Search PubMed⌕ Search

Biomedical subjects

J C Job

Publications and source records attributed to J C Job.

At least 37 records · Page 2Linked to original sources
PubMed1991

The binding of different biosynthetic and extracted human growth hormones to the growth hormone-binding protein of human serum: a comparative study.

This study of the human growth hormone binding protein (GHBP) was undertaken using several samples of hGH, extractive or recombinant, from different origins. They were labelled in identical conditions and assayed by gel chromatography after incubation with three human sera having different levels of binding activity. For each serum the binding activities of the five recombinant hormones were very close and significantly higher (P less than 0.005) then the binding activities of the 2 extractive hormones. A radioactive peak which appeared in the zone of high molecular weights was more important with extractive than with recombinant hormones (P less than 0.01). This peak increased with the ageing of the tracer and appeared even when the tracer was incubated in the absence of serum. Thus, it is for its main part not related to another binding protein but, more likely, to a polymerization of the hormone. These data point out the importance of accurate technical conditions to have a reproducible assay for GHBP and to interpret the results in studies of growth disturbances.

Adult↗
PubMed1991

Comparative study of biosynthetic human growth hormone immunogenicity in growth hormone deficient children.

The immunogenicities of six recombinant human growth hormone (rhGH) preparations, from KABI (A rhGH191 and B rhGH192), Eli Lilly (C), Nordisk (D), Sanofi (E) and Serono (F), used to treat 260 GH-deficient children, have been compared using a common specific and sensitive procedure for antibody determination. For this purpose we developed two immunoassays: a competitive liquid radioimmunoassay using 125I-rhGH, and an immunometric solid enzymoimmunoassay in which the rhGHs were immobilized. Blood samples were collected from the GH-deficient children before treatment and after 3, 6, 9, 12, 18 and 24 months of therapy. Human GH antibodies were detected in children treated with 3 of the 6 rhGH preparations. Seven percent of the patients treated with hormone A, 14% with hormone B and 22% with hormone C formed antibodies against the respective rhGH. Differences in capacity and affinity of the hGH antibodies were observed between these anti-GH-positive groups. They could be divided into 2 groups according to their immunopotency. One group (7, 14 and 6% of the patients treated with hormones A, B and C, respectively) developed anti-hGH antibodies with very low binding capacities (30-100 fmol/ml). The other group (16% of the patients treated with hormone C) developed IgG-type antibodies to hGH with higher binding capacities (200-1,200 fmol/ml) and a measurable binding affinity (Ka = 10(8) M-1). These hGH antibodies partially inhibited the binding of labeled GH to its specific liver membrane receptor. However, because of their low titer, they did not inhibit growth in the treated children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Three-year results of treatment with growth hormone, alone or associated with oxandrolone, in girls with Turner syndrome. The Kabi Collaborative Study Group.

22 girls with Turner syndrome aged 10.8 +/- 2.4 years with bone age 8.58 +/- 1.32 years, randomized in two groups, were treated for 3 years with either growth hormone (GH), 0.1 U/kg daily (group A), or GH, 0.1 U/kg, plus oxandrolone, 0.06 mg/kg (group B). This resulted in a sharp increase in growth rate for the first year of treatment, followed in the second and third years by a growth rate near to the normal mean for age. The growth velocity was better in group B, the difference being significant during the first year only. After 3 years, the predicted adult height had increased by 2.1 cm as a mean in group A and by 4.5 cm in group B, with important individual variations, resulting in a gain of at least 3 cm in 3/10 patients of group A and 9/12 of group B. No metabolic or other side effects occurred. These 3-year data confirm that GH improves the predictable height in Turner girls. They suggest that it may be useful for at least 3 years and that adding a small dose of oxandrolone for 2 years in girls aged more than 8 years could be of good practice. However, earlier and more protracted treatment with GH has to be studied with the hope to better improve the predictable adult height.

Adolescent↗
PubMed1991

[Laron type dwarfism. Study of GH binding protein in 3 cases].

Laron's type dwarfism (LTD) has clinical features very close to those of congenital isolated growth hormone (GH) deficiency, contrasting with high plasma levels of GH and a complete lack of growth improvement during treatment trials with exogenous GH. Three new cases are presented here. The plasma GH-binding protein (GHBP), which has been recently isolated and identified as similar to the extracellular part of the liver-cells receptor to GH, is lacking in two of the three patients and subnormal in their heterozygous parents, these data suggesting a defect of the GH receptor or of its extracellular part. In contrast, the third patient and her parents had normal plasma levels of GHBP, suggesting that the clinically and biologically obvious lack of receptivity to GH is either at the post-receptor level or limited to the intracellular part of the receptor. These data contribute to demonstrate that there are at least two different genetic defects leading to clinical LTD.

Carrier Proteins↗
PubMed1990

A possible common origin of "Y-negative" human XX males and XX true hermaphrodites.

We have studied nine patients aged 1 month to 16 years with 46, XX karyotypes and testicular tissue. Some of these patients were followed through puberty. Phenotypically, two presented normal and seven abnormal external genitalia (AG). Among this latter group, four showed hypospadias and three true hermaphroditism (TH). The endocrine data were similar in all three groups: testosterone levels were within normal limits during puberty, decreasing in adulthood; gonadotrophin levels were above the control values at mid puberty. Histologies of the two sub groups of AG patients were identical up to 5 years of age and presented differences when compared with controls, regardless of the ovarian part of the ovotestis. However, in patients older than 8 years, germ cells disappeared and dysgenesis became obvious. In one patient, the ovarian zone of the gonad was detected only after complete serial sections of the removed gonad were examined. Southern blot analysis with Y-DNA probes displayed Y-specific material for the classic 46 XX males and a lack of such sequences for all patients with AG and TH. Based on these findings, we postulate that 46, XX males with AG and 46, XX TH may represent alternative manifestations of the same genetic defect. These data together with those concerning familial cases of 46, XX males with AG and 46, XX TH suggest an autosomally (or pseudoautosomally) determined mechanism.

Adolescent↗
PubMed1990

Assay of growth hormone levels in human plasma using commercial kits: analysis of some factors influencing the results.

The reliability of growth hormone (GH) assays, performed in 39 different laboratories, using five different immunoassay kits was evaluated. It was found that the variability in GH levels measured by different commercial assay kits may be due to human factors, as well as differences between the kits. The influence of the variation in amount of circulating GH, during provocative testing and spontaneous secretory episodes, on the results of GH assay was also evaluated. It was found that large molecular weight forms of GH may be underestimated by some assay kits.

Child↗
PubMed1990

Growth hormone response to a bolus injection of 1-44 growth-hormone-releasing hormone in very short children with intrauterine onset of growth failure.

The release of growth hormone (GH) during the 120 min following a bolus venous injection of 1-44 GH-releasing hormone (GHRH) 2 micrograms/kg was studied in 52 prepubertal children aged 8.4 +/- 2.1 years, having a nonfamilial growth deficiency of prenatal onset (-3.26 +/- 1.13 SDS at birth, -3.22 +/- 0.88 SDS at the time of study) and a normal response to conventional GH stimulation tests. GH release reached a peak level of 96.1 +/- 60.2 microU/ml, being significantly higher than that found in 68 non-GH-deficient very short children whose growth failure had a postnatal onset, and not significantly correlated with the response to conventional tests. 26 of the 52 intrauterine growth retardation (IUGR) patients were re-tested with GHRH in similar conditions after 6-12 months of daily subcutaneous injections of GH and 2 days without. They reached at the second test a peak plasma GH level of 91.7 +/- 56.1 microU/ml, not different from their response to the first test. These data could be taken into consideration for long-term studies of the clinical effects of GH in IUGR children with persisting severe growth deficiency.

Child↗
PubMed1990

Results of long-term growth hormone replacement therapy in children: when and how to treat?

Up to now, the end results of treatment in GH deficiency (GHD) have not been as good as expected. Probably the main cause has been the delay in diagnosing GHD in short children, resulting in a very insufficient height at the onset of puberty. The need for early diagnosis and treatment must be emphasized. This agrees with the well-documented data demonstrating (1) that catch-up growth obtained in any treatable growth disorder has a limited duration, and (2) that the effect of GH replacement, whatever the doses and modes of therapy, is maximal during the first year and wanes during the following years. There are still many questions regarding the appropriate GH replacement dose. The height gain during the first year of treatment has been correlated with the logarithm (decimal or natural) of the dose in several groups of patients receiving GH 3 times/week. The initial dose-response relationship is better with GH 6 times/week. For the following years, no dose/response ratio has been demonstrated, and the final height-to-dose relations are still to be investigated. A dose increase after 2 years or more may improve the growth rate, but also with secondary waning. Thus, long-term prospective dose-response studies are needed. The first period of one such study is presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1990

High-affinity serum growth-hormone-binding protein, absent in Laron-type dwarfism, is diminished in heterozygous parents.

Human serum high-affinity growth-hormone-binding protein (GHBP), as determined by incubation with 125I-GH followed by chromatography on AcA 44 gel minicolumns, is lacking in patients with Laron-type dwarfism (LTD). We found that the specific binding of 125I-GH to high-affinity GHBP in normal human serum (m +/- SD) was 11.5 +/- 1.8% in 10 children 2-3 years old, 15.3 +/- 2.2% in 10 children 5-8 years old, and 19.3 +/- 2.9% in 15 adults 20-40 years old. It was 0.3% in a 2-year-old child with LTD, and 10.6 +/- 11.3% in his parents. It was 0.1% in another child with LTD, 7 years old, and 14.4 and 14.8% in his parents. The mean value in the heterozygous parents (12.8 +/- 2.1%) was significantly lower (p less than 0.001) than control values. A void volume peak (VVP) of radioactivity, corresponding to the so-called low-affinity GHBP which eluted at the void volume in chromatographs of normal sera remained unchanged with sera of patients with LTD or of their parents and appeared even after incubations of the tracer without serum. This study (1) shows that high-affinity GHBP is diminished in heterozygotes with LTD; (2) confirms that high-affinity GHBP and VVP are independently regulated, and (3) suggests that a part of the VVP may not be related to GH binding to some serum components.

Adult↗
PubMed1990

Growth hormone secretion during sleep. II. Interrelationships between growth hormone secretion, insulin-like growth factor I and sex steroids.

The serum levels of insulin-like growth factor I (IGF I), dehydroepiandrosterone sulfate (DHAS), testosterone (T) and estradiol (E2) have been measured in 78 prepubertal and 57 early pubertal patients referred for short stature, at the same time when their secretion of GH was evaluated both during nocturnal sleep and by two conventional stimulation tests. According to the results of GH measurements they were considered as having a normal secretion of GH (group I), a complete GH deficiency (group II), a partial GH deficiency (group III), low responses to stimuli with normal secretion during sleep (group IV) or a nocturnal neurosecretory dysfunction (group V). Though widely scattered, the IGF I levels showed the following characteristics: a significant increase at puberty from 0.77 to 1.29 U/ml (p less than 0.001) in the so-called endocrinologically normal patients of group I, not in the other groups; in the prepubertal patients of group I, a correlation of IGF I with chronological age (r = 0.47, p less than 0.005) and bone age (r = 0.52, p less than 0.002); significantly reduced IGF I levels in patients of group II having complete GH deficiency (p less than 0.001); no significant differences between prepubertal patients with partial or atypical GH deficiency from groups III, IV, V and prepubertal patients from group I; lower pubertal levels in groups III, IV, V than in pubertal patients from group I (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Laron-type dwarfism: heterogeneity of the biochemical abnormality in 3 children and their parents].

The authors report three cases of Laron-type dwarfism (LTD) having clinical features similar to those of congenital growth hormone (GH) deficiency, but with high levels of plasma GH and a lack of effect of exogenous GH on their growth. The main plasma growth hormone binding protein (GHBP), recently identified and considered as being identical to the extracellular part of the cell receptor to GH, was absent in two of the three patients, and lower than normal in their parents, suggesting a defect of the cell GH receptor. The third patient and his parents had a normal level of GHBP, suggesting a defect limited to the intracellular domain of the receptor or lying beyond the receptor. The conclusion is that there are two different biochemical abnormalities corresponding to LTD.

Adult↗
PubMed1990

[Relation of the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the beginning of puberty in patients of short stature].

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGFI was slightly but highly significantly correlated to the growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated together.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1990

[The relation between the secretion of growth hormone (GH), somatomedin C/IGF I (IGF I) and steroids before and after the onset of puberty in patients of small stature].

Somatomedin C/IGF I, dehydroepiandrosterone sulfate (DHAS), testosterone (T) or estradiol (E2) have been measured in 154 patients of a previous study in which growth hormone (GH) responses to classical pharmacologic stimuli and spontaneous growth hormone secretion during sleep were compared in short children before and at the beginning of puberty. Five groups were identified: Group I, normal growth hormone secreting children; group II, completely growth hormone deficient; group III, partially growth hormone deficient; group IV, with normal sleep secretion and low responses to stimuli; group V, with the reverse situation. The somatomedin C/IGF I levels were widely dispersed. In group I, the mean +/- SEM levels of somatomedin C/IGF I were 0.77 +/- 0.047 U/ml before puberty and 1.36 +/- 0.142 U/ml in early pubertal patients, with a relation to age (r = 0.52, p less than 0.001). The difference between prepubertal and pubertal patients was significant. In groups II to V, there was no pubertal rise of somatomedin C/IGF I. In group II, the mean IGF I level was 0.48 +/- 0.05 U/ml, significantly lower than in prepubertal patients of group I. In groups III, IV and V, it was 0.7 +/- 0.069 U/ml, 0.8 +/- 0.059 U/ml, and 0.73 +/- 0.059 U/ml respectively, not different from prepubertal patients of group I, but significantly lower than in early pubertal patients of the same group. In prepubertal patients, somatomedin C/IGF I was slightly but highly significantly correlated to growth hormone sleep secretion (r = 0.27, p less than 0.001) and to dehydroepiandrosterone sulfate (r = 0.36, p less than 0.001), but growth hormone and dehydroepiandrosterone sulfate were not correlated with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1989

Early diagnosis and early treatment of growth hormone deficiency.

In the past, growth hormone (GH) deficiency has usually been diagnosed too late in dwarfed children, so that substitution therapy was not able to obtain a final height in the normal range for most of them. Complete catch-up of growth in hypopituitary patients needs early diagnosis and early treatment. This requires: (1) that full attention be paid to any insufficiency of length or height increment in infants and young children; (2) that evaluation of GH secretion be performed in spite of the practical difficulties encountered in small patients, and (3) that the interpretation of hormonal measurements be carefully discussed. Though the overall results obtained to date in treating very young GH-deficient children have not been completely satisfactory, it is certain that those whose height was within or near the limits of -2 SD at the onset of treatment maintained a normal height. The relationship of end results with the doses of GH used remains to be investigated. Future results will probably be improved more by earlier diagnosis and by using daily injections than by an increase in the annual dose of GH.

Age Factors↗
PubMed1989

The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency.

The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below -2 SD in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1-2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.

Adolescent↗
PubMed1989

[Elevated levels of plasma 4-ene steroids in a case of congenital deficiency of 3 beta-hydroxysteroid dehydrogenase].

Plasma hormones have been evaluated from birth to six months in a boy with male pseudohermaphroditism due to congenital 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency. At birth, plasma 17-hydroxyprogesterone (17-OHP) was slightly elevated while cortisol was within the normal range. Both 17-OHP and testosterone (T) were increased the fifth day. At the age of 2 months, only the baseline level of 17-hydroxypregnenolone (17-OH5P) was slightly elevated and the diagnosis of 3 beta-HSD deficiency was established in view of the excessive response of 17-OH5P and dehydroepiandrosterone (DHA) to Synacthen administration. There was an important increase of T and dihydrotestosterone in response to chorionic gonadotropin (hCG) administration while no significant variation of the other studied steroids was observed. These results suggest that the determination of plasma 17-OH5P seems to be the best tool to diagnose congenital 3 beta-HSD deficiency. The increase of 17-OHP is the result of 17-OH5P conversion in peripheral tissues. Though T response to hCG is rather normal, a partial testicular deficiency of 3 beta-HSD cannot be excluded. The ambiguous genitalia observed in this boy with normal plasma T levels might suggest that T production might have been deficient at the time when urethral-fold fusion occurred.

17-alpha-Hydroxypregnenolone↗
PubMed1988

Insulin-like growth factor I receptors on human erythrocytes from normal children: relationship with age.

The binding of insulin-like growth factor I (IGF I) on red blood cells has been studied in 13 children aged 8 months to 11 years and in 10 adults. The Scatchard analysis showed a curvilinear regression. In adults, the specific binding was 4.1% of the tracer, the mean number of high affinity receptor sites per cell (Ro1) being 0.88 (K1 = 10.74 nM-1) and the mean number of low affinity receptors sites (Ro2) per cell being 7.14 (K2 = 0.37 nM-1). In children the specific binding ranged from 3 to 6.5%. Ro1 ranged from 0.40 to 3.13 (K1 from 3.48 to 13.61 nM-1). Ro2 ranged from 2.88 to 17.25 (K2 from 0.03 to 0.65 nM-1). The most striking fact was the close positive correlation between the specific binding and the age of children (r = 0.914, P less than 0.001). These data suggest that the high growth velocity of young children, concomitant with the low plasma levels of IGF I which are physiological during infancy and early childhood, does not result from an increased binding of IGF I to cell receptors.

Aging↗