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Biomedical subjects

L C James

Publications and source records attributed to L C James.

25 records · Page 2Linked to original sources
PubMed1990

The effect of dual inhibitor, SK&F 86002, on helper T cell functions.

SK&F 86002, a mixed cyclooxygenase-lipoxygenase inhibitor, was examined for its effects on helper T cell functions. The drug was found to inhibit concanavalin A-induced mitogenesis of splenic T cells (IC50 = 13 microns), the mixed lymphocyte response (IC50 = 16 microM), and proliferation of antigen specific T cells (cloned line, IC50 = 11 microM; uncloned line, IC50 = 13 microM). In contrast, another mixed cycloxygenase-lipoxygenase inhibitor, BW775c, did not have such effects at non-cytotoxic levels. These T cell functions are believed to be dependent on the effects of elaborated IL-1. SK&F 86002 has been shown to inhibit the production of mature IL-1 (IC50 = 1 microM), possibly accounting for the anti-inflammatory effects of the drug in rheumatoid arthritis models. In an in vivo model of contact sensitivity, SK&F 86002 was able to inhibit mouse footpad swelling, demonstrating additional anti-inflammatory activity. As an inhibitor of IL-1 synthesis or release, SK&F 86002 may be useful for the treatment of T cell-dependent inflammation.

Animals↗
PubMed1988

Relative allergenic potential of four proteases used as contact lens cleaners.

The general use of enzymatic cleaners for soft contact lenses has led to reports of incidents of allergic reactions in previously sensitized patients. In light of this, experiments were performed to assess the relative allergenic potential of four such enzymes: papain, subtilisin A, subtilisin B, and pancreatin. Mice immunized intraperitoneally (i.p.) with either subtilisin A or papain exhibited little serum immunoglobulin E (IgE), even after tertiary doses of protein. Primates immunized intradermally (i.d.) with the four enzymes showed various levels of response to challenges: none to papain, mild to moderate to subtilisin A and pancreatin, and severe to subtilisin B. Finally, guinea pigs instilled ocularly with enzymes weekly for 15 weeks exhibited significant hyperemia and chemosis only to the positive control protein, ovalbumin, and not to any of the enzymes tested. We conclude that three of the four enzymes tested have low potential to sensitize human beings, and, further, that animal models may find increased use in screening products of biotechnology.

Allergens↗
PubMed1985

Epidermal growth factor stimulates tyrosine phosphorylation of specific proteins in permeabilized human fibroblasts.

We have investigated the epidermal growth factor (EGF)-stimulated tyrosine-specific protein kinase activity in quiescent cultures of diploid human fibroblasts that have a well characterized mitogenic response to EGF. We developed a method of permeabilizing cells with digitonin or other agents that permitted the rapid labeling of cellular proteins with exogenously added [gamma-32P]ATP while allowing only about 25% of marker cytosolic enzymes to escape from the cells. When phosphatases were inhibited with zinc and vanadate, EGF induced up to 8-fold stimulation of the incorporation of radioactivity from [gamma-32P]ATP into a 35-kDa band on sodium dodecyl sulfate gels. Alkali treatment of gels showed that EGF stimulated the phosphorylation of bands with apparent molecular masses of 170, 45, 35, 26, 22, and 21 kDa. Phosphoamino acid analysis was performed on the 170- and 35-kDa bands and revealed that the EGF-stimulated phosphorylation was on tyrosyl residues. The 35-kDa band was resolved into four spots by two-dimensional gel electrophoresis. The most acidic form was the most prominent and it was precipitated by an antiserum against a 35-kDa protein from A-431 cells; heretofore, this protein has only been reported to be phosphorylated in an EGF-dependent manner by A-431 membranes in vitro (Fava, R. A., and Cohen, S. (1984) J. Biol. Chem. 259, 2636-2645). This antiserum also precipitated a 35-kDa phospho-protein from extracts of intact [32P]orthophosphate-labeled fibroblasts which was phosphorylated on tyrosine in an EGF-dependent manner. None of the forms of the 35-kDa phosphoproteins labeled in permeabilized cells were immunologically related to the 34-kDa protein that is a substrate for the tyrosyl kinase encoded by Rous sarcoma virus. Other mitogens (serum, insulin, platelet-derived growth factor, and thrombin) did not detectably stimulate phosphorylation in permeabilized cells.

Adenosine Triphosphate↗
PubMed1979

The wavelength dependence of 8-methoxypsoralen photosensitization of radiation-enchanced reactivation in a mammalian cell-virus system.

The combined effect of 8-methoxypsoralen (8-MOP) and ultraviolet (UV) radiation on the ability of an irradiated mammalian cell (CV-1) to reactivate UV-irradiated mammalian virus (Herpes simplex) was tested. Prior treatment of cells with 8-MOP was found to increase Radiation-Enhanced Reactivation (RER) at one wavelength (297 nm) in the far ultraviolet but not at others (240-289 nm). This same treatment induced RER in the near UV (302-370 nm) and the visible region (380-400 nm). An action spectrum for the photo-sensitized induction of this cellular parameter was obtained. This action spectrum is consistent with the absorption spectrum for 8-MOP and the theory that damage to DNA is, at least in part, responsible for Radiation-Enhanced Reactivation.

Animals↗