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Biomedical subjects

G Koch

Publications and source records attributed to G Koch.

At least 325 records · Page 18Linked to original sources

A reduction in the activity of the Na+, K+-pump in dimethylsulfoxide-treated Friend erythroleukemia cells is not due to partial inactivation of the Na+, K+-ATPase.

Treatment of Friend-erythroleukemia cells with 1.5% dimethylsulfoxide (DMSO) caused a decrease in ouabain sensitive 86Rb+-uptake beginning six to seven hours after DMSO addition indicating a reduced function of the Na+, K+-pump. However, analysis of the ouabain sensitive 86Rb+-uptake after Na+-preloading of the cells as well as measurements on the Na+, K+-ATPase activity in isolated membrane fragments revealed that no inhibition of the Na+, K+-ATPase occurred during the first 12 hours. On the contrary the Na+, K+-ATPase activity was initially enhanced and then returned to control levels during the early phase of induction by DMSO. On the other hand, 22Na+-transport into DMSO-treated cells was reduced similar to the ouabain sensitive 86Rb+ uptake in cells without Na+ preloading. The piretanide sensitive 86Rb+-uptake, due to the Na+, K+, 2Cl - cotransport system was inhibited after seven hours exposure to DMSO. Some three hours after DMSO addition the incorporation of 35S-methionine into proteins began to decrease, which was accompanied with or followed by a reduction in the methionine uptake of DMSO treated cells. Membrane-potential-dependent tetraphenylphosphonium cation uptake was not altered relative to the controls in the first 12 hours following DMSO addition. These results suggest that the reduced activity of the Na+, K+-pump in Friend cells after DMSO exposure is not due to inhibition of the Na+, K+-ATPase, but most probably due to a smaller Na+-influx, which results from inhibition of Na+-cotransport processes (amino acid uptake, Na+, K+, 2Cl - cotransport system).

Animals↗

Analysis of DNA distributions from flow cytometry. Validation of an automatic procedure against simulated data.

A recently proposed automatic procedure for analyzing DNA distribution from flow cytometric data is extensively tested against simulated data. After a discussion of the procedure itself and of the simulation program, the results obtained are reported. They are evidence of the reliability of the procedure in extracting the proper underlying DNA distribution from sets of data obtained under various simulated instances. The different sources of error are then analyzed, along with their quantitative effects on the fit of the fluorescence histogram.

Computers↗

Protein kinase activity in purified poliovirus particles and empty viral capsid preparations.

Preparations of purified poliovirus type 1, strain Mahoney, and empty viral capsids contain a protein kinase activity. The gamma-phosphoryl group of [32P]ATP is transferred to all of the capsid proteins. Viral proteins phosphorylated in vitro are recognized by antiserum directed against isolated viral capsid proteins, indicating that phosphorylation does not alter the antigenic sites to such an extent that the recognition by antibodies is abolished. Viral capsid protein phosphorylation exposes new antigenic sites and leads to a destabilization of the virions. The transfer of 32P to viral proteins is linear for 90 min at 37 degrees C in the presence of 10 mM-Mg2+ at pH 8.1. Reducing agents or virus-stabilizing agents (such as arildone) reduce the kinase activity and result in a different pattern of capsid protein phosphorylation.

Animals↗

Differential substrate specificity of DNA polymerase beta and of a DNA polymerase induced by herpes simplex virus type 2 towards thymidine triphosphate analogues.

Several triphosphates of 5-substituted deoxyuridine (dU), such as 5-ethyl-, 5-n-propyl-, 5-n-hexyl- and 5-isopropyldeoxyuridine triphosphates and 5-trifluorothymidine triphosphate are substrates for HeLa cell DNA polymerase beta (2'-deoxynucleoside-5'-triphosphate:DNA-deoxynucleotidyltransferase, EC 2.7.7.7) and for a DNA polymerase isolated from HeLa cells infected with herpes simplex virus type 2 (HSV-2) strain 75. At the concentration tested (50 microM), all these analogues were incorporated more readily into DNA by the virus-coded enzyme than by DNA polymerase beta from the host cell. The DNA polymerase coded by HSV-2 showed an affinity for deoxythymidine triphosphate (dTTP) and the analogues studied higher than that of DNA polymerase beta. Analogues are preferential substrates for the viral enzyme, since they readily substitute for dTTP during synthesis in vitro. In contrast, arabinosylthymine-5'-triphosphate was readily incorporated into DNA by the host cell DNA polymerase beta, but inhibited the DNA polymerase specified by HSV-2.

DNA Polymerase I↗

Factors influencing the accumulation of tetraphenylphosphonium cation in HeLa cells.

Exposure of HeLa cells to tetraphenylphosphonium cation (TPP+) results in a rapid accumulation intracellularly, and a steady-state level is reached within 10 min. Accumulation of [3H]TPP+ in HeLa cells is reduced under the following conditions: (i) after preincubation of cells in buffered saline or in medium containing two- to fourfold higher concentrations of amino acids, (ii) exposure to the alkylating agent L-1-tosylamido-2-phenyl-ethylchloromethyl ketone, (iii) ouabain-mediated inhibition of the Na+, K+ ATPase, and (iv) high external K+ concentrations. In contrast, addition of serum increases the uptake of TPP+. In synchronized cells, intracellular levels of TPP+ differ at various stages of cell cycle and are lowest in mitosis.

Biological Transport, Active↗

Pooling 12 nomifensine studies for efficacy generalizability.

Twelve parallel group, randomized, double-blind studies of nomifensine's safety and efficacy in the treatment of depressed patients were combined into three pools according to common protocols. This approach permitted evaluation of 1) efficacy results for studies with moderate-sized pools of patients, 2) the degree to which efficacy was generalizable to depressed patients in the general population, and 3) the conditions under which pooled active vs. active (imipramine vs. nomifensine) studies could be regarded as pivotal in support of efficacy. Results showed that nomifensine's superiority over placebo was generalizable to patients with a wide range of characteristics, including age 60 years or older. An appropriate statistical profile of more pronounced nomifensine responders would include patients with a duration of present episode less than 4 months who are acutely depressed, exhibit more severe symptoms, and have been previously hospitalized or treated with other psychotropic medications. A comprehensive assessment and power analysis of the pooled active vs. active studies provided strong evidence for comparability of nomifensine and imipramine.

Adolescent↗

Fluorine concentration in primary tooth enamel in 6-year-olds after 3 years of daily intake of fluoride-containing tablets (Fludent).

The purpose of this study was to determine the posteruptive uptake of fluorine in primary tooth enamel after daily consumption of a fluoride-containing sucking tablet for three years. The material consisted of 17 children, who had been advised to suck on 1 NaF tablet (Fludent, 0.25 mg F) daily at bedtime from 3 to 6 years of age (test group), and 17 children without tablet supply (control group). No other fluoride preparation was used during the period. A chemical biopsy method, described by Koch et al. (1982), was used to determine the fluorine concentration in enamel at the age of 6. Two consecutive layers on the upper central primary incisors of each child were etched off by perchloric acid. Chemical analysis of the test solutions was used to determine the thickness of the enamel layers and the fluorine content. Statistical evaluations were performed by analysis-of-variance. The results showed that fluorine was incorporated in primary tooth enamel as a topical effect of the fluoride tablet intake. There was a statistically significant difference (p less than 0.05) between the groups regarding fluorine measured on the layers combined and in the out layer (approximately equal to 5 micron thick), but not in the inner layer (approximately equal to 8 micron). It was concluded that the posteruptively increased enamel fluorine concentration probably contributes to the caries-preventive effect of NaF tablets.

Biopsy↗

[Preoperative localization diagnosis of parathyroid adenomas in 72 cases of primary hyperparathyroidism by selective catheterization of neck veins and parathyroid hormone determination].

In 72 cases of primary hyperparathyroidism, selective venous catheterization was performed preoperatively to localize parathyroid adenomas. Diagnosis of primary hyperparathyroidism was proved by operation in all but 5 cases, in which no adenomas could be found intraoperatively. By venous catheterization of the neck and upper region of the thorax, an average of 10 blood samples per patient were taken. Parathyroid hormone was estimated by radioimmunoassay with high sensitivity against the intact PTH-molecule and carboxy-terminal fragments. Only in 24 out of 72 cases was localization of parathyroid adenomas prognosticated correctly with respect to side and height, while in a total of 38 cases localization on the right or left side only could be determined preoperatively. These unsatisfactory results can be improved only by a much more extensive catheterization technic which would be justified only in patients already operated on before without success. The final evaluation of non-invasive methods, e.g. ultrasonics and computerized tomography, is still under discussion.

Adenoma↗

Effect of H2-receptor blockade by ranitidine on ulcer healing and gastric acid secretion in patients with gastric and duodenal ulcers.

The effect of treatment for 4 weeks with the H2-receptor antagonist ranitidine 200 mg daily on ulcer healing, clinical symptoms and antacid consumption, and on gastric acid secretion, was studied in a double blind trial in 48 patients with a total of 50 endoscopically confirmed duodenal, prepyloric or corporeal gastric ulcer. Patients whose ulcers did not show complete healing within 28 days were continued openly on ranitidine for up to a further 4 weeks. Endoscopy, basal gastric acid secretion (BAO) and pentagastrin-stimulated maximal secretion (PAO) studies were performed at 2-week intervals. After four weeks, 73% of the gastro-duodenal ulcers in the ranitidine group showed complete healing versus 42% in the placebo group (p less than 0.05). Gastric acid secretion was considerably inhibited both under basal (89%; p less than 0.001) and maximal challenge (71%; p less than 0.001) conditions. The inhibitory effect was still pronounced 13-15 h after administration of ranitidine 100 mg. Symptoms and the need for antacids were significantly reduced. Ranitidine appears to be an efficacious, safe and well tolerated medicine principle for the treatment of gastro-duodenal ulcer disease.

Adult↗

Fluorescence spectrophotometric study of structural alterations in the capsid of poliovirus.

Concerted structural alterations of viral proteins in the capsid of poliovirions are induced after adsorption to specific receptors on the host cells. Similar changes occur in vitro during exposure to low and high pH, elevated temperature or to denaturing agents. These structural alterations can be monitored conveniently by recording changes in the intrinsic fluorescence of the poliovirus-capsid and by following the fluorescence intensity after addition of ethidium bromide to virus particles. Application of these fluorescence techniques reveals that the uncoating of the virions in vitro occurs in two distinct steps: 1. entry of ions, e.g. ethidium bromide, 2. development of sensitivity of the virion RNA to RNase and release of the RNA. We confirm different structural stabilities of the virions at several pH values to elevated temperatures and a stabilizing effect of arildone on poliovirions.

Capsid↗

On the inverse problem in flow cytometry recovering DNA distribution from FMF data.

The problem of recovering DNA distribution from cytofluorometric experimental data was investigated. Theoretical analysis led to a convenient formulation of the problem and to uniqueness results for its solution. A minimization algorithm has been implemented to get the optimal estimate of G1, S, G2, and M phase percentages. This algorithm was tested in some experimental cases.

Animals↗

Aspects of hormonal regulation of lipolysis during exercise: effects of chronic beta-receptor blockade.

Exercise-induced lipolysis and hormones possibly involved in the regulation of lipid metabolism in association with exercise (plasma catecholamines, ACTH, HGH, TSH, insulin) were studied in 11 WHO stage 1 to 2 hypertensive men (mean age 37 years) during a 30-min steady-state submaximal (65% of VO2 max) and near-maximal exercise seated on a bicycle ergometer. To assess the contribution of the sympathetic system to the regulation of lipolysis and to define the type of beta-receptors mediating the catecholamine effects on lipolysis, all patients were again studied under identical conditions after a 4-week treatment with the beta-1-beta-2-receptor antagonist pindolol (15 mg daily) and with the beta-1-receptor blocker acebutolol (500 mg daily). Eight patients were even restudied after a 16-month treatment with acebutolol. Plasma glycerol levels increased progressively (P less than 0.001) during exercise reflecting increased exercise-induced lipolysis. The concomitant significant rise of noradrenaline, adrenaline, ACTH, and HGH and the parallel fall in plasma insulin suggest that all these hormones are involved in the adjustment of exercise-induced lipolysis. However, the impaired catecholamine-induced lipolysis under beta-receptor blockade was not accompanied by significant compensatory increases of ACTH, HGH, or TSH or a fall in insulin during exercise. Both beta-receptor antagonists resulted in a similar 27% inhibition of lipolysis confirming that the catecholamine-induced increase of lipolysis is mainly mediated via beta-1-adrenoceptors. After 16 months of treatment with acebutolol, the degree of inhibition of the exercise-induced lipolysis was unchanged. However, FFA were significantly reduced (28%, P less than 0.05) and HGH significantly (100%, P less than 0.05) increased.

Acebutolol↗

beta-adrenoceptor blockade and physical activity: cardiovascular and metabolic aspects.

This paper assesses mechanisms that may contribute to the higher incidence of increased muscle fatigue during exercise and reduced exercise performance as observed with selective compared with non-selective beta-adrenoceptor antagonists. Published data and the results obtained in 8 healthy subjects (mean age 23 years) studied before and after acute beta-adrenoceptor blockade with pindolol (nonselective, 10 mg) and metoprolol (beta 1-receptor selective, 100 mg) suggest that the differences in the cardiovascular and respiratory effects between the 2 types of antagonists are marginal and cannot explain the discrepancies concerning exercise perception and performance. Conversely, basic differences between the 2 types of antagonists were shown in different groups of hypertensive men (mean age 32 years) studied before and after 4 weeks of treatment with pindolol (15 mg), and with metoprolol (200 mg) and acebutolol (cardioselective, 500 mg), by single crossover technique. Whereas lipolysis was similarly inhibited by both selective and non-selective antagonists, hypoglycaemia occurred only under non-selective blockade. It apparently reflects the inhibition of glycogen breakdown; concomitant rises in plasma adrenaline and ACTH probably reflect counter-regulatory mechanisms.

Acebutolol↗

Nitrous oxide-oxygen sedation in dental care.

The aim of this study was to evaluate the dental treatments under nitrous oxide-oxygen sedation carried out during 1 yr by the first 45 Swedish dentists trained at probationary courses in the use of the technique. Special emphasis was placed on evaluating the risk and incidence of side effects. Data from 1719 treatment sessions in 823 patients, mainly children, were analyzed. Standardized sedation technique was used and the maximum level of nitrous oxide administered was set at 60%. About 90% of the patients showed excellent or fair acceptance. Factors influencing the acceptance were the patient's age, history of psychiatric disorders, mental retardation and occurrence of side effects. In 4.5% of the treatment sessions the patient experienced side effects, e.g. restlessness, vomiting or nausea, during treatment and in 0.9% after the treatment session. The side effects were mainly mild. No correlation was found between side effects and the nitrous oxide concentration used, length of treatment, patient's age or health classification. It is concluded that nitrous oxide-oxygen sedation is an excellent and safe aid to dental care.

Adolescent↗

Composite retained onlay bridges. A follow-up study in adolescents.

A follow-up study of composite retained onlay bridges inserted to replace permanent anterior teeth in adolescents was performed. The material comprised 100 bridges and the dominating reasons for replacement of teeth were aplasia and trauma. Clinical controls were performed every six months and the mean observation time was 34 months. (Range 11-59 months). Seventyone bridges were functioning without complications during the observation period. Dislodgement occurred in 29 bridges on 54 different occasions. Dislodgement was seen more frequently in boys. The dominating reason for dislodgement was new trauma during sports activities or fights, which occurred more frequently in patients with trauma as the original reason for replacement of teeth. Owing to the tooth-preserving potential and reversibility, it is considered a valuable method of replacing missing anterior teeth in young individuals. Further investigations should concentrate on technical development aimed at achieving optimum retention and on clinical evaluation over longer periods.

Adolescent↗