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Biomedical subjects

R Brauner

Publications and source records attributed to R Brauner.

At least 19 recordsLinked to original sources
PubMed1992

XY sex reversal associated with a deletion 5' to the SRY "HMG box" in the testis-determining region.

The human testis-determining factor resides within a 35-kilobase (kb) region of the Y chromosome immediately adjacent to the pseudoautosomal boundary. A candidate gene for human sex determination (SRY) was isolated in this region. Here, we describe a study of 25 cases of XY females with pure gonadal dysgenesis for mutations on the Y chromosome short arm, including SRY. Southern blotting revealed a sex-reversed female harboring a deletion extending from approximately 8 kb from the pseudoautosomal boundary of the Y chromosome to at least 33 kb and no more than 60 kb upstream, toward the centromere. The deletion begins no more than 1.8 kb upstream from the first ATG of the SRY open reading frame present in the clone pY53.3. To our knowledge, no mutation has been described previously outside the SRY "HMG box" on the short arm of the Y chromosome, which is associated with sex reversal. Since the 5' extent of the SRY transcriptional unit has not been defined, the deletion may remove upstream exons of SRY and/or transcriptional regulatory motifs, either situation resulting in lack of testicular development. It cannot be formally excluded that the mutation removes a second locus, independent of SRY, that is critical for sex determination. Denaturant gradient gel electrophoresis analysis of the SRY open reading frame in the remaining 24 cases revealed de novo single base-pair transitions in the SRY conserved domain in 4 cases.

Amino Acid Sequence↗
PubMed1992

[Determination of growth hormone binding protein in a normal population and in subjects with short stature due to growth hormone resistance].

With the procedure which uses gel-filtration and high pressure liquid chromatography (HPLC) the authors measured the GH-binding proteins in 96 healthy subjects aged 6 months to 40 years. In the blood 45% of the GH is bound to the BP. The diagnosis was confirmed by our method in 13 patients with Laron type dwarfism and in four patients the GH receptor defect had been proved. The parents, the brothers and sisters showed significantly lower GH-BP II (principal GH-BP) levels. Possible regulation of GH-binding proteins in human plasma was examined. Eight children with isolated GH deficiency had a very low level of plasma GH binding activity (mean +/- SEM) (10.2 +/- 1.1% of radioactivity). Under GH treatment the hormone binding to high affinity BP (GH-BP II) increased in every patient to reach the mean value of 18.5 +/- 1.4%. This increase was related to a higher binding capacity without any significant change in the binding affinity. In nine boys with pubertal delay, the GH specific binding to peak II-BP (GH-BP II) was found to be normal (30.6 +/- 3.7%); it decreased significantly following testosterone treatment. In four boys with precocious puberty, the specific GH binding to peak II BP was low (16.6 +/- 1.1%). It increased significantly to 21.6 +/- 1.1% of radioactivity after treatment with LH-RH analogue. GH and testosterone have an opposite role in the regulation of the high affinity GH-BP.

Adolescent↗
PubMed1992

[Analysis of human growth hormone-binding protein in plasma by high pressure liquid chromatography].

A technique using high pressure liquid chromatography gel filtration was used to evaluate GH-binding proteins (GH-BPs) in human plasma; eluate was monitored for radioactivity in a gamma-detection system connected to a computer. Plasma (200 microliters) was incubated with 125I-human (h) GH (200,000 cpm) at 4 degrees C for 20 hours. Our GH binding assay offers important gains in terms of rapidity and resolution; it has permitted a clear separation and characterization of the two GH-binding components present in human plasma.

Carrier Proteins↗
PubMed1992

Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty.

The factors influencing the final height of central precocious puberty patients treated with gonadotrophin releasing hormone (GnRH) analogues remain a critical issue. This study compares the predicted final height before and after GnRH analogue therapy to identify predictive factors for final height. Fourteen girls with idiopathic central precocious puberty were treated with a GnRH analogue. All had an active non-regressive form before therapy, full and permanent suppression of oestrogenic activity during therapy (duration greater than 2 years, 3.1 +/- 0.3 years, mean +/- SEM), and the pubertal pituitary-ovarian axis had normalized in all of them 1 year after the cessation of therapy. The mean predicted final height increased from 152 +/- 1.8 cm before therapy to 162.2 +/- 1.2 cm (P less than 0.01) at the last evaluation performed 4.5 +/- 0.3 years after the onset of therapy. The mean gain in predicted final height between the onset of therapy and the last evaluation was 10.2 +/- 1.1 cm. It was correlated with the following data recorded at the onset of therapy: bone age advance over chronological age (r = 0.66, P less than 0.02), predicted final height at the onset of therapy (r = -0.76, P less than 0.001), and the difference between the target height and the predicted height at onset of therapy (r = 0.76, P less than 0.001). We conclude that GnRH analogue therapy is more likely to improve final height prognosis in girls who initially present with a markedly advanced bone age and a great difference between their target and predicted heights. Both these parameters reflect the severity of the disease at diagnosis.

Body Height↗
PubMed1992

Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood.

Ovarian transposition in adults has been shown to protect ovarian function in about 60% of cases by reducing ovarian exposure to less than 4 to 7 Gy. We therefore evaluated the effect of ovarian transposition during childhood or adolescence. Eighteen girls had ovarian transposition performed at a mean (+/- SEM) age of 9.4 +/- 1.2 years (range, 1.2 to 16 years). Twelve were prepubertal and six had menstruated at the time of ovarian transposition. The initial abnormalities were Hodgkin disease (5 cases), iliac Ewing sarcoma (3), medulloblastoma (2), ovarian seminoma (1), and vaginal or uterine tumor (7). The irradiation was external in 11 cases and local by vaginal curietherapy in 7 cases. Fifteen girls received chemotherapy. The ovarian transposition was bilateral in 15 patients and unilateral in 3 cases; in the latter the other ovary had been destroyed by the tumor or by abdominal irradiation. Ovaries were placed just below the iliac crest (15 cases) or posterolateral to the uterus (3); thus, the calculated ovarian radiation dose was up to 9.5 Gy. At the time of evaluation (8.6 +/- 0.9 years after ovarian transposition), 16 girls had menstruated and 2 remained amenorrheic because of major lesions of the vagina and uterus caused by the vaginal curietherapy. Basal plasma gonadotropin values were normal. Ovulation was documented in seven cases. Two pregnancies occurred. Complications of ovarian transposition were present in four patients: intestinal occlusion, dyspareunia, functional ovarian cysts, and pelvic adhesions with tubal obstruction. We conclude that ovarian transposition, performed before abdominopelvic irradiation during childhood, can preserve ovarian function. Longer follow-up is required to assess the risk of ovarian dystrophy because of vascular lesions or chemotherapy.

Adolescent↗
PubMed1992

Magnetic resonance imaging in the diagnosis of growth hormone deficiency.

Forty-six patients with idiopathic growth hormone deficiency were examined by magnetic resonance imaging at a mean (+/- SEM) age of 9 +/- 1 years (range 15 days to 20 years). They were classified into two groups according to MRI images: group 1 (n = 29) had pituitary stalk interruption syndrome and group 2 (n = 17) had normal pituitary anatomy. All patients with pituitary stalk interruption had a pituitary height at less than -2 SD for age; three had no visible anterior pituitary lobe. By contrast, the pituitary height was less than normal in only 10 patients (60%) with normal pituitary anatomy. Growth hormone deficiency was transient in one of the seven patients with normal pituitary anatomy and height. The group with pituitary stalk interruption had the first symptom of growth hormone deficiency at an earlier age (2.8 +/- 0.6 vs 5.5 +/- 1.2 years; p less than 0.001), were of smaller stature (-4 +/- 0.2 vs -3 +/- 0.2 SD; p less than 0.01) and had lower GH peak response to provocative testing (3 +/- 0.4 vs 5 +/- 0.5 ng/ml; p less than 0.001) than did the group with normal pituitary anatomy. Their pituitary gland was also shorter (2.5 +/- 0.2 vs 3.5 +/- 0.2 mm; p less than 0.01). All the patients with multiple pituitary deficiencies except one (n = 19) belonged to this group. One girl with pituitary stalk interruption and deficiencies in growth hormone and thyroid-stimulating hormone had advanced central precocious puberty. We conclude that the evaluation of the shape and height of the pituitary gland by MRI is an additional tool for the diagnosis of growth hormone deficiency. The presence of pituitary stalk interruption confirms this diagnosis and is predictive of multiple anterior pituitary deficiencies. The lack of a significant increase in perinatal abnormalities in this group and the association of pituitary stalk interruption with microphallus and with facial or sella abnormalities suggest that this appearance may have an early antenatal origin. The finding of a familial case of pituitary stalk interruption suggests a genetic origin.

Child↗
PubMed1992

Effect of growth hormone on the low level of growth hormone binding protein in idiopathic short stature.

OBJECTIVE: Growth hormone receptor status was assessed in children with idiopathic short stature by evaluating plasma growth hormone-binding protein before and under GH therapy. DESIGN: Among 22 children presenting idiopathic short stature, 15 were randomly selected to be treated with GH (1.2 IU/kg/week); they were studied before and under GH therapy. Untreated patients served as a control group for age and GH effect. PATIENTS: Twenty-two prepubertal children, aged 5-11 years, were studied. They presented growth retardation of -2.8 +/- 0.1 SDS (mean +/- SEM). All had normal GH secretion and their mean IGF-I plasma level was normal. MEASUREMENT: Growth hormone-binding protein was measured using high pressure liquid chromatography gel filtration. The specific binding of 125I-hGH to the growth hormone-binding protein was expressed as a percentage of the total radioactivity. RESULTS: Specific binding of 125I-hGH to the high affinity growth hormone-binding protein was low with a mean +/- SEM value of 11.1 +/- 0.9% of radioactivity. In the treated group, growth hormone-binding protein increased significantly after 3 months of treatment; it reached 21.1 +/- 1.0% of radioactivity (mean +/- SEM) in the eight children who have been treated for 18 months. In the seven untreated children, the growth hormone-binding protein value increased to 16.2 +/- 1.1% after 18 months; this value is significantly lower than that found in the GH-treated children, demonstrating that the GH effect is greater than the age-related increase in the growth hormone-binding protein. A positive correlation was found between IGF-I plasma levels and growth hormone-binding protein and also between growth velocity and growth hormone-binding protein. CONCLUSIONS: The low growth hormone-binding protein and the response to high doses of GH suggest partial GH resistance at the receptor level, in this group of children with idiopathic short stature.

Carrier Proteins↗
PubMed1992

The capacity to increase GH secretion at puberty reflects the severity of GH deficiency.

This study evaluates the effect of the spontaneous pubertal increase in sex steroids on GH secretion in GH-deficient patients. Fifteen patients (10 boys, 5 girls) with idiopathic isolated GH deficiency diagnosed before puberty (GH peak < 8 micrograms/l after 2 arginine insulin stimulation tests) were reevaluated for their GH secretion using the same test after completion of their hGH therapy and puberty. Their ages at diagnosis and at the last evaluation were 8.2 +/- 0.7 (SE) (range 4.9-14.9) and 17.8 +/- 0.3 years (15-23), respectively. The data at diagnosis and at last evaluation showed that (1) the mean height increased from -4 +/- 0.3 to -2.5 +/- 0.3 SD (p < 0.01), (2) the mean GH peak increased from 4.4 +/- 0.3 (1.6-8) to 7.6 +/- 0.8 micrograms/l (2-13.2, p < 0.01); at the last evaluation, 8/15 patients had GH peak > 8 micrograms/l and (3) the mean plasma insulin-like growth factor I increased from 0.28 +/- 0.05 to 0.42 +/- 0.03 U/ml (n = 6, p < 0.05). The mean increase in the GH peak was 3.2 micrograms/l (-3 to 10.6). It was negatively correlated with the degree of growth retardation at diagnosis (r = -0.74, p < 0.005). We conclude that the increase in the GH peak at puberty in patients with GH deficiency reflects the severity of GH deficiency and that a corrective factor of the cutoff number is necessary for the diagnosis of GH deficiency in puberty.

Adolescent↗
PubMed1992

Precocious puberty in girls: pituitary height as an index of hypothalamo-pituitary activation.

The pituitary heights in 47 girls having breast development before 8 yr were measured by magnetic resonance imaging and compared to the normal values for age and to clinical and laboratory data. They were classified into 3 groups: 1) premature thelarche (PT), isolated breast development with plasma estradiol less than 74 pmol/L (8 cases); 2) mild form of central precocious puberty (CPP1) with an LH/FSH peak ratio after the LH-releasing hormone test less than 1 (22 cases); 3) classical form of CPP (CPP2) with an LH/FSH peak ratio greater than 1 (17 cases). All girls with CPP had breast and pubic hair development before 8 yr, accelerated growth velocity, and no intracranial lesion. The mean ages at breast development [7.2 +/- 0.4 (SE), 6.5 +/- 0.4, and 7.2 +/- 0.3 yr] and the mean times between breast development and magnetic resonance imaging evaluation (0.8 +/- 0.1, 0.8 +/- 0.2, and 0.9 +/- 0.1 yr) were similar in the 3 groups. The mean pituitary heights were 4.9 +/- 0.2 in PT, 5.1 +/- 0.2 in CPP1, and 6.2 +/- 0.2 mm in CPP2. They were not significantly different in PT and CPP1 but were significantly greater in CPP2 than in PT (P < 0.001) or CPP1 (P < 0.001). Individual values of pituitary height were compared to those of age-matched girls: they were greater than or equal to mean +/- 2 SD in 8% of PT, 32% of CPP1, and 70% of CPP2. In the CPP group, the pituitary height was correlated with the LH/FSH peak ratio [correlation coefficient (r = 0.52, P < 0.01] and plasma estradiol (r = 0.60, P < 0.01). Four patients with high pituitary height despite LH/FSH peak ratios less than 1 had an increase of their breast development within 1 yr. We conclude that the pituitary height is normal for age in girls with premature thelarche or a mild form of CPP. Conversely, pituitary height is in the pubertal range in girls with the classical form of CPP. Its correlation with LH/FSH peak ratio suggests that pituitary height reflects changes in the degree of hypothalamo-pituitary activation and may provide an indication of its future development. It may therefore help in decisions on LH-releasing hormone analog therapy in certain cases.

Analysis of Variance↗
PubMed1991

Polygraphic sleep patterns and growth hormone secretion in children after cranial irradiation.

The effects of radiotherapy on subsequent growth hormone (GH) secretion and sleep organization was studied by simultaneous evaluation of spontaneous sleep-related GH secretion (SSRGHS), arginine-insulin tolerance test (AITT) and polygraphic sleep recording in a follow up of 19 children who underwent surgical removal of an intracranial tumour and cranial radiotherapy 1-7 years previously. Electrophysiological patterns of sleep phases, the amount and distribution of sleep stages were normal, suggesting that the procedure utilized should not entail modifications of SSRGHS per se. Long-term after radiotherapy SSRGHS and AITT GH responses were lower than those of the medium-term group. The lack of correlation between SSRGHS and AITT GH secretion suggests that SSRGHS and AITT measure different aspects of GH secretion. The highest value of GH plasma level (peak) corresponded to slow wave sleep, mainly during the first non-rapid eye movement-rapid eye movement (NREM-REM) cycle, in practically all the patients. Although the SSRGHS synchronization with SWS of the first NREM-REM cycle was preserved, no sleep measure was correlated with the SSRGHS. The usefulness of polygraphic monitoring of sleep patterns was confirmed.

Arginine↗
PubMed1991

Height of normal pituitary gland as a function of age evaluated by magnetic resonance imaging in children.

MR anatomy of hypothalamo-hypophyseal axis is well established. However data about pituitary gland height (PGH) in children are sparse. A retrospective study was therefore performed in 60 children (30 boys and 30 girls) aged from 8 days to 21 years. All these children had MR for various neurological diseases. Patients with hypothalamo-hypophyseal disease and intracranial hypertension were excluded. The PGH was measured on a strict midline sagittal T1 weighted scan 3 to 7 mm thick. A positive linear correlation was found in children aged from 1 year to puberty followed by a plateau. In the first year of life a negative linear correlation was found. A positive linear correlation was found between PGH and statural height as well.

Adolescent↗
PubMed1991

Dwarfism with gloomy face: a new syndrome with features of 3-M syndrome.

Nine children with primordial dwarfism are described and a new syndrome is delineated. The significant features of this syndrome include facial dysmorphism with gloomy face and very short stature, but no radiological abnormality or hormone deficiency. Mental development is normal. The mode of inheritance seems to be autosomal recessive because of consanguinity in three of the four sibships. Some overlap with the 3-M syndrome is discussed but the autonomy of the gloomy face syndrome seems to be real.

Child, Preschool↗
PubMed1991

Idiopathic central precocious puberty in girls as a model of the effect of plasma estradiol level on growth, skeletal maturation and plasma insulin-like growth factor I.

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Development↗
PubMed1991

Human plasma growth hormone (GH)-binding proteins are regulated by GH and testosterone.

Possible regulation of GH-binding proteins (GH-BPs) in human plasma was examined. Eight children with isolated GH deficiency had a very low level of plasma GH-binding activity (10.2 +/- 1.1% of radioactivity). Under GH treatment the hormone binding to the high affinity BP (peak II-BP) increased in every patient to reach the mean value of 18.5 +/- 1.4%. In one patient, Scatchard plot analysis indicated that this increase was related to a higher binding capacity without any significant change in the binding affinity. A positive correlation existed between the GH-binding activity and insulin-like growth factor-I plasma levels. In nine boys with pubertal delay, the GH-specific binding to peak II-BP was normal (30.6 +/- 3.7% of radioactivity); it decreased significantly after testosterone treatment. In four boys with precocious puberty, the specific GH binding to peak II-BP was low (16.6 +/- 1.1%). It increased significantly to 21.6 +/- 1.1% of radioactivity after treatment with a LHRH analog. A negative correlation existed between plasma testosterone levels and GH binding to peak II-BP in boys presenting pubertal delay or precocious puberty. The high affinity GH-BP is regulated, and among the factors that play a role in this regulation, GH and testosterone have opposite effects.

Adolescent↗
PubMed1991

Regulation of the growth hormone binding proteins in human plasma.

The plasma high affinity growth hormone binding protein corresponds to the extracellular binding domain of the liver membrane receptor. A distinct higher molecular weight protein, which binds GH with low affinity and high capacity, is present in the human plasma. In man, the biosynthesis and the exact functions of the GH binding proteins have to be clarified. The GH binding proteins are differently regulated; they are under a multihormonal control. The high affinity binding protein is low in neonates, increases after the first year of life, and reaches its highest value in young adult, without sex differences. GH is able to induce the high affinity binding protein, whereas sex steroids can decrease it. States of GH resistance, such as chronic renal failure, and certain idiopathic short statures, are associated with low levels of GH binding protein; in Laron-type dwarfism a defect of the GH receptor gene probably results in the absence of plasma GH binding activity. Recent findings on the regulation of the GH binding protein in man support a parallel regulation of liver membrane GH receptors and plasma binding protein.

Aging↗