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R Pearson

Publications and source records attributed to R Pearson.

At least 19 recordsLinked to original sources
PubMed1992

Coupled down-regulation of the RB retinoblastoma and c-myc genes antecedes cell differentiation: possible role of RB as a "status quo" gene.

The ability of the well known morphogen, retinoic acid (RA), as well as 1,25-dihydroxy-vitamin D3 (VD), whose receptor complex binds a DNA consensus sequence related to that of the retinoic acid receptor, to regulate expression of the retinoblastoma (RB) tumor suppressor gene in a context of induced cell differentiation was characterized. HL-60 human promyelocytic leukemia cells were induced to undergo myeloid or monocytic terminal cell differentiation by these agents. To investigate the potential coupling between down-regulation of RB and c-myc oncogene expression with cell differentiation, dose response relationships for the induced down-regulation of RB and c-myc expression were compared with each other and with induced cell differentiation. The total amount of RB protein per cell increased as cells advanced through the cell cycle, but the amount of RB protein relative to the total cell mass remained approximately constant. Treated with RA or VD, an early progressive decrease in cellular content of the RB protein occurred in all cell cycle phases well before any cell cycle modulation or phenotypic differentiation. For a differentiation-defective variant HL-60 cell line, failure to differentiate was preceded by a failure to down-regulate cellular levels of the RB protein. In dose response experiments, progressively increasing RA or VD concentrations caused progressively greater reductions in RB as well as c-myc expression with an increasing fraction of cells terminally differentiating. For both RA and VD, the dose response relationships for reductions in RB and c-myc expression were similar suggesting that their down-regulation may be coupled. These observations are consistent with a model whereby RB expression acts as a cellular brake to sustain a developmentally ordained state of differentiation (i.e., preserve the "status quo"); and the down-regulation of heterogeneously distributed RB protein per cell below a threshold is part of the metabolic cascade culminating in terminal cell differentiation. Thus, RB may have a role in this developmental context.

Calcitriol↗
PubMed1992

Continuous ambulatory peritoneal dialysis and renal transplantation: a ten-year experience in a single center.

OBJECTIVE: To assess whether a renal graft outcome is dependent on the modality of dialysis prior to transplantation and to assess risk of peritonitis and catheter-related problems posttransplantation. DESIGN: Retrospect analysis of the outcome of a first cadaveric renal transplantation from hemodialysis (HD) and CAPD patients over a ten-year period. PATIENTS: Out of a total of 905 renal transplants over a ten-year period, 699 were first grafts; 500 of these (241 on CAPD, 259 on hemodialysis) were analyzed while the remaining (incomplete data, predialysis, pediatric) were assessed for graft and patient survival only. MAIN OUTCOME: Graft and patient survival cases were identical in the two groups (five-year graft survival: CAPD 67%, hemodialysis 66%; five-year patient survival: CAPD 88%, hemodialysis 87%). CAPD posttransplant was necessary in 37 patients, while 10 developed peritonitis mostly related to CAPD use and responded to appropriate therapy. Routine catheter removal posttransplant was undertaken between 8 and 12 weeks. CONCLUSION: Excellent graft and patient survival is achieved independent of the modality of dialysis prior to transplantation. Peritoneal dialysis can be used postgrafting, but there is a risk of peritonitis, which can be successfully managed with antibiotics and catheter removal. Great care is needed in executing the dialysis and catheter care after transplantation.

Adult↗
PubMed1991

Mutational analysis of the transin (rat stromelysin) autoinhibitor region demonstrates a role for residues surrounding the "cysteine switch".

The family of mammalian extracellular matrix metalloproteases (MMPs) are secreted by cells in an inactive (latent) proenzyme form. A highly conserved amino acid sequence, PRCGVPDV, is found near the COOH-terminal end of the pro-domain of these MMPs and believed to act as an "autoinhibitor." Recent studies (Springman, E. B., Angleton, E. L., Birkedal-Hansen, H., and Wart, H. E. V. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 364-368) indicate the Cys of this sequence ligands to the active-site zinc keeping the proenzyme in an inactive state, and mutational analysis (Sanchez-Lopez, R., Nicholson, R., Gesnel, M. C., Matrisian, L. M., and Breathnach, R. (1988) J. Biol. Chem. 263, 11892-11899) suggests that the conserved residues surrounding this Cys are required for latency. We have constructed 16 new site-directed mutations of the PRCGVPDV autoinhibitor region of the MMP transin (rat stromelysin) and tested whether these mutant enzymes are produced in a latent or activated form. We find that the conserved Arg as well as the Cys are essential for maintaining latency. The Cys cannot be replaced by other zinc-liganding amino acids, and the Arg cannot be replaced by Lys. Residues immediately surrounding the Cys are sensitive to even conservative amino acid substitutions. We show that a synthetic peptide PRCGVPDV is capable of acting as a weak inhibitor of transin and that replacement of the Cys with a Ser abolishes inhibition by the peptide. A review of the current knowledge of MMP substrate specificity in combination with these new results suggests that the PRCGVPDV sequence does not inhibit activity by mimicking the known substrates of the protease.

Amino Acid Sequence↗