Fulminant course of herpes simplex virus reactivation in an apparently immunocompetent woman.
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Acyclovir↗
Biomedical subjects
W Verhagen
Publications and source records attributed to W Verhagen.
Immunological gap in the infectious animal model for biliary atresia.
BACKGROUND: Extrahepatic biliary atresia (EHBA), the etiology of which still remains unclear, occurs exclusively in newborns and has recently been simulated in an animal model. It is possible to trigger an EHBA corresponding to the human disease by means of intraperitoneal infection of newborn Balb/c mice with rhesus rotavirus (RRV). The aim of the present study was to determine the conditions and circumstances for inducing biliary atresia in this model focusing on first-line immunological aspects. METHODS: Newborn as well as pregnant Balb/c mice were intraperitoneally infected with RRV. RESULTS: The highest incidence of cholestasis (86%) was achieved by infection with 10(6) PFU/ml RRV within the first 12 h postpartum, resulting in EHBA with a lethality of 100%. However, the later the newborn mouse is infected, the less likelihood there is that EHBA is triggered. Additionally, the incidence of biliary atresia in this model depends on the quantity of the virus that is given intraperitoneally. However, the development of biliary atresia is not correlated to the virus in the liver. The antepartum infection of pregnant mice does not induce EHBA in the offspring. Female mice that are immunized against RRV protect their newborns from developing RRV-induced cholestasis and EHBA. This protection is transmitted transplacentally and not by breast milk. CONCLUSION: It is obvious that a temporary immunological gap is essential for virally induced EHBA. Further studies should focus on specific parameters of the immune system of newborn mice in this biliary atresia model.
Aging↗
Evolution of poliovirus type I during 5.5 years of prolonged enteral replication in an immunodeficient patient.
Poliovirus type 1 was isolated from an immunodeficient patient 4 days after onset of paresis (IS1) and after 5.5 years of prolonged enteral virus replication (IS2). Antigenic characterization revealed that IS1 was Sabin 1-like, whereas IS2 reacted like poliovirus 1 Mahoney. Complete genomic sequencing demonstrated the phylogenetic relationship (94.9% identity) of IS1 and IS2, which differed from the most closely related Sabin 1 by 5.4 and 8.3%, respectively. Both isolates had revertant-like mutations at nucleotides 480 and 6203. Deduced amino acid sequences indicated significant changes between IS1 and IS2 at the neutralizing antigenic site 1. Prolonged enteral replication, evolution, and shedding of poliovirus by immunodeficient patients should be considered in the poliovirus eradication strategy.
5' Untranslated Regions↗
Evaluation of serological screening of cadaveric sera for donor selection for cornea transplantation.
Human corneas are explanted for grafting as late as 72 h after death, for example, from medical examiner cases. Currently, infection of the donor with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) is excluded in most cornea banks by serological testing of the cadaveric serum only. The reliability of this strategy was investigated by testing paired cadaveric and premortem sera of 33 potential donors. Results were discordant in 17 of 33 donors by at least one assay. Most frequently, HBsAg enzyme-linked immunosorbent assay (ELISA) yielded false-positive results with the cadaveric serum (16 of 33 serum pairs). Virus safety of the graft was affected in a single case, which was HCV antibody negative in the cadaveric serum, but positive in the premortem serum (confirmed by HCV-RIBA strip immunoassay). Forensic DNA profiling by polymerase chain reaction (PCR) of both serum samples confirmed that these were derived from the same individual. In conclusion, the results indicate that serological testing of cadaveric sera is not a reliable method for screening of potential cornea donors, and may not be sufficient for the virus safety of cornea grafts. Therefore, other screening strategies such as detection of viral nucleic acids by PCR should be evaluated.
Adult↗
Patient to patient hepatitis B transmission during heart biopsy procedures. A report of the European Working Party on Viral Hepatitis in Heart Transplant Recipients.
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Biopsy↗
Determination of the concentration of influenza virus antihaemagglutinin antibody molecules of the IgG class and of the equilibrium constant by use of enzyme immunoassay titres determined for graded epitope concentrations.
A new technique for determining the concentration of influenza virus antihaemagglutinin antibody molecules of the IgG class (A) and of the equilibrium constant K of paratope-epitope interaction is described. The method is based on determining enzyme immunoassay (EIA) titres of antibody with graded epitope concentrations: EIA titres were defined in terms of the antibody dilution yielding a fixed amount of antibody adsorbed per ml (= 6.21 x 10(10)). Adsorption of antibody depends on the concentration of paratopes and epitopes allowed to react and on the equilibrium constant. For the use of a constant concentration of epitopes, the paratope concentration needed to yield the desired degree of antibody adsorption decreases with increasing avidity. Therefore, the EIA titres increase both with increasing avidity and increasing antibody concentration. When graded epitope concentrations are used for determining the EIA titres of a given serum, the titres are influenced in a similar manner by the antibody concentration of the serum and the increase of titres with increasing epitope concentration reflects avidity. The equilibrium constant found is subsequently used to determine the concentration of free antibody at the dilution meeting the definition of EIA titre and the product of EIA titre and the sum of free and bound antibody at this dilution gives the number of antibody molecules present in the test serum. A panel of 118 antisera was tested comparatively for A and K using the new method and by means of the guanidine titre ratio test and equilibrium filtration. The values obtained agreed well with each other. This novel technique offers the advantage that it can be easily adapted for use with other viruses.
Animals↗
Interaction of alveolar macrophages and respiratory syncytial virus.
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract illness in infants. However, the mechanisms leading to resolution of RSV infections are poorly understood. Since alveolar macrophages play an important role in defending the respiratory tract against infectious agents we investigated the interactions of RSV with these cells. Murine alveolar macrophages were challenged in vitro with RSV at different multiplicities of infection. The percentage of macrophages expressing viral antigen was determined by staining with monoclonal anti-RSV antibodies and evaluation by fluorescence microscopy or FACS analysis. The ability of macrophages to support virus replication was measured by a plaque forming assay on HEp-2 cells. Cell lysates of macrophages contained only small amounts of viable RSV in comparison to disrupted HEp-2 cells. The amount of viable RSV as well as the percentage of macrophages expressing viral antigen decreased rapidly over time. Activated macrophages had a reduced virus load in comparison to resting macrophages. RSV infected macrophages released biologically active tumor necrosis factor (TNF) in a virus dose dependent manner. In contrast, a high virus inoculum resulted in reduced microbicidal activity and oxygen radical production. Our results suggest that RSV infection influences different functions of alveolar macrophages in various ways. Since TNF is thought to restrict viral replication in several cell types it may play a role in limiting virus replication.
Animals↗
Method for determining the equilibrium constant and the concentration of influenza virus IgG antihaemagglutinin antibody molecules by use of EIA titres determined with and without guanidine hydrochloride.
A novel technique for determining the concentration of influenza virus antihaemagglutinin antibody molecules (A) of the IgG class and their equilibrium constant (K) is described which is based on recording EIA (enzyme-linked immunosorbent assay) guanidine titre ratios R (EIA titre determined in the absence of guanidine divided by EIA titre determined in the presence of 0.25 M guanidine hydrochloride). K is determined by using a regression line relating values of K to values of R. The line was established by testing antisera comparatively for K by means of equilibrium filtration and for R by EIA. The assay of A is based on the finding that the concentration of antibody molecules adsorbed at serum dilutions yielding an O.D. reading of 0.9 in the EIA test is within the experimental limits constant. Since K is known, this point of reference can be used to calculate A. For a panel of 57 influenza antisera, the A and K values determined by equilibrium filtration agreed well with the respective values determined by use of the novel technique.
Animals↗
Nosocomial hepatitis B virus infections in cardiac transplant recipients transmitted during transvenous endomyocardial biopsy.
Between March 1986 and September 1990, 67 of 243 cardiac transplant recipients in outpatient care at our clinic became hepatitis B virus surface antigen (HBsAg) positive after operation. The HBsAg of 63 patients belonged to the subtype ay, suggesting a common source of infection. These 63 cases and 103 controls with negative hepatitis B virus (HBV) serology were studied in order to analyse the outbreak. The sources of infection were patients who were chronic HBsAg carriers. Infection was transmitted at the time of endomyocardial biopsy, if performed on the same day and in the same room after biopsy of an HBsAg positive patient. The most likely mode of HBV transmission was droplet contamination of instruments and/or medication vials used for subsequent patients. Performing biopsies on HBsAg positive and negative patients in separate rooms resulted in the termination of the outbreak.
Adult↗
Influence of MHC on the oncogenicity and immunogenicity of polyoma virus BK in rats.
The oncogenicity of the human papovavirus, type BK, was examined in the Lewis strain of inbred rats, possessing the recombinant alleles "a" and "u" on the MHC TR1 locus. It was found that only haplotypes containing "a" within the B/D locus but not within the A and the C locus of the RT1 region were associated with resistance to the oncogenic potential of BKV and with the capacity of animals to form BKV T antigen antibody. By contrast, the presence of "u" or "l" within the MHC B/D region was linked to the reverse phenotype characterized by sensitivity to the oncogenic effect of BKV and failure to yield T antibody response up to 6 months after inoculation with BK. These results present further evidence of the function as an immune control gene of the B/D region of the RT1 locus of rat MHC.
Animals↗
Influence of formalin fixation on the detection of cytomegalovirus by polymerase chain reaction in immunocompromised patients and correlation to in situ hybridization, immunohistochemistry, and serological data.
The possibility of detecting cytomegalovirus (CMV) in formalin-fixed tissues by polymerase chain reaction (PCR) was evaluated in necroposies from lung tissues in a total of 24 patients who either had received organ transplants or were immunocompromised. PCR using two different pairs of primers for amplification of the major immediate early antigen of CMV was performed on fresh tissues and tissues fixed for 24, 48, and 72 h in neutral buffered formalin and compared to immunohistochemistry (IHC) and in situ hybridization (ISH). The fresh tissues of nine patients with serological evidence for acute CMV infection were all positive for CMV by PCR. After formalin fixation, the majority of the patients failed to show distinct signals with one or both pairs of primers as measured by densitometry. In contrast to this, fresh tissues of 15 patients without signs of an acute CMV infection were found either negative or weakly positive by PCR. Using IHC or ISH, positive results were observed only in five of nine and four of nine patients with acute CMV infection, respectively. These data demonstrate that, if only formalin-fixed tissue is available, PCR for CMV detection should be performed using two pairs of primers and should be supported by IHC.
Adolescent↗
Tumour induction by transplacental infection with polyoma virus of the F1 generation of Wistar rats.
Intravenous polyoma virus inoculation into pregnant Wistar rats resulted in transplacental infection of the foetus, causing tumours and hydronephroses. Cyclosporin A reduced these effects significantly.
Animals↗
Comparative investigation of the hemagglutinin epitopes of influenza virus A/Brazil/11/78 (H1N1). and its escape variants.
A method described previously for determining the concentration of influenza virus antihemagglutinin antibody molecules, the number of epitopes per virus particle and the equilibrium constant of virus antibody interaction was adapted to the use with escape variants (EVs), produced by multiplication of influenza virus A/Brazil (H1N1) in presence of monoclonal antibody directed to each of the four hemagglutinin sites (Sa, Sb, Ca and Cb). The EVs were found to possess an altered antigenic site, which was both antigenic and immunogenic. By use of selected EVs and antibody preparations, the number of epitopes per antigenic site was determined and it was found that each of the four sites was represented by about 390 epitopes per virus particle, suggesting that each of the about 400 hemagglutinin spikes per virion possessed one epitope of the specificity Sa, Sb, Ca and Cb. Alteration of site Sa but not of site Ca increased the avidity of antibody to react with the unchanged sites.
Antibody Affinity↗
Effect of acyclovir on herpes simplex virus infected neuronal, glial, and neurohybridoma cells in vitro.
Herpesvirus type 1 could be propagated most efficiently in cultured fetal neurons, to a lesser extent in NG108-15 neurohybridoma cells, and with the lowest titer in glial cells. Herpesvirus type 2 could not be cultured in neurohybridoma cells, and in fetal neurons a titer 100-fold lower than for herpesvirus type 1 was obtained. Cells infected with herpesvirus type 1 were used in an infectivity assay for acyclovir dose-response studies. The ED50 values were 7.4 nmol/l for fetal neurons, 180 for neurohybridoma cells, and 275 nmol/l for glial cells.
Acyclovir↗
[The AIDS problem in accident surgery].
In trauma surgery there is a particularly high proportion of patients in the age group most at risk of infection with AIDS. The result of an epidemiological study in our patients (HIV screening of all patients scheduled for surgery at a trauma center over 18 months) showed a prevalence of 0.1%. Specific therapeutic strategies must be developed to deal with the weakened immunity of HIV-infected patients. Fracture treatment in HIV-infected hemophiliacs is a special problem. Homogenous bone transplantation is described with reference to HIV. The particular danger of injury in trauma surgery is also investigated. The chain of infection is illustrated and used to demonstrate the precautions that can be taken against nosocomial HIV infections. Following infection with fluids containing HIV, specific measures must be taken. The legal aspects of HIV-antibody testing in the Federal Republic of Germany are elucidated. Finally, the problems of general preoperative HIV-antibody testing are discussed.
Acquired Immunodeficiency Syndrome↗
Recent influenza virus A infections in forensic cases of sudden unexplained death.
84 forensic necropsy cases with a history of sudden unexpected death and where no acceptable cause of death was found at autopsy (= cases of sudden unexplained death, SUD) were found to have a significantly higher rate of influenza A (H 3 N 2) infection than did matched controls of the general population and a group of forensic necropsy cases with known cause of death (NON-SUD cases). By contrast, the group of SUD cases was found to have no significantly increased infection rate with influenza H 1 N 1 and B virus, parainfluenza viruses, RS virus, adenovirus, and cytomegalovirus. The influenza A associated SUD cases had a significantly higher rate of pathological and histological findings previously described for cases of primary viral pneumonia than did SUD cases without recent influenza A infection and NON-SUD cases. These findings suggest that virological examination of SUD cases could be helpful in order to determine the probable cause of death. A considerable portion of the influenza associated SUD cases occurred during interepidemic influenza periods. Therefore, such cases could be a useful source for monitoring the interepidemic spread of influenza virus.
Autopsy↗
Serological evidence of recent influenza virus A (H 3 N 2) infections in forensic cases of the sudden infant death syndrome (SIDS).
40 forensic SIDS cases were found to have a significantly higher rate of serologic evidence of recent influenza A (H 3 N 2) infection than did matched controls. In contrast, the SIDS cases had serologically no significantly increased infection rate with influenza H 1 N 1 and B virus, parainfluenza virus, RS virus, adenovirus, and cytomegalovirus. SIDS cases with recent influenza infection had a significantly higher rate of histological findings as described for primary viral pneumonia than did SIDS cases without influenza infection. SIDS cases with recent influenza infection occurred much more frequently during epidemic than during interepidemic influenza A (H 3 N 2) periods. Our results confirm previous reports that SIDS cases have an increased rate of respiratory virus infections. However, they cannot prove a causal relationship between influenza infection and death. Since our SIDS cases comprised 75 per cent of cases aged more than three months, our results pertain essentially to cases of this age group.
Antibodies, Viral↗
Comparative investigation of monoclonal and polyclonal antibodies directed against strain-specific and common antigenic sites on influenza H1N1 virus hemagglutinin.
Antibodies directed against strain-specific and common antigenic sites of H1N1 influenza virus hemagglutinin were tested comparatively, using monoclonal antibodies raised against strain A/Brazil/11/78 and polyclonal antibodies directed against strains A/Brazil/11/78, A/USSR/97/77, A/PR/301/54, and A/FM/1/47. The patterns of competition between antibodies for adsorption onto homologous virus indicated that the monoclonals comprised antibodies directed to each of the two strain-specific (Sa and Sb) and common antigenic sites (Ca and Cb) of virus hemagglutinin. Polyclonal strain-specific antibodies (SSA) yielded the competition patterns of mixtures of anti-Sa and anti-Sb antibodies and polyclonal common antigen antibodies (CAA) yielded those of mixtures of antibodies directed against sites Ca and Cb, indicating that the polyclonal preparations comprised a similar repertoire of antibodies, as represented by the panel of monoclonals. This conclusion was confirmed by determining, by means of equilibrium filtration, the number of epitopes per homologous virion(s) recognized by antibody preparations and their mixtures. Polyclonal SSA and CAA gave s values not significantly different from those of mixtures of the corresponding monoclonal antibodies. The strains tested were found to possess equivalent numbers of strain-specific and common epitopes per virion. The competition between antibodies was further examined in terms of the additiveness of s values they recognize in simultaneous reactions. No competition was observed for the monoclonal antibody pairs anti-Sa/anti-Ca, anti-Sa/anti-Cb and anti-Sb/anti-Cb, indicating that these antibodies combined with nonoverlapping epitopes. Polyclonal SSA and CAA yielded partial competition. The equilibrium constants (K) of comparable SSA and CAA were within the same range, and SSA and CAA did not influence their binding avidity when allowed to react simultaneously with homologous virus.
Animals↗