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Biomedical subjects

E Canalis

Publications and source records attributed to E Canalis.

180 records · Page 10Linked to original sources

Effect of platelet-derived growth factor on DNA and protein synthesis in cultured rat calvaria.

Platelet-derived growth factor (PDGF), a peptide isolated from human platelets, was studied for its effects on bone formation by examining the synthesis of DNA, collagen and noncollagen protein in cultures of 21 day fetal rat calvaria. PDGF, at concentrations of 0.6-200 ng/ml, increased the incorporation of 3H-thymidine into acid insoluble residues in calvaria cultured for 24-96 hr; PDGF also increased the bone DNA content. After 24 hr of culture, PDGF caused a dose-dependent stimulation of 3H-proline incorporation into noncollagen protein (NCP) and a small stimulation of its incorporation into collagenase-digestible protein (CDP). After 96 hr of culture, PDGF did not affect NCP but inhibited the labeling of CDP. The PDGF stimulatory effect on the incorporation of 3H-thymidine was seen in both the periosteum and periosteum-free calvarium while that on the labeling of NCP was seen in the central nonperiosteal bone. Histological sections showed a threefold increase in the mitotic index after colcemid arrest in PDGF-treated bones. The stimulatory effect of PDGF on the incorporation of 3H-thymidine was enhanced by cortisol. These studies indicate that PDGF stimulates bone DNA synthesis and has a no specific stimulatory effect on protein synthesis in short-term cultures.

Animals↗

Determination of serum 17 alpha-hydroxyprogesterone by liquid chromatography.

17 alpha-Hydroxyprogesterone, cortisol, and 11-deoxycortisol were extracted with methylene chloride, separated by liquid chromatography, identified by their retention times, and quantitated by monitoring the absorbance at 254 nm. The method is specific and sensitive to as little as 2.5 ng of 17 alpha-hydroxyprogesterone. Mean analytical recovery of added 17 alpha-hydroxyprogesterone was 99% (SD 11%) and the CV for the same or different assays ranged from 3.5 to 9.4%. 6 beta-Hydroxyprogesterone was used as the internal standard. Concentrations of 17 alpha-hydroxyprogesterone in serum of normal men and women were less than 2.5 micrograms/L, but women in the luteal phase of the menstrual cycle had higher values. Mean 17 alpha-hydroxyprogesterone content in serum from mixed cord blood of normal newborns was 28.1 (SD 13.8) micrograms/L. Results by this method correlated well (r = 0.97) with results by radioimmunoassay, but were somewhat higher.

Adrenal Hyperplasia, Congenital↗

Stimulation of DNA and collagen synthesis by autologous growth factor in cultured fetal rat calvaria.

Conditioned medium derived from organ or cell cultures prepared from 19- to 21-day fetal rat calvaria stimulated the incorporation of [3H]proline collagen and of [3H]thymidine into DNA in organ cultures of the same tissue. Addition of cortisol enhanced the effect on collagen but not on DNA synthesis. These effects appeared to be due to a nondialyzable and heat-stable growth factor.

Animals↗

Hyperparathyroidism in the elderly.

Primary hyperparathyroidism seems to be increasing in incidence in elderly patients. Their symptoms are somewhat different from those encountered in younger patients, the most striking difference being the increase in the number of patients with mental changes. Twenty-nine patients, 23 women and 6 men, were treated at two community hospitals. Surgery was successful in all instances with no postoperative mortality and a low rate of complications. When properly evaluated, elderly patients tolerate parathyroid exploration very satisfactorily.

Adenoma↗

Effect of fibroblast growth factor on cultured fetal rat calvaria.

Normal rat or human serum causes a greater incorporation of 3H-proline into bone collagenase digestible protein (CDP) and noncollagen protein (NCP) than does serum from hypophysectomized animals or hypopituitary humans. In the present study, we have tested fibroblast growth factor (FGF), a peptide isolated from bovine pituitary glands that has been shown to stimulate RNA and DNA synthesis in various mesodermal cells, for its effects on cultured fetal rat calvaria. The major effect of FGF appeared to be a stimulation of periosteal fibroblastic cell proliferation. Incorporation of 3H-thymidine into DNA was increased at concentrations of 10--1000 ng/ml; the effect appeared after 12 hr, was sustained for 96 hr, and could not be ascribed to an effect on 3H-thymidine uptake. Total DNA content was increased and histologic sections showed an increase in the number of mitoses in periosteal fibroblasts after colemid arrest. These effects were accompanied by an increase in the uptake and incorporation of 3H-uridine, a decrease in the incorporation of labeled proline into CDP, and a small and variable increase in the incorporation of proline into NCP. Cortisol opposed the effects of FGF on 3H-thymidine and 3H-uridine incorporation. Insulin did not alter the effect of FGF on 3H-thymidine incorporation, but FGF decreased the stimulatory effect of insulin on the labeling of CDP. The effect of FGF on thymidine incorporation and collagen synthesis was not altered by indomethacin. The major effect of FGF in calvaria is to increase DNA synthesis and stimulate the proliferation of periosteal fibroblasts. It does not appear to be the pituitary-dependent factor in serum that stimulates 3H-proline incorporation into CDP and NCP in calvaria.

Animals↗

Effect of insulinlike growth factor I on DNA and protein synthesis in cultured rat calvaria.

Insulinlike growth Factor I (IGF I), a growth hormone-dependent peptide or somatomedin, was studied for its effects on bone formation by examining the synthesis of DNA, collagen, and noncollagen protein in cultures of 21-d fetal rat calvaria. IGF I caused a dose-dependent stimulation of the incorporation of [3H]thymidine into DNA at concentrations of 0.1--100 nM; the effect appeared after 6 h, was maximal at 12 h, and was sustained for 96 h. IGF I also increased the bone DNA content, IGF I at 0.1--3 nM had a small stimulatory effect on the incorporation of [3H]proline into collagenase-digestible protein (CDP) whereas 30 nM IGF I caused a two- to threefold increment and had a maximal effect. A smaller effect on the labeling of noncollagen protein (NCP) was also observed. The effect of CDP and NCP appeared and was maximal after 12 h and was sustained for 96 h. IGF I increased the total collagen content of bones. The IGF I stimulatory effect on the incorporation of [3H]thymidine was seen in both the periosteum and periosteum-free calvarium, whereas that on the labeling of CDP was seen only in the central, osteoblastic-rich, non-periosteal bone. Histological sections showed a 10-fold increase in the mitotic index after Colcemid arrest in IGF I-treated bones, the mitoses were equally distributed in the periosteum and central portions of the calvarium. Insulin had a stimulatory effect on the incorporation of [3H]proline into CDP and NCP and 1 nM--1 microM similar to the effect of IGF I. In contrast, high insulin concentrations (0.1 and 1 microM) were required to increase the incorporation of [3H]thymidine, and insulin did not affect DNA content. Cortisol decreased the stimulatory effect of IGF I on DNA labeling but greatly enhanced the stimulatory effect of IGF I on the incorporation of [3H]proline into CDP. Triiodothyronine and parathyroid hormone increased the incorporation of [3H]thymidine and were additive to IGF I. Triiodothyronine did not affect the labeling of CDP, but parathyroid hormone inhibited it and opposed the effect of IGF I. These studies indicate that IGF I stimulates bone DNA, collagen, and NCP synthesis in vitro. IGF I and insulin have similar effects on bone collagen synthesis but IGF I stimulates the synthesis of DNA at physiological concentrations, and insulin does not.

Animals↗

Direct stimulation of bone resorption by epidermal growth factor.

Epidermal growth factor, isolated from mouse submaxillary glands (mEGF) and human urine (hEGF; urogastrone), and fibroblast growth (FGF) have been tested for their effect on bone resorption by measuring the release of previously incorporated 45Ca from cultured fetal rat long bone shafts. mEGF produced significant but slow stimulation of bone resorption which was maximal at 30 ng/ml and was not blocked by indomethacin, flufenamic acid, or R0 20-5720, structurally unrelated inhibitors of prostaglandins synthesis. mEGF increased thymidine incorporation in long bones at 1 ng/ml, a concentration which did not stimulate resorption. hEGF at 3-30 ng/ml produced a more rapid stimulation of resorption, which was also unaffected by inhibition of prostaglandin cyclooxygenase. Neither mEGF nor hEGF increased the concentration of prostaglandin E in the medium after 5 days of culture. FGF failed to stimulate resorption at concentrations of up to 1000 ng/ml. We conclude the EGF, but not FGF, is a direct stimulator of bone resorption. In contrast to the previously reported findings in mouse calvaria, this stimulation is not dependent on prostaglandin synthesis. Since there is abundant hEGF in human urine, this factor could be responsible for the calcium-mobilizing activity recently found in human urine concentrates.

Animals↗

Serum cortisol and 11 deoxycortisol by liquid chromatography: clinical studies and comparison with radioimmunoassay.

We describe a liquid-chromatographic procedure for separating and measuring cortisol and 11-deoxycortisol in serum. We quantitated these steroids in patients who were undergoing various tests of pituitary and (or) adrenal function and compared the results with those obtained by two radioimmunoassays done in two different laboratories. Results of 48 tests done in 37 functionally normal humans are presented. Cortisol values for sera collected in the morning as determined by liquid chromatography were (mean +/- SD) 134 +/- 54 micrograms/L. Serum cortisol concentrations increased from 136 +/- 65 to 321 +/- 80 micrograms/L 60 min after injecting synthetic corticotropin and increased from 107 +/- 46 to 242 +/- 31 micrograms/L after insulin-induced hypoglycemia. Serum cortisol decreased from 142 +/- 49 to 26 +/- 20 micrograms/L after oral administration of metyrapone, while 11-deoxycortisol increased from less than 10 to 210 +/- 53 micrograms/L. Serum cortisol measured less than 10 micrograms/L the morning after oral ingestion of dexamethasone. Results of the dynamic tests of adrenal function correlated well with previously reported studies. However, the cortisol values obtained by our technique were generally lower than those obtained by radioimmunoassay, possibly owing to lack of specificity of the latter methods used here for comparison. In contrast, values for 11-deoxycortisol were the same by both methods. The present studies confirm the usefulness of liquid chromatography for measuring these two steroids in serum during tests of pituitary and adrenal function. Future refinements of the technique should continue to increase its clinical applications.

17-Hydroxycorticosteroids↗

Abnormal gonadotropin secretory responses to LRH in transsexual women after diethylstilbestrol priming.

To determine whether female transsexuals have abnormal hypothalamic-pituitary feedback control, pituitary LH and FSH secretory responses to synthetic LRH (100 micrograms iv) were measured in nine female transsexuals with normal menstrual cycles before and after a 7-day course of treatment with diethylstilbestrol (DES; 2 mg/day). Control groups included five heterosexual women and seven heterosexual men. Pituitary responses to LHR in heterosexual women studied in the early follicular phase increased markedly after DES administration and were clearly different from responses in men, which were all inhibited by DES. Responses to LRH in nine transsexual women studied in the early follicular phase differed strikingly from normal women in that gonadotropin responses were not enhanced by DES. The finding that the responses of female transsexuals to DES and LRH were intermediate between the female and the male patterns suggests that a biological abnormality accompanies the psychological abnormality in such patients.

Adult↗

Growth hormone, skeletal growth factors and osteoporosis.

Bone remodeling is regulated by systemic hormones and growth factors acting in concert to maintain normal bone mass. Growth hormone has important effects on bone metabolism and acts by stimulating the production of insulin-like growth factor (IGF) I in the liver. Conditions of growth hormone deficiency have decreased bone mass that could be modified by growth hormone administration. Skeletal cells synthesize a variety of growth factors with diverse properties and levels of regulation. IGF I and II seem to play a major role in the local regulation of bone remodeling, and other growth factors have important mitogenic properties. Skeletal growth factors may be regulated at the level of synthesis, activation, receptor binding or binding proteins. Growth factors such as IGF I could be considered for the systemic treatment of various bone disorders, or drugs could be developed to modify the synthesis or activity of the locally produced factors. Additional research should result in the development of novel approaches to the treatment of osteoporosis.

Journal Article↗

Outcome of patients after curative resection of pulmonary metastases.

BACKGROUND: Resective surgery can play a role in solitary pulmonary metastasis or in a few multiple metastases of the lungs. METHODS: We performed a retrospective analysis of the cure rate and survival in patients with pulmonary metastases after surgical resection. Inclusion criteria included no evidence of extrapulmonary metastases or local control of the primary neoplasia. Selective adjunctive therapy was added when applicable. RESULTS: Twenty-five out of 53 patients with resected pulmonary metastases are still alive and disease free. After a 5-year period of follow-up the cure rate obtained was 42%. CONCLUSIONS: In selected patients, resective surgery of solitary or limited multiple pulmonary metastases should be useful, offering the patients a high rate of curability and long term survival. These positive results suggest that adjunctive therapies should be added after resective surgery.

Humans↗