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Biomedical subjects

G M Janssen

Publications and source records attributed to G M Janssen.

47 records · Page 3Linked to original sources

White cell system changes associated with a training period of 18-20 months: a transverse and a longitudinal approach.

In the present study 60 males and 18 females were monitored during an 18- to 20-month training period, during which the training distance was gradually increased. The training period was divided into three periods of 6, 5, and 7 months, respectively. The first, second, and third periods were concluded with a 15-, 25-, and 42-km road race, respectively. The competitive distance always exceeded the maximal distance covered in any previous training session. The effect of training was investigated for the number of leukocytes, number of the subpopulations, and the percentage of white cells with a higher peroxidase activity (HPX cells). The measuring points were the start of the study (used as a reference value) and 1 week before and 1 week after three contests (15, 25, and 42 km). The results of all measuring points were compared transversely and longitudinally. Transversely the leukocytes hardly changed in the course of the study both in males and females, except a decrease of HPX cells. Longitudinally it appeared that Nvar and CVp90 of the numbers of leukocytes could not be calculated in males or in females. These findings suggest that a homogeneous population of leukocytes developed with respect to number and age.

Adaptation, Biological↗

Platelet system changes associated with a training period of 18-20 months: a transverse and a longitudinal approach.

The effect of training for a 42-km run was investigated for the platelet count, the platelet distribution width (PDW), the mean platelet volume (MPV), and the plateletcrit (PCT). The measuring points were the start and 1 week before and 1 week after each contest (15, 25, and 42 km). For the starting position we reassessed the reference value for each platelet parameter. The results of all measuring points were compared transversely and longitudinally. As a result of the transverse approach, we found a significant decrease of the platelet count and of the MPV, which means a decrease of total thrombocytic clotting capacity with increasing training intensity. The longitudinal approach showed large intraindividual variations for all platelet parameters during the course of the study, expressed as high values for Nvar and CVp90.

Adult↗

Occurrence of running injuries in adults following a supervised training program.

To study the occurrence of running-related injuries, a group of 115 volunteers were supervised in a training program. These subjects who had limited or no running experience were asked to keep a diary in which they registered information on the training program and injuries. Ultimately, 63% of the diaries fulfilled the criteria for inclusion into longitudinal analysis. The training program (18-20 months) consisted of three phases, each phase finished with a contest (15 km, 25 km, and a marathon, respectively). The participants were individually supervised by an experienced coach with special attention to physiologic training and injury-preventive aspects. Eighty-five percent (n = 62) of the research population sustained at least one injury during the experiment. They reported in total 174 injuries. The number of injury cases per week increased gradually over the experimental period; however, when expressed per unit of exposure time (i.e., 1000 training hours), it showed a decline. There was a significant correlation between the number of injured volunteers and the distance covered during the training at the start of the training program. The anatomic distribution of the injuries is in agreement with findings in the literature. There was also a possible preference for the localization of injuries to the lower leg and Achilles tendon on the left side of the body.

Adult↗

Phosphorylation of elongation factor 1 beta by an endogenous kinase affects its catalytic nucleotide exchange activity.

Elongation factor 1 beta (EF-1 beta) from Artemia is phosphorylated to a high percentage at serine 89 by an endogenous kinase present in EF-1 beta gamma. Protein sequencing of EF-1 beta revealed that this serine residue is located N-terminally of an acidic cluster of amino acids, (formula; see text) which is critical for casein kinase II-type substrate recognition. A number of compounds known to influence casein kinases were studied, revealing that the kinase activity as present in EF-1 beta gamma belongs to the class of casein kinase II. The rate of nucleotide exchange on EF-1 alpha as catalyzed by EF-1 beta was found to be affected reversibly by the state of phosphorylation of EF-1 beta. In the presence of dephosphorylated EF-1 beta, the exchange rate is almost twice as large compared to the rate in the presence of phosphorylated EF-1 beta. Rephosphorylation of dephosphorylated EF-1 beta diminishes the activity of the protein again. The role of casein kinase II-type enzymes in modulating the function of proteins involved in polypeptide synthesis is discussed.

Amino Acid Sequence↗

Kinetic studies on the role of elongation factors 1 beta and 1 gamma in protein synthesis.

An equilibrium isotope exchange technique was used to measure in an Artemia system the catalytic influence of elongation factor (EF) 1 beta gamma on the dissociation of GDP from the complex of elongation factor 1 alpha.[3H] GDP in the presence of an excess of free GDP. The kinetic data demonstrate that, in analogy to procaryotes, dissociation of GDP occurs via the formation of a transient ternary complex of EF-1 alpha.GDP.EF-1 beta gamma. The rate constants for the dissociation of GDP from EF-1 alpha.GDP and from the ternary complex EF-1 alpha.GDP.EF-1 beta gamma were found to be 0.7 x 10(-3) and greater than or equal to 0.7 s-1, respectively. The equilibrium association constants of GDP to EF-1 alpha.EF-1 beta gamma and of EF-1 beta gamma to EF-1 alpha.GDP were found to be 2.3 x 10(5) and 4.2 x 10(5) M-1, respectively. Judged from the known elongation rate in vivo and kinetic constants of nucleotide exchange, it was estimated that the recycling of EF-1 alpha may be a rate-controlling step in eucaryotic translation. As a model for GTP exchange, the formation of the ternary EF-1 alpha.guanylyl (beta gamma-methylene)diphosphonate.EF-1 beta gamma complex was also studied. It was observed that both an increase of the level of aminoacyl-tRNA and of temperature favored the dissociation of this complex, thereby enabling EF-1 beta gamma to recycle as a catalyst. This behavior would explain the frequent occurrence of a heavy form of elongation factor 1 in extracts of the eucaryotic cell.

Algorithms↗

Elongation factor 1 beta gamma from Artemia. Purification and properties of its subunits.

The guanine nucleotide exchange factor, elongation factor 1 beta gamma (EF-1 beta gamma) has been purified from Artemia cysts using an improved method. The protein consists of two distinct polypeptides with relative molecular masses of 26,000 (EF-1 beta) and 46,000 (EF-1 gamma). A nucleoside diphosphate phosphotransferase activity often found in EF-1 beta gamma preparations has been completely separated from the actual guanine nucleotide exchange stimulatory activity of EF-1 beta gamma, thus indicating that nucleotide diphosphate phosphotransferase is not an intrinsic property of EF-1 beta. Both EF-1 beta gamma and EF-1 beta have been shown to stimulate the following three reactions to a comparable degree: (a) exchange of GDP bound to EF-1 alpha with exogenous GDP; (b) EF-1 alpha-dependent binding of Phe-tRNA to ribosomes; (c) poly(U)-dependent poly(phenylalanine) synthesis. However, a significantly higher nucleotide exchange rate was observed in the presence of EF-1 beta gamma compared to EF-1 beta alone. Concerning elongation factor 1 gamma (EF-1 gamma) the following observations were made. In contrast to EF-1 beta, pure EF-1 gamma is rather insoluble in aqueous buffers, but the tendency to precipitate can be partially suppressed by the addition of detergents. In particular, EF-1 gamma partitions solely into the detergent phase of Triton X-114 solutions. EF-1 gamma is also more susceptible to spontaneous, specific fragmentation. It is remarkably that about 5% of the cellular pool of EF-1 beta gamma was found to be present in membrane fractions, under conditions where no EF-1 alpha was detectable in these fractions. Furthermore it was noted that EF-1 beta gamma copurified strongly with tubulin on DEAE-cellulose. Moreover, it was observed that from a mixture of EF-1 beta gamma and tubulin, EF-1 gamma coprecipitates with tubulin using a non-denaturating immunoprecipitation technique. These findings suggest that EF-1 gamma has a hydrophobic domain and interacts with membrane and cytoskeleton structures in the cell.

Animals↗

Exercise-induced changes in the percentage of free testosterone and estradiol in trained and untrained women.

We have studied the effect of exercise on the percentage of free plasma estradiol 17-beta (E2) and testosterone (T) in 13 untrained (UT) and 8 trained (marathon runners, MR) eumenorrheic women. All women performed a standardized bicycle ergometer (UT) or treadmill (MR) test in the follicular and luteal phases of their menstrual cycles (15-min consecutive work loads of 60%, 70%, and 80% VO2 max to exhaustion). Blood was drawn through an indwelling venous catheter at 15 and 2 min before and immediately after exercise. Free E2 and T was assayed by centrifugal ultrafiltration using undiluted plasma at 37 degrees C (basal samples) and 39 degrees C (exercise samples). Statistical analysis was performed by a two-tailed paired t test. In the UT, the basal percentage of free E2 was measured to be 1.55% +/- 0.24% (mean +/- SD) in the follicular phase and 1.62% +/- 0.32% in the luteal phase (differences NS). In the MR, these values were 1.22% +/- 0.25% and 1.25% +/- 0.12% for the follicular and luteal phases, respectively. The differences between the groups were not significant. Exercise did not provoke significant changes in free E2 in either of the groups. Constrastingly, exercise induced a significant (P less than 0.02) increase in the percentage of free T from 1.56% +/- 0.27% to 2.1% +/- 0.36% and from 1.6% +/- 0.27% to 2.12% +/- 0.33% in the UT in the follicular and luteal phases, respectively. In the MR, the free percentage of T increased from 1.04% +/- 0.39% to 1.6% +/-0.16% (follicular phase) and from 1.24% +/- 0.22% to 1.67% +/- 0.18% (P less than 0.02).

Adult↗

Effect of a 3-month endurance training program on metabolic and multiple hormonal responses to exercise.

We have investigated the effect of a 3-month endurance training program (running and cycling) on plasma hormone responses during standardized bicycle ergometer work (15-min consecutive work loads of 60%, 70%, 80%, and eventually 90% VO2 max) in eight previously untrained eumenorrheic women. The subjects were investigated before and after training both in the follicular and luteal phases of the menstrual cycle (between the 7th-10th and 20th-25th days of their menstrual cycle, respectively). Blood was obtained 15 and 2 min before the onset of exercise and at the end of each work load from an indwelling catheter. In each sample, the plasma concentrations of estradiol 17 beta (E2), progesterone (P), testosterone (T), androstenedione (delta 4-A), dehydroepiandrosterone sulfate (DHEA-S), prolactin (PRL), and adrenocorticotropic hormone (ACTH) were assayed in duplicate by RIA; lactate was assayed as well. The hormone concentrations were expressed in absolute as well as in relative values. After training basal DHEA-S and ACTH levels were significantly (P less than 0.05) lower in both phases of the menstrual cycle, whereas basal luteal phase E2 and T levels were significantly (0.05 greater than P greater than 0.01) lower after training. Exercise induced significant increments in the relative values of all hormones in both phases (0.05 greater than P greater than 0.001). After training, T and DHEA-S increased relatively more pronounced (0.05 greater than P greater than 0.02) in the follicular and luteal phase, respectively.

Adrenal Cortex Hormones↗

Lack of effect of cimetidine on pharmacodynamics and kinetics of single oral doses of R- and S-acenocoumarol.

The kinetics and dynamics of single doses (5 mg p.o.) of the optical isomers of acenocoumarol (R-AC and S-AC) were followed in healthy subjects and the effect on them of cimetidine 800 mg/day was also investigated. The AC enantiomers differed greatly in their pharmacokinetics. The mean residence time (MRT) of R-AC was about 10 times longer than that of S-AC, 15 h vs 1.2 h. There was no difference in the volume of distribution. Depression of blood clotting activity (Thrombotest) was observed only after administration of R-AC. The inactivity of S-AC as a vitamin K antagonist must be ascribed to its short MRT. Cimetidine did not affect the acute oral kinetics of R- and S-AC, nor did it affect the anticlotting activity of R-AC. The urinary excretion pattern of the 6- and 7-hydroxylated AC metabolites was not altered during cimetidine treatment. Although the present studies showed no effect of cimetidine on the pharmacokinetics and dynamics of acenocoumarol, the findings of Serlin et al. suggest that cimetidine should not be administered during acenocoumarol therapy.

Acenocoumarol↗

Ibuprofen: plasma concentrations in man.

The plasma levels of ibuprofen were measured in five healthy subjects who took 600 mg tablets of ibuprofen twice daily, three times daily and four times daily in a crossover study. Peak plasma levels were obtained 1 hour after the first dose in all but one subject (slow absorber), the mean peak value being 51.3 micrograms X ml-1 (range 39.4-63.7 micrograms X ml-1). After the repeated dose regimens of two, three or four times daily of ibuprofen, the peak levels achieved were in a similar range to those seen after the first dose: Twice daily 39.4-66.4 micrograms X ml-1; Three times daily 43.6-63.3 micrograms X ml-1; Four times daily 44.1-58.4 micrograms X ml-1. There was no evidence of accumulation of the drug and no side-effects occurred during the trial.

Adult↗

Phenylbutazone-hydroxycoumarol interactions. Effects on steady state disposition, hepatocellular distribution, and biliary excretion of (S)-acenocoumarol in rats.

The effect of phenylbutazone on the disposition of (S)-acenocoumarol in the rat was studied at steady state conditions of distribution and elimination. (S)-Acenocoumarol was administered by constant rate infusions (1 microgram/min). The biliary excretion of 6- and 7-hydroxylated acenocoumarol was followed and the intrahepatic distribution was investigated. Phenylbutazone (50 mg/kg) increased the plasma unbound fraction about 4-fold. (S)-Acenocoumarol plasma clearance was enhanced (2.8 +/- 0.15 vs. 1.54 +/- 0.14 ml/min) but the unbound plasma clearance was reduced by 50% (67 +/- 9 vs. 140 +/- 27 ml/min). Phenylbutazone caused an intrahepatic redistribution of (S)-acenocoumarol, i.e. the drug shifted from the cytosol to the 10,000g pellet. The cytosolic unbound concentration, however, was increased. The (S)-acenocoumarol content in the microsomal fraction was not affected. The biliary excretion rate of total metabolite (free plus conjugated) comprised 50% of the (S)-acenocoumarol infusion rate in controls and was slightly stimulated (+20%) by phenylbutazone. The biliary excretion of free metabolites, however, was greatly increased (62 +/- 7 vs. 22 +/- 6 ng/min for 6-hydroxy-acenocoumarol; 337 +/- 38 vs. 141 +/- 32 ng/min for 7-hydroxy-acenocoumarol). This effect is probably due to stimulation of a hepatic biliary transport system; the rate constant for transport of 7-hydroxy-acenocoumarol was enhanced 5-fold (0.107 +/- 0.03 vs. 0.021 +/- 0.007 min-1).

Acenocoumarol↗