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Biomedical subjects

J R Hansen

Publications and source records attributed to J R Hansen.

18 recordsLinked to original sources

MR imaging of the pituitary gland in central precocious puberty.

Cranial magnetic resonance imaging was performed in 17 children with central precocious puberty (CPP) and 19 aged-matched controls to compare the appearance of the pituitary gland. Gland size was measured on T1-weighted sagittal and coronal images. The gland was graded according to the concavity or convexity of the upper surface, and the signal intensity of the gland was assessed visually. The mean pituitary volume in 13 CPP children without hypothalamic tumor (292.6 mm3) was significantly greater than that in normal controls (181.35 mm3). The mean volume for the four CPP children with hypothalamic tumor was smaller (145.0 mm3). Compared to controls, the upper pituitary surface in CPP patients appeared convex in a higher proportion. The anterior pituitary was isointense to pons in all patients and controls. Although the posterior pituitary bright spot was present in 14 controls and 11 CPP patients, none with hypothalamic tumor showed it.

Astrocytoma

Assessment of depot leuprolide acetate dose-adequacy for central precocious puberty.

The development of GnRH analogs (GnRHa) has made it possible to treat children with central precocious puberty (CPP). This treatment may prevent adult short stature due to premature epiphyseal fusion. Achievement of this goal, however, is dependent upon adequate suppression of gonadal steroid production as a result of GnRHa-induced pituitary desensitization and decreased gonadotropin release. A depot formulation of a GnRHa [leuprolide acetate (dLA)] is being used by many clinicians for the treatment of CPP, but studies to establish the optimal dose of dLA have not been performed. In this study we evaluated the effectiveness of dLA (7.5 mg, im, every 4 weeks). Six children (7-10 yr old) with CPP treated with dLA were assessed clinically and divided into two groups: A (incompletely suppressed) and B (well suppressed). Each group had overnight blood sampling and a GnRH stimulation test the following morning. LH pulses were analyzed and compared to 11 normal prepubertal children. Mean LH concentration, LH curve area, LH pulse frequency, and mean LH pulse amplitude were significantly greater (P less than 0.03) in group A than in group B or the normal prepubertal children. There was no significant difference among the three groups in GnRH-stimulated peak LH release. These results indicate that dLA (7.5 mg, im, every 4 weeks) does not produce complete desensitization in all children with CPP and suggest that overnight monitoring of LH release is more sensitive than GnRH stimulation testing for the assessment of dLA dose adequacy.

Child

Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls.

BACKGROUND AND DESIGN: Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. RESULTS: Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. CONCLUSION: Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty.

Adolescent

Heart rate monitoring of physical activity in children and adolescents: the Muscatine Study.

To assess the usefulness of whole-day heart rate monitoring as a quantitative measure of physical activity in children, the activity of 76 children and adolescents (ages 6 to 17 years), randomly selected from a school population, was measured during a typical summer day using a light-weight, nonrestrictive heart rate telemetry unit. A 12-hour recall and a simple self-rating of usual activity questionnaire were also administered on the same day. An additional 12-hour recall questionnaire was administered on another day. Within 1 month of the heart rate monitoring, the skinfold measures, peak aerobic capacity, and sexual maturation were assessed. Data analysis indicated that activity as measured by telemetry was related to questionnaire recall on the monitored day (r = .50), nonmonitored day (r = .32), and self-rating (r = .35); level of activity as measured by telemetry was related to peak aerobic capacity in girls (r = .36) but not in boys (r = -.06); body fat was related inversely to activity (r = -.32); and prepubescent children were more active than post- and pubescent children (P less than .003). No difference was found in activity level between boys and girls (P greater than .05). This study suggests that for children whole-day heart rate monitoring is an objective, nonobtrusive method for measuring physical activity; and maturation, but not gender, is an influential mediating factor for activity.

Adolescent

Clinical management issues in males with sex chromosomal mosaicism and discordant phenotype/sex chromosomal patterns.

The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.

Adolescent

Gonadotropin-releasing hormone modulation of protein kinase-C activity in perifused anterior pituitary cell cultures.

The ability of GnRH to modulate protein kinase-C (PKC) activity was examined in perifused rat pituitary cell cultures. Under these conditions, LH release and GnRH receptor number remained unchanged after repeated pulses of 1 nM GnRM, whereas PKC (measured both enzymatically and by radioligand assay) showed an initial increase in kinase activity after the first pulse of GnRH (approximately 2-fold), followed by down-regulation of PKC activity with subsequent pulses of the releasing hormone. It was also observed that the GnRH-stimulated down-regulation of PKC was dependent on the presence of extracellular calcium, which was not the case for the initial up-regulation of PKC. These findings are consistent with a modulating role of the GnRH receptor on PKC activity through a Ca2(+)-dependent process. This study also provides further evidence that GnRH-stimulated LH release and PKC activity can be uncoupled.

Animals

Human collagen genes encoding basement membrane alpha 1 (IV) and alpha 2 (IV) chains map to the distal long arm of chromosome 13.

At least 20 genes encode the structurally related collagen chains that comprise greater than 10 homo- or heterotrimeric types. Six members of this multigene family have been assigned to five chromosomes in the human genome. The two type I genes, alpha 1 and alpha 2, are located on chromosomes 17 and 7, respectively, and the alpha 1 (II) gene is located on chromosome 12. Our recent mapping of the alpha 1 (III) and alpha 2 (V) genes to the q24.3----q31 region of chromosome 2 provided the only evidence that the collagen genes are not entirely dispersed. To further determine their organization, we and others localized the alpha 1 (IV) gene to chromosome 13 and in our experiments sublocalized the gene to band q34 by in situ hybridization. Here we show the presence of the alpha 2 type IV locus also on the distal long arm of chromosome 13 by hybridizing a human alpha 2 (IV) cDNA clone to rodent-human hybrids and to metaphase chromosomes. To our knowledge, these studies represent the only demonstration of linkage between genes encoding both polypeptide chains of the same collagen type.

Amino Acid Sequence

Relative roles of calcium derived from intra- and extracellular sources in dynamic luteinizing hormone release from perifused pituitary cells.

GnRH releases LH from pituitary gonadotropes by a calcium-dependent mechanism. Previous studies in static cell cultures have not revealed a role for intracellular-derived calcium during GnRH-stimulated LH release. In the present study we have reexamined this possibility using a perifusion system, which permits a more dynamic assessment of early cellular events. Chelation of extracellular calcium by EGTA and calcium channel blockade by methoxyverapamil prevented sustained LH release. A component of early LH release occurred independently of extracellular calcium mobilization. This previously unrecognized aspect of LH release was shown to be dependent upon intracellular calcium. The molecular mechanism by which this calcium-dependent signal is translated into a cellular response does not appear to be mediated by calmodulin or protein kinase C, whereas sustained LH release appears mediated by calmodulin. While calcium derived from extracellular sources is still viewed as the major messenger for sustained LH release, these experiments provide evidence for the involvement of intracellular-derived calcium during early GnRH-stimulated LH release.

Animals

Reye syndrome associated with aspirin therapy for systemic lupus erythematosus.

A 14-year-old girl in whom Reye syndrome developed during aspirin therapy for an inflammatory disorder proven to be systemic lupus erythematosus is reported. This case and similar cases of Reye syndrome in patients with juvenile rheumatoid arthritis suggest that an etiologic relationship exists between salicylate therapy and Reye syndrome in children with collagen vascular disorders.

Adolescent

Circulating dopamine-beta-hydroxylase (DbetaH) and catecholamines in a paediatric phaeochromocytoma.

1. Circulating catecholamines and dopamine-beta-hydroxylase (DbetaH) have been studied in a child with bilateral phaeochromocytoma. 2. Venous catheterization showed a great increase in catecholamine efflux from the left adrenal vein while DbetaH activity in the latter was only slightly elevated. 3. Circulating catecholamines fluctated greatly while DbetaH activity decreased gradually during the removal of the tumours. 4. Post-operatively, circulating catecholamines declined to normal values while DbetaH activity returned to pre-operative levels. 5. It is concluded that these tumours released circulating catecholamines independent of an exocytotic secretion of DbetaH and that the circulating DbetaH reflected the activity of the sympathetic nervous system.

Adrenal Gland Neoplasms