Variability in the urinary excretion of growth hormone in children: a comparison with other urinary proteins.

As a basis for assessment of the clinical validity of urinary GH (uGH) measurements in children, the day-to-day variability in renal handling of GH has been compared with that of albumin, N-acetylglucosaminidase (NAG) and creatinine. Five overnight urine specimens were collected over a 2-week period from 78 healthy children (aged 5-16 years), 20 of normal stature and 58 with growth disorders; ten children were classified as GH-deficient (GHD) and 48 were designated short normal (SN). The variability of excretion of each substance was expressed as a coefficient of variation (C.V.) which was not influenced by expressing the urine results as total mass excreted, concentration, excretion rate or as a ratio to creatinine. There was considerable night-to-night variability in the excretion of all substances (mean C.V. values for all groups: 56% for albumin, 41% for GH, 33% for NAG and 27% for creatinine). No differences were found in the variability of GH excretion between males and females, nor between prepubertal and pubertal subjects. The mean C.V. for uGH excretion ranged from 37% in normal and 35% in SN children to 52% in those with GHD (P < 0.05). Assay variation rather than a change in renal protein handling accounted for the large variations in uGH concentrations of < 5 pg/ml, thus contributing to the high uGH C.V. of the GHD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Hirschsprung's disease and mongolism.

Two mongoloid patients with Hirschsprung's disease are presented. Mongoloid children who have severe constipation should be investigated for Hirschsprung's disease.

Immunolocalization of estrogen receptor protein in the mouse blastocyst during normal and delayed implantation.

We previously showed that estrogen receptor (ER) mRNA is present in preimplantation mouse embryos. The apparent synthesis of ER mRNA by the blastocyst at the time of implantation when estrogen is required was of special interest. A demonstration of the presence of ER protein would support the idea that estrogen can act directly on the embryo. The mouse embryo at the blastocyst stage is differentiated into two cell types, the trophectoderm and the inner cell mass. To determine whether ER mRNA is translated into ER protein and its cell-specific distribution, immunocytochemical analyses were performed in mouse blastocysts. ER protein was detected in all cell types of the normal, dormant, or activated blastocyst. To trace the fate of ER in these cell types, immunocytochemistry was performed in implanting blastocysts and early egg cylinder stage embryos developed in culture. Again, ER was detected in all cells of the implanting blastocyst. At the early egg cylinder stage, continued expression of ER was observed in cells derived from the inner cell mass or the trophoblast. In trophoblast giant cells, ER was concentrated in small regions of the nucleus, possibly the nucleoli, which was similar to that observed in dormant and activated blastocysts. The embryonic expression of ER at such early stages in a broad array of cells suggests that ER may have a general role during early development.

The influence of age, size, pubertal status and renal factors on urinary growth hormone excretion in normal children and adolescents.

Overnight urinary growth hormone (GH) excretion was measured in 528 schoolchildren (aged 4-16 years) whose heights and weights were between the third and 97th centiles. Urinary GH increased significantly with age, reaching a maximum in boys at 15-years-old and in girls at 13-years-old. Peak levels were five and three times higher in boys and girls respectively than in 4-year-olds. Maximum urinary GH excretion was seen at breast stages 3 and 4 in girls and at genital stage 4 in boys followed by a decline in both sexes at stage 5. Boys excreted more GH than girls during prepubertal and pubertal years. During prepubertal years there were fluctuations of urinary excretion of GH with age. Height, weight and pubertal status predicted 31% of the variability of urinary excretion of GH, and urinary excretion of creatinine, albumin and N-acetylglucosaminidase (NAG) predicted 52% of the variability. The importance of establishing sound age and sex-related reference ranges for urinary growth hormone is stressed before application of this test to children with growth disorders.

Restoration of visual responses following transplantation of intact retinal sheets in rd mice.

PURPOSE: To correlate the functional outcomes with histologic findings following transplantation of fetal retinal sheets in rd mice, and to investigate the mechanisms of visual function restoration. METHODS: Twenty-one postnatal day 31-38 rd/rd (C3H/HeJ) mice were transplanted in one eye with retinal sheets (1.0 x 0.4 mm) obtained from embryonic day (E) 17 enhanced-green-fluorescent protein (eGFP) mice. Five mice underwent sham surgery without insertion of tissue. Four to five weeks after transplantation, visual responses to a light flash were recorded across the superior colliculus (SC) in seven eyes of seven transplanted mice that had clear corneas and lenses, and in all five sham surgery mice. Following the SC recording, the eyes were enucleated and processed for immunohistochemistry and examined using confocal microscopy. RESULTS: In three out of the seven eyes (43%), positive responses were recorded in the SC in an area topographically corresponding to the placement of the transplant in the host retina. No responses were recorded in the untreated eyes of 5-week-old and 9-week-old rd/rd mice, and in the 9-week-old sham surgery mice. In contrast, visual responses were recorded over the entire SC in normal eyes. The response onset latencies of the 3 transplanted mice with responses were similar to those of normal control mice. The organization of the graft did not appear to correlate as expected with the electrophysiology results, as eyes with well-organized, laminated grafts showed no response whereas the three light-responsive eyes had rosetted or disorganized grafts. All three light-responsive eyes demonstrated much higher levels of recoverin immunoreactivity in the host retina overlying the graft compared with untreated age-matched rd/rd mice. CONCLUSION: Restoration of the SC visual response does not appear to depend on a well-organized transplant in the rd mouse. Increased recoverin-staining in the host retina in light-responsive animals suggested that host cone rescue was the likely mechanism of vision restoration in this transplant model.