[Results of intranasal administration of synthetic luteinizing hormone-releasing hormone for nondescended testes].
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Biomedical subjects
Publications and source records attributed to M Jansen.
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We have isolated 3 cDNA clones encoding human IGF-II and a variant of IGF-II. The amino acid sequence encoded by the IGF-II cDNA is identical to the sequence previously described [(1978) FEBS Lett. 89, 283-286]. In the amino acid sequence predicted by the IGF-II variant cDNA, the Ser residue 29 in the B-domain has been replaced by an Arg-Leu-Pro-Gly sequence. The corresponding mRNAs probably arise by alternative splicing of a common RNA precursor. The IGF coding region of the cDNA inserts is flanked by sequences encoding a signal peptide and a carboxy-terminal peptide indicating that both human IGF-II and its variant are synthesized as precursors.
A cDNA probe corresponding to mRNA encoding human somatomedin-C/insulin-like growth factor I (IGF-I) was used for the chromosomal assignment of the IGF-I gene. Southern-blot hybridization analysis of DNA from human-Chinese hamster somatic cell hybrids showed that the IGF-I gene is located on chromosome 12. Comparison of the chromosomal assignments of the IGF-I gene and two other members of the insulin gene family, with three c-ras oncogenes, reveals a remarkable association of the two gene families.
A cDNA probe corresponding to mRNA encoding a closely related variant of human insulin-like growth factor II (IGF-II) was used for the chromosomal assignment of the IGF-II gene. Southern blot hybridization analysis of DNA from human-Chinese hamster somatic cell hybrids showed that the human IGF-II gene is located on chromosome 11. Using the same IGF-II variant probe, a cosmid was isolated which contains the human IGF-II gene. Restriction enzyme analysis revealed that the gene encoding IGF-II has a discontinuous structure and contains at least four exons.
The following order of genes on the short arm of human chromosome 11 (11p) was determined previously: parathyroid hormone (PTH)-the beta-globin gene cluster (HBBC)-HRAS1/insulin. Although it is generally agreed that HRAS1 (formerly termed c-Ha-ras-1) and the insulin gene are close to each other [1-4 centimorgans (cM)], their order on chromosome 11p is still in question. We have now added three other genes, those for catalase, calcitonin, and insulin-like growth factor II (IGF-II), to this map of chromosome 11p by use of restriction site polymorphisms adjacent to these genes in classical linkage analysis. Most importantly, we find no evidence of linkage between the catalase and HBBC loci. In addition, our data indicate that the calcitonin gene is located between the catalase gene and the PTH gene. Our best estimate of the distance between the catalase and calcitonin gene is approximately 16 cM, while that between the calcitonin and PTH genes is approximately equal to 8 cM. In agreement, very loose linkage was found between the catalase and PTH loci (approximately 26 cM). Since the catalase locus has been mapped to 11p13, these data support the view that the PTH, HBBC, HRAS1, and insulin loci are located on the distal short arm of chromosome 11. The IGF-II gene is tightly linked to both the HRAS1 oncogene and the insulin gene since no recombinants were observed between the IGF-II and the HRAS1/insulin loci. Thus, based on our linkage analysis we propose that the most likely gene order for the short arm of chromosome 11 is centromere-catalase-calcitonin-PTH-HBBC-HRAS1/insulin-tel ome re and that the IGF-II gene is very close to both the HRAS1 and the insulin genes.
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Post-microsomal supernatants from Drosophila melanogaster and rat liver homogenates were investigated with respect to their glutathione S-transferase (GST) activity. It appeared that the Drosophila transferase did not conjugate the epoxides styrene-7,8-oxide and 1,2 epoxy-3(p-nitrophenoxy)-propane. Attempts to isolate the Drosophila GST isozymes by means of the well-documented method for the purification of the rat liver transferases failed, because the Drosophila transferases did not bind to CM-cellulose. Purification by subsequent ion exchange on DEAE-cellulose, molecular sieving on Sephadex G-100 and hydroxylapatite chromatography, revealed three active fractions from Drosophila cytosol and five active fractions from rat liver cytosol, using 1-chloro-2,4-dinitrobenzene as the electrophilic substrate. None of the Drosophila active fractions catalyzed the conjugation of glutathione with the epoxides mentioned. It is concluded that there are important differences between the GST systems of both species, resulting in differences in the metabolic fate of chemicals that are substrates for glutathione conjugation. This has to be taken into account in the evaluation of genotoxicity testing in Drosophila of potentially harmful compounds.
Plasma renin activity (PRA), aldosterone (PA), sodium and potassium concentration were measured in 107 healthy infants and children under basal conditions of normal diet and recumbency. Urinary aldosterone (UAldo), sodium and potassium were also measured (n = 51). A significant (P less than 0.001) age-related decrease in PRA (r = -0.67), PA (r = -0.67), UAldo (r = -0.56) was observed, with a striking scatter of values especially in infancy. The reninangiotensin-aldosterone system (RAAS) was also studied after stimulation by standardised sodium restriction during 4 days, followed by acute postural change (n = 40). After salt restriction a rise of PRA and UAldo was noted, but a rise in PA could not be demonstrated in children aged 0-6 months. The influence of postural change on the RAAS seems more important in older children. The reported values not only in basal but also in stimulated conditions allow study of the RAAS in diseases such as salt loss and hypertension.
Female gymnasts have a delayed onset and probably retarded progression of puberty. The aim of this study was to test the hypothesis that the delay in onset of puberty in gymnasts as compared to girl swimmers is modulated by a lower estrone level due to a smaller amount of body fat. The sex-hormone and gonadotropin levels of 46 gymnasts and 37 girl swimmers of the same biological maturation (breast development: M = 1 or M = 2) were studied. In each subject the following hormones were measured in plasma: estrone, 17-beta-estradiol, DHEAS, testosterone, androstenedione, LH, and FSH. In prepubertal children (M = 1) the levels of estrone, testosterone, and androstenedione were lower in the gymnastic group as compared to the swimming group. In the early pubertal (M = 2) gymnastic and swimming groups these hormone levels were no longer different. The other hormone levels were not significantly different in either the prepubertal groups or the early pubertal ones. Within the total prepubertal group there is a clear relationship between the estrone levels and the levels of testosterone and androstenedione, but not between estrone and 17-beta-estradiol, nor between the calculated fat mass and any of the hormone levels. It appears that the androstenedione and testosterone levels are responsible for the difference in estrone level, rather than the amount of body fat.
The disappearance rate of endogenous renin from the circulating blood after bilateral nephrectomy was studied in 4 puppies aged 16-21 days. Mean half-times of the fast and slow component of the disappearance curves of renin were 9.15 min +/- 0.87 (SD) and 84.0 min +/- 16.8 (SD), respectively. These values are not different from the values reported for adult dogs in the literature. The metabolic degradation of renin is not different between young and adult dogs and does not contribute to the elevated plasma renin activity in the puppy.
Basal plasma renin activity (PRA), angiotensin I and II (AI, AII), angiotensin-converting enzyme (ACE) activity and plasma aldosterone (PA) and sodium and potassium concentration were simultaneously measured in 55 healthy recumbent children aged between 1 week and 13 years. A significant (P less than 0.001) age-related decrease for PRA (r = -0.73), AI (r = -0.72), AII (r = -0.51) and PA (r = -0.71) was observed but not for ACE (r = 0.26, P = 0.06). After correction for age the correlation between PRA or PA and AI or AII was still significant (P less than 0.005). The strong correlation between AI and AII in the group as a whole (r = 0.82, P less than 0.001) and also in separate age groups, and an AI to AII ratio which was not different between the various age groups suggest that ACE activity in this age range is not rate-limiting for AII generation.
The influence of venepuncture on plasma renin activity (PRA), cortisol, and serum noradrenaline and adrenaline concentration in infants and children was evaluated by comparing values obtained immediately on insertion of an indwelling intravenous line (venepuncture value) and 5 and 60 minutes later. PRA values 5 min after venepuncture in the total group of infants and children were significantly higher (P less than 0.001) than venepuncture values. There was no significant difference between PRA values at 60 min compared to venepuncture or 5 min values. A well performed venepuncture does not systematically affect the PRA values obtained. A significant difference between values for noradrenaline, adrenaline and cortisol at the various points of time could not be demonstrated. The number of lower values for noradrenaline and adrenaline at 60 min, however, prevailed. The stress of a well performed venepuncture is not an explanation for the greater scatter of basal PRA levels in infants and young children.
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Two patients, a boy of 8 and a women of 60 years of age, had higher than normal levels of serum total thyroxine (T4), free T4, (FT4), FT4 index, and reverse triiodothyronine, but normal serum triiodothyronine (T3) levels. The pituitary-thyroid axis could be normally stimulated by thyrotropin-releasing hormone, suggesting euthyroidism at the pituitary level. High levels of serum T4-binding globulin decreased during T3 treatment in the boy. Studies show that in these patients a raised serum FT4 is necessary to produce in the peripheral tissues sufficient amounts of T3 for biological action. Two possible mechanisms for a basic defect underlying this newly recognised syndrome are proposed: inhibition of T4 transport into tissue cells and reduced intracellular 5'-deiodinase activity catalysing T4 to T3 conversion.
A new case of ring chromosome 2 is described and compared with the five cases hitherto reported. The clinical picture includes a severe pre- and postnatal growth failure, microcephaly, psychomotor retardation, and some minor dysmorphic features. Cytogenetic studies revealed a ring 2 structure and aneuploidy. Banding analysis failed to demonstrate a substantial loss of chromosomal material. Enzymologic studies revealed a decrease of red cell acid phosphatase activity suggesting the localization of its gene inthe 2p25 leads to 2 pter region.
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The results of reintroduction of mineralocorticoid substitution therapy (9-alpha-fluorohydrocortisone) in five children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency are described. All children had shown a salt-losing syndrome in infancy, but were off mineralocorticoids during several years; at the start of this study they all had elevated plasma renin activity (PRA). Four of them had increased and fluctuating pregnanetriol excretion during the year preceding reintroduction of mineralocorticoids, indicating poor control despite substantial substitution with hydrocortisone: 26 +/- 1.9 mg/m2/day (mean +/- S.E.M.). Reintroduction of mineralocorticoid therapy at ages 5.0-9.4 years resulted in a marked improvement of control, significant reduction in hydrocortisone requirements (to 17.6 +/- 1.4 mg/m2/day) and improvement in linear growth. The data suggest that, in all children with CAH and elevated PRA, continuation throughout childhood of mineralocorticoid therapy in addition to glucocorticoid therapy is necessary for optimal control and linear growth.
Several rapid bioassays are in use to detect, by means of mutagenicity, the formation of reactive metabolites from foreign compounds during their metabolism in the organism. Of these bioassays, the fruitfly Drosophila melanogaster was investigated with respect to its capacity to biotransform xenobiotics. By spectral analysis it was shown that in microsomal preparations of Drosophila the cytochromes P-450 and b5 are present. Microsomes appeared to possess aryl hydrocarbon hydroxylase and epoxide hydratase activities, while post-microsomal supernatants were able to conjugate appropriate compounds with glutathione and phosphate. As yet, glucosyl- and sulfotransferase activities can not be detected. The activities are compared to similar activities in rat liver.