Biomedical subjects

C Meitinger

Publications and source records attributed to C Meitinger.

12 recordsLinked to original sources

PubMed1994

Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless.

Epstein-Barr virus nuclear antigen 2 (EBNA-2) plays a crucial role in B cell immortalization by Epstein-Barr virus (EBV), most probably by its ability to transactivate several cellular and viral genes. Recently, we showed that EBNA-2 interacts with the TP1 promoter of EBV through a cellular protein. In this report we provide evidence that this protein is recombination signal binding protein (RBP)-J kappa, highly conserved in evolution, and originally isolated by its ability to bind to the J kappa-type V(D)J recombination signal sequence. To identify the cellular protein interacting with the TP1 promoter, we performed electrophoretic mobility shift assays using binding sequences of known transcription factors, that carry partial homology to the crucial sequences of the EBNA-2 responsive element (EBNA-2RE), as competitor. Competition assays revealed the RBP-J kappa recognition site as a very efficient competitor of cellular TP1 promoter binding protein. In parallel, we purified the protein to homogeneity from Raji cells by two ion-exchange columns and affinity purification using the EBNA-2RE coupled to magnetic beads. Affinity purified fractions separated on SDS-PAGE revealed a single predominant band after silver staining which was recognized by anti-RBP-J kappa monoclonal antibody. These purified fractions exhibited binding specificity for EBNA-2RE and EBNA-2. In vitro-translated murine RBP-2 cDNA reacted with EBNA-2RE and EBNA-2 in the same fashion as the affinity purified protein. The interaction between RBP-J kappa and EBNA-2 is a prerequisite for EBNA-2-mediated transactivation of the TP1 promoter.

3T3 Cells↗

PubMed1994

Crucial sequences within the Epstein-Barr virus TP1 promoter for EBNA2-mediated transactivation and interaction of EBNA2 with its responsive element.

EBNA2 is one of the few genes of Epstein-Barr virus which are necessary for immortalization of human primary B lymphocytes. The EBNA2 protein acts as a transcriptional activator of several viral and cellular genes. For the TP1 promoter, we have shown previously that an EBNA2-responsive element (EBNA2RE) between -258 and -177 relative to the TP1 RNA start site is necessary and sufficient for EBNA2-mediated transactivation and that it binds EBNA2 through a cellular factor. To define the critical cis elements within this region, we cloned EBNA2RE mutants in front of the TP1 minimal promoter fused to the reporter gene for luciferase. Transactivation by EBNA2 was tested by transfection of these mutants in the absence and presence of an EBNA2 expression vector into the established B-cell line BL41-P3HR-1. The analysis revealed that two identical 11-bp motifs and the region 3' of the second 11-bp motif are essential for transactivation by EBNA2. Methylation interference experiments indicated that the same cellular factor in the absence of EBNA2 binds either one (complex I) or both (complex III) 11-bp motifs with different affinities, giving rise to two different specific protein-DNA complexes within the left-hand 54 bp of EBNA2RE. A third specific complex was shown previously to be present only in EBNA2-expressing cells and to contain EBNA2. Analysis of this EBNA2-containing complex revealed the same protection pattern as for complex III, indicating that EBNA2 interacts with DNA through binding of the cellular protein to the 11-bp motifs. Mobility shift assays with the different mutants demonstrated that one 11-bp motif is sufficient for binding the cellular factor, whereas for binding of EBNA2 as well as for efficient transactivation by EBNA2, both 11-bp motifs are required.

Animals↗

PubMed1979

[Oral immunization of newborn infants against pertussis].

A group of 148 newborn babies was subdivided into four groups. Subsequent to after oral application of killed pertussis bacteria (1-3 times; control) all developed agglutinating resp. precipitating antibodies. There was a clear relation between the given quantity of Oral Pertussis Vaccine and the antibody titer. The problem has been discussed, whether it will be possible to get a protection of newborn children against whooping cough within the first weeks of life and, simultaneously, to avoid side effects.

Administration, Oral↗

PubMed1977

[Prophylactic procedures to prevent respiratory distress syndrome in prematures (author's transl)].

A controlled trial of antepartum glucocorticoid treatment for prevention of Respiratory Distress Syndrome (RDS) or Hyaline Membrane Syndrome (HMS) was carried out. 91 mothers, in whom premature delivery threatened between 27 and 37 weeks of gestation, were given intramuscular injections of 8-12 mg of betamethasone as well as medication inhibiting uterine activity (tocolytica and sedation) and strict bedrest to delay premature delivery for at least 24 to 48 hours. A control group of 118 mothers, who were hospitalized late and premature delivery could not be delayed, had no betamethasone treatment. There was no significant differerence in the incidence of Respiratory Distress Syndrome in premature infants in both groups, but there was a 50% lower mortality rate of Respiratory Distress Syndrome in the betamethasone treated group, due to a milder course of Respiratory Distress Syndrome Disease. Harmful effects from corticosteroids given to pregnant women prior to premature delivery were not observed in our group. The prophylactic treatment with betamethasone to diminish the mortality rate of Respiratory Distress Syndrome is therefore considered encouraging and profitable.

Betamethasone↗

PubMed1975

[Prevention of respiratory distress syndrome with betamethasone. Preliminary communication].

A controlled trial of antepartum glucocorticoid treatment for prevention of respiratory distress syndrome in premature infants was carried out. 37 mothers, in whom premature delivery threatened between 28 and 37 weeks of gestation, were given intramuscular injections 8-12 mg of betamethasone as well as medication inhibiting uterine activity and strict bedrest to delay premature delivery for at least 24 to 48 hours. In comparison with a control group of 16 mothers, who received tocolytic and sedative medication and were on strict bedrest and another control group of 42 untreated patients, there was no difference in the 3 groups concerning the incidence of respiratory distress syndrome in premature infants, but there was a lower perinatal mortality rate of respiratory distress syndrome in the betamethasone treated group, than in the controls, possibly due to a milder course of respiratory distress syndrome disease by accelerating functional maturation of the fetal lung with betamethasone.

Apgar Score↗

PubMed1974