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A Silbergeld

Publications and source records attributed to A Silbergeld.

52 records · Page 3Linked to original sources
PubMed1989

Serum GH binding protein activities identifies the heterozygous carriers for Laron type dwarfism.

Measurement of GH-binding protein activity and IGF-I was carried out in the sera of 13 patients with Laron type dwarfism, a syndrome caused by a lack of GH receptors which leads to impairment of IGF-I generation, and those of 16 of their close relatives. GH binding protein activity was measured by incubating 125I-hGH with 100 microliters serum in the presence and in the absence of excess unlabelled hGH, followed by separation of specifically bound 125I-hGH binding protein complexes from free 125I-hGH by gel filtration. The results are expressed as percent specific binding relative to an adult reference serum. IGF-I was determined by RIA after acid extraction on octadecylsilane silica columns. All Laron type dwarfism patients had no, or only negligible GH binding protein activity, which supports the evidence that serum GH binding protein corresponds to the extracellular domain of the membranal GH receptor. Eight of the 16 relatives had serum GH binding protein activity more than 2 SD below the mean for age, a finding considered to denote heterozygocity for their molecular defect disease. The significant correlation (p less than 0.001) between serum GH binding protein activity and IGF-I levels supports this conclusion. The ability to define heterozygotes of Laron type dwarfism will be helpful in genetic counselling.

Adolescent↗
PubMed1989

Growth hormone increases plasma levels of insulin-like growth factor (IGF-I) in a teleost, the gilthead seabream (sparus aurata).

A heterologous radioimmunoassay (RIA) was applied for the determination of immunoreactive (IR)--insulin-like growth factor (IGF-I) in a teleost, the gilthead seabream (Sparus aurata). Serial dilutions of the fish plasma gave a linear curve when added to constant amounts of 125I-labelled human IGF-I(53-70) and antiserum prepared against this fragment. The RIA was used to study the effect of GH on plasma levels of IR-IGF-I in S. aurata. A single injection of human recombinant GH (1 micrograms/g) resulted in a significant increase in IR-IGF-I at 29, 48 and 72 h, when compared with saline-injected fish. This novel observation suggests that in fish, as in mammals, circulating IGF-I levels are modulated by GH.

Animals↗
PubMed1988

A comparison of IGF-I levels measured by two commercially available radioimmunoassays.

Insulin-like growth factor I levels were measured in a parallel fashion in 77 extracted sera using the INCSTAR RIA (radioimmunoassay) and in the EDTA plasma of the same subjects by the NICHOLS RIA. The subjects suffered from untreated hGH deficiency, short stature, delayed and precocious puberty and acromegaly. Significant differences (P less than 0.05) were found between the mean IGF-I levels of all groups using both RIA systems. However, using the INCSTAR RIA, 85% of IGF-I values in untreated hGH deficiency were below normal, and a rise in IGF-I detected in the sera of all 5 patients who were treated with hGH. Using NICHOLS RIA, 55% of basal IGF-I values were below normal and a hGH-stimulated rise in IGF-I was found in only two of the treated patients. The INCSTAR RIA seems more precise and reproducible than the NICHOLS RIA and enables better discrimination of hGH-deficient patients from age-matched controls.

Acromegaly↗
PubMed1986

Insulin-like growth factor I (IGF-I) in healthy children, adolescents and adults as determined by a radioimmunoassay specific for the synthetic 53-70 peptide region.

A radioimmunoassay (RIA) specific for the synthetic 53-70 peptide region of human insulin-like growth factor I (IGF-I) was used to determine IGF-I in the serum of 191 healthy newborns, children and adolescents and in 26 adults. The results compare favourably with reported values obtained using RIA systems for the native IGF-I molecule. Intra- and inter-assay CV were 3.3 and 7.2% respectively. In childhood, mean +/- SD IGF-I levels rise from 6.0 +/- 3.5 nmol/l in newborns to 16.5 +/- 4.0 nmol/l at 8-11 years in both sexes. At the onset of puberty, IGF-I levels in females (24.9 +/- 6.6 nmol/l) are significantly (P greater than 0.005) higher than in males (17.2 +/- 4.2 nmol/l). With further pubertal development IGF-I levels continue to rise, reaching peak values at pubertal stage P4 (40.6 +/- 4.5 nmol/l in males, 42.8 +/- 5.1 nmol/l in females) and decline thereafter to lower values during adulthood: 16.5 +/- 5.8 nmol/l (males) and 24.2 +/- 7.0 nmol/l (females) (P greater than 0.001). In pubertal males, IGF-I correlates significantly with height (r = 0.66, P less than 0.001), bone age (r = 0.69, P less than 0.001) and growth velocity (r = 0.64, P = 0.025) as well as with testosterone levels (r = 0.69, P less than 0.001). In pubertal females a significant correlation is found between IGF-I and height (r = 0.55, P less than 0.020). The ready availability of a simple, precise and reproducible IGF-I RIA, should contribute much to evaluating the importance of IGF-I measurements in normal growth and in the diagnosis and therapy of various growth disorders.

Adolescent↗
PubMed1985

[Nanism with high values of GH and no generation of somatomedin after hGH (Laron's syndrome). Clinico-biochemical study of 8 cases].

Eight familial cases with Laron type dwarfism (LTD) are presented. An autosomic recessive transmission seems to be possible with clear predominance in females (6/2). This syndrome first described in Jewish people is probably frequent in our country, with clear historic Jewish antecedents in some of our cases. Some features like prenatal growth deficiency, disproportion between face and calvarium and high levels of inmunoreactive GH distinguish clearly LTD from isolated GH-deficiency. The incapability of hGH to increase low somatomedin activity confirms diagnosis. Moreover low or null nitrogen retention after hGH excludes an inactive GH as a cause of dwarfism.

Adult↗
PubMed1984

The effect of serum growth factors and xyloside on molecular aging of proteoglycan in embryonal chick cartilage.

The effects of normal human serum, insulin-like growth factor and beta-D-xyloside on the synthesis of proteoglycan, as well as their differential effect on the synthesis of chondroitin sulfate and keratan sulfate side-chains, were studied in chick embryonal cartilage. The glycosaminoglycans found in the incubation medium were mainly intact carbohydrate moieties of partially degraded proteoglycan molecules, whereas the tissue-bound glycosaminoglycans were of intact proteoglycan molecules. In incubations with normal human serum, the synthesis of the chondroitin sulfate side-chains of the tissue-bound glycosaminoglycans was preferentially stimulated, while the percentage of medium glycosaminoglycan (out of the total glycosaminoglycan in tissue and medium) was reduced, compared to control incubations. In incubations with insulin-like growth factor, the synthesis of the keratan sulfate side-chains of the tissue-bound glycosaminoglycan was preferentially stimulated, whereas the percentage of the medium glycosaminoglycan resembled that of control incubations. In incubations with xyloside, a marked reduction of tissue-bound glycosaminoglycan was noticed, mainly of chondroitin sulfate chains, and only a slight decrease in keratan sulfate chains. Human serum of various age groups stimulated proteoglycan synthesis in embryonal chick cartilage to almost the same extent. However, sera from babies and adults were found to stimulate chondroitin sulfate chains preferentially, whereas serum of aged subjects preferentially enhanced the synthesis of keratan sulfate chains. These findings suggest that the synthesis and/or degradation of the various types of glycosaminoglycan chains (chondroitin sulfate and keratan sulfate) of cartilage proteoglycan can be regulated differentially by serum growth factors. Secondly, the growth hormone-mediated serum factor (insulin-like growth factor) seems to play a role in molecular aging of proteoglycans.

Adolescent↗
PubMed1981

The effect of insulin-like growth factor (IGF) and of human serum on steps in proteoglycan synthesis.

Embryonic chick pelvic cartilages were incubated in the presence of insulin like growth factor (IGF) (1 - 100 microunits/ml), as well as normal human serum (5%), with radiolabelled precursors of proteoglycan (PG) synthesis: L-[3-3H]serine, D-[6-3H]glucosamine and [35S]Na2SO4. IGF alone (1 - 15 microunits/ml), stimulated in a dose-dependent manner D-[6-3H]glucosamine incorporation into tissue-bound and soluble isolated glycosaminoglycan (GAG) chains. L-[3-3H]serine incorporation into PG molecules was not stimulated by IGF (1 - 100 microunits/ml), despite the increase in the uptake of this precursor into intact cartilage. [35S]Na2SO4 incorporation was unaffected by IGF. Serum promoted the uptake of all three precursors into tissue-bound glycosaminoglycans. It was postulated that IGF could stimulate proteoglycan synthesis not only by elongating existing chondroitin sulphate chains but also by increased synthesis of other sugar chains e.g. keratan sulphate and oligosaccharides.

Animals↗
PubMedDate not supplied

Decreased insulin-like growth factor-I receptor sites on circulating mononuclear cells from children with acute leukemia.

Insulin-like growth factor-I (IGF-I) is a known mitogen for various cell types, including those of the hematopoietic cell system. To study the role of IGF-I in the neoplastic process of leukemia in children, the authors have determined the number of IGF-I binding sites on circulating mononuclear cells of children with acute leukemia as compared to normal children, using binding assays. The IGF-I binding sites per cell on peripheral mononuclear cells of children with leukemia decreased compared to those of the control group (411 +/- 73 and 1334 +/- 227, respectively, p < .001), while their affinity increased (Kd = 0.14 +/- 0.04 and 0.43 +/- 0.16, respectively, p = .05). Furthermore, in the patients, the number of the IGF-I binding sites was significantly lower in the subgroup of the peripheral mononuclear cells, which included lymphocytes and monocytes, as compared to their number in the peripheral blast cells (254 +/- 43.6 and 536 +/- 98.6, respectively, p = .02). A significant reduction was found in serum GHBP levels in the patients as compared to the controls (28.21 +/- 1.93 and 35.83 +/- 2.90, respectively, p = .02), while serum IGF-I and growth hormone levels were similar in patient and control groups. These results suggest a possible involvement of IGF-I in childhood acute leukemia, but further studies are needed to establish whether IGF-I plays a role in this disease.

Adolescent↗
PubMedDate not supplied

A case of Laron syndrome diagnosed in Slovenia.

We report the first case of Laron syndrome (LS) diagnosed in Slovenia. The boy, a product of non-consanguineous Slovenian parents of normal height, presented with slow growth and motor development since birth. At age 4 and 6 years, he had all the characteristic signs of LS, identical to those in growth hormone deficiency (GHD). Laboratory tests showed hypoglycemia, markedly elevated plasma hGH, low serum insulin-like growth factor-1 (IGF-1) with no rise after exogenous hGH, and low serum growth hormone binding protein (GHBP). A sister of the maternal grandfather is short (145 cm) and was found to have below normal serum GHBP, findings compatible with heterozygocity for this disorder.

Child↗
PubMedDate not supplied

Short term effect of intranasal administration of hexarelin--a synthetic growth hormone-releasing peptide. Preliminary communication.

Twice or three times daily intranasal administration of the hexapeptide hexarelin for 7 days to children with short stature and normal growth hormone (GH) secretion evoked a significant rise in serum levels of insulin-like growth factor-1 (IGF-1) and alkaline phosphatase. There was also a significant, within normal limits, rise of thyroid stimulating hormone (TSH) without evidence of thyroxine suppression.

Administration, Intranasal↗
PubMedDate not supplied

Growth hormone treatment increases circulating lipoprotein(a) in children with chronic renal failure.

Cardiovascular disease is the major cause of death in chronic renal failure (CRF) patients managed by dialysis or kidney transplantation. Whilst the use of human growth hormone (hGH) is of established benefit in CRF children particularly in those with short stature, in the present study we assessed in CRF children the effect of hGH treatment on circulating lipoprotein(a) [Lp(a)], a genetically determined cardiovascular risk factor. We studied 15 CRF children treated by dialysis or conventional therapy and after kidney transplantation. Overnight fasting blood samples were collected immediately before and after 6 months hGH treatment. In all but one of the children there was a significant increase in serum Lp(a) over the 6 month treatment period -(+)66.7% over the basal levels (range 14 to 180%). After the hGH treatment, in six children Lp(a) levels were elevated to above 300 mg/l, the cut-off level for increased coronary artery disease (CAD) risk. Concomitantly/children also had an increase in serum levels of IGF-I (+96.4%) and insulin (+85.8%). All children had an accelerated growth velocity during the treatment; there was no effect on serum creatinine. Our study shows that hGH treatment in CRF children, though beneficial in its growth promoting effects, increases the already characteristically high levels of serum Lp(a), a risk factor for CAD, and that serum Lp(a) monitoring during treatment with hGH may be useful in evaluating future cardiovascular risk.

Adolescent↗
PubMedDate not supplied

Intronic mutation in the growth hormone (GH) receptor gene from a girl with Laron syndrome and extremely high serum GH binding protein: extended phenotypic study in a very large pedigree.

Laron syndrome (LS) is a hereditary form of GH resistance due to molecular defects in the GH receptor (GHR). Most of the identified mutations are located in the extracellular domain of the receptor, resulting in a lack of serum GHBP in the majority of LS patients. We present an LS patient with supranormal levels of serum GHBP, in addition to 35 of her relatives. The proband is a 3.5 year-old Druse girl with severe short stature (height SDS -5.1), high GH (250 micrograms/l), low IGF-I (2.7 nmol/l) and IGFBP-3 (410 micrograms/l), both unresponsive to exogenous GH. The binding capacity of the serum GHBP was 22 nM (adult reference serum, 0.7 nM), with an affinity constant Ka = 1.9 x 10(9) M-1 comparable to that of normal sera (Ka = 1.7-2.1 x 10(9) M-1). The apparent MW of the GHBP was approximately 60-80 kDa, similar to that of control sera. In the proband's sister, parents, grandparents and uncles, extremely high GHBP values were observed (43.0 +/- 4.8 RSB, n = 10) compared with normal adults (0.81 +/- 0.06 RSB) (p << 0.001). The remaining subjects had normal or moderately elevated GHBP levels. Serum GH in adults with high GHBP was significantly elevated above control values (6.0 +/- 0.9 micrograms/l vs 0.76 +/- 0.13 microgram/l, p < 0.001). Serum IGF-I and IGFBP-3 levels were normal in all the subjects, with the exception of an aunt (IGF-I 3.9 nmol/l) and the proband's sister (IGFBP-3 460 micrograms/l). All the subjects' heights were within the normal range. Analysis of the GHR gene performed in the proband revealed an as yet undescribed homozygous intronic point mutation. It consists of a G-->T substitution at nucleotide 785-1 preceding exon 8, a sequence that encodes the transmembrane domain. This mutation, which destroys the invariant dinucleotide of the splice acceptor site, is expected to alter GHR mRNA splicing and to be responsible for skipping exon 8. The resulting truncated protein that retains GH binding activity is probably no longer anchored in the cell membrane, affecting signal transmission in the homozygous patient and causing high GHBP levels in the heterozygous relatives.

Adolescent↗
PubMedDate not supplied

Serum leptin in obese patients with Laron syndrome before and during IGF-I treatment.

Fifteen patients with primary GH resistance (Laron syndrome, LS) were studied before and during 6 months of daily replacement treatment with IGF-I. The main findings were that patients with LS and normal or high serum GH binding protein (GHBP) were less obese than those with a negative GHBP, and that serum leptin levels varied with body mass as in other types of obesity.

Adult↗
PubMedDate not supplied

Serum insulin-like growth factor-I (IGF-I) levels during long-term IGF-I treatment of children and adults with primary GH resistance (Laron syndrome).

Serum IGF-I levels were measured in 14 patients (9 children and 5 adults) with Laron syndrome (LS) during long-term treatment by IGF-I. Recombinant IGF-I (FK-780, Fujisawa Pharmaceutical Co. Ltd., Japan) was administered once daily subcutaneously before breakfast for 3-5 years to the children and for 9 months to the adults. The initial daily dose was 150 micrograms/kg for children and 120 micrograms/kg for adults. Before initiation of treatment the mean overnight fasting levels of serum IGF-I in the children was 3.2 +/- 0.8 nmol/l (mean +/- SEM), rising to 10 +/- 1.7 nmol/l during long-term treatment even on a dose of 120 micrograms/kg/day. The serum IGF-I levels 4 hours after injection rose from 31.2 +/- 3.5 to 48 +/- 2 nmol/l. In the adult patients, the initial basal IGF-I was 4.1 +/- 0.7 nmol/l, rising to 16.1 +/- 3.84 nmol/l after 8-9 months treatment. Serum IGF-I levels at 4 hours after injection rose in the adult patients from 24.1 +/- 5.8 up to 66.8 +/- 15.4 nmol/l. A progressively increasing half-life during long term exogenous administration of IGF-I to patients with Laron syndrome was demonstrated by following serum IGF-I dynamics after injection. Based on the fact that no antibodies to IGF-I were detected and on findings in previous studies, it is speculated that the increasing serum IGF-I levels during long-term IGF-I treatment are caused by an increase in serum IGFBP-3 induced by chronic IGF-I administration. It is concluded that treatment with IGF-I necessitates regular monitoring of serum IGF-I levels; in patients in whom the age adjusted maximal levels are exceeded, a reduction of the daily IGF-I dose is indicated to avoid undesirable effects.

Adolescent↗
PubMedDate not supplied

Discrimination between growth hormone (GH) deficiency of hypothalamic or pituitary origin: an aid in selecting patients for GH-releasing hormone (RH) prolonged therapy.

Eleven patients with GH deficiency (GHD) underwent i.v. GH-RH tests (1 mu/kg); 7 had idiopathic GH deficiency (IGHD) and 4 had multiple pituitary hormone deficiencies (MPHD)--diagnosed on the basis of the insulin hypoglycemia, clonidine and sleep tests. One test was done before and the other after five s.c. injections of 1 microgram/kg GH-RH given in the evening. There were three types of response: four patients in whom there was an increase of human GH (hGH) to twice the former level, from 11.6 +/- 4.9 to 22.8 +/- 7.3 ng/ml following priming (a partial hypothalamic lesion); five patients in whom there was no response to the pharmacological tests but the same rise of approximately 13 ng/ml in hGH in response in both acute GH-RH tests (partial pituitary lesion); and two patients with no response to the pharmacological and acute GH-RH tests (pituitary lesion). In all except one patient there was no change in the serum IGF-I values after 5 days priming with GH-RH. It is suggested that patients with a partial GHD due to a hypothalamic lesion might benefit from long-term therapy with GH-RH.

Adolescent↗