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Biomedical subjects

D K Vallance

Publications and source records attributed to D K Vallance.

At least 19 recordsLinked to original sources
PubMed1995

Inhibition of interleukin-1-induced effects in synoviocytes transduced with the human IL-1 receptor antagonist cDNA using an adenoviral vector.

In this report, we present data showing that a recombinant adenoviral vector (Ad.RSVIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist protein (IL-1ra) can genetically modify synoviocytes both in vitro and in vivo. Human synoviocytes infected with Ad.RSVIL-1ra in vitro expressed and secreted high levels of human IL-1ra that were detected by ELISA of tissue culture supernatants. New Zealand White rabbits that received intra-articular injections of Ad.RSVIL-1ra expressed transgenic IL-1ra in synoviocytes, and secretion was detected for at least 4 weeks post-infection. Further, biological activity of the transgenic IL-1ra was demonstrated by its ability to inhibit IL-1-induced prostaglandin E2 (PGE2) synthesis in vitro and IL-1-induced glycosaminoglycan (GAG) degradation in vivo. These data demonstrate that recombinant adenoviral vectors can mediate the intra-articular expression of anti-inflammatory proteins and may be a reasonable method to deliver therapeutically relevant proteins for the regional treatment of synovial inflammation.

Adenoviridae↗
PubMed1995

Immunosuppressive treatment of the pulmonary manifestations of progressive systemic sclerosis.

In this article, we review recent studies on the use of immunosuppressive agents in autoimmune diseases, especially cyclophosphamide. In addition, we begin with a special section on the treatment of scleroderma lung disease, including controversies regarding the indications for immunosuppressive therapy. Scleroderma lung disease is justifiably regarded as one of the "frontiers of medicine" because of its gravity, its often rapidly progressive nature, and the urgency with which improved therapy is needed.

Autoantibodies↗
PubMed1995

A recombinant adenoviral vector expressing a soluble form of VCAM-1 inhibits VCAM-1/VLA-4 adhesion in transduced synoviocytes.

Intra-articular injection of recombinant adenovirus has been shown to be a feasible approach to the introduction of genetic reagents into synovial tissues in vivo. Rheumatoid arthritis (RA) is an autoimmune disorder characterized by the infiltration of lymphocytes and monocytes into inflamed synovium. It has been hypothesized that the recruitment of T lymphocytes/monocytes into sites of chronic inflammation is mediated by enhanced binding of very late antigen-4 (VLA-4) to vascular cell adhesion molecule-1 (VCAM-1) expressed on microvascular endothelial cells. Additional evidence suggests that VLA-4 binding continues to be important within the inflamed synovial membrane, where it appears to play a role in T cell retention and activation. A feasible therapeutic strategy for RA could be to utilize a soluble congener of the VCAM-1 molecule to block VLA-4 binding. In order to test this concept, a recombinant serotype Ad5 human adenovirus encoding a secreted form of VCAM-1 (Ad.CBsVCAM) was constructed. Human synoviocytes were readily infected in vitro with Ad.CBsVCAM, and sVCAM-1 expression and processing were analyzed by immunoprecipitation studies. Secretion of transgenic sVCAM was identified by ELISA of tissue culture supernatants, and biological activity was demonstrated with cell adhesion assays. In vivo, transgenic sVCAM-1 expression was determined by immunohistochemical analysis and in situ hybridization of synovial tissue, and secretion of transgenic sVCAM-1 was demonstrated by ELISA of tidal knee lavage fluid. The results showed that recombinant adenovirus can mediate the expression of a biologically active sVCAM-1 by synoviocytes in vivo and suggest that this strategy may be useful for inhibiting T lymphocyte retention and activation within rheumatoid synovium.

Adenoviridae↗
PubMed1994

Immunosuppressive drug therapy.

Interstitial lung disease frequently complicates rheumatic disorders, especially polymyositis-dermatomyositis, rheumatoid arthritis, systemic sclerosis, and mixed connective tissue disease. In this article, we review the current data supporting the use of azathioprine, cyclophosphamide, chlorambucil, cyclosporine, and methotrexate in the management of chronic interstitial pneumonitis-fibrosis. The literature addressing the utility of these immunosuppressive-cytotoxic agents, however, consists almost entirely of anecdotal successes and small, uncontrolled series. Although no convincing data have proven that the use of any of these agents with or without corticosteroids is superior to therapy with corticosteroids alone, the literature may suggest a slight long-term survival advantage when either azathioprine or cyclophosphamide is added to prednisone therapy. Studies in which cyclosporine was used, however, have been less encouraging. Data regarding the use of chlorambucil and methotrexate are too sparse to permit any conclusions. Further controlled studies are required to clarify the role of these immunosuppressive agents in the treatment of interstitial lung disease.

Adrenal Cortex Hormones↗
PubMed1968

Metabolism of megestrol acetate by rat adrenal glands in vitro.

Megestrol acetate is metabolized by homogenates of rat adrenal glands to three more polar metabolites Y(2), Y(3) and Y(4). Their structures were investigated by microchemical reactions, paper chromatography, and ultraviolet and infrared spectroscopy. Metabolite Y(3) was identified as 17alpha-acetoxy-11beta-hydroxy-6-methyl-pregna-4,6-diene-3,20-dione, its oxidation product being identical with authentic 17alpha-acetoxy-6-methylpregna-4,6-diene-3,11,20-trione. It is suggested that metabolite Y(2) is 17,18-dihydroxy-6-methylpregna-4,6-diene-3,20-dione and that it also exists in the form of an alpha-ketol formed between the 18-hydroxyl and 20-oxo groups. Metabolite Y(4) is probably a tautomeric form of metabolite Y(2) as they were partially interconverted on chromatography and also have similar properties.

Acetates↗