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Biomedical subjects

G Frey

Publications and source records attributed to G Frey.

At least 37 records · Page 2Linked to original sources
PubMed1996

Detection of DNA damage after hyperbaric oxygen (HBO) therapy.

Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, exposure to high concentrations of oxygen is known to induce damage to cells, possibly due to an increased oxygen radical production. As reactive oxygen species also cause DNA damage, we investigated the DNA-damaging effect of HBO with the alkaline version of the single cell gel test (comet assay). Oxidative DNA base modifications were determined by converting oxidized DNA bases to strand breaks using bacterial formamidopyrimidine-DNA glycosylase (FPG), a DNA repair enzyme, which specifically nicks DNA at sites of 8-oxo-guanines and formamidopyrimidines. HBO treatment under therapeutic conditions clearly and reproducibly induced DNA damage in leukocytes of all test subjects investigated. Increased DNA damage was found immediately at the end of the treatment, while 24 h later, no effect was found. Using FPG protein we detected significant oxidative base damage after HBO treatment. DNA damage was detected only after the first treatment and not after further treatments under the same conditions, indicating an increase in antioxidant defences. DNA damage did not occur when the HBO treatment was started with a reduced treatment time which was then increased stepwise.

Adult↗
PubMed1996

[From animal automatons to scientific questioning--reflections on the development of veterinary medicine in the 18th century].

Descartes wanted to prove the cosmos to be a machine which God had made run. The animals, too, were machines which functioned like robots. In the 18th century the animal machine of Descartes was being discussed and eventually negated. The animal was considered a being with a soul and an intellect. Therefore an animal was to be looked at as a creation of God-nearly like a human being. Reimarus (About the animals' soul, 1760) and Germershausen (About sheep breeding, 1789), tried to be fair to animals while handling them. They negated the machine model of Descartes but accepted his scientific language. They transferred his vocabulary into their treatises. In this way they installed this new vocabulary into their scientific terminology--an important requirement for the instutitionalisation of veterinary medicine.

Animals↗
PubMed1996

HMGI-C expression patterns in human tissues. Implications for the genesis of frequent mesenchymal tumors.

Cytogenetically visible aberrations of chromosomal region 12q14-15 in a variety of frequent benign human tumors reflect rearrangements of the HMGI-C gene. The mechanisms by which the HMGI-C gene contributes to tumorigenesis are mostly unknown, although frequently aberrant transcripts containing exons 1 to 3 of HMGI-C and ectopic sequences from other genes due to breaks within the third intron of HMGI-C are detectable. This is the first report analyzing human tissue samples mainly of mesenchymal origin by a highly sensitive polymerase-chain-reaction-based approach detecting HMGI-C expression. We found HMGI-C expression in embryonic tissue but no expression in any of several adult tissues tested except for two myometrial tissues. These data suggest that HMGI-C is mainly expressed in human tissues during embryonal and fetal development. Thus, its particular role for tumor development may be due to the expression of at least exons 1 to 3 rather than to the formation of fusion transcripts.

Adult↗
PubMed1993

ATP-inhibited and Ca(2+)-dependent K+ channels in the soma membrane of cultured leech Retzius neurons.

The properties of one ATP-inhibited and one Ca(2+)-dependent K+ channel were investigated by the patch-clamp technique in the soma membrane of leech Retzius neurons in primary culture. Both channels rectify at negative potentials. The ATP-inhibited K+ channel with a mean conductance of 112 pS is reversibly blocked by ATP (Ki = 100 microM), TEA (Ki = 0.8 mM) and 10 mM Ba2+ and irreversibly blocked by 10 nM glibenclamide and 10 microM tolbutamide. It is Ca2+ and voltage independent. Its open state probability (Po) decreases significantly when the pH at the cytoplasmic face of inside-out patches is altered from physiological to acid pH values. The Ca(2+)-dependent K+ channel with a mean conductance of 114 pS shows a bell-shaped Ca2+ dependence of Po with a maximum at pCa 7-8 at the cytoplasmic face of the membrane. The Po is voltage independent at the physiologically relevant V range. Ba2+ (10 MM) reduces the single channel amplitude by around 25% (ATP, TEA, glibenclamide, tolbutamide, and Ba2+ were applied to the cytoplasmic face of the membrane). We conclude that the ATP-dependent K+ channel may play a role in maintaining the membrane potential constant--independently from the energy state of the cell. The Ca(2+)-dependent K+ channel may play a role in generating the resting membrane potential of leech Retzius neurons as it shows maximum activity at the physiological intracellular Ca2+ concentration.

Adenosine Triphosphate↗
PubMed1993

pH recovery from intracellular alkalinization in Retzius neurones of the leech central nervous system.

1. Neutral-carrier pH-sensitive microelectrodes were used to investigate intracellular pH (pHi) recovery from alkalinization in leech Retzius neurones in Hepes- and in CO2-HCO3(-)-buffered solution. The Retzius neurones were alkaline loaded by the addition and subsequent removal of 16 mM acetate, by changing from 5% CO2-27 mM HCO3- to 2% CO2-11 mM HCO3- or by changing from CO2-HCO3(-)- to Hepes-buffered solution. 2. In Hepes-buffered solution (pH 7.4) the mean pHi was 7.29 +/- 0.11 and the mean membrane potential -44.7 +/- 5.9 mV (mean +/- S.D.; n = 83). 3. The rate of pHi recovery from alkalinization increased with decreasing pH of the bathing medium (pHb). pHi changed about 0.30 pH units for a pHb unit change. 4. A decrease of extracellular buffer concentration (Hepes concentration lowered from 20 to 5 mM) caused an acidification of extracellular and intracellular pH and an acceleration of pHi recovery from alkalinization. 5. A depolarization of the Retzius cell membrane-induced by increasing the K+ concentration of the bathing medium from 4 to 20 mM (delta Em = 16.5 +/- 5.5 mV) or from 4 to 40 mM (delta Em = 24.8 +/- 3.5 mV)--evoked a decrease of pHi and an acceleration of pHi recovery from alkalinization. 6. The H+ current blocker Zn2+ (0.5 mM) inhibited pHi recovery from alkalinization at resting membrane potential as well as during depolarization. The inhibition was more pronounced during depolarization. 7. In Cl(-)-free, CO2-HCO3(-)-buffered solution pHi recovery from an alkaline load by changing from 5% CO2-27 mM HCO3- to 2% CO2-11 mM HCO3- was slowed by 48-71%. The rate of pHi recovery from an alkaline load induced by changing from CO2-HCO3- to Hepes buffer was reduced by 33-56% in Cl(-)-free solution. The removal of external Cl- did not affect pHi recovery in Hepes-buffered solution. 8. The pHi recovery from alkalinization was DIDS-insensitive in CO2-HCO3(-)- as in Hepes-buffered solutions and was not slowed in the absence of external Na+. 9. It is concluded that in Retzius neurones pHi recovery from alkalinization is mediated by a passive voltage-dependent H+ influx along the electrochemical proton gradient. In the presence of CO2-HCO3- buffer a DIDS-insensitive Cl(-)-HCO3- exchanger additionally regulates pHi after an intracellular alkaline load. It cannot be excluded that intracellular processes (e.g. H+ release from organelles, metabolic H+ production) are also involved in pHi recovery from alkalinization.

Alkalies↗
PubMed1992

Transcription in vitro and in vivo of the 7S RNA gene associated with the ribosomal RNA operon in the hyperthermophilic archaeon Methanothermus fervidus.

The gene encoding the archaeal 7S RNA in the hyperthermophile Methanothermus fervidus is linked to a tRNA(Ser) and rRNA operon in the arrangement 5'-7S RNA-14nt-tRNA(Ser)-196nt-16S rRNA and the promoter directing transcription of this 7S RNA gene has now been identified. Initiation of transcription of the 7S RNA gene has been shown to occur both in vivo in M. fervidus and in vitro, using a Methanococcus thermolithotrophicus derived cell-free transcription system, at the first G residue within the initiator sequence ATGG, located 6 bp upstream of the 5' end of the 7S RNA coding region. Cotranscription of the 7S RNA and tRNA(Ser) has been demonstrated in vitro.

Base Sequence↗
PubMed1992

Transcription in vivo and in vitro of the histone-encoding gene hmfB from the hyperthermophilic archaeon Methanothermus fervidus.

Immediately upstream of the hmfB gene, in a DNA fragment cloned from Methanothermus fervidus, are two identical tandemly repeated copies of a 73-bp sequence that contain the sequence 5'TTTATATA, which conforms precisely to the consensus TATA box element proposed for methanogen promoters. By using this duplicated region as the template DNA and a cell-free transcription system derived from Methanococcus thermolithotrophicus, transcription in vitro was found to initiate at two identical sites 73 bp apart, each 25 bp downstream from a TATA box, thus providing strong evidence for the functional conservation of this transcriptional signal in two phylogenetically very diverse methanogens. Transcription of the hmfB gene in vivo in M. fervidus was found to occur at only one of these sites, and consistent with this observation, recloning and sequencing of this intergenic region after its amplification by the polymerase chain reaction demonstrated that the genome of M. fervidus contains only one copy of the 73-bp sequence upstream of the hmfB gene. Since the second copy of the 73-bp sequence, presumably generated artifactually during the original hmfB cloning, functioned equally well as a promoter in the M. thermolithotrophicus transcription system, all information needed by the heterologous RNA polymerase to initiate transcription accurately in vitro must be present within this sequence. The hmfB gene encodes HMf-2, one of the two subunits of HMf, an abundant DNA binding protein in M. fervidus which binds to DNA molecules in vitro, forming nucleosomelike structures. Cell-free transcription was inhibited by adding HMf or eucaryotic core histones at protein-to-DNA mass ratios of 0.3:1 and 1:1, respectively, whereas the archael histonelike protein HTa from Thermoplasma acidophilum inhibited transcription in vitro only at much higher protein-to-DNA mass ratios and the bacterial histonelike protein HU from Escherichia coli had no detectable effect on transcription.

Archaeal Proteins↗
PubMed1992

[Bilateral Gradenigo syndrome--on the value of an integrated therapy concept including hyperbaric oxygenation and chronic destructive inflammation of the skull base].

The case of a 30-year-old female with bilateral Gradenigo's syndrome is presented in order to detail commonly applied therapy. In particular, the importance of a comprehensive therapeutic approach is emphasized that includes such adjuvant therapeutic options as hyperbaric oxygenation and the administration of specific immunoglobulins. Indications, therapeutic benefits and limitations of treatment modalities are discussed in relationship to current concepts of therapy.

Adult↗
PubMed1991

Control regions of an archaeal gene. A TATA box and an initiator element promote cell-free transcription of the tRNA(Val) gene of Methanococcus vannielii.

To identify the DNA sequences required for initiation of transcription in archaea, the 5'-flanking region of the tRNA(Val) gene of Methanococcus vannielii was modified by deletions, restructuring and site-directed mutagenesis, and the tRNA encoding sequence was replaced by a fortuitous Escherichia coli sequence. The effects of these mutations on promoter function were tested in an homologous cell-free transcription system. The DNA region from position -35 to +9 relative to the transcription start site was sufficient for maximal initiation of cell-free transcription. Removal of the DNA region between -35 and -30 reduced initiation by a factor of 2. Deletions extending to position -24 almost completely abolished specific transcription. Analysis of 16 site-specific mutations in the region from -33 to +2 provided evidence that a conserved A + T-rich sequence (TATA box), centered at -25, is essential for initiation of transcription. Single point mutations in six positions of the TATA box reduced initiation of transcription from 0.2 to 0.01 of wild-type levels. A second conserved motif at the transcription start site (consensus ATGC) could be replaced by some sequences containing a pyrimidine-purine dinucleotide but appeared necessary for a maximal rate of gene transcription. Mutations altering the spacing between the two conserved elements demonstrated that initiation occurs at a strictly defined distance of 22 to 27 base-pairs downstream from the TATA box. Our results support the conclusion that the TATA box is the major DNA region mediating promoter recognition, influencing the efficiency of transcription and specifying the site of transcription initiation. This Methanococcus promoter element closely resembles in structure and function the TATA box of promoters of eukaryotic protein-encoding genes transcribed by RNA polymerase II.

Base Sequence↗
PubMed1991

[Neither propranolol nor the vasodilating beta-blocker carvedilol have a direct effect on coronary resistance vessels].

Seventeen patients with coronary heart disease were included in a double-blind randomized study. They received either 5 mg of carvedilol or 6 mg of propranolol intravenously. Heart rate, aortic pressure, mean coronary sinus pressure and coronary flow (thermodilution) were measured, and coronary resistance and rate-pressure product were calculated before and 15 min after the infusion, which lasted 10 min. Carvedilol lowered significantly (p less than 0.05) heart rate (mean 76 to 69/min), aortic pressure (mean 153/80 to 135/72 mm Hg), rate-pressure product (mean 117 to 93 mm Hg/min) and coronary flow (mean 114 to 94 ml/min). Coronary resistance and coronary flow related to rate-pressure product showed no significant change after carvedilol. Propranolol lowered heart rate (mean 76 to 64/min; p less than 0.05) and rate-pressure product (mean 109 to 96 mm Hg/min; ns). Aortic pressure, coronary flow, coronary resistance, and coronary flow related to rate-pressure product showed no significant change after propranolol. Thus, carvedilol lowered rate-pressure product more markedly than propranolol on account of its acute blood-pressure lowering effect. Neither drug seems to have a direct influence on coronary resistance vessels.

Adrenergic beta-Antagonists↗
PubMed1990

[Danger in cave diving].

A diving accident fatal for two divers, that occurred in the Blautopf-cave near Ulm, FRG, is reported. The circumstances fundamental in precipitating the fatal outcome are discussed. As a consequence accident- or life insurance coverage has become one of the prerequisites to obtain the official permit to dive in this cave.

Adult↗
PubMed1990

An archaebacterial cell-free transcription system. The expression of tRNA genes from Methanococcus vannielii is mediated by a transcription factor.

Our understanding of the mechanism of RNA biosynthesis in archaebacteria is limited, due in part to the inability of purified RNA polymerases to transcribe purified genes accurately in vitro. In the present study, we show that cell extracts of Methanococcus vannielii and Methanococcus thermolithotrophicus purified by gradient centrifugation synthesize a distinct transcript from templates harboring a cloned homologous tRNA(Val) and tRNA(Arg) gene. The in vitro transcripts initiate with GTP at the same sites as in Methanococcus cells. About 60% of the sequence of the in vitro RNA products was analyzed by dideoxyterminated primer extension and found to be identical with that of the precursors of tRNA(Val) and tRNA(Arg). This finding indicates that this RNA polymerase fraction both initiates and terminates transcription faithfully in vitro. After purification of a cell-free extract (S-100) of M. thermolithotrophicus by phosphocellulose chromatography, the endogenous RNA polymerase has lost its ability to transcribe the tRNA(Val) gene accurately. The activity directing specific expression of this template was reconstituted by the addition of a protein-fraction devoid of RNA polymerase activity. Thus, a transcription factor appears to be required for accurate cell-free expression of tRNA genes from M. vannielii.

Base Sequence↗
PubMed1990

Influence of carvedilol and propranolol on coronary blood flow.

A total of 17 patients with angiographically proven coronary artery disease and at least one stenosis blocking greater than or equal to 70% of the left anterior descending or circumflex artery were included in a double-blind, randomized study. They received either 5 mg carvedilol or 6 mg propranolol intravenously. Heart rate, aortic pressure, mean coronary sinus pressure and coronary flow (thermodilution) were measured and coronary resistance and the rate-pressure product were calculated before and 25 min after injection. Carvedilol significantly (P less than 0.05) lowered the heart rate (mean, 76 to 69 beats/min), aortic pressure (mean, 153/80-135/72 mm Hg), rate-pressure product (mean, 117-93 mm Hg/min), and coronary flow (mean, 114-94 ml/min). Coronary resistance (mean, 0.97-1.07 mm Hg x min/ml) and coronary flow related to the rate-pressure product (mean, 1.0-1.02 ml/mm Hg) showed no significant change after carvedilol treatment. Propranolol lowered the heart rate (mean, 76-64/min; P less than 0.05) and rate-pressure product (mean, 109-96 mm Hg/min; not significant). Aortic pressure (mean, 145/72-147/74 mm Hg), coronary flow (mean 109-101 ml/min), coronary resistance (mean, 1.1-1.2 mm Hg x min/ml), and coronary flow related to the rate-pressure product (mean, 1.12-1.19 ml/mm Hg) showed no significant change after propranolol administration. Following single application, carvedilol lowered the rate-pressure product more markedly than did propranolol on account of its acute blood-pressure-lowering effect. No differences in the hemodynamic effects of carvedilol and propranolol were found. Neither drug seems to influence the adaption of coronary flow to myocardial oxygen demand.

Adrenergic beta-Antagonists↗
PubMed1989

An archaebacterial promoter sequence assigned by RNA polymerase binding experiments.

To identify an archaebacterial promoter sequence, nuclease protection studies with the purified RNA polymerase of Methanococcus vannielii were performed. The enzyme binds specifically both at protein-encoding (hisA and methyl CoM reductase, component C) and tRNA-rRNA genes. The binding region of the RNA polymerase extends from 30 base pairs (bp) upstream (-30) to 20 bp downstream (+20) from the in vivo transcription start site. This finding indicates that the archaebacterial enzyme recognizes promoters without transacting transcription factors. The DNA segment protected from nuclease digestion by bound RNA polymerase contains an octanucleotide sequence centered at -25, which is conserved between the protein-encoding and the stable RNA genes. According to the specific binding of the enzyme to only DNA-fragments harbouring this motif, we propose the sequence TTTATATA as the major recognition signal of the Methanococcus RNA polymerase. Comparison of this motif with published archaebacterial DNA sequences revealed the presence of homologous sequences at the same location upstream of 36 genes. We therefore consider the overall consensus TTTATAATA as a general element of promoters in archaebacteria. In spite of the specific binding of the enzyme, most preparations of the Methanococcus vannielii RNA polymerase are unable to initiate transcription at the correct sites in vitro. Here we present first evidence for the possible existence of a transcription factor conferring the ability to the enzyme to initiate and terminate transcription specifically in vitro.

Archaea↗
PubMed1989

[Principles of acute management of the severe diving accident].

The basics of the acute management of severe diving accidents are outlined by means of 25 patients (20 patients presented with decompression sickness, 5 suffered from a barotrauma of the lungs with consecutive air embolism) treated at our facilities. Contrary to widespread notion, disturbed vital functions have to be treated by intensive care measures, prior to the definite recompression therapy. These are: (1) Treatment of generalized or localized tissue hypoxia secondary to bubble-generation; (2) puncture of a (valvular-) pneumothorax after a pulmonary barotrauma; (3) haemodynamic stabilization when cardiac or spinal shock is present; (4) improvement of the rheological situation. When vital functions are unstable or endangered, these patients must not be transported in a monoplace chamber. This type of chamber does not leave any access to the patient in case of a deteriorating status. Since the severe diving accident mostly turns out to be a problem of intensive care medicine in close combination with the recompression therapy, the continuous integration of the recompression protocol with a comprehensive intensive care therapy is considered crucial.

Adult↗
PubMed1988

An archaebacterial RNA polymerase binding site and transcription initiation of the hisA gene in Methanococcus vannielii.

Transcription initiation of the hisA gene in vivo in the archaebacterium Methanococcus vannielii, as determined by nuclease S1 and primer extension analyses, occurs 73 base pairs (bp) upstream of the translation initiation site. Binding of M. vannielii RNA polymerase protects 43 bp of DNA, from 35 bp upstream (-35) to 8 bp downstream (+8) of the hisA mRNA initiation site, from digestion by DNase I and exonuclease III. An A + T rich region, with a sequence which conforms to the consensus sequence for promoters of stable RNA-encoding genes in methanogens, is found at the same location (-25) upstream of the polypeptide-encoding hisA gene. It appears therefore that a TATA-like sequence is also an element of promoters which direct transcription of polypeptide-encoding genes in this archaebacterium.

Bacterial Proteins↗
PubMed1988

Coronary hemodynamics during left and right coronary arteriography with an ionic and nonionic contrast medium.

The direct effects of ionic amidotrizoate (iodine content 370 mg/ml, osmolality 2.1 osmol/kg) and nonionic iopamidol (iodine content 370/ml, osmolality 0.8 osmol/kg) on the coronary circulation were intraindividually compared in 10 patients suffering from coronary heart disease. In accordance with a double-blind, crossover protocol, both contrast media were injected into the left and right coronary arteries (8 ml and 5 ml per injection, respectively). Injections of both dyes into the left coronary artery caused a similar decrease in heart rate. The prolongation in the QT interval was significantly greater after amidotrizoate (p less than 0.05). Systolic (p less than 0.01) and diastolic (p less than 0.05) aortic pressures decreased to a greater extent following amidotrizoate injection. Each contrast agent produced a similar increase in coronary sinus flow, but iopamidol resulted in a smaller decrease in coronary vascular resistance (p less than 0.05). After right coronary artery injections, both contrast media caused bradycardia and prolongation of the QT interval, a decrease in systolic and diastolic aortic pressure, a rise in coronary sinus flow, and a lowering of coronary vascular resistance. Though most changes were more pronounced following amidotrizoate injection, the differences in the ionic and the nonionic agent were not statistically significant. Thus, after selective coronary arteriography, both contrast media caused a transient drop in coronary vascular resistance and a rise in coronary sinus flow despite a decrease in aortic pressure. The effects of amidotrizoate were more marked, which might be attributed to the higher osmolality of this ionic contrast medium. Coronary hemodynamics, however, usually returned to baseline values within 1 minute.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗