca(2+)-independent pathway following VLA-5 binding disconnects the cadherin-catenin-actin complex within the endothelial cells. The loss of cadherin function causes the loss of contact to the neighboring endothelial cells and thus could represent an important mechanism in HCMV-induced cellular transendothelial migration and disruption of the endothelial integrity.

Cell Adhesion↗
PubMed1999

Proinflammatory potential of cytomegalovirus infection. specific inhibition of cytomegalovirus immediate-early expression in combination with antioxidants as a novel treatment strategy?

We observed the effects of antiviral therapy on CMV and/or oxidative-stress-induced stimulation of proinflammatory molecules including interleukin-8 (IL-8), melanoma growth stimulatory activity-alpha (GRO-alpha) and intercellular adhesion molecule 1 (ICAM-1) using human foreskin fibroblasts. Ganciclovir, foscarnet or cidofovir completely suppressed virus replication, as demonstrated by CMV late (L) antigen production. These drugs did not influence CMV immediate-early (IE) antigen expression and had no effects on CMV-induced cellular changes in IL-8, GRO-alpha and ICAM-1 levels. Phosphorothioate oligonucleotide (ISIS 2922) suppressed both CMV IE and L antigen by 99%. ISIS 2922 completely suppressed CMV-induced upregulation of both chemokines and ICAM-1. Induction of oxidative stress by H(2)O(2) upregulated IL-8 expression. Oxidative stress and CMV infection showed synergistic effects on IL-8 expression. ISIS 2922 only partially inhibited the upregulation of IL-8 in infected cells treated with H(2)O(2), whereas cotreatment with ISIS 2922 and antioxidants inhibited the upregulation almost completely. The results showed that inhibition of CMV IE expression alone or in combination with antioxidants is promising for the treatment of CMV disease.

Antigens, Viral↗
PubMed1999

In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from subjects coinfected with human immunodeficiency virus and Leishmania infantum.

To explore the type 1 and type 2 cytokine profile in cases coinfected with human immunodeficiency virus (HIV) and Leishmania infantum, production of interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) was investigated in mitogen-stimulated and unstimulated peripheral blood mononuclear cell cultures from eight HIV/Leishmania coinfected subjects matched with eight anti-HIV-positive subjects with no evidence of Leishmania coinfection. Levels of IL-4 and IL-2R increased significantly from the baseline levels in the peripheral blood mononuclear cell supernatants of HIV/Leishmania coinfected subjects following stimulation with phytohemoagglutin, whereas the postchallenge concentration of IFN-gamma was significantly increased in the HIV-infected group. The levels of IL-4 and IL-10 were significantly higher in the HIV/Leishmania group throughout evaluation. Post-stimulation IFN-gamma production was significantly higher in the HIV-positive group in comparison with that of the HIV-Leishmania coinfected subjects. These observations support the notion that a Th2 cytokine response is present during a Leishmania infection, even among HIV-coinfected individuals.

Adult↗
PubMed1999

Chlamydia trachomatis and male infertility: chlamydia-IgA antibodies in seminal plasma are C. trachomatis specific and associated with an inflammatory response.

BACKGROUND: There is controversy over the role of asymptomatic genital tract infection by Chlamydia trachomatis, its optimal diagnosis, and its place in the etiology of male infertility. OBJECTIVE: Comparison of direct detection of Chlamydia trachomatis in semen with the presence of chlamydia-antibodies in seminal plasma and serum, together with parameters of the spermatogram, in men of infertile relationships. STUDY DESIGN: Prospective clinical study. SETTING: University hospital tertiary referral center. SUBJECTS AND METHODS: Two groups of consecutive andrological patients (n = 89 and n = 36) were investigated as follows: semen analysis, including concentration of granulocyte-elastase; detection of C. trachomatis in semen samples and first void urine by polymerase chain reaction (PCR) and antigen-ELISA (Celisa); detection of chlamydia antibodies in serum and seminal plasma by recombinant antibody-enzyme-linked immunosorbent assay (rELISA) and of Chlamydia trachomatis specific antibodies by the ImmunoComb-Chlamydia-Bivalent test. RESULTS: In 2/125 (1.6%) semen samples Chlamydia trachomatis DNA was detected by PCR. Genus specific anti-chlamydia-IgA was found in 12/122 (9%) of the seminal plasmas. This IgA appeared to be specific for C. trachomatis. Seminal plasmas with chlamydia-IgA antibodies showed higher PMN-elastase levels than IgA negative samples (P < 0.04). Chlamydia-IgG antibodies were present in 27/89 (30%) of the sera, but in only five of these 27 sera (19%) were the antibodies detected specific for C. trachomatis. There were no associations between any of these variables and the parameters of the routine semen analysis. CONCLUSION: IgA-chlamydial antibodies in seminal plasma appeared to be specific against C. trachomatis and were associated with an inflammatory response in the male genital tract.

Adult↗
PubMed1998

Persistent human cytomegalovirus infection induces drug resistance and alteration of programmed cell death in human neuroblastoma cells.

Infection with human cytomegalovirus (HCMV) is a common and generally asymptomatic affection in childhood. Its role in neuroblastoma (NB) patients has not yet been elucidated. As evidence grows that HCMV interacts with apoptotic signaling due to the interaction of HCMV gene products with cellular proteins of apoptotic pathways, we used human NB cell line UKF-NB-2 persistently infected with HCMV strain AD169 to study the effects of long-term HCMV infection on programmed cell death of neuroectodermal tumor cells. The cells designated UKF-NB-2AD169 continued to produce infectious virus in successive subcultures over a period of more than 1 year. Up to 20% of cells expressed viral genes or produced infectious virus after initiation of infection. UKF-NB-2AD169 cells were significantly less sensitive to the cytotoxic agents cisplatinum and etoposide than parental (noninfected) UKF-NB-2 cells. These effects were associated with decreased ability of UKF-NB-2AD169 cells to undergo apoptosis and continuous viral replication. UKF-NB-2AD169 cells showed increased levels of antiapoptosis Bcl-2 protein (up to 12-fold), whereas expression of p53 and c-myc was not changed. Treatment of UKF-NB-2AD169 cells with ganciclovir, abolishing virus production, reestablished sensitivity to chemotherapy, lowered Bcl-2 expression, and facilitated inducibility of apoptosis to the level of the parental cell line. The results demonstrate that persistent HCMV infection confers resistance to cytotoxic agents on neuroectodermal tumor cells and protects from apoptosis, probably due to increased levels of Bcl-2 protein. Hence, it is conceivable that HCMV infection before or during tumorigenesis may contribute in some NB patients to failure of therapy.

Antigens, Viral↗
PubMed1998

[Transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease].

Different diseases of the transmissible spongiform encephalopathy (TSE) group are known to affect humans and various animals. Owing to the bovine spongiform encephalopathy (BSE) epidemic and the description of the new variant of Creutzfeldt-Jakob disease (nvCJD), which is probably linked to BSE, TSE received much attention. The nature of the causative agent is still disputed; none of the proposed concepts (prions, viruses) can explain all features. It is clear, however, that there is a genetic component in susceptibility to infection and in development of disease and that transmission may cross the species barrier. This paper gives an overview of the first results and latest developments of basic TSE research that has focused on in vivo early diagnosis and the prevention of possible (also iatrogenic) transmission.

Animals↗
PubMed1998

Influence of hepatitis G virus coinfection on the clinical course of chronic hepatitis C.

Hepatitis G virus (HGV) is a parenterally transmitted virus, frequently associated with hepatitis C virus infection. Hepatitis G virus RNA was detected by reverse transcription-polymerase chain reaction in the serum of 40 patients with chronic hepatitis C. Nine (22.5%) patients had evidence of hepatitis G virus viraemia. No significant epidemiological or virological differences could be demonstrated between subjects infected with both hepatitis G virus and hepatitis C virus and subjects infected with hepatitis C virus alone. Aminotransferase values were comparable between the two groups, whereas higher levels of cholestatic enzymes (P< 0.001) were reported in the hepatitis G virus/hepatitis C virus-positive patients. A liver biopsy was performed on all 40 patients no later than 6 months before recruitment. The mean histological activity index did not differ between hepatitis G virus-positive and hepatitis G virus-negative patients, whereas specific histological features such as macrovesicular steatosis, portal granulomas, and bile duct damage were more commonly observed among the coinfected patients. The results indicate that coinfection with hepatitis G virus probably does not have a significant effect on hepatitis C virus-induced hepatic damage.

Adult↗
PubMed1998

Reduction of diagnostic window by new fourth-generation human immunodeficiency virus screening assays.

In order to reduce the diagnostic window between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new screening enzyme-linked immunosorbent assays (ELISAs) which permit the simultaneous detection of HIV antigen and antibody have been developed. Two fourth-generation assays, HIV DUO (Biomérieux) and HIV Combi (Boehringer Mannheim), for the combined detection of HIV antigen and antibody, were compared with a third-generation assay (HIV-1/HIV-2 3rd Generation Plus enzyme immunoassay [EIA]; Abbott) and a p24 antigen test (HIV-1 Ag monoclonal; Abbott). A total of 17 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 255 potentially cross-reactive serum samples were tested. Ten seroconversions were detected an average of 8.1 days earlier with HIV DUO and 7.5 days earlier with HIV Combi than with the third-generation ELISA. Overall, in the 17 seroconversion panels tested, HIV DUO detected HIV-1 infection an average of 4.8 days and HIV Combi detected infection an average of 4.4 days earlier than HIV-1/HIV-2 3rd Generation Plus EIA. HIV antigen was detected with HIV DUO and HIV Combi in all of the 15 cell culture supernatants infected with different HIV-1 subtypes, including subtype O. With fourth-generation assays, considerably fewer false-positive results (n = 4 to 6) were obtained, in comparison with the third-generation EIA (n = 18). Fourth-generation assays permit an earlier diagnosis of HIV infection than third-generation antibody screening assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion.

AIDS Serodiagnosis↗