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M B Ranke

Publications and source records attributed to M B Ranke.

At least 19 recordsLinked to original sources
PubMed1992

Increased insulin-like growth factor-II tissue concentrations during compensatory kidney growth in infantile rats.

Insulin-like growth factor (IGF)-I and IGF-II serum and kidney tissue concentrations were measured in compensatory kidney growth in infantile and adult rats. We hypothesized that the known switch from IGF-II in fetal life to IGF-I in adult life may be responsible for the different modes of compensatory kidney growth, which are mainly characterized by hyperplasia in infantile rats and hypertrophy in adult rats. While IGF-I serum concentrations increased with age in infantile rats, kidney tissue concentrations of IGF-I showed a similar increase in both age groups after uninephrectomy. In adult rats, serum and kidney tissue concentrations of IGF-II were unchanged by uninephrectomy. In infantile rats, however, a significant increase in both serum and kidney concentrations of IGF-II was observed with a maximum at day 5 after uninephrectomy. To investigate if compensatory kidney growth is dependent on hyperperfusion of the remnant kidney, the left renal artery was clipped in infantile rats. The clipped kidney showed growth retardation despite normal kidney tissue concentrations of IGF-I and IGF-II. The contralateral kidney was enlarged and IGF-II kidney concentrations were elevated. However, animals with one clipped kidney and nephrectomy of the contralateral kidney showed compensatory kidney growth of the clipped kidney combined with increased IGF-II kidney tissue concentrations. We conclude that IGF-II mainly promotes compensatory kidney growth in infantile rats by hyperplasia. Hyperperfusion of the remnant kidney seems to be unnecessary for initiation of compensatory kidney growth.

Aging↗
PubMed1992

IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF-I.

OBJECTIVE: The aim of the study was to investigate the serum levels of IGFBP-3, the major IGF-I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF-I treatment. DESIGN AND PATIENTS: Eight Laron type dwarfism patients (four children and four adults) were treated for 7 days by one daily s.c. injection of biosynthetic IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood was sampled in the fasting state before and 1 and 7 days after the last injection. RESULTS: It was found that IGF-I administration significantly reduced plasma hGH levels with recovery after one week of no treatment. Serum IGFBP-3 was abnormally low (0.70 +/- 0.37 mg/l) and decreased significantly further during IGF-I treatment (to 0.48 +/- 0.28 mg/l) (P less than 0.065). CONCLUSIONS: The finding that serum IGFBP-3 is low in Laron type dwarfism, a disease due to molecular defects in the GH receptor, is compatible with the hypothesis that this IGF binding protein is GH-dependent. On the other hand the decrease during IGF-I administration and concomitant suppression of GH secretion may denote either that GH activity is not completely blocked in this syndrome or that there are additional mechanisms regulating IGFBP-3 synthesis.

Adolescent↗
PubMed1991

Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) were studied in children with end-stage renal failure (ESRF, n = 31) and chronic renal failure (n = 11) with residual glomerular filtration. Somatomedin bioactivity in patient sera was found to be decreased while IGF-I and IGF-II levels by radio-immunoassay (RIA) were normal. In contrast, IGFBP-1 and IGFBP-3 levels (measured by RIA) were markedly increased in uraemia. Excess IGFBP was shown to be able to bind IGF by determination of the free IGF binding capacity. Using high-performance liquid chromatography a shift of the IGFBP-3 profile to low molecular weight components could be demonstrated in ESRF. Affinity cross-linking experiments showed that these low molecular weight IGFBP-3 immunoreactive forms are biologically active. In normal urine only IGFBP-3 forms smaller than 60 kDa were detected with a major peak at 12-20 kDa. Removal of excessive IGFBP from patient sera by affinity chromatography on an IGF-II Sepharose column resulted in a significant increase in somatomedin bioactivity. Model calculations on the interaction of IGF and IGFBP using empirical data suggested a reduction of IGF secretion in uraemia by an order of magnitude. It is concluded: (1) that renal failure causes an accumulation of low molecular weight IGFBP, (2) that the resulting excess of IGFBP acts as a somatomedin inhibitor, and (3) that in uraemia there is a relative growth hormone resistance with respect to IGF production.

Adolescent↗
PubMed1991

Insulin-like growth factors and their binding proteins in human follicular fluid.

Increasing evidence suggests that insulin-like growth factors I and II (IGF-I, IGF-II) have a regulatory role in animal granulosa cells. This study was undertaken to investigate the presence of IGF-I and IGF-II, as well as that of their binding proteins (BP), IGFBP-1 and IGFBP-3 in human serum and follicular fluid (FF). Preovulatory FF was obtained from 51 patients undergoing in-vitro fertilization. The IGFBP-1 level was found to be significantly higher (P less than 0.01) in FF than in serum, whereas IGF-I and IGFBP-3 values remained markedly lower (P less than 0.01) in FF. Serum IGF-II levels were slightly but not significantly elevated compared to values obtained in the FF of patients. A positive correlation (P less than 0.001) between individual serum and FF levels was observed only for IGF-I. When a group of poor responders was compared to patients with normal stimulation characteristics, no significant difference was found in either IGF or IGFBP levels in the FF. It is concluded that IGFBP-1 is produced locally, whereas the serum may possibly be the major source of IGF-I. No clear conclusions can be drawn regarding the source of FF IGF-II and IGFBP-3. Neither the absolute level nor the relationship of IGFs to their transport proteins could explain the poor response to ovarian stimulation.

Body Fluids↗
PubMed1991

Clinical spectrum of the syndrome of growth hormone insensitivity. Advisory Committee on Growth Hormone Insensitivity.

A survey of 46 patients with suspected growth hormone (GH) insensitivity is presented. Clinical details and plasma samples from these patients were analysed centrally. A diagnostic score based on basal levels of GH and insulin-like growth factor I (IGF-I), IGF-I response to GH (0.1 U/kg daily for 4 days) and height SDS was determined for all patients to identify those with GH insensitivity. A total of 29 such patients was identified (14 males and 15 females; age range, 3.2-22.6 years). Their mean height SDS was -6.0 (range, -8.9 to -2.6), mean weight SDS was -2.9 (range, -5.2 to 1.2). Pubertal development was delayed in three out of three boys and two out of six girls of pubertal age. Their basal GH level was 32.4 mU/l (range, 0.8-158.2 mU/l) and mean basal IGF-I level was 33.6 ng/ml (range, 20-97 ng/ml). None of the 29 patients showed a significant serum IGF-I response to injections of GH.

Adolescent↗
PubMed1991

Left middle finger metacarpophalangeal growth in Turner syndrome. Normal values and changes after growth hormone treatment.

Tubular bone length of the left middle finger was determined by analysis of 259 hand radiographs of 118 patients with Turner syndrome (TS). Specific standards for TS children were developed and compared with those of normal children. The results show that in TS the growth pattern of the tubular bones of the left middle finger parallels statural growth and is not disproportional to height. In 14 patients with TS the length of the tubular finger bones was determined before and after a 1-year treatment with recombinant human growth hormone (rhGH) (mean dose 2.8 IU/m2 BSA/day). No disproportionate increment in the length of these bones compared to the respective height change was observed. The data suggest that over a short period of time the relatively high doses of growth hormone given in TS are unlikely to induce acromegaloid hand growth. The derived standards may serve to monitor hand growth in relation to height in TS during treatment in long-term trials with rhGH.

Adolescent↗
PubMed1991

Short-term changes in serum insulin-like growth factors (IGF) and IGF binding protein 3 after different modes of intravenous growth hormone (GH) exposure in GH-deficient patients.

Virtually all circulating insulin-like growth factors I and II (IGF-I and IGF-II) are bound to specific binding proteins (IGFBP), of which IGFBP-3 is the quantitatively most important. The mechanisms regulating the close coordination between serum levels of IGFs and IGFBP-3 is poorly understood. We therefore evaluated the temporal association of serum IGF-I, IGF-II, and IGFBP-3 measured by RIAs after well defined short-term GH exposure in GH-deficient patients. Six patients (mean +/- SE age: 20.5 +/- 1.1 yr) each underwent three GH study protocols in random order. Each study was preceded by 4 weeks without GH therapy. Two units of GH were administered iv as either: 1) two boluses, 2) eight boluses, or 3) a constant infusion. The duration of each study was 44 h including at least 16 h after termination of GH administration. Increments in serum IGF-I occurred 4-6 h after initiated GH exposure in all studies. In the two-bolus study the IGF-I increase was modest with mean +/- SE peak values of 12.4 +/- 2.1 nmol x L-1 after GH administration. In the eight bolus and constant infusion studies significantly higher IGF-I levels were generated: 17.0 +/- 2.2 nmol x L-1 (8 bolus) and 18.8 +/- 1.1 h nmol x L-1 (infusion). In contrast the time course change in serum IGF-II did not differ in the three studies, and it was characterised by a sluggish increase of approximately 30% evidenced after 16-20 h. The changes in IGFBP-3 were almost identical in the three studies. After a lag phase of approximately 18-20 h a gradual increase of approximately 40%, which had not ceased at the end of the study period, was observed. The molar ratio of serum IGF-I plus IGF-II:serum IGFBP-3 remained constant with values between 0.8-0.9 except in the constant infusion experiment, in which the ratio increased significantly with time reaching a mean peak value, which exceeded 1.0, after 24 h. Our data suggest that a pulsatile GH pattern is not superior to constant GH levels as regards generation of IGFs and IGFBP. The earlier increase in serum IGF-I compared to IGF-II and IGFBP-3 suggests that IGF-I may be the main regulator of IGFBP-3 production. Accordingly, the slow increase in serum IGF-II, which paralleled that of IGFBP-3, could indicate that serum IGF-II levels mainly depend on the concentration or binding site availability of IGFBP-3.

Adult↗
PubMed1991

Immunoreactive insulin-like growth factor binding protein-3 in the culture of human luteinized granulosa cells.

Granulosa cells from human preovulatory follicles were cultured under serum-free conditions to investigate the presence of immunoreactive insulin-like growth factor binding protein-3 (IGFBP-3). IGFBP-3 levels were measured by a radioimmunoassay developed against the acid-stable subunit of the protein. The antiserum had no cross-reactivity to the low molecular weight GH-independent IGFBP-1. Granulosa luteal cells exhibited a continuous release of IGFBP-3 into the culture medium during the whole time (6 days) of the incubation. A dose-dependent increase in IGFBP-3 was observed when the cells were treated by dibutyryl cAMP. Cycloheximide suppressed almost completely both the basal and the stimulated production of IGFBP-3. The smallest effective dose of dibutyryl cAMP enhancing the progesterone release was lower than that for IGFBP-3. The different time course of IGFBP-3 and progesterone secretion to dibutyryl cAMP treatment, as well as the failure of progesterone to elicit IGFBP-3 increase alone, do not support the participation of progesterone in the IGFBP-3 production of granulosa cells. It is concluded that 1. immunoreactive IGFBP-3 is produced by cultured granulosa luteal cells; 2. its synthesis is regulated by physiological intracellular mechanisms.

Bucladesine↗
PubMed1991

Approaches to the evaluation of growth and growth disorders in children after bone marrow transplantation (BMT).

Since impaired growth may occur as a long--term consequence in children treated with BMT this aspect of development needs particular attention for various reasons. Primarily, in each affected child parameters relevant for the evaluation of growth need to be documented regularly from the beginning in a prospective mode. In addition, treatment protocols should contain elements of a standardized follow-up for the documentation and evaluation of the endocrine, the nutritional and the emotional situation of the patient. This will eventually allow us to define--and hopefully avoid--adverse elements within complex treatment modalities--including BMT--for various malignant diseases. Thus it will be possible to develop a rational approach for the therapy of persistent adverse events following attempts of treatment primarily directed to ensure survival.

Bone Marrow Transplantation↗
PubMed1991

Growth response in prepubertal children with idiopathic growth hormone deficiency during the first two years of treatment with human growth hormone. Analysis of the Kabi Pharmacia International Growth Study.

From the large database of patients enrolled in the Kabi Pharmacia International Growth Study (KIGS), 289 prepubertal patients with idiopathic growth hormone deficiency (GHD), treated for 2 years with growth hormone (GH) substitution therapy, were selected. A multiple regression analysis was performed to determine both the auxological factors characterizing the patients at the beginning of the first and second years on GH therapy and the respective treatment modalities relevant to the magnitude of the growth response. It was observed that during the first year on GH therapy the magnitude of the growth response was negatively correlated with chronological age and height SDS, and positively correlated with target height SDS, GH dose (IU/kg/week) and frequency of GH injections. During the second year the growth response was negatively correlated with chronological age and the first-year GH dose (IU/kg/week), and positively correlated with height velocity during the first year, GH dose (second year), and injection frequency (second year). The data suggest that the forces of 'catch-up'--auxologically entrenched within the distance between target height SDS and height SDS--no longer prevail during the second year of GH therapy. The inverse influence of the first-year GH dose in the two yearly phases of growth suggests that optimizing GH treatment must be attempted by analysing growth in response to GH over longer periods of time and considering that the growth process is influenced by interactive factors.

Age Factors↗
PubMed1990

The Marfan syndrome--analysis of growth and cardiovascular manifestation.

Forty-eight children and adolescents (mean age 10.5 years, range 1.25-18 years) with clinical evidence of Marfan syndrome were studied. Height and weight percentiles were established. Cardiac dimensions and morphology were studied by M-mode and 2D-echocardiography. At diagnosis left atrial and left ventricular end-diastolic diameter and left ventricular posterior wall thickness were within normal limits except in a few adolescent patients. Interventricular septum was thickened in about 20% and aortic diameter increased in 56% of the patients. An additional 13% of patients developed aortic dilation during the study period. At diagnosis regression analysis revealed a significant (P less than 0.05) correlation of the aortic diameter, septal thickness and the posterior left ventricular wall thickness and body surface area. Follow up studies of 19 patients allowed documentation of the development of aortic root dilation.

Adolescent↗
PubMed1990

Growth-stimulating effects of recombinant human growth hormone in children with end-stage renal disease.

Because patients with uremia have evidence for growth hormone resistance, we investigated whether this resistance can be overcome by administration of recombinant human growth hormone in supraphysiologic doses in children with severe uremia. Nine stunted children with end-stage renal disease (median age 5.8 years, median bone age 2.7 years) were treated with recombinant human growth hormone, 4 IU/m2/day subcutaneously, for a period of 1 year. Median height velocity was increased from 4.4 cm/yr before therapy to 8.0 cm/yr during treatment. Negative values for height velocity standard deviation scores for chronologic age were improved from a median of -2.6 to +1.5 without advancing bone age more than chronologic age. The growth hormone-insulin-like growth factor I resistance may be explained in part by the increased serum concentration of the high molecular weight insulin-like growth factor binding protein despite normal insulin-like growth factor I serum concentration. Treatment with recombinant human growth hormone improved the ratio between the serum concentrations of insulin-like growth factor I and its binding protein, and normalized the somatomedin bioactivity in the growth cartilage bioassay.

Age Determination by Skeleton↗