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Biomedical subjects

K Kjeldsen

Publications and source records attributed to K Kjeldsen.

At least 109 records · Page 6Linked to original sources

Revaccination of adults against diphtheria. I: Responses and reactions to different doses of diphtheria toxoid in 30-70-year-old persons with low serum antitoxin levels.

Studies of diphtheria antitoxin levels in serum from adult populations have indicated high frequencies of unprotected subjects. Serum from 351 randomly selected Danes between 30 and 70 years old has been assessed for antitoxin concentration; 123 persons among these, who had low antibody levels, received one vaccination with 2 Lf, 5 Lf or 12 Lf diphtheria toxoid. Side-reactions were recorded, and antibody levels were studied 4 weeks later. Antitoxin concentration following vaccination increased markedly to above protective level in 83% of those vaccinated. Of subjects, who could document a complete primary vaccination series, only one receiving 2 Lf 31 years after primary vaccination did not attain protective antitoxin level. Minor local reactions only were recorded among subjects who did not respond serologically to vaccination. Frequencies of more pronounced reactions experienced by serologically responding subjects depended on dose and were 15%, 14% and 23% respectively. It was concluded that a single vaccination of the present adult Danish population will induce protective antibody levels so frequently that the effect of herd immunity will secure against epidemics if future diphtheria outbreaks are experienced. To secure individual protection, vaccination history and/or serological assessments have to be explored in order to decide whether a single vaccination is sufficient.

Adult↗

K+-dependent 3-O-methylfluorescein phosphatase activity in crude homogenate of rodent heart ventricle: effect of K+ depletion and changes in thyroid status.

The total Na+-K+-ATPase activity in rodent heart ventricle was quantified by determination of K+-dependent, ouabain suppressible 3-O-methylfluorescein phosphatase activity. A K+-dependent phosphatase activity of 0.80 mumol/min per g wet wt was obtained from crude homogenate of heart ventricle from 4-week-old guinea pigs. The anticipated association between K+-dependent phosphatase activity and Na+-K+-activated ATP hydrolysis could be clearly demonstrated in the crude homogenate. Based upon a molecular activity of 550/min the corresponding cardiac glycoside receptor concentration in the crude homogenate was 1450 pmol/g wet wt. In crude homogenate of heart ventricle from 3-month-old rats the K+-dependent phosphatase activity was 1.16 mumol/min per g wet wt. Following 4 weeks of K+ depletion of the rats, a decrease of 13% in total K+ content of the heart ventricle was seen. This was associated with a 14% decrease in K+-dependent phosphatase activity. The induction of hypo- and hyperthyroidism for 3 weeks in rats was followed by a decrease of 27% and an increase of 13% in K+-dependent phosphatase activity, respectively.

Animals↗

Immunity against diphtheria 25-30 years after primary vaccination in childhood.

In Denmark primary vaccination against diphtheria is offered in the 5th, 6th, and 15th month of life with doses of 50 Lf. Only those doing military service are routinely revaccinated (with 12 1/2 Lf, given once). 403 persons offered primary vaccination 25-30 years ago were screened for diphtheria antitoxin titres by the use of neutralisation and haemagglutination tests. 19% of these (10% of the males and 26% of the females) were unprotected (less than 0.01 IU/ml). Among those not revaccinated 22% had antitoxin titres below protective level. This accords with the continuing decline of diphtheria antitoxin titre after vaccination. Among those revaccinated against diphtheria in adolescence 5% became unprotected. Thus, persons who were offered primary vaccination against diphtheria 25-30 years ago may be susceptible to diphtheria and its toxic complications. So may those revaccinated more than 10 years ago. Should diphtheria emerge in a community those who received their primary vaccination more than 2 years ago or revaccination more than 10 years ago ought to be revaccinated. Revaccination is also advisable for those travelling to countries with endemic diphtheria. Moreover, since 10% of the present population were unprotected against tetanus it seems advisable to increase the immunity against diphtheria and tetanus by routine revaccination with a combined diphtheria-tetanus vaccine. Only a documented history of vaccinations should be relied on when a decision is being made as to whether to carry out primary vaccination or revaccination.

Adult↗

Effects of ouabain, age and K-depletion on K-uptake in rat soleus muscle.

The relationship between the number of 3H-ouabain binding sites and the Na, K-pump mediated K-uptake has been characterized in rat soleus muscle. By brief exposure to 3H-ouabain (1 X 10(-6)-1 X 10(-5) mol/l) in vitro, it could be measured that 19-94% of the ouabain binding sites had been occupied. This was associated with a proportionate decrease in the ouabain suppressible K-uptake indicating that under strictly standardized conditions, measurements of 3H-ouabain binding sites quantify functional Na,K-pumps. When 3 week old rats were K-depleted for a further week followed by K-repletion 2 h before measurements, the 3H-ouabain binding site concentration was 61% lower than in age-matched control soleus muscles. However, the ouabain suppressible K-uptake was only reduced by 35%, partly because intracellular Na remained higher in the muscles obtained from K-depleted rats. From the 1st to the 4th week of life, the 3H-ouabain binding site concentration increased 2.9-fold. In contrast, the ouabain suppressible K-uptake decreased by a factor 3.5. Accordingly, in muscles from 1 week old rats, the ouabain suppressible K-uptake per 3H-ouabain binding site was 10-fold higher than in muscles from 4 week old rats. This difference could not be accounted for by changes in intracellular Na, total or extracellular water. It may be related to differentiation and change in structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Estimation of stability of [3H]-ouabain binding site concentration in rat and human skeletal muscle post mortem.

The post mortem stability of the [3H]-ouabain binding site concentration and 3-O-methylfluorescein phosphatase (MFPase) activity was evaluated in rat skeletal muscle. As compared with the values measured in fresh tissue, the [3H]-ouabain binding site concentration in rat soleus muscle only dropped by around 1% per hour post mortem and a significant decrease was only seen after 12 h (15%, p less than 0.02). The 3-O-MFPase activity in rat gastrocnemius muscle showed a similar decrease. After 4 days, both parameters had dropped by 65% (p less than 0.001). In contrast, when intact fresh rat soleus muscles were incubated in Krebs-Ringer bicarbonate buffer at 20 degrees C for 4 days no significant decrease was seen in the [3H]-ouabain binding site concentration. In 10 human subjects the concentration of [3H]-ouabain binding sites was measured in specimens of the vastus lateralis muscle obtained within half an hour and at 6 and 12 h post mortem. The relative decrease after 6 h was insignificant (8%, p less than 0.30), whereas it was significant after 12 h (29%, p less than 0.005). These results have shown that the [3H]-ouabain binding sites in human skeletal muscle are resistant to post mortem degradation during the first 6 h after death. This makes it possible to perform measurements post mortem of the [3H]-ouabain binding site concentration in human skeletal muscle.

Aged↗

Significance of skeletal muscle digitalis receptors for [3H]ouabain distribution in the guinea pig.

The importance of specific digitalis glycoside binding sites in skeletal muscle for the digitalis glycoside distribution in the guinea pig was evaluated using [3H]ouabain and [3H]digoxin binding assays. Measurements of [3H]ouabain binding capacity (EOmax) in gastrocnemius and heart muscles in vitro gave values of 474 +/- 15 and 1,092 +/- 39 pmol/g wet wt., respectively, in 4-week-old guinea pigs. Hence the total amount of [3H]ouabain binding sites in skeletal muscle and the heart was around 42,700 and 1,200 pmol, respectively. The apparent dissociation constants (Kd) for ouabain receptor interaction was 0.7 X 10(-7) and 1.5 X 10(-7) M for skeletal muscle and heart, respectively. Comparison of [3H]ouabain and [3H]digoxin binding revealed that these drugs are competitive. From birth to maturity the concentration of [3H]ouabain binding sites in guinea pigs decreased from 803 +/- 58 to 304 +/- 28 pmol/g wet wt. in gastrocnemius muscle and from 1,458 +/- 31 to 1,079 +/- 19 pmol/g wet wt. in the heart. After i.p. injection, measurements of the distribution of [3H]ouabain in plasma, skeletal muscle and the heart showed an almost equal relative specific occupancy of digitalis glycoside receptors in skeletal muscle and the heart: When 10% of the digitalis receptors in the heart were occupied by [3H]ouabain, 13% of those in the skeletal muscles were occupied. It was calculated that 1 hr after the i.p. administration of [3H]ouabain the amount of [3H]ouabain specifically bound to the skeletal muscles and the heart corresponded to 5 times and 1/10 the amount available in the extracellular pool, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Immunity against tetanus and effect of revaccination 25-30 years after primary vaccination.

Fall off in tetanus immunity and the effect of late revaccination were investigated in a randomly selected group of Danes aged 25-30. Routine reinforcing doses of tetanus toxoid are not customary in Denmark except at injury and when there are certain occupational risks. 11% of the total group of 418 had antitoxin titres below that required for protection (ie, less than 0.01 IU/ml, determined by neutralisation technique). In those who had received only primary vaccination an exponential fall off in immunity was seen, and 25-30 years after primary vaccination, 28% had serum antitoxin concentrations below the level of protection. Up to 30 years after primary vaccination, one reinforcing dose of tetanus toxoid adsorbed by aluminium hydroxide was sufficient to induce protective titres of antitoxin. There were no serious side-effects and it was concluded that routine reinforcing doses of tetanus toxoid should be given before the age of 20 in Denmark and other countries where primary vaccination is given in the first years of life.

Adult↗

Effect of thyroid function on number of Na-K pumps in human skeletal muscle.

To evaluate the effect of thyroid function on the number of Na-K pumps in skeletal muscle, the number of 3H-ouabain binding sites was measured in biopsy specimens from the vastus lateralis muscle of euthyroid subjects and patients with hypothyroidism or hyperthyroidism. In hypothyroidism there was a decrease of 50% in 3H-ouabain binding sites, and in hyperthyroidism there was an increase of 68% in 3H-ouabain binding sites. When thyroid status became normal after treatment the number of 3H-ouabain binding sites also became normal. There were significant correlations between several thyroid function tests and the number of 3H-ouabain binding sites. Free T4-index gave the highest r value (0.87). These changes may account for the variations in digitalis sensitivity associated with thyroid disorders.

Adult↗

(Na+ + K+)-ATPase activity of crude homogenates of rat skeletal muscle as estimated from their K+-dependent 3-O-methylfluorescein phosphatase activity.

A highly sensitive fluorimetric assay using 3-O-methylfluorescein phosphate as substrate was used in the determination of K+-dependent phosphatase activity in preparations of rat skeletal muscle. The gastrocnemius muscle was chosen because of mixed fibre composition. Crude, detergent treated homogenate was used so as to avoid loss of activity during purification. K+-dependent phosphatase activities in the range 0.19-0.37 mumol X (g wet weight)-1 X min-1 were obtained, the value decreasing with age and K+-deficiency. Complete inhibition of the K+-dependent phosphatase was obtained with 10(-3) M ouabain. Using a KSCN-extracted muscle enzyme the intimate relation between K+-dependent phosphatase activity and (Na+ + K+)-activated ATP hydrolysis could be demonstrated. A molecular activity of 620 min-1 was estimated from simultaneous determination of K+-dependent phosphatase activity and [3H]ouabain binding capacity using the partially purified enzyme preparation. The corresponding enzyme concentration in the crude homogenates was calculated and corresponded well with the number of [3H]ouabain binding sites measured in intact muscles or biopsies hereof.

Animals↗

The age-dependent changes in the number of 3H-ouabain binding sites in mammalian skeletal muscle.

The influence of age on the binding of 3H-ouabain in skeletal muscle has been characterized in rats, mice and guinea pigs. Measurements performed using biopsies and intact fibers obtained from different types of rat muscles showed that from birth to the 4th week of life, the number of 3H-ouabain binding sites per unit weight increases up to 5-fold, followed by almost the same relative decrease to a plateau around 250 pmol/g wet wt at an age of 22 weeks. These changes were not associated with any major alterations in apparent KD (1.7-3.1 X 10(-7) M) dissociation rate or heterogeneity in binding characteristics. Measurements of 3-O-methylfluorescein phosphatase activity, an enzyme activity which is closely correlated to the Na-K-ATPase activity, confirmed the 3H-ouabain binding data. In mice, the number of 3H-ouabain binding sites showed similar, albeit less pronounced changes with age, a maximum being reached at the 4th week of life. In guinea pigs, the number of 3H-ouabain binding sites per unit weight decreased by 60% from birth to maturity. The results indicate that the early development and differentiation of individual skeletal muscles is associated with a marked increase in the number of Na-K-pumps (when expressed as pmol/muscle), until at maturity a plateau is reached. However, when expressed as pmol/g wet wt the increase is followed by a decrease to a plateau. This may in part account for the relatively low digitalis sensitivity seen in infants as compared to newborn and mature individuals.

Aging↗

Effect of K-depletion on 3H-ouabain binding and Na-K-contents in mammalian skeletal muscle.

K-depletion induced by K-deficient fodder led to hypokalemia, decreased K-content and increased Na-content in skeletal muscle of rats. The heart showed similar, although more modest changes, whereas brain, erythrocytes and liver maintained virtually constant Na-K-contents. K-depletion decreased total binding capacity for 3H-ouabain by up to 76%, an effect which could be demonstrated both in vitro and in vivo. Following 3 weeks of K-depletion, the apparent KD for 3H-ouabain binding to rat soleus was 1.3 X 10(-7) M as compared to 2.4 X 10(-7) M in controls. Also in mice and guinea pigs, K-depletion induced a selective loss of K from muscle and decreased 3H-ouabain binding capacity. K-depletion induced by diuretics or fluorohydrocortisone gave similar effects. The effects of K-depletion on 3H-ouabain binding capacity were confirmed by measurements of 3-O-methylfluorescein phosphatase activity, an enzyme activity which is closely correlated to the Na-K-ATPase activity. Following readministration of K, the K-contents of plasma and muscle reached control levels in 24 hours, but 3H-ouabain binding capacity was not normalized until after 6 days of K-repletion. In mammalian skeletal muscle, K-depletion leads to a marked and reversible reduction in 3H-ouabain binding capacity, which may be secondary to the selective loss of K or gain of Na.

Animals↗