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D Jahn

Publications and source records attributed to D Jahn.

66 records · Page 4Linked to original sources

The use of single sample clearance estimates to probe hepatic drug metabolism in rats. II.

1. Single sample clearance estimates, Cl, were calculated for each of five drugs employed as probes of hepatic drug-metabolizing activity in rats. Probe drugs were theophylline, phenytoin, valproic acid, antipyrine, and S-warfarin. Cl values were calculated for each probe in animals pretreated with phenobarbital, isosafrole, beta-naphthoflavone, or clofibrate. Control animals were pretreated with vehicle only. 2. A clearance index (c.i., probe Cl after pretreatment divided by probe Cl control) was calculated for each probe and each pretreatment regimen, and data were consolidated to give different probe-based handprints of the pretreatment effects. 3. S-Warfarin was the least specific probe as its c.i. was greater than 1.0 subsequent to each pretreatment. Theophylline appeared to be the most selective probe since its c.i. deviated significantly from unity (3.56) only after beta-naphthoflavone pretreatment. Phenytoin exhibited c.i. values less than unity after each pretreatment indicating that it may not, when used as a single sample probe of hepatic drug-metabolizing activity, effectively discriminate between inductive or inhibitory effects of xenobiotics. 4. Multi-probe-based handprints of hepatic drug-metabolizing activity structured from simple single sample estimates of probe clearance have potential in the rapid screening of xenobiotic-induced alterations of drug-metabolizing enzyme activity.

Animals↗

Ethosuximide disposition kinetics in rats.

1. Single and multiple dose disposition kinetics of ethosuximide were studied in male Sprague-Dawley rats following intravenous administration. 2. The plasma disappearance of a single 35 mg/kg dose followed for 75 h was not linear. A dose-ranging study suggested that the apparent non-linearity of ethosuximide's plasma disappearance might be due to enzyme induction over time with the drug exhibiting a faster elimination from 24 h onward. 3. Ethosuximide, after only two daily doses of 35 mg/kg/day, shortened pentobarbital-induced sleep in rats. The clearance of ethosuximide was also significantly faster after four daily 35 mg/kg doses than after a single 35 mg/kg dose. 4. Single sample clearance estimates calculated from ethosuximide concentrations prior to enzyme induction, viz. up to 24 h post-dose, were practically identical to multiple sample clearance values. Both single and multiple sample clearances were calculated assuming linear rather than non-linear elimination.

Animals↗

Transcription complexes for various class III genes differ in parameters of formation and stability towards salt.

RNA polymerase III faithfully transcribes the genes for ribosomal 5 S RNA, tRNA(1Met) or adenovirus VA RNA in vitro in the presence of required transcription factors. These genes display distinct differences in the kinetics of transcription complex formation and in their response to excess template. In contrast to tRNA and VA RNA synthesis, 5 S RNA synthesis displays a lag phase of 15 minutes before the onset of transcription and is clearly inhibited by high concentrations of template. Once formed, transcription complexes for the RNA polymerase III genes listed can be isolated by glycerol gradient centrifugation and display a remarkable stability against transient treatment with high salt concentrations. Complexes for 5 S RNA and tRNA remain functionally active up to 2.5 M-KCl. The activity of transcription complexes for VA RNA, however, is significantly diminished after treatment with high salt concentrations. This effect is shown to be due to an irreversible loss of transcription factors. RNA polymerase III is dissociated by high salt concentrations from all the transcription complexes studied but remains part of these complexes during the normal reinitiation cycle at 60 mM-KCl. An additional method for the purification of partial transcription complexes was developed that involves equilibrium centrifugation on cesium sulfate gradients. This method completely releases TFIIIB from 5 S complexes and a core complex, composed of the 5 S RNA gene, factors IIIA and IIIC, is retained. In the case of tRNA and VA RNA, core complexes are obtained that remain partly associated with TFIIIC and TFIIIB. These results indicate a qualitatively and/or quantitatively different interaction of individual factors in different polymerase III transcription complexes.

Genes↗

Association of RNA polymerase III with transcription factors in the absence of DNA.

The gene for tRNAMet1 from Xenopus oocytes was transcribed in a cell free system with components isolated from a HeLa cell-free extract. It was found that, apart from the established assembly of transcription factors IIIB and IIIC on tRNA genes into stable transcription complexes, these factors can also associate with the enzyme in the absence of DNA to form a functional polymerase III complex. These complexes can be isolated in a highly active form from the bulk of other cellular proteins by mild methods such as gel filtration or density gradient centrifugation. When associated with RNA polymerase III into a functional complex, the transcription factors IIIB and IIIC can clearly be differentiated from free transcription factors, which individually display a much lower relative molecular mass. The polymerase complexes are stable against 1 M KCl, rendering unlikely that they represent fortuitous aggregates including RNA polymerase III and transcription factors IIIB and IIIC. These complexes are sensitive to dilution and, whereas transcription factor IIIC binds to the enzyme more tightly, factor IIIB tends to leak from the complex upon dilution of the protein concentration. From these results it is clear that in addition to their function as DNA-binding protein(s), transcription factors IIIB and IIIC can directly interact with RNA polymerase III without prior binding to the promoter region of the gene to be transcribed.

Animals↗

Pulmonary hydrogen and methane excretion following ingestion of an unabsorbable carbohydrate: a study of twins.

Pulmonary excretion of hydrogen and methane after administration of an unabsorbable disaccharide (lactulose) was determined in 228 adult Hungarian twins, 60 monozygous (MZ) and 54 dizygous (DZ) pairs. More than 98% of the subjects (224 of 228) excreted large amounts of hydrogen between 90 and 180 min after lactulose administration. Methane excretion in the fasting state was observed in 124 of 228 of the probands (54.4%), and 68 of 228 (29.8%) produced additional methane in response to lactulose ingestion. In contrast to hydrogen production, both methane excretion and production were significantly more frequent in females than in males. In the total group, and more distinctly in females, the correlation between peak hydrogen and methane concentrations was negative. Twin concordance of fasting methane excretion and lactulose-induced methane production was near 70% in both MZ and DZ pairs. Heritability estimates of methane excretion and production based on intrapair correlation and variance were smaller than unity, and intrapair correlation coefficients were larger in twin pairs living apart than in those living in the same household. Methane excretion is comparatively frequent in the Hungarian population, and a substantial proportion of fasting methane excreters (55%) produce additional methane from lactulose. The sex difference of methane excretion appears to be characteristic of European populations. The twin data disprove regular Mendelian inheritance of methane production and are suggestive of genetic effects in a multifactorial system.

Adult↗

Neonatal respiratory distress syndrome in the calf.

Thirty-five calves were delivered by caesarean section near to term. During the operation amniotic fluid was collected for determination of the lecithin/sphingomyelin (L/S) ratio. Clinical examination of the calves and analysis of blood gas concentration (venous blood) were carried out within the first hour of life. Fifteen out of 35 calves under examination did not show clinical or blood gas disorders in the course of the first hour of life. In these calves, the L/S ratio, which represents a measure for the maturity of the surfactant system, averaged 2.6. The other 20 calves, however, developed a respiratory distress syndrome together with a progressive respiratory and metabolic acidosis within the first hour of life. The L/S ratio in the animals affected with respiratory distress syndrome reached an average value of 1.5 which was significantly below that of the calves not suffering from respiratory distress. Eleven of the 20 calves which developed respiratory distress syndrome died within the first 60 hours of life. The most striking findings in the post mortem examinations of these animals were intracranial haemorrhages and pulmonary lesions (hyaline membranes, interstitial and alveolar oedema). On the basis of the significantly lower L/S ratio and the post mortem findings, it is to be assumed that the respiratory distress syndrome in calves, equally with that in infants, is attributable to a surfactant deficiency.

Amniotic Fluid↗

Table manners.

Although hospitals today exist in a competitive environment, the recent Survivor television program is not the best model. It has pushed competition to the extreme: the winner takes all at any cost. It is whether or not you win the game, and no holds barred on how you play.

Economic Competition↗