Biomedical subjects
Publications and source records attributed to R M Schimpff.
Experimental conditions for preparation of plasma and the interference of the heparin (liquemine) on the somatomedin bioassay were studied. Results showed the significant inhibitory effect of liquemine, increasing with the delay before centrifugation, on the interpretation of the results of the assay.
Explore the source record for details and available documents.
The effects of TRH and oral glucose loading on the release of GH were investigated in 10 children or adolescents with constitutional tall stature. Eight of these children had a family history of above average height. The mean (and SEM) baseline GH levels (3.12 +/- 2.0 ng/ml) were similar to those in control subjects. Somatomedin activity, measured by sulfate incorporation into chick embryo cartilage, was elevated. Oral glucose loading caused an early significant increase in plasma GH at 30 min in 2 of these subjects and a late rise at 180 min in 4 others. Intravenous injection of synthetic TRH (0.2 mg/m2) caused a marked increase in plasma GH (17 +/- 3.0 ng/ml) in 7 of the 10 patients; the peak of GH was observed within the first hour after the injection of TRH in 3 cases, while a later peak was observed in the second hour after injection in 4 others. Peak plasma PRL (47 +/- 3.8 ng/ml) and TSH (20 +/- 1.2 microU/ml) levels in response to TRH were normal. These results suggest a disorder of hypothalamo-pituitary regulation of GH secretion in certain children with apparently constitutional tall stature. Similar findings in a probably preacromegalic girl are reported.
These data describe the effects of purified preparations of several growth factors on thymidine incorporation into phyto-haemagglutinin-activated (PHA) human lymphocytes. The somatomedins selected for this study included human somatomedins A and C, insulin-like growth factors (IFG1 and IGF2) and multiplication stimulating activity (MSA). Assays were carried out with and without serum. Complementary assays were performed with a low-molecular serum ultrafiltrate added to somatomedin C and to MSA. We found that all the peptides tested, except MSA, stimulated thymidine incorporation into PHA-activated lymphocytes in a dose-dependent manner, even though different doses were required to obtain a response. The data reported point out the multiplicity and the interrelationships of the serum factors involved in the stimulation of human cells growth.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The age-related variations in the growth-promoting activity of human plasma have been studied from birth (cord blood) to adulthood using a bioassay which measures the incorporation of tritiated thymidine into lectin-activated human lymphocytes. Cord blood values were low (0.69 +/- 0.004 U/ml). A definite increase was found at 5 days of age, correlating with the level at birth. Higher levels were attained after 1 month of age, with a 2-fold increase during the first months of life. Lower values were found in children 1-10 yr old, and high levels were found during puberty. This pattern, different from those of sulfation activity and plasma somatomedins suggests that factors other than somatomedins may be involved in growth stimulation during the first year of life in humans.
Explore the source record for details and available documents.
Sulfation and thymidine activities were measured in 14 insulin-treated diabetic children aged 4 to 16 years. Mean plasma sulfation activity was 0.86 +/- SEM 0.09 U/ml, values being highly significantly negatively correlated with Hb A1c (r = 0.663, p less than 0.01) and with 24 hours glucosuria (r = 0.764, p less than 0.001). Mean plasma thymidine activity was 1.04 +/- SEM 0.09 U/ml) but not with the other parameters. No relationship was found between sulfation and thymidine activities and insulin concentrations in the same samples. Additionally mean plasma transferrin concentration was 2.732 +/- SEM 0.152 U/ml, not significantly different from normal values. These data demonstrate that, in diabetic children treated by insulin, sulfation factor level is closely correlated to the quality of the control of the metabolic disorder. In contrast, thymidine activity of plasma appears to be unaffected by the level of glycemic regulation.
Normal human explants from liver and from connective tissues (aponeurosis or skin) incubated in vitro released sulphation activity measurable in chick embryo cartilage. Addition of human Growth Hormone (hGH) at physiological levels (10 ng/ml) increased the sulphation activity after 6 hours incubation time. Higher doses failed to increase the sulphation activity produced by connective tissues and decreased the sulphation activity produced by the liver.
The in vitro stimulation of [3H]thymidine uptake into lectin-activated lymphocytes in the presence of various sera was studied. The mean precision of the assay is 5%, and the study of the confidence intervals shows variations from 4% to 12%. Compared to a normal reference serum (fixed as 1 U/ml), the serum thymidine uptake stimulating activity (mean +/- SEM) was 1.04 +/- 0.07 U/ml in normal adult males, 2.63 +/- 0.48 U/ml in acromegalic patients, 1.51 +/- 0.13 U/ml in constitutional dwarfism and 0.37 +/- 0.04 U/ml in untreated hypopituitary dwarfism with a significant difference between the groups (P less than 0.001). In patients with hypopituitarism a single im hGH dose (6 mg/m2 increased the thymidine uptake stimulating activity of serum within 24 to 48 h following injection. The effects of directly adding hGH, insulin and T3 to the assay, have been studied: pharmacological concentrations are required to produce only a slight effect. Physiological concentration of a purified preparation of somatomedin A stimulated thymidine uptake and its effect is increased in the presence of serum. These data demonstrate that [3H]thymidine uptake into lectin-activated lymphocytes is stimulated by a GH-dependent serum factor. The data suggest that this method should be proposed for an accurate and sensitive biological evaluation of serum thymidine uptake stimulating activity.
Serum somatomedin activity was measured in 43 sera from 22 children aged 5 to 15 years operated on for a craniopharyngioma. All had a complete growth hormone deficiency and none received growth hormone therapy. At the time of the study, hydrocortisone therapy was given 29 times and thyroid powder 33 times. In these conditions, a highly significant correlation was found (r = 0.652, p less than 0.001) between somatomedin activity and growth velocity during the past three months. A negative correlation was also found with serum cortisol in patients who did not receive hydrocortisone (r = 0.654, P less than 0,05) and a positive correlation with serum concentrations of T4 (r = 0.640, p less than 0.05) and %3 (r = 0.956, p less than 0.001) in patients who did not receive thyroid powder. In contrast, no correlation was found with serum prolactin and insulin concentrations. These data establish than in children operated for craniopharyngioma, growth is related to a generation of somatomedin independent of growth hormone secretion, and closely controlled by endogenous secretions of cortisol and thyroid hormones.
The authors describe a new technique of biological quantitative determination of the somatomedin activity in human plasma by incorporation of tritiated thymidine into human lymphocytes treated by specific activator. This method is more simple, faster, and more sensitive than the biological assays described so far.
Serum somatomedin (SM) activity measured as sulphation factor on chick embryo cartilage was determined in peripheral (PV), hepatic (HV) and renal (RV) veins or 36 mongrel dogs. Mean SM activity +/- SEM was 0.53 +/- 0.03 U/ml in peripheral and hepatic veins, and 0.61 +/- 0.04 U/ml in renal vein (P less than 0.005). When the gradient of SM activity in hepatic or renal vein to that in peripheral vein, [HV]-[PV] or [HV]-[PV], was plotted versus SM activity in peripheral blood [PV], a negative correlation was found in the case of hepatic but not of renal blood. These data indicate that the kidney may be a production site of SM activity, whereas the liver is differently implicated in the overall regulation of SM activity.
Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = -0.711, P less than 0.001) and was preceded by a fall of Tf (r = -0.610, P less than 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginine-induced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = -0.608, P less than 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P less than 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.
The aim of this work was to study the early effects of an intravenous growth hormone (GH) injection on serum somatomedin (SM) activity in samples from peripheral (PV), hepatic (HV) and renal (RV) veins in dogs: 5 dogs were given one bovine growth hormone (bGH) injection, 1 dog was given 5 different doses of human growth hormone (hGH) and 6 control dogs were given saline. In bGH-treated dogs, a significant increase of SM activity occurred in the three vessels without difference between vessels. An early paradoxical decrease of serum somatomedin activity appeared in the dogs given more than 1.15 IU/kg. In the dog given hGH, the response of SM activity was significantly related to the hGH dose in the PV and not in the other vessels. These data seem to indicate that other sites than the liver and the kidney are involved in the production of GH-induced serum somatomedin activity. Following GH injection as well as in basal status, the liver may be implicated in the regulation of serum somatomedin activity.
Plasma transferrin is significantly positively correlated to the growth velocity in normal children and children with various growth disorders. In hypopituitary dwarfs, both plasma transferrin and somatomedin are significantly lower than in controls. Acute variations of the plasma transferrin levels could be involved in the regulation of the GH secretion by a feedback mechanism. Yet, transferrin is neither a somatomedin or a somatomedin-binding protein, and the mechanisms relating growth to transferrin remain unknown.
Explore the source record for details and available documents.