Search PubMed⌕ Search

Biomedical subjects

D A Lawrence

Publications and source records attributed to D A Lawrence.

At least 199 records · Page 11Linked to original sources
PubMed1977

Further studies of the action of methionyl adenylate on chick embryo fibroblasts.

Methionyl adenylate (Met-AMP) inhibits protein synthesis by interacting with methionyl-tRNA synthetase. Addition of 1--3 mM inhibitor to chick embryo fibroblasts rapidly stops protein synthesis and DNA synthesis but not RNA synthesis. These effects can be reversed by renewal of the medium. The extent and reversibility of protein and DNA syntheses depend on the concentration of MetAMP in the cultures, the length of exposure and the cellular density. MetAMP is recognised by several enzymes as substrate and/or as inhibitor. MetAmp is degraded to methionol plus 5'-adenylic acid by 5'-phosphodiesterase. Adenosine deaminase, adenylic acid deaminase and 3':5'-phosphodiesterase cannot use MetAMP as substrate but the last enzyme is inhibited. The presence of MetAMP in cultures provokes a small but reproducible increase in the level of methionyl-tRNA synthetase and 5'-phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Immunoglobulins cytophilic for human lymphocytes, monocytes, and neutrophils.

The cytophilic activity of human myeloma proteins of different classes and subclasses for lymphocytes, monocytes, and neutrophils was investigated. Binding of both unaggregated immunoglobulins (Ig) and Ig aggregated with rabbit F(ab)2 anti-Fab fragment sera was determined. Lymphocytes bound unaggregated IgG1 and IgG3 proteins, but none of the proteins of the other classes. In contrast, after aggregation, IgG of all subclasses and IgE proteins bound to lymphocytes; aggregated proteins of the other classes did not bind. Monocytes bound unaggregated IgG1 and Ig3 better than Ig4 whereas the binding of proteins of other classes was insignificant. Neutrophils bound unaggregated IgG1 and IgG3 proteins and, in addition, IgA1, IgA2, secretory IgA, and IgG4 proteins. After aggregation, the neutrophils bound more Ig of all classes; however, the differences between the amounts bound remained similar to the amounts of unaggregated proteins. The native structure of the Ig molecule is necessary for the maintenance of complete activity, because Fc fragments bound less than intact Ig, and reduction and alkylation abolished cytophilia. The Fc receptors on all cell types tested showed no specificity for any of the respective cytophilic IgG subclasses; however, neutrophils appear to have separate receptors for IgG and IgA proteins.

Antibodies↗
PubMed1974

Stimulation of antibody production to the hapten 2,4-dinitrobenzene by affinity labeled murine lymphoid cells. I. Ability of affinity labeled murine lymphoid cells to activate the in vivo immune response.

The ability of meta-nitrobenzenediazonium fluoborate (m-NBDF)-labeled thymus and spleen (S) cells to transfer immunity to 2,4-dinitrophenyl (DNP) into irradiated syngeneic recipients was investigated. There was a significant increase in the number of anti-DNP plaque-forming cells (PFC) when m-NBDF-labeled thymus cells and normal spleen cells, or normal thymus cells and m-NBDF-labeled spleen cells were transferred, but not when both thymus- and S-cell populations were labeled and injected together into irradiated recipients. The ability of these cell populations to cooperate and enhance the in vivo immune response to DNP is discussed. The T cells seem to be actively involved in the development of this response; they participate beyond the mere role of carrying and presenting antigen to the B cells. It is suggested that cell to cell contact between T and B cells may be an important factor in the elicitation of an immune response. In addition, the cellular interaction is affected by irradiating the thymus cell preparation and the initiating interaction required for antibody synthesis probably occurs within 48 h after injecting the cell populations into the syngeneic irradiated recipients.

Animals↗
PubMed1973

2,4-Dinitrophenyl receptors on mouse thymus and spleen cells.

A higher percentage of specific antigen-binding cells can be detected not only in normal CBA/J mouse spleen cell preparations (0.99%), but also in the normal thymus cell preparations (0.15%) with the use of [(125)I]2,4-dinitrophenyl-human IgG (DNP-HGG) as compared with most other antigens employed under similar conditions. The receptors on these cells are mainly specific for the DNP group as shown by the inhibition studies with DNP-lysine and the other DNP conjugates. In addition, it was shown by the inhibition studies with DNP-lysine that the thymus cells seem to have a lower avidity for DNP than the spleen cells. Preincubation of cell suspensions with antisera to immunoglobulins showed that the DNP-HGG antigen-binding cells in the thymus are inhibited predominantly with anti-micro-chain serum and the spleen cells with both anti-micro-chain and anti-gamma-chain sera; both cell populations were also significantly inhibited with the antisera to kappa-chains and Fab fragments. These data indicate that the nature of the receptor on the T cell differs from that on the majority of spleen cells.

Animals↗
PubMed1972

Regulation of the methionine feedback-sensitive enzyme in mutants of Salmonella typhimurium.

Assay of the first enzyme unique to methionine biosynthesis, homoserine-O-transsuccinylase, in metJ and metK regulatory mutants of Salmonella typhimurium showed that synthesis of the enzyme was derepressed seven- and fourfold, respectively. The possibility of noncoordinate regulation of the methionine enzymes is discussed. In metA feedback-resistant mutants, the enzyme activity can be inhibited in vitro by 10 mmS-adenosylmethionine but not by 10 mm l-methionine; hence, the synergistic inhibition found for the wild-type enzyme is not effective in these latter mutants.

Acyltransferases↗
PubMedDate not supplied

Long-term exposure to methotrexate induces immunophenotypic changes, decreased methotrexate uptake and increased dihydrofolate gene copy number in Jurkat T cells.

Methotrexate (MTX) treatment of rheumatoid arthritis may require increasing doses to maintain clinical efficacy. An overall plateau of clinical response is reached after only six months of treatment. To study the immunologic, biochemical and genetic effects of MTX on T cells, the Jurkat T cell line was made MTX-resistant by serial addition of methotrexate sodium into culture medium. Cells proliferated and divided successfully in MTX concentrations ranging to 15 microM. MTX resistance of Jurkat T cells in vitro was accompanied by significantly (P < 0.05) decreased expression of CD2, CD3, CD4, CD28, and CD69, IL-2 production, and MTX uptake assessed by cell association or disassociation of 3[H]-MTX or fluoresceinated MTX (FMTX), respectively. In addition, there was DHFR gene amplification and increased levels of DHFR in all resistant cell lines. Both permanent and transient phenotypic changes developed in resultant cell lines exposed to increasing concentrations of MTX in vitro. Expression of CD4 and CD25 and sensitivity to MTX returned to near-parental levels after removal of MTX from culture medium, whereas expression of CD26 and MTX uptake were significantly increased. Expression of CD2, CD3, CD69 and IL-2 production as well as the DHFR levels did not return to the parental phenotype after removal from MTX. We conclude that MTX-cultured cells express depressed levels of cell-surface markers vital for T cell function and activation. The return of enhancement of these cell-surface markers critical to T cell activation suggests a possible mechanism for the severe flares experienced by rheumatoid arthritis patients when drug treatment is discontinued.

Antigens, Differentiation, T-Lymphocyte↗