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Biomedical subjects

B R MacDonald

Publications and source records attributed to B R MacDonald.

30 records · Page 2Linked to original sources
PubMed1986

Recombinant human transforming growth factor-alpha stimulates the formation of osteoclast-like cells in long-term human marrow cultures.

Transforming growth factor-alpha (TGF-alpha) is synthesized by a variety of tumor cell lines and stimulates osteoclastic bone resorption in vitro. The mechanism by which TGF-alpha increases osteoclast activity is unknown. We used a human marrow culture system that forms osteoclast-like multinucleated cells (MNCs) to determine the effects of recombinant human TGF-alpha on MNC formation. Addition of 0.01 ng/ml TGF-alpha for the 1st week followed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the subsequent 2 wk significantly increased MNCs. Treatment of these cultures with TGF-alpha without later addition of 1,25(OH)2D3 did not increase MNC formation. Autoradiographic studies revealed that TGF-alpha stimulated proliferation of precursors for MNCs, and 1,25(OH)2D3 increased their rate of fusion into MNCs. Addition of murine epidermal growth factor (EGF) (0.1 ng/ml) followed by 1,25(OH)2D3 also significantly stimulated MNC formation. These data suggest that TGF-alpha and EGF may stimulate bone resorption by increasing the proliferation of osteoclast precursors, which leads to increased numbers of osteoclasts.

Bone Marrow↗
PubMed1986

Parathyroid hormone stimulates the proliferation of cells derived from human bone.

Despite its acute inhibitory effect on bone formation in vitro, PTH has been shown to have an anabolic effect on bone in vivo and to stimulate cell proliferation in osteoblastic cell lines and organ cultures. We have examined the effects of PTH on cells derived from human trabecular bone and compared these effects with those on human skin fibroblasts. Human bone cells have the capacity to synthesize type I collagen and osteocalcin, and to respond to 1,25-dihydroxyvitamin D3 with an increase in the synthesis of osteocalcin and alkaline phosphatase. PTH stimulated adenylate cyclase activity at both low and high cell density. However, the same concentrations of hormone stimulated the proliferation of these cells only when they were cultured at a high cell density. The effect of PTH was bone cell specific in that no proliferative effect of PTH was detected in cultures of human skin fibroblasts obtained from the same donor and cultured under the same conditions. The effect of PTH on DNA synthesis by human bone cells may be important in the generation of a long term anabolic response to PTH.

Bone and Bones↗
PubMed1985

1,25-Dihydroxyvitamin D3 causes formation of multinucleated cells with several osteoclast characteristics in cultures of primate marrow.

1,25-Dihydroxyvitamin D3 induces cells derived from mononuclear phagocytes such as HL-60 and U937 to differentiate to macrophage-like cells and causes alveolar macrophages to form multinucleated cells in vitro. Since the osteoclast is thought to be derived from early marrow cells of the macrophage lineage, we cultured normal primate marrow mononuclear cells in medium containing 1,25-dihydroxy-vitamin D3. We found that large multinucleated cells (3-30 nuclei per cell) formed after 2-3 weeks of culture. Addition of 1,25-dihydroxyvitamin D3 to these cultures markedly stimulated multinucleated cell formation. Other vitamin D analogues, parathyroid hormone, prostaglandin E2, and calcitonin failed to stimulate multinucleated cell formation. However, calcitonin inhibited the stimulation of multinucleated cell formation by 1,25-dihydroxyvitamin D3. The multinucleated cells that formed in these cultures contained a tartrate-resistant acid phosphatase activity, a marker enzyme for osteoclasts. This activity was increased by 1,25-dihydroxyvitamin D3 and parathyroid hormone, and calcitonin inhibited the increase in acid phosphatase activity stimulated by these compounds. Ultrastructurally, the multinucleated cells had several features similar to those of osteoclasts. These data suggest that the multinucleated cells in our culture have several characteristics of osteoclasts and that the potent bone-resorbing activity of 1,25-dihydroxyvitamin D3 in vivo and in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclasts.

Acid Phosphatase↗
PubMed1984

Effects of bovine parathyroid hormone and 1,25-dihydroxyvitamin D3 on the production of prostaglandins by cells derived from human bone.

Local production of prostaglandins by osteoblasts may be important in controlling the bone resorbing activity of some hormones which have receptors on osteoblasts. We have demonstrated that osteoblast-like cells derived from human bone can incorporate [14C]arachidonic acid into phospholipids and synthesise immunoreactive PGE. Parathyroid hormone increases both the release of incorporated arachidonic acid and the synthesis of PGE. This is the first demonstration of modulation of bone cell prostaglandin synthesis by a bone resorbing hormone.

Arachidonic Acid↗
PubMed1984

Studies of the growth of human bone-derived cells in culture using aqueous two-phase partition.

Human bone cells, maintained in culture, have been subjected to partitioning in an aqueous two-phase system on a countercurrent distribution apparatus. A broad cell distribution was obtained indicating cell-surface heterogeneity. Two major cell populations were identified which appeared to be growing at different rates. The 'fast'-growing cells had a less hydrophobic cell surface than the 'slow'-growing cells. Possible relationships of these cell populations with osteoblast differentiation and the potential importance of this technique in studies of osteoblast differentiation are discussed.

Bone and Bones↗
PubMed1984

Scrotal lymphangioma.

Congenital malformations of the intrascrotal lymphatic system may form cystic masses. A case of a lymphangioma arising in Colles fascia is presented. This rare clinical entity should be included in the differential diagnosis of cystic lesions of the external male genitalia. Total surgical excision is the treatment of choice.

Child, Preschool↗
PubMed1984

Systemic hemodynamic and regional blood flow effects of LY141865, a selective dopamine receptor agonist.

Intravenous infusion of LY141865 (20 micrograms/kg) lowered systemic vascular resistance in anesthetized dogs resulting in a fall in mean arterial blood pressure. These effects require an intact nervous system and involve dopamine receptors as they were abolished by hexamethonium or sulpiride pretreatment. LY141865 does not appear to interact with adrenergic receptors because it did not increase diastolic blood pressure or cardiac rate of normal or hexamethonium-treated dogs, and yohimbine pretreatment did not antagonize its systemic vasodilator and hypotensive actions. Hemodynamic analysis demonstrated that infusion of LY141865 (20 and 100 micrograms/kg i.v.) resulted in persistent arterial hypotension due solely to reduced systemic vascular resistance; aortic blood flow index was maintained. LY141865 produced slight bradycardia and sustained increments in stroke volume index at the highest tested dose. Left ventricular filling pressure was unchanged by LY141865. Regional blood flows to heart, stomach, colon, small intestine, kidneys and marrow-laden bone were not changed during hemodynamic alterations produced by LY141865, although evidence of arteriovenous shunting of blood was observed in skin and skeletal muscle. Comparable systemic vasodilation and arterial hypotension induced by infusion of nitroglycerin reduced gastric and colonic blood flows, but did not produce detectable shunting. The composite data are interpreted to be a reflection of the ability of LY141865 to interact with DA2 dopamine receptors and thereby inhibit neurogenic release of norepinephrine. The present results and known oral efficacy of LY141865 lend further support for the development and use of dopamine receptor agonists for the treatment of cardiovascular disease.

Animals↗
PubMed1984

Primate cardiovascular responses mediated by dopamine receptors: effects of N,N-di-n-propyldopamine and LY171555.

Administration of N,N-di-n-propyldopamine (DPDA) (1-100 micrograms/kg i.v.) and LY171555 (1-100 micrograms/kg i.v.) produced dose-related arterial hypotension accompanied by bradycardia in anesthetized rhesus monkey. The cardiovascular effects of DPDA were of brief duration, whereas hypotension and bradycardia induced by LY171555 were sustained. Pretreatment of monkeys with sulpiride (0.5 mg/kg i.v.) abolished the blood pressure and cardiac rate-lowering effects of DPDA and LY171555. During the time course of cardiovascular alterations produced by LY171555 (100 micrograms/kg i.v.), increments in cardiac rate due to electrical stimulation of the right stellate ganglion were inhibited. This effect also was abolished by sulpiride treatment. The antagonism of neural tachycardia by LY171555 was selective, as the drug had no concomitant inhibitory action on cardiac rate or diastolic blood pressure responses to exogenous norepinephrine. Hemodynamic analysis demonstrated that DPDA (20-200 micrograms/kg i.v.) and LY171555 (1-10 micrograms/kg i.v.) each lowered arterial blood pressure, without reflex tachycardia, by dilating the systemic vasculature; cardiac output and stroke volume were maintained. Furthermore, left ventricular minute work and stroke work were reduced by each drug in association with systemic hypotension. The data suggest that DPDA and LY171555 produce cardiovascular responses by inhibiting neurogenic release of norepinephrine through an interaction with D-2 dopamine receptors. The present primate data also support the potential clinical utility of dopamine receptor agonists in treating cardiovascular disease.

Animals↗
PubMed1977

Ultrastructure of the dikaryotic form of Cyathus bulleri Brodie.

The fine structure of the dikaryotic form of Cyathus bulleri Brodie was generally found to be similar to that of other hyphal forms of the Basidiomycetes. The nuclear walls were doubled, porous and in some cases connected to the endoplasmic reticulum. The presence of typical as well as filamentous and U-shaped mitochondria was confirmed. Other cellular structures and organelles, among them vacuoles, vesicular and myelinoid-like bodies, often associated with the cell membranes, glycogen and ribosomes were also observed in the cytoplasm. The presence of the dolipore/parenthesome apparatus and clamp connections typical of the Basidiomycetes was established.

Basidiomycota↗