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Biomedical subjects

M B Ranke

Publications and source records attributed to M B Ranke.

226 records · Page 13Linked to original sources

Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes.

Suspensions of rat hepatocytes isolated enzymatically by the method of Berry and Friend were used to study the binding of 125I-labeled human (hGH) and bovine (bGH) growth hormones and ovine prolactin (oPRL). Displacement of these labeled hormones by their unlabeled analogues was analyzed by means of Scatchard plots and affinity constants (K) and the number of binding sites per cell (q) were calculated. Specificity of binding was studied using hGH, bGH oPRL and rat growth hormone (rGH) and rat prolactin (rPRL). Rat hepatocytes contained two types of binding sites which bound hGH. The first, somatogenic, was specific for the growth-promoting hormones bGH and rGH. The second, lactogenic, was specific for lactogenic hormones, oPRL and rPRL. Human GH, which has both lactogenic and growth-promoting properties in rodents, bound to both sites. The somatogenic binding sites were present in both males and females, and the number of sites was similar in females and in males and was not affected by hypophysectomy. The lactogenic binding sites were present only in females, and the number of lactogenic and somatogenic sites was similar (40,000/cell). The affinity of hGH for the lactogenic binding sites was less than for the somatogenic (0.37 X 10(9) vs. 1 X 10(9)M-1). The lactogenic binding sites were lost when female rats were hypophysectomized and could not be restored by estrogen treatment.

Animals↗

Formation of uniparental disomy 7 delineated from new cases and a UPD7 case after trisomy 7 rescue. Presentation of own results and review of the literature.

Maternal uniparental disomy for the entire chromosome 7 (matUPD7) has been reported several times in Silver-Russell syndrome (SRS) and growth-restricted patients. Here we present our results from the analysis of an abortion with confined placental mosaicism (CPM) for trisomy 7 which showed a maternal meiotic origin of the trisomy in the placenta and rescue to maternal UPD7 in foetal membrane. Furthermore, two newly detected SRS cases with maternal UPD7 revealed isodisomy and partial heterodisomy, respectively. Summarising these results with those published previously on the origin of UPD7, similar numbers of isodisomy (n=11) and cases with complete or partial heterodisomy (n=12) have been reported. In respect to the different formation mechanisms of UPD, complete isodisomy should be the result of a post-zygotic mitotic segregation error, whereas heterodisomic UPDs should be caused by trisomic rescue after meiotic non-disjunction events. In maternal UPD7, 50% of cases seem to be caused by post-zygotic mitotic segregation errors, which is similar to the situation in trisomy 7. This result corresponds to the situation in trisomy 8 but is in contrast to observations in the frequent aneuploidies. Thus, the different findings in these aberrations reflect the presence of multiple factors that act to ensure normal segregation, varying in importance for each chromosome.

Abnormalities, Multiple↗

Measuring IGF-I, IGFBP-2 and IGFBP-3 from dried blood spots on filter paper is not only practical but also reliable.

OBJECTIVE: The aim of this study is to adapt measurements of IGF-I, IGFBP-2 and IGFBP-3 to dried blood filter disk assays. METHODS: Measurements of the three analytes in serum samples and in the corresponding blood spotted onto filter paper were compared by applying standard radioimmunoassays. RESULTS: In paired experiments, the quantity of all antigens measured on dried filter spots showed an excellent correlation to that in serum (R>0.88) and in addition this correlation was independent of the whole blood hematocrit value. Recovery of IGF-I, IGFBP-2 and IGFBP-3 in experiments using recombinant standards mixed with whole blood was well correlated with the recovery of the plasma fraction on the filter paper. All of the blood spot assays showed a inter- and intra-assay variation of less than 10% and the blood spots were stable over a period of more than 5 months stored at -20 degrees C. CONCLUSIONS: Taken together, these data clearly demonstrate that such a filter paper assay is a reliable procedure to monitor changes of IGF-I, IGFBP-2 and IGFBP-3 content in blood. The obvious advantages of this methods concerning storage, handling and shipping of blood probes helps to solve the logistics of centralised measurements of these three analytes.

Adult↗

[Combined hypophyseal function test in children with homozygous beta-thalassemia].

Nowadays, endocrine problems like retarded sexual maturation and growth deficiency, lead to substantial suffering in patients with beta-thalassemia major. The aim of the present study is the differentiation between a possible insufficiency of the pituitary gland and dependent target organs, respectively. 12 patients (age 1.9-18.10 years) were examined by means of a combined pituitary function test. The corticotropic axis turned out to be normal as shown by a regular stimulation of cortisol in all patients tested. The thyrotropic function was unaffected in all children: elevated levels of TSH pointed to primary hypothyroidism. Pubertal values of LH and FSH were found in only 3 out of 7 patients at pubertal age. In 10 out of 12 children, stimulation led to a rise in STH levels above 10 ng/ml. On the whole, there was no evidence for pituitary insufficiency in beta-thalassemia major.

Adolescent↗

[Adrenocortical nodular hyperplasia as a cause of Cushing syndrome in the neonatal period].

The case report of a female child born preterm (30th wk of gestation) who developed symptoms of Cushing's syndrome beginning in the neonatal phase is presented. The disease was caused by a unilateral adreno-cortical nodular hyperplasia and was successfully treated by unilateral adrenalectomy. Preoperative treatment with ketoconazole and metyrapone proved to be effective. Symptoms of Cushing's disease including hypertrophic cardiomyopathy were completely reversible within one month after surgery.

Adrenal Hyperplasia, Congenital↗

[Pubertas praecox in McCune-Albright syndrome--case report and review of the literature].

A patient is presented with the syndrome of polyostatic fibrous dysplasia and precocious puberty (PP). The endocrinopathy in McCune-Albright-syndrome (MAS) has formerly been ascribed to a central (hypothalamic) origin. In this patient the PP was caused by a luteinized follicular cyst, suggesting autonomous hyperfunction of this gland. High serum estradiol levels returned to normal after cystectomie. The review of the literature suggests the peripheral origin of PP to be more frequent in younger age groups (under 6 years). It appears possible that peripheral hypersecretion of sexual steroids may cause a rise of gonadotropins secondarily followed by true PP in older children provided such longstanding hypersecretion leads to a generalized maturation of the body including skeletal maturation. Treatment in pseudoprecocious puberty seems to be not effective with LH-RH-analogues. Cyproteroneacetate alone or in combination with a LH-RH analogue gave the impression of being more successful. Cystectomy can lead to a cure but a recurrence of ovarian cysts is possible. A combination of surgical and drug therapy may be beneficial under these circumstances. Until now there is no sufficient treatment for polyostotic fibrous dysplasia.

Child, Preschool↗

Growth hormone treatment in dilated cardiomyopathy.

Treatment with human recombinant growth hormone (GH) has yielded conflicting results in patients with congestive heart failure. We analyzed the baseline somatotrophic axis in 50 patients with dilated cardiomyopathy. Then, a double-blind, randomized, placebo-controlled study of GH was performed. We randomly allocated these patients to treatment with subcutaneous GH (2 IU daily) or placebo for a minimum of 12 weeks. The primary end-points were the effect on left ventricular (LV) mass and systolic wall stress. The secondary endpoint was LV ejection fraction. Severity of heart failure as determined by cardiac index, LV end-diastolic diameter, and plasma noradrenaline concentrations correlated markedly with baseline serum insulin-like growth factor-1 (IGF-1) levels. Patients in the GH group had an increase in LV mass compared with the placebo group (p = 0.0001). There was no significant difference in LV systolic wall stress, mean blood pressure, or systemic vascular resistance between the two groups. New York Heart Association (NYHA) functional classification and distance in 6-minute walk test remained unchanged. The change in IGF-1 concentrations between GH and placebo group was notably related (p = 0.0001) to the change in LV mass (p = 0.0001). The GH-induced increase of IGF-1 predicted the changes of ejection fraction (p < 0.05). A marked increase of ejection fraction of 7% was observed in patients whose IGF-1 increased by more than the median increase, in comparison to the patients with an increase below the median (p = 0.03). Serum levels of IGF-1 reflecting GH secretion are diminished in relation to severity of heart failure in patients with dilated cardiomyopathy. GH-induced increases of IGF-1 of more than 80 pg/mL caused notable improvement of ejection fraction. There is a marked increase in LV mass in patients with dilated cardiomyopathy given GH. Changes in LV mass are related to changes in serum IGF-1 concentrations.

Biomarkers↗