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Biomedical subjects

G Bauer

Publications and source records attributed to G Bauer.

At least 289 records · Page 16Linked to original sources
PubMed1994

Reconstitution of complete SV40 DNA replication with purified replication factors.

The identification and purification of human cell proteins required for the production of form I DNA following DNA replication from the simian virus 40 (SV40) origin is described. Using these proteins, complete SV40 DNA replication was reconstituted with only purified DNA replication factors: SV40 large tumor antigen (TAg), replication protein A (RPA), DNA topoisomerases I and II, DNA polymerase alpha-primase, replication factor C (RFC), the proliferating cell nuclear antigen (PCNA), DNA polymerase delta, maturation factor 1 (MF1), and DNA ligase I. MF1, a 5' to 3' exonuclease and DNA ligase I were both identified as essential components for production of covalently closed circular relaxed (form I) DNA. MF1 is probably the same exonuclease previously shown by others to function during DNA synthesis on artificial DNA templates or in conjunction with DNA polymerase alpha from the SV40 origin. Combined with these previous studies, our results suggest that MF1 functions to remove an RNA primer attached to every Okazaki fragment during lagging strand DNA synthesis. Interestingly, whereas mammalian DNA ligase I functioned in the reconstituted replication system, mammalian DNA ligase III did not substitute and the phage T4 DNA ligase functioned inefficiently, suggesting that DNA ligase I has a specific role as a replicative DNA ligase in eukaryotic cells.

Animals↗
PubMed1994

Transforming growth factor beta-treated normal fibroblasts eliminate transformed fibroblasts by induction of apoptosis.

Transforming growth factor beta (TGF-beta) induces normal fibroblasts to perform an inhibitory effect directed against transformed cells (P. Höfler, I. Wehrle, and G. Bauer, Int. J. Cancer, 54: 125-130, 1993). Coculture of normal fibroblasts with transformed cells, either resistant to G 418 or expressing Mx antigen detectable by specific immunofluorescence, allowed discrimination between three theoretical mechanisms of inhibition: irreversible inhibition of proliferation; reversion to the nontransformed phenotype; or elimination of transformed cells. Our data demonstrate that normal fibroblasts treated with TGF-beta are able to eliminate transformed cells by induction of apoptosis. Sensitivity against TGF-beta-induced elimination seems to be a general feature of in vitro-transformed cell lines. TGF-beta-induced elimination of transformed fibroblasts by their untransformed counterparts is proposed as a potential potent control point in carcinogenesis, which may lead to the suppression of transformed cells.

3T3 Cells↗
PubMed1994

IgA directed against early antigen of Epstein-Barr virus is no specific marker for the diagnosis of nasopharyngeal carcinoma.

The aim of this study was to evaluate the significance and specificity of IgA directed against Epstein-Barr virus (EBV)-specific early antigens (EA) for the unequivocal diagnosis of nasopharyngeal carcinoma (NPC). Therefore, sera from patients with diseases other than NPC, selected on the basis of elevated antibody titres against EBV antigens, were compared to sera from NPC patients with regard to the presence of IgA directed against EBV viral capsid antigen (VCA-IgA) and IgA directed against EA (EA-IgA). Four hundred forty-seven out of 7,508 non-NPC sera tested showed high titres (> 512) of IgG directed against Epstein Barr viral capsid antigen (VCA-IgG) and positive VCA-IgA (> or = 32). Two hundred twenty-seven of these sera were compared to 51 VCA-IgA-positive sera from NPC patients regarding the titre of EA-IgA. 60.7% of VCA-IgA-positive NPC sera showed positive EA-IgA, however 33% of VCA-IgA-positive non-NPC patients also exhibited EA-IgA. This result demonstrates that EA-IgA is not specific for NPC and does not allow an unequivocal serological diagnosis of NPC in individual cases. It seems therefore to be of questionable use for screening programs in NPC low-risk areas. The data do not contradict the usefulness of this marker for monitoring of patients treated for NPC and for screening programmes in high-risk areas.

Adult↗
PubMed1994

Avidities of IgG directed against viral capsid antigen or early antigen: useful markers for significant Epstein-Barr virus serology.

Classical Epstein-Barr virus (EBV) serology can be misleading in some cases due to the variability of the viral capsid antigen (VCA)-IgM response, persistent or reactivated VCA-IgM, or loss of anti-EBNA-1 during suppression of the cellular immune system. Therefore, we studied the usefulness and significance of avidity determinations of VCA-IgG and EA-IgG to achieve unequivocal interpretation of serological results. Avidities of EBV capsid antigen-specific IgG (VCA-IgG) and early antigen-specific IgG (EA-IgG) were determined by indirect immunofluorescence during and after acute EBV infection. Low-avidity antibodies were removed from antigen-antibody complexes by incubation with 6 M urea for 3 minutes. The analysis of 105 sera taken at defined time spans with regard to the onset of clinical symptoms allowed us to determine the kinetics of maturation of avidity of VCA-IgG. All sera had low-avidity antibodies at the onset of disease. More than 90% of the sera showed an avidity index below 0.25 during the first 10 days after the onset of disease. Fifty percent of the sera exhibited an avidity index of 0.25 or above 20-30 days after the onset of clinical symptoms. Sera from past infections uniformly exhibited avidity indices of 0.5 or 1. Avidity of EA-IgG may still be low when avidity of VCA-IgG is already borderline or high, thus allowing further differentiation of acute and recent infections. Avidity determination represents an important additional marker of serology in classical cases and allows diagnosis in aberrant cases, such as acute infections with low or undetectable VCA-IgM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Activation of a varicella-zoster virus-specific IgA response during acute Epstein-Barr virus infection.

The influence of an acute Epstein-Barr virus (EBV) infection on the serological parameters of persistent varicella-zoster virus (VZV) and herpes simplex virus (HSV) was studied. Sera from 161 patients with infectious mononucleosis caused by EBV and 178 age-matched controls were tested for HSV- and VZV-specific IgA. 98.7 percent of VZV-IgG-positive controls were negative for VZV-IgA, pointing to the stringent control of latent VZV in healthy individuals. During acute EBV infection, 33.8% of VZV-IgG-positive infectious mononucleosis patients produced VZV-specific IgA. This result may be explained either by reactivation of VZV due to transient suppression of cellular immune functions during acute EBV infection or by polyclonal stimulation caused by EBV. Due to the high incidence of HSV-IgA in healthy HSV-IgG-positive individuals, only a marginal effect of acute EBV infection on the appearance of HSV-specific IgA was found.

Adolescent↗
PubMed1994

The effects of brain lesions on the course of chronic epilepsies.

The effect of intercurrent brain lesions on the characteristics of chronic epilepsies has not yet been the subject of detailed investigation. We therefore retrospectively examined this issue for idiopathic, cryptogenic as well as symptomatic chronic epilepsies in patients documented in routine investigations at our outpatient seizure unit between the occurrence of epilepsy and commencement of the study. The clinical criteria for inclusion in this study were brain injury by trauma, stroke or intracerebral hemorrhage, documented by CT scan, and the occurrence of this so-called index event in patients with established chronic epilepsy. These requirements were met by 63 patients (40 male, mean age 44.8 years, SD 14.7 a; 23 female, mean age 43.1 years, SD 16.4 a). Seizure characteristics, EEG recordings as well as seizure frequencies before and after the index event were compared. Patients and controls were observed for a mean time of 22.12 years (SD 7.33 a) and 22.01 years (SD 11.31 a), respectively. Two patients presenting with generalized seizures prior to brain injury underwent a change in seizure characteristics. One control (without intercurrent brain lesion; matched for age, sex, age at onset of seizure disorder and classification of seizure disorder) primarily presenting with partial seizures evolving to generalized seizures showed changed seizure characteristics. These changes are statistically insignificant (McNemar test for the significance of changes). Seizure frequencies decreased significantly after brain injury. EEG recordings mirrored clinical findings with additional focal aspects according to brain lesion. These findings are discussed mainly with respect to the cofactorial etiology of epilepsies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Differentiation of primary from secondary anti-EBNA-1-negative cases by determination of avidity of VCA-IgG.

BACKGROUND: Serological techniques are used to determine Epstein Barr virus (EBV) etiology of a constellation of signs or symptoms related to lymphadenopathy, fever, respiratory tract infection, mononucleosis, hepatitis, thrombocytopenia or neurological disorder. Anti-Epstein Barr Nuclear antigen (EBNA)-1 is regularly negative during the first 3-4 weeks after the onset of clinical symptoms indicating acute EBV infection (primary anti-EBNA-1-negative). It may, however, also be negative in immunocompromised convalescent individuals (secondary anti-EBNA-1-negative) such as tumor patients, HIV-positive patients and transplant recipients. OBJECTIVES: The aim of this study was to determine the frequency of secondary anti-EBNA-1-negative cases and to find a way to distinguish them from primary anti-EBNA-1-negative cases using anticomplementary immunofluorescence (ACIF) and enzyme immunoassay (EIA). STUDY DESIGN: All sera sent to our institute for EBV serology during one year were routinely tested for Viral Capsid antibody (VCA)-IgM, VCA-IgG and anti-EBNA-1. RESULTS: VCA-IgG-positive/anti-EBNA-1-negative cases (13.5% of total VCA-IgG-positive) comprised 55% primary and 45% secondary anti-EBNA-1-negative cases. Detection of secondary anti-EBNA-1-negative cases was independent of the method used, i.e., ACIF or EIA. VCA-IgG retained its high avidity in secondary anti-EBNA-1-negative cases, whereas primary anti-EBNA-1-negative cases taken during the early phase of acute infection showed low avidity of VCA-IgG. CONCLUSION: Determination of the avidity of VCA-IgG routinely and in concert with standard serodiagnosis (VCA-IgG, VCA-IgM, anti-EBNA-1) can enable the differentiation of primary and secondary anti-EBNA-1-negative cases.

Journal Article↗
PubMed1994

Phytohemagglutinin-inducible p24 in peripheral blood mononuclear cells as a predictor of human immunodeficiency virus type 1 vertical transmission and infant clinical status.

We sought to determine whether the detectability of phytohemagglutinin-inducible p24 (PHA-p24) in short term cultures of peripheral blood mononuclear cells correlates with an increased risk of vertical transmission among human immunodeficiency virus type 1 (HIV-1)-infected pregnant women and more severe symptomatology among HIV-1-infected infants. The assay for PHA-p24 was performed on specimens obtained from HIV-1-infected women during their pregnancy and from infants during the first 6 months of life. Infants were followed prospectively to determine HIV-1 infection outcome and symptomatology. Among PHA-p24 positive women 9 of 19 (47.4%) gave birth to HIV-1-infected infants compared with 4 of 25 (16.0%) of PHA-p24-negative women (P = 0.02). Among women who tested PHA-p24-positive and had a CD4+ lymphocyte count < 500 cells/mm3, 8 of 15 (53.3%) gave birth to HIV-1-infected infants compared with 4 of 26 (15.4%) not meeting these conditions (P = 0.01). Among HIV-1-infected infants 4 of 5 (80%) of those testing PHA-p24-positive by one month of age developed an opportunistic infection or encephalopathy by 12 months of age, compared with none of the 11 infants testing PHA-p24-negative (P = 0.003). We conclude that PHA-p24 may be a useful in vitro measure for increased risk of vertical transmission among HIV-1-infected pregnant women and increased risk for rapid development of severe disease among HIV-1-infected infants.

Female↗
PubMed1994

Effect of 2',3'-didehydro-3'-deoxythymidine in an in vitro hollow-fiber pharmacodynamic model system correlates with results of dose-ranging clinical studies.

We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human immunodeficiency virus (HIV) type 1 MN were exposed to 2',3'-didehydro-3'-deoxythymidine (D4T) in vitro in a hollow-fiber model which simulates the plasma concentration-time profile of D4T in patients. Drug concentration was adjusted to simulate continuous intravenous infusion, or an intravenous bolus administered twice daily. The effect of the dosing regimen was measured with viral infectivity, p24 antigen, and reverse transcriptase or PCR for unintegrated HIV DNA. Dose deescalation studies on a twice-daily dosing schedule predicted a minimum effect dose of 0.5 mg/kg of body weight per day which correlated with the results of a clinical trial. Antiviral effect was demonstrated to be independent of schedule for every 12-h dosing versus continuous infusion. Finally, at or near the minimal effect dose, efficacy appeared to depend on the viral load. The ability of this in vitro pharmacodynamic model to assess the response of HIV-infected cells to different doses and schedules of antiviral agents may be useful in the design of optimal dosing regimens for clinical trials but requires validation with other types of antiretroviral agents.

Cell Line↗
PubMed1994

Seizure types and epileptic syndromes in adults.

Classifications of epileptic seizures and syndromes have been made in 2,956 patients of the adult seizure unit in Innsbruck, Austria, according to the ILAE proposals. In general, both classification schemes can be used in daily clinical work. Some difficulties arise with the subdivision of absence seizures and the lack of subdivision of myoclonic seizures. With idiopathic epilepsies characterized by generalized tonic-clonic seizures, the strict diagnostic separation according to diurnal occurrence occasionally leads to arbitrary classifications. The subdivison of localization-related epilepsies should rather be based on etiological factors than on the suspected anatomical site of the epileptogenic focus.

Adult↗