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Biomedical subjects

M Jung

Publications and source records attributed to M Jung.

At least 199 records · Page 11Linked to original sources
PubMed1995

Studies on the active-site structure of C3-like exoenzymes: involvement of glutamic acid in catalysis of ADP-ribosylation.

Various C3-like ADP-ribosyltransferases like Clostridium botulinum exoenzyme C3, C limosum transferase, B cereus transferase and a transferase from Staphylococcus aureus (EDIN) selectively modify the low-molecular mass GTP-binding proteins RhoA,B,C. UV-irradiation of C limosum transferase in the presence of [carbonyl-14C]NAD resulted in radiolabeling of Glu-174. Concomitantly, ADP-ribosyltransferase and NAD glycohydrolase activities were inhibited. Site-directed mutagenesis of Glu-174 (E174D, E174Q) which resulted in more than 1000-fold reduction of enzyme activity, suggests that the glutamic acid residue is essentially involved in the catalytic action of C3-like transferases. These findings support the view that all bacterial ADP-ribosyltransferases share a similar active-site structure.

ADP Ribose Transferases↗
PubMed1995

Pneumatic dilation in achalasia with a low-compliance balloon: results of a 5-year prospective evaluation.

To evaluate long-term efficacy and side effects after pneumatic dilation with low-compliance balloons, 40 patients with achalasia were prospectively studied during a 5-year period. All patients were investigated before, 4-6 weeks after, and at 28 +/- 15 months (final visit) after pneumatic dilation. Additionally, 12 patients underwent 24-hour esophageal pH-metry before and 26 +/- 14 months after dilation. Initial symptomatic success was obtained in 35 of 40 patients (87.5%). The remaining five and another seven patients with recurrent dysphagia underwent a second dilation, and two of these patients finally underwent esophagomyotomy. Effective dilation was reflected by a significant decrease of the symptom scores (p < 0.01) and an increase of the gastric cardia diameter both at 4-6 weeks after dilation and at the final visit (p < 0.01). Dilation reduced the lower esophageal sphincter pressure from 28.3 +/- 0.8 mmHg to 16.4 +/- 6.4 mmHg at the 4-6 weeks exam and to 14.7 +/- 5.5 mmHg at the final visit, respectively (p < 0.01). Neither the diameter of the esophageal body nor the motility of the tubular esophagus was affected by pneumatic. Esophageal pH-metry showed an increase of the number and duration of reflux episodes (pH < 4) after dilation (p < 0.05), whereas only one patient reported heartburn and another asymptomatic patient revealed esophagitis I0 at endoscopy. Therefore, pneumatic dilation with low compliance balloons proved to be safe and long lasting treatment of achalasia. Although prolonged esophageal acid exposure was measurable after dilation, clinically relevant gastroesophageal reflux occurred in only 5% (n = 2).

Catheterization↗
PubMed1995

Does peri-operative guanethidine prevent reflex sympathetic dystrophy?

The use of intravenous guanethidine blocks is an accepted treatment for established reflex sympathetic dystrophy (RSD). Some units administer intravenous guanethidine peri-operatively with the intention of protecting their patients from post-operative dystrophy. There have been no studies confirming this protective effect of peri-operative guanethidine. Between 1992 and 1994 we performed a prospective randomized double blind study in 71 patients undergoing fasciectomy for Duputyren's disease. Peri-operative guanethidine did not prevent post-operative RSD in our series.

Analysis of Variance↗
PubMed1995

Microbial and mammalian metabolism studies on the semisynthetic antimalarial, deoxoartemisinin.

PURPOSE: Deoxoartemisinin is a semisynthetic antimalarial with potential for treatment of multiple drug resistant malaria. Metabolism studies were conducted to aid in future drug development. METHODS: Microbial model systems were employed which have been shown to be good predictors of mammalian drug metabolites. Metabolism studies using rats were also performed. RESULTS: Three microbial metabolites of deoxoartemisinin were identified (2, 3, and 4). Metabolite 3 was also found in rat plasma. HPLC/MS analyses were performed on the rat plasma using 2, 3, and 4 as standards. All metabolites were thoroughly characterized by 1H and 13C-NMR. An additional rat plasma metabolite was revealed and it was shown not to be 9 alpha-hydroxyartemisinin. CONCLUSIONS: Deoxoartemisinin was metabolized to three microbial metabolites. Metabolism by rats showed the presence of two metabolites in the plasma, one of which was the same as the microbial metabolite.

Animals↗
PubMed1995

Effect of endoscopic sphincterotomy on sphincter of Oddi manometry results in patients with or without papillary stenosis.

Patients with fibrotic papillary stenosis (PS) are at high risk for sphincter of Oddi-re-stenosis after endoscopic sphincterotomy (ES). Therefore, a prospective trial was conducted to assess the acute and long-term effects of ES on sphincter of Oddi motor function in patients with papillary stenosis. The immediate effects of ES were studies by endoscopic manometry in 12 patients with PS, and in 15 patients with common bile duct stones (CBDS, control group). Furthermore, after a median follow-up of 15 months, 11 from those 12 patients with papillary stenosis were reinvestigated with ERCP and manometry. Complete ES (defined by a common bile duct pressure and a basal sphincter of Oddi-pressure (BSOP) < 5 mm Hg) was achieved in 13/15 CBDS-patients, but only in 3/12 patients with PS (p<0.01), although sphincterotomy was extended to the maximal length as judged endoscopically. Four patients with PS had a residual BSOP > 20 mm Hg. However, all patients with PS became symptom-free immediately after ES. The phasic sphincter motility was not affected significantly different in both groups of patients (p = 0.25). Those patients with a residual BSOP > 20 mm Hg after ES developed sphincter of Oddi-re-stenosis during the follow-up (3 patients) or revealed re-stenosis at the control examination after follow-up (1 patient). After the follow-up manometrically defined complete sphincterotomy was furtheron demonstrable in only 2/11 patients with papillary stenosis. In conclusion, ES revealed a decreased efficacy to eliminate the sphincter of Oddi motor function in a substantial number of patients with papillary stenosis. This may explain the remarkably high rate of sphincter of Oddi-re-stenosis after sphincterotomy in these patients.

Adult↗
PubMed1994

Fibroblast growth factor-4 enhanced G2 arrest and cell survival following ionizing radiation.

Fibroblast growth factors (FGFs) bind to cell membrane receptors and activate signal transduction pathways related to cell growth, angiogenesis, and tumorigenesis. FGFs have been shown to be abundantly expressed in some of the human tumors, which are known to be poorly responsive to radiation therapy. Using adrenal cortical carcinoma cells genetically engineered to express FGF-4, we have tested cellular survival following exposure to ionizing radiation. We report here that FGF-4 enhances cellular capacity to survive ionizing radiation. Furthermore, cell cycle analysis shows a pronounced increase in the duration of G2 arrest, suggesting perturbation of a cell cycle checkpoint. These findings implicate fibroblast growth factor-mediated signal transduction in cellular resistance of human tumors to radiation therapy.

Cell Survival↗
PubMed1994

Elongation factor 1 delta is enhanced following exposure to ionizing radiation.

We have used the technique of differential display of mRNA to investigate gene expression patterns in a human squamous carcinoma cell line, SCC-35, following exposure to ionizing radiation. We observed that elongation factor 1 delta (EF-1 delta) expression increased within 2 h of radiation exposure with maximum expression at 8 h. These data identify EF-1 delta as a radiation-inducible gene. Cell cycle analysis shows that EF-1 delta expression enhancement precedes G2 arrest in these cells, suggesting that EF-1 delta may participate in the G2-M cell cycle checkpoint.

Base Sequence↗
PubMed1994

Porcine (GT)n sequences: structure and association with dispersed and tandem repeats.

Loci containing (GT)n repeats were isolated from three different plasmid libraries with inserts of porcine genomic DNA between 140 and 200, 200 and 300, and 350 and 400 bp. Sequencing showed that the average repeat length and the fraction of perfect repeats were increased in the libraries containing longer inserts (> or = 200 bp). The polymorphism of (GT)n loci containing at least 10 repeat units was analyzed using the polymerase chain reaction and an automated DNA sequencer. Nearly all tested loci are polymorphic and can therefore be used as marker loci for gene mapping and for other applications. The (GT)n loci were categorized into three classes: (1) loci containing the (GT)n repeats associated with a SINE element, (2) loci containing the (GT)n repeats associated with one or more other simple repeats, and (3) loci containing (GT)n as the only detected repetitive element. At most loci of the first class, the (GT)n repeat was in a fixed configuration adjacent to the 3' end of the SINE. The findings support the notion of clustering of different repeat types in the mammalian genome.

Animals↗
PubMed1994

In vitro and in vivo characterisation of glial cells immortalised with a temperature sensitive SV40 T antigen-containing retrovirus.

An oncogene-carrying replication-defective retrovirus was used to establish immortalised lines of murine glial cells. Primary cultures of early postnatal cerebellar cells were infected with a retrovirus based on the Murine Moloney Leukemia Virus containing a temperature-sensitive mutant of the Simian Virus 40 large T antigen (SV40 T) oncogene and a gene coding for resistance to the antibiotic G418. Infected cells were selected in G418 and after several in vitro passages cells expressing the O4 antigen were established as a cell line. At a later time point O4-positive single-cell clones were established. Two different types of clones were obtained: 1) "plastic" clones consisting of cells which initially had a morphological and antigenic phenotype of young glial precursor cells but which gradually lost these features, and 2) "stable" cell clones including a clone with the immunological and electrophysiological characteristics of Schwann cells. Culture of the latter cells in the presence of 1 mM dibutyryl cyclic adenosine monophosphate for a period of at least 10 days induced a change in shape and a shift in antigen expression towards a more "differentiated" maturation stage. When the SV40 T O4-positive immortalised cell line isolated on the cell sorter was transplanted into demyelinated lesions in adult rats, cells were observed ensheathing axons and forming limited amounts of PNS-type myelin. Glial cells immortalised with a temperature-sensitive mutant of the SV40 T oncogene thus retain many physiological properties of their primary culture counterparts and can be induced to undergo limited differentiation in vitro and in vivo. These cell lines, which represent immature CNS glia or Schwann cells, are providing useful tools for investigating the role of cell surface antigens involved in neuron-glial interactions.

Animals↗
PubMed1994

Neuropharmacological characterization of SR 140333, a non peptide antagonist of NK1 receptors.

SR 140333 (1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl) piperidin-3-yl]ethyl]-4-phenyl-1-azonia-bicyclo[2.2.2]octane , chloride), a potent non peptide ligand of the substance P (SP) NK1 receptor subtype with high affinity for NK1 receptors from both rat cortical membranes and human IM9 cells (Ki = 0.02 nM and 0.01 nM, respectively) was studied in vivo on various effects induced by NK1 agonists in rats and mice. SR 140333 given intraperitoneally (i.p.) in mice antagonized dose-dependently and in a stereoselective manner the scratching responses induced by intracerebroventricular SP and septide (ID50 = 0.73 and 0.08 mg/kg, respectively) and the turning behavior elicited by intrastriatal SP and septide (ID50 = 0.07 and 0.06 mg/kg, respectively). This compound had little effect on the scratching responses and the turning behavior elicited by [Sar9, Met(O2)11]-SP. When SR 140333 was coadministered with the peptide agonist, the compound reduced the scratching responses elicited by SP, [Sar9, Met(O2)11]-SP and septide injected intrathecally (i.t.) in mice (ID50 = 72.0, 64.3 and 52.5 ng i.t., respectively). SR 140333 antagonized the salivation induced by SP, [Sar9, Met(O2)11]-SP and septide in rats (ID50 = 0.13, 0.18 and 0.09 mg/kg i.p., respectively). SR 140333 abolished the facilitation of the tail-flick reflex induced by noxious heat in rats (total reversal at 0.06 mg/kg, i.p.). This compound was also found to inhibit the turning behavior induced by intrastriatal apomorphine in mice (ID50 = 0.1 mg/kg, i.p.). In conclusion, these results indicate that SR 140333 behaves as a potent, selective and centrally active NK1 receptor antagonist.

Animals↗
PubMed1994

Transformation of human epidermal keratinocytes with fission neutrons.

The biological effects of exposures to high LET radiations have particular relevance to radiation protection and risk assessment. Since most cancers are of epithelial origin, it is important to obtain a better understanding of radiation-induced oncogenic transformation in this cell type. Accordingly we have initiated studies to determine whether immortalized human epidermal keratinocytes (RHEK) can be transformed with high LET radiations. Exponentially growing RHEK cells were treated with single doses (1, 10, 25, 50 and 100 cGy) of 0.85 MeV fission neutrons from the Janus reactor. Neutron exposure led to the development of morphologically altered cells and foci formation after 6 weeks at confluence. These transformed cultures grew with an increased saturation density, exhibited anchorage-independent growth and formed tumors in athymic mice. Single-strand conformational polymorphism analysis and DNA sequencing demonstrated the absence of point mutations in codons 12/13 and 61 in the Ha-ras, Ki-ras, or N-ras genes and exons 4-9 of the p53 tumor suppressor gene. These studies demonstrate that high LET radiations (fission neutrons) can transform immortalized human epithelial cells to a malignant phenotype that does not appear to involve mutations in either the cellular p53 or ras genes.

Animals↗