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J E McCormack

Publications and source records attributed to J E McCormack.

At least 37 records · Page 2Linked to original sources
PubMed1991

Analysis of class II MHC structure in thymic nurse cells.

During the course of thymocyte maturation, the processes of positive selection and tolerance induction are mediated by interactions between thymocyte T-cell receptors and MHC molecules on thymic stromal cells. The means by which these seemingly contrary processes can be mediated by interactions between the same molecules has long been a source of controversy. One idea which has been put forward is that the MHC molecules in different microenvironments of the thymus are not the same. We have tested this hypothesis by examining class II transcripts derived from thymic cortical epithelial cells known as thymic nurse cells, reasoning that alternative splicing of primary transcripts might give rise to a positively selecting MHC molecule. However, we found no evidence for alternative splicing of these transcripts. These results are presented and discussed with regard to implications for possible mechanisms of positive selection.

Amino Acid Sequence↗
PubMed1991

Changes in phosphorylation of myc oncogene and RB antioncogene protein products during growth arrest of the murine lymphoma WEHI 231 cell line.

The expression of the protein products of the c-myc oncogene and retinoblastoma susceptibility gene (RB) was investigated during either goat anti-mouse immunoglobulin (GaMIg)- or phorbol ester (TPA)-induced growth arrest of the murine B-lymphoma cell line WEHI 231. Previously we have demonstrated that c-myc mRNA levels increase within 1-2 h of treatment, return to control levels by 4 h, and decline below these values by 24 h of treatment. Here we demonstrate that the level of c-myc protein synthesis and mRNA change in parallel. The predominant c-myc protein expressed during the time course is the one initiated at the AUG codon (P2). The myc protein synthesized following 1-2 h of anti-immunoglobulin or TPA treatment migrates more slowly in a polyacrylamide gel as a result of increased phosphorylation. This hyperphosphorylation was no longer detectable by 4-6 h of treatment. Furthermore, the hyperphosphorylated myc protein appears to be more readily extractable with salt than the hypophosphorylated form. The product of the RB gene is present in multiple phosphorylation states in exponentially growing WEHI 231 cells. By 8 h of GaMIg or TPA treatment, a hypophosphorylated form begins to be detectable and significant levels were seen by 15 h. Thus post-translational control of both c-myc and RB expression occurs during the growth arrest of WEHI 231 cells. These changes in phosphorylation may play a role in mediating the cessation of proliferation of these cells.

Animals↗
PubMed1987

Independent regulation of transcription of the two strands of the c-myc gene.

Previously we demonstrated the existence of transcripts from the noncoding strand of a rearranged, truncated c-myc gene in murine plasmacytomas in which this oncogene is translocated to an immunoglobulin constant-region gene element (M. Dean, R. B. Kent, and G. E. Sonenshein, Nature [London] 305:443-446, 1983). Here we report on the transcription of the two strands of a normal, unrearranged c-myc gene. We examined the effects of gene rearrangements, growth state transitions, and differentiation on the relative levels of usage of the two strands. Transcription from intron 1 to exon 3 of the murine c-myc gene was studied in in vitro nuclear runoff assays. The level of transcription of the noncoding strand across this region of a germ line c-myc gene in a murine B-cell lymphoma line was comparable to the level observed in plasmacytomas with translocated c-myc genes. Rapid changes in transcription of the coding strand of the c-myc gene could be seen during growth arrest of WEHI 231 cells and during activation of splenic T lymphocytes. Transcription of the noncoding strand was constitutive during these growth state transitions and during activation of primary cultures of quiescent calf aortic smooth muscle cells as well. In contrast, differentiation of murine erythroleukemia cells was accompanied by an early drop in transcription of the two strands of this gene. The ramifications of these findings with respect to measurements of c-myc gene transcription and to the regulation of this gene are discussed.

Animals↗
PubMed1986

Transcriptional and posttranscriptional control of c-myc gene expression in WEHI 231 cells.

Incubation of WEHI 231 cells, derived from a murine B-cell lymphoma, with antisera directed against its surface immunoglobulin results in the inhibition of growth within 24 h. Previously, we demonstrated that this treatment selectively affects cytoplasmic levels of c-myc mRNA (J. E. McCormack, V. H. Pepe, R. B. Kent, M. Dean, A. Marshak-Rothstein, and G. E. Sonenshein, Proc. Natl. Acad. Sci. USA 81:5546-5550, 1984). An initial increase in the cytoplasmic mRNA level is followed by a precipitous drop. We now show that the early increase results from a dramatic increase in the rate of c-myc gene transcription, as well as from partial stabilization of the mRNA in the cytoplasm. The later decrease results from a shutdown in transcription of the c-myc gene and a return to the normal lability of the cytoplasmic c-myc mRNA. Treatment with phorbol ester, like treatment with anti-immunoglobulin sera, inhibited WEHI 231 cell growth and caused similar changes in cytoplasmic c-myc mRNA levels, which can also be related to alterations in c-myc gene transcription. These results indicate that the control of c-myc gene expression in B cells is effected through regulation at multiple levels.

Animals↗
PubMed1984

Specific regulation of c-myc oncogene expression in a murine B-cell lymphoma.

The c-myc oncogene has been implicated in a wide spectrum of B-cell neoplasias. In normal cells, the level of expression of the c-myc gene correlates with growth status. In the present study, we examined the effect of receptor-mediated inhibition of growth on c-myc expression in a B-cell lymphoma. The murine lymphoma line WEHI 231 has been characterized as an early B cell; it bears surface-bound IgM and has unrearranged c-myc genes. Following treatment of a WEHI 231 culture with anti-mouse Ig antiserum, the cells undergo one round of division and further proliferation is inhibited. We observed that this treatment specifically affected cytoplasmic levels of c-myc mRNA. An initial early increase is followed by a precipitous drop such that by 4 hr (after exposure) the amount of c-myc mRNA is below control values by a factor of approximately equal to 10. The drop in c-myc precedes cessation of DNA synthesis. During the 2- to 4-hr period, c-myc mRNA had a maximal half-life of between 20 and 30 min. In contrast, even 24 hr after anti-Ig exposure, the amounts of most major mRNAs, including mu heavy chain and actin, were not significantly altered. These results indicate that expression of an unrearranged c-myc gene can be selectively responsive to receptor-mediated regulatory events.

Animals↗
PubMed1983

Personal sampling impactor with respirable aerosol penetration characteristics.

Single stage impactors with penetration characteristics approximating those of the BMRC, AEC and ACGIH respirable criteria have been developed for use as personal samplers. Three impactors were built for flow rates of 2 L/min. Experimental calibration data of these impactors are compared to the respective respirable criteria for which they were designed. Oil soaked impaction plates were used in these impactors so particles impacting on the plates would always strike an oiled surface and not bounce from the plate. Experiments with coal dust using these plates showed little particle bounce. Finally, a procedure is introduced by which samplers can be designed with penetration characteristics that differentiate between the AEC and ACGIH respirable criteria.

Aerosols↗