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M Lipp

Publications and source records attributed to M Lipp.

At least 127 records · Page 7Linked to original sources

E1A-dependent trans-activation of the human MYC promoter is mediated by the E2F factor.

E2F is a cellular transcription factor that binds to two sites in the adenovirus E2 promoter. Previous experiments have implicated E2F in the E1A-dependent transactivation of the E2 gene since levels of active E2F increase markedly during adenovirus infection in parallel with the increase in E2 transcription, and an E2F binding site can confer E1A inducibility to a heterologous promoter. Here we show that E2F binds to two sequence elements within the P2 promoter of the human MYC gene which are within a region that is critical for promoter activity. The MYC promoter can be trans-activated in an E1A-dependent manner and site-directed mutagenesis demonstrates that these E2F elements are essential for trans-activation. Finally, we also find that adenovirus infection of quiescent cells results in a stimulation of the endogenous MYC gene. We conclude that the activation of the E2F factor, which is likely responsible for the activation of viral E2 transcription, is also responsible for the E1A-dependent induction of MYC transcription.

Adenovirus Early Proteins↗

Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma.

Chromosomal translocations in Burkitt lymphoma and mouse plasmacytomas typically lie within or near the protooncogene MYC. In some instances, however, these tumors contain variant translocations with breakpoints located more distant from and downstream of MYC, in a domain commonly known as pvt-1. Until now, there has been no evidence that pvt-1 marks the location of a functional gene. Here we report the identification of a large transcriptional unit in human DNA that includes pvt-1. We have designated this unit as PVT. PVT begins 57 kilobase pairs downstream of MYC and occupies a minimum of 200 kilobase pairs of DNA. Some of the translocations that occur downstream of MYC in Burkitt lymphoma transect PVT; others lie between the two genes. None of the translocations we have studied appear to enhance transcription from an intact allele of PVT (indeed, they may inactivate that transcription), but some are associated with the production of abundant and anomalous 0.8- to 1.0-kilobase RNAs that contain the 5' exon of PVT and sequences transcribed from the constant region of an immunoglobulin gene (the reciprocal participant in the translocation). Identification of PVT should facilitate the exploration of how translocations downstream of MYC and insertions of retroviral DNA in the vicinity of pvt-1 might contribute to tumorigenesis.

Base Composition↗

Nuclear factor E2F mediates basic transcription and trans-activation by E1a of the human MYC promoter.

Transcription from one of the two initiation sites, P1 and P2, of the dual human MYC promoter seems to be essential in all proliferating cells. To identify proteins and target structures for MYC regulation, a DNA region was analyzed that is critical for P2 promoter activity. Here, we show that a nuclear factor binds to a DNA element within P2, which is conserved perfectly between mouse and man and displays a striking homology to the E1a-inducible E2 promoter of adenovirus type 5 (Ad5). We demonstrate that the same transcription factor, defined recently as E2F, which plays an essential role in the activation of adenovirus early promoters and enhancers, also interacts as a dominant nuclear factor with the MYC promoter. The presence of an intact E2F binding site is required for basic expression and for trans-activation of the P2 promoter by E1a proteins. The human MYC promoter is the first cellular target described for E2F. The results suggest that expression of MYC might be regulated via modulation of E2F by cellular 'E1a-like' factors.

Base Sequence↗

Three breakpoints of variant t(2;8) translocations in Burkitt's lymphoma cells fall within a region 140 kilobases distal from c-myc.

The variant translocations t(2;8) in Burkitt's lymphoma cells join band q24 of chromosome 8, distal from c-myc, to the Igkappa locus, with considerable variation in the location of the breakpoints on chromosome 8. We report the cloning and molecular characterization of a chromosome 8 region, distal from the c-myc locus, which encompasses the breakpoints of the Burkitt's lymphoma cell lines BL64, BL21, and LY91 within 11 kilobase pairs, termed provisionally bvr-1 (Burkitt's variants' rearranging region 1). Using probes from the c-myc, the bvr-1, and the human pvt-1 loci obtained by chromosome walking coupled with pulsed-field gel electrophoresis, we have constructed a physical map of the region 3' of c-myc. We map bvr-1 and pvt-1 about 140 and 260 kilobase pairs, respectively, distal from c-myc.

Base Sequence↗

Trans-activation of human MYC: the second promoter is target for the stimulation by adenovirus E1a proteins.

The detailed mechanisms leading to transcriptional activation of the human MYC oncogene in general as well as in certain tumor cells are poorly understood. In view of the ability of a number of viral oncogenes to stimulate transcription in trans, the identification of cellular target genes could contribute to the understanding of components of the transformation process. It is demonstrated that the human MYC promoter is such an efficient target for the trans-acting activity mediated by E1a proteins of adenoviruses (Ad). Using the chloramphenicol acetyltransferase (CAT) gene as a marker for promoter activity, co-transfection of constructs containing both MYC promoters and most of the untranslated first exon with plasmids expressing the E1a gene of different adenoviruses stimulates CAT activity up to 24-fold. Trans-activation depends upon the presence of the second promoter (P2), and transcription is initiated at the authentic cap site of P2. This observation is confirmed by the behaviour of stably transformed cell lines carrying single or multiple copies of MYC-cat constructs, which were transfected either with E1a-expressing plasmids, infected with Ad5, or fused with 293 cells constitutively expressing E1a protein. These results suggest that E1a proteins can lead to an imbalance of the regulation of the human MYC gene, which might be a sufficient prerequisite for initiation and progression of transformation.

Adenoviridae↗

[The microlaryngeal tube--a new tube for direct laryngoscopy in the ENT field].

We describe our experience with a new orotracheal tube with low-pressure cuff for anesthesia during endoscopic laryngeal surgery. Twelve consecutive patients (ASA groups II and III) undergoing microlaryngoscopy for diagnostic or operative reasons were intubated orotracheally with the tube. No complications associated with intubation or anesthesia occurred. In comparison with normal armored tubes (i.e. Woodbridge tubes), the microlaryngeal tube gives the surgeon better operating conditions and still permits conventional intermittent positive pressure ventilation without excessive increases in ventilation pressure. The advantages from the low-pressure cuff could only be seen in 7 patients. With this foregoing restriction, we recommend the use of the new microlaryngeal tube for anesthesia during microlaryngoscopy.

Female↗

[Frequency and severity of throat complaints following general anesthesia with the insertion of various endotracheal tubes].

Laryngeal and pharyngeal complaints following general anaesthesia are well-known problems. The frequency, extent, and intensity reported in several studies are at variance. Such transient postoperative problems should not be considered equivalent to traumatic airway injuries caused by endotracheal intubation. A decrease in the incidence of slight airway complications was to be expected with the introduction of low-pressure-cuff tubes, however a few studies have reported just the opposite result. This study was designed to investigate the incidence, intensity, and duration of postoperative airway symptoms with special emphasis on cuff construction (low-pressure-high-volume cuff (LPC) vs high-pressure-low-volume cuff (HPC)). Our double-blind study included 500 patients. The acceptance criteria were: operation outside the head and neck region, no throat pack or gastric tube. The subjects were divided randomly into five groups, each group consisting of 100 patients: Group A: red rubber tubes (HPC); Group B: latex-spiral tubes (HPC); Group C: PVC tubes (LPC); Group D: PVC tubes with rediffusion system (LPC); Group E: face mask. The patients of groups A-D underwent oral intubation using lidocaine gel 2%; adequate cuff inflation was determined just after intubation. The patients were questioned every 24 h for 2 days postoperatively using an analogue scale and "open" and "closed" questions. The single groups were comparable in age, sex, height, weight, number of smokers, duration of operation (only groups A-D), and preoperative diseases of the upper airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Changes in temporomandibular joint functions in various general anesthesia procedures].

In a clinical study conducted in 1986 on 100 patients, we were able to demonstrate that intubation leads to the occurrence of temporary disturbances of the stomatognathic system. To verify these results, a double-blind study was conducted involving 140 patients of ASA groups I and II. Further acceptance criteria were: operation outside of the head and neck area, no throat pack or gastric tube, and the requirement of dental antagonists on the left and right side. Group composition: Group A: oral intubation with a laryngoscope (n = 50); Group B: nasal intubation using a fiberoptic endoscope (n = 40); Group C: face mask (n = 50) Groups A and B were divided at random. Balanced anesthesia was performed for all patients. In group B, after nasal intubation the mandible was placed and fixed in the habitual occlusion position. The patients had a dental examination preoperatively and on 1st, 2nd and 3rd postoperative day. Parallel to this study, we also interviewed 400 patients after routine intubation anesthesia with regard to postoperative temporomandibular joint (TMJ) symptoms. Groups A, B, and C were comparable in age, sex, height, weight, preoperative values of maximal mandibular movement, and pathological findings of the TMJ (Tables 1-3); the only differences were a longer mean duration of surgery in groups A and B than in group C (P greater than 0.05) and that women described more stomatognathic disorders in the preoperative medical history than men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Target sequences for cis-acting regulation within the dual promoter of the human c-myc gene.

Recombinant plasmids of the human c-myc promoter-leader region and the bacterial chloramphenicol acetyltransferase (cat) gene were constructed. After transfection into different rodent and human cells, the 862-base-pair (bp) PvuII fragment carrying both c-myc promoters and 350 bp of the untranslated leader conferred 1/15 to 1/30 of the CAT activity mediated by the simian virus 40 promoter. The presence of additional sequences upstream of the PvuII fragment had an overall negative effect on c-myc promoter activity detectable by titration analysis with small amounts of transfected plasmid DNA. The analysis of numerous deletion constructs in the c-myc promoter-leader region as well as S1 mapping experiments demonstrated that the high CAT activity depended largely on the presence of the second promoter. By cotransfection of c-myc-cat constructs with plasmids carrying different parts of the c-myc promoter locus, targets for positively acting cellular factors were identified. Two positive regulatory elements were mapped within the 862-bp PvuII fragment. One was localized within the 248-bp PvuII-SmaI fragment -101 to -349 bp upstream of the first cap site and the other within the 142-pb XhoI-NaeI fragment of the first exon, comprising positions -95 to +47 relative to the second cap site. We conclude that the dual promotor of the human c-myc gene represents a strong eucaryotic promotor regulated by cooperation of positively and negatively acting cellular transcription factors.

Acetyltransferases↗