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Biomedical subjects

R G Russell

Publications and source records attributed to R G Russell.

At least 217 records · Page 12Linked to original sources
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

Stimulation by human interleukin 1 of cartilage breakdown and production of collagenase and proteoglycanase by human chondrocytes but not by human osteoblasts in vitro.

Human articular chondrocytes in culture synthesise collagenase and neutral proteoglycanase in response to addition of a 12-17 kDa protein produced by cultured human monocytes. This factor copurifies with interleukin 1, as assessed by lymphocyte activating factor activity, on gel filtration chromatography and isoelectric focusing. The interleukin 1 and chondrocyte-stimulating activities are destroyed by pretreatment of the material with phenylglyoxal. The same materials also promote the release of glycosaminoglycans from cultures of intact bovine nasal cartilage. The proteoglycanase activity release from chondrocytes appears to be a metalloproteinase because it is inhibited by EDTA and not by phenylmethylsulphonyl fluoride (PMSF), and because detection of its activity is dependent on the presence of 4-aminophenylmercuric acetate. Human osteoblast-like cells do not respond to this factor by increased proteinase production, but are stimulated to produce prostaglandins. These results suggest that interleukin 1 has activities upon non-immune cells which promote the degradation of connective tissue matrices. Human osteoblasts do not synthesise neutral collagen- and proteoglycan-degrading enzymes and thus are unlikely to be directly responsible for the matrix degradation which occurs during bone resorption.

Animals↗
PubMed1984

In vitro activation of human chondrocytes and synoviocytes by a human interleukin-1-like factor.

Monocytes have been shown to secrete factors which stimulate the destruction of cartilage. Since one of the monocyte products, interleukin-1 (IL-1), has been shown to stimulate the release of collagenase and prostaglandin E from synoviocytes, we have investigated whether IL-1 is also responsible for chondrocyte activation. Purified preparations of IL-1 derived from human blood monocytes stimulated the production of prostaglandin E and plasminogen activator by human articular chondrocytes. After Sephadex G-75 chromatography, the lymphocyte-activating and the chondrocyte-activating activities of IL-1 eluted together in the regions corresponding to the void volume and to Kav = 0.2-0.3 (Mr 30,000-45,000) and Kav = 0.5-0.65 (Mr 12,000-17,000). The major peak of stimulating activity was the 12,000-17,000 dalton peak. Upon further analysis of the 12,000-17,000 dalton peak by isoelectric focusing, the major peak of lymphocyte-activating factor activity was recovered at a pI of 6.3 with a minor peak at 4.6-5.3. Similar patterns of activity were observed when the fractions were assayed for the stimulation of the production of prostaglandin E and plasminogen activator by human chondrocytes and of prostaglandin E by human synoviocytes. Treatment of the partially purified lymphocyte activating factor with phenylglyoxal reduced the thymocyte-stimulating activity 99% and the chondrocyte-stimulating activity 100%. These results suggest that IL-1 may stimulate the degradation of connective tissues during inflammation.

Cartilage, Articular↗
PubMed1984

Enhanced production of prostaglandins and plasminogen activator during activation of human articular chondrocytes by products of mononuclear cells.

We have examined the way in which products of cultured human blood mononuclear cells activate human articular chondrocytes. Conditioned medium from mononuclear cells enhanced the production of prostaglandin E by cultured human chondrocytes and also stimulated fibrinolytic activity in these cultures. These two effects may be interrelated, since the increased fibrinolysis in response to products of mononuclear cells was partially inhibited by indomethacin, an inhibitor of prostaglandin biosynthesis. The increased fibrinolysis is probably attributable to plasminogen activator, since it was strongly dependent on the presence of plasminogen. Increased amounts of PGE and chondroitin sulphate were also released from intact fragments of cartilage exposed to medium from cultured mononuclear cells. The time course and dose dependence of these effects were studied. The addition of exogenous arachidonic acid markedly enhanced production of PGE2. Ultrogel AcA54 was used to fractionate medium from cultured mononuclear cells and the chondrocyte-stimulating activity eluted with an apparent molecular weight between 12 000 and 25 000 daltons. Adherent and non-adherent mononuclear blood cells were also partially separated and conditioned medium from each was assayed for chondrocyte-stimulating factors. Both populations released factor(s) which increased the production of prostaglandin E by chondrocytes, but more activity came from the adherent mononuclear cells. The possible interrelationship between the chondrocyte activating factor studied here and others described in the literature is discussed.

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

Production of osteocalcin by human bone cells in vitro. Effects of 1,25(OH)2D3, 24,25(OH)2D3, parathyroid hormone, and glucocorticoids.

Cells have been cultured from human bone that possess several characteristics of osteoblasts, including the capacity to produce osteocalcin (bone Gla protein). In these cultures the production of osteocalcin is dependent on 1,25(OH)2D3 but is not affected by 24,25(OH)2D3 either alone or in combination with 1,25(OH)2D3. Two glucocorticoids, prednisolone and deflazacort, reverse the stimulation of osteocalcin synthesis by 1,25(OH)2D3 in a dose-dependent manner (10(-9) - 10(-6)M). Parathyroid hormone also inhibits osteocalcin production in a dose-dependent fashion (0.2-5 IU/ml). These results demonstrate that human bone cell cultures may be of considerable value in investigating the hormonal and pharmacologic regulation of the production of osteocalcin and other bone proteins in vitro.

24,25-Dihydroxyvitamin D 3↗
PubMed1984

Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis.

Our study was designed to investigate the mechanism of the stromal reaction in experimental ocular infection of murine eyes with herpes simplex virus (HSV). Severe stromal keratitis with scarring occurred in BALB/c mice after infection of the scarified cornea but similar reactions did not occur in athymic mice. However, if athymic mice were given adoptive transfers of lymphoid cells, a severe necrotizing and ulcerative keratitis accompanied by scarring resulted. The lesion progressed more quickly in recipients of lymphoid cells specifically immune to HSV and containing cytotoxic T-lymphocyte activity. In such mice, necrosis and ulceration were marked on the sixth day after transfer compared with 9-12 days for those given nonimmune cells. Removal of T-lymphocytes from the immune lymphoid population by treatment with specific antiserum and complement abrogated the adoptive transfer of the stromal reaction. Our results further demonstrate that stromal keratitis represents a host immunopathologic response to HSV infection in which T-lymphocytes are essential participants. Multiple mechanisms of T-cell immunopathology appear to be operating, including a reaction mediated by cytotoxic T-lymphocytes.

Animals↗
PubMed1983

Effects of retinol and dexamethasone on cytokine-mediated control of metalloproteinases and their inhibitors by human articular chondrocytes and synovial cells in culture.

Human articular chondrocytes in culture produced large amounts of specific mammalian collagenase, gelatinase and proteoglycanase when exposed to dialysed supernatant medium derived from cultured human blood mononuclear cells (mononuclear cell factor) or to conditioned medium, partially purified by fractionation with ammonium sulphate (60-90% fraction), from cultures of human synovial tissue (synovial factor). Human chondrocytes and synovial cells also released into culture medium an inhibitor of collagenase of apparent molecular weight about 30 000, which appeared to be similar to the tissue inhibitor of metalloproteinases synthesised by tissues in culture. The amounts of free collagenase inhibitor were reduced in culture media from chondrocytes or synovial cells exposed to mononuclear cell factor or synovial factor. While retinol inhibited the production of collagenase brought about by mononuclear cell factor or synovial factor, it restored the levels of inhibitor, which were reduced in the presence of mononuclear cell factor or synovial factor. Dexamethasone markedly reduced the production of collagenase by synovial cells, while only partially inhibiting factor-stimulated collagenase production by chondrocytes. Addition of puromycin as an inhibitor of protein synthesis reduced the amounts of both collagenase and inhibitor to control or undetectable levels.

Cartilage, Articular↗
PubMed1983

Thymoma in the dog: two case reports and review of 20 additional cases.

A 7-year-old German Shepherd Dog had a large cranial mediastinal mass that had resulted in chronic weight loss. A diagnosis of benign thymoma was made by transthoracic needle biopsy. The thymoma was removed surgically and the dog recovered without complications. At 4 months after surgery, the dog's activity was improved and it had gained weight. A 12-year-old mixed-breed dog was admitted for evaluation of dependent edema of the neck. Thoracic radiography revealed pleural effusion and lesions in the right lung and left scapula. Neoplastic epithelial cells were found in a needle aspiration specimen from the scapular lesion. The dog was euthanatized and necropsied. The primary tumor, a malignant thymoma, filled the cranial mediastinum and had invaded the cranial vena cava. Metastasis was confirmed in the right lung, liver, and left scapula. Eight cases of thymoma in the dog were retrieved from the Veterinary Medical Data Program. In 5 of the cases, the tumor was benign. The 3 dogs with malignant thymoma developed cranial vena caval syndrome, and they were euthanatized or died. Four of the dogs with benign thymoma were euthanatized for reasons unrelated to the tumor. One dog with benign thymoma was free of tumor when examined 5 years after surgical removal of the tumor.

Animals↗
PubMed1983

Drug treatment of primary hyperparathyroidism: use of clodronate disodium.

Clodronate disodium (dichloromethylene diphosphonate), a specific inhibitor of bone resorption, was given by mouth (1.0-3.2 g daily) to nine patients with primary hyperparathyroidism for two to 32 weeks so that its clinical and metabolic effects could be evaluated. Bone resorption decreased in all patients as judged by a fall in the fasting urinary calcium to creatinine and hydroxyproline to creatinine ratios. Serum calcium concentration was increased in all patients before treatment and fell in response to treatment to values near the upper end of the normal range. Hypercalcaemia and hypercalciuria recurred when treatment was stopped. In three patients treated for longer than 19 weeks clodronate failed to sustain the reduction in serum calcium concentration but the concentration remained below pretreatment values. These results suggest that clodronate may be of use in the medical management of primary hyperparathyroidism, particularly in patients in whom suppression of bone disease is desirable before surgery or in whom surgery is contraindicated.

Aged↗
PubMed1983

Ultrastructural abnormalities of muscle and neuromuscular junction differentiation in a bovine congenital neuromuscular disease.

The syndrome of arthrogryposis and palatoschisis (SAP), an inherited syndrome of muscular hypotonia in Charolais cattle, was used as an experimental model to study neuromuscular differentiation. The ultrastructural development of muscle, peripheral nerve, and neuromuscular junctions was studied to determine the sequence of events preceding hypotrophic changes in the skeletal muscles of affected calves at birth. Dorsiflexion of the metatarsophalangeal joints in the hindlimbs occurred in fetuses older than 3 months of age, but hypotrophic changes in skeletal muscle, manifested as small fibers scattered among larger and occasional degenerating fibers, was not apparent until late in gestation, affecting 8-month-old fetuses and neonatal calves. Electron microscope and enzyme histochemistry studies disclosed differentiation of skeletal muscle into fiber types which is consistent with changes expected from disuse and does not indicate a primary myopathic abnormality. Abnormal differentiation of neuromuscular junctions (NMJ), composed of several separated axonal endings terminating in shallow synaptic gutters, indicated impaired maturation of the synapse. The earliest indication of abnormal NMJ was observed in a 5-month-old SAP fetus. The clinical signs and pathologic changes found in the neuromuscular junction and skeletal muscle of SAP fetuses are consistent with an embryologic defect occurring during development of the central nervous system (CNS) that affects the integrated function of the motor neurons to the limbs. However, diversification of myofibers by histochemistry and ultrastructural parameters is evidence that the intrinsic physiologic properties of spinal motor neurons were retained.

Animals↗
PubMed1983

The presence in normal plasma, serum and platelets of factors that stimulate the production of prostacyclin (PGI2) by cultured endothelial cells.

1. The effect of plasma and serum from normal subjects on the production of prostacyclin by cultured porcine endothelial cells was investigated. 2. Both plasma and serum from all subjects studied significantly stimulated the production of prostacyclin by cultured endothelial cells, measured by the radioimmunoassay of its stable metabolite 6-oxoprostaglandin F1 alpha. 3. Serum caused a consistently greater stimulation than plasma from the same individual. The stimulation was dose-dependent and inhibited by indomethacin. Heparin added to serum also inhibited this response. 4. Extracts from isolated washed platelets were tested for their ability to increase prostacyclin production. Extracts from platelets which had been induced to aggregate and release their granule contents in response to thrombin, caused stimulation. 5. These results indicated the invariable presence in plasma and serum of factors that stimulate the production of prostacyclin by endothelial cells in vitro. At least one of these factors is derived from platelets. These factors may be involved in the regulation of prostacyclin production by the vascular endothelium under normal conditions and in disease states.

6-Ketoprostaglandin F1 alpha↗