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Biomedical subjects

R Pearson

Publications and source records attributed to R Pearson.

At least 37 records · Page 2Linked to original sources

Catecholamine and cortisol levels in Oxford college rowers.

Urinary catecholamines and cortisol levels in two teams of Oxford college eight oarsmen were compared on three different day types: training days, racing days, and non-rowing days. Adrenaline and cortisol were raised on racing and training days compared to non-racing days. Noradrenaline was raised on training days, reflecting longer periods of physical exercise during training. There was evidence of a progressive lowering of adrenaline output over consecutive race days and that the outcome of the races had an effect on both adrenaline and cortisol. In addition to this there seemed to be differences in cortisol levels between the two teams of rowers on both racing days and non-rowing days.

Adult↗

A protective "concealed" antigen from Boophilus microplus. Purification, localization, and possible function.

A membrane protein that can be used successfully to vaccinate cattle against the tick Boophilus microplus has been purified and characterized. The mature protein, which is referred to as Bm91, has an apparent m.w. of 86,000, an isoelectric point of 4.8 to 5.2, and is glycosylated, with an affinity for lentil lectin. Bm91 is of relatively low abundance, with approximately 300 to 400 micrograms being recovered from 1 kg of semiengorged adult female ticks. The protein is located largely in the salivary gland and gut of these ticks. Partial amino acid sequence data for the protein show striking similarities to that of mammalian angiotensin-converting enzyme, suggesting that the Ag may have an enzymatic function. The protein seems not to be recognized by sera from cattle with extensive exposure to ticks under natural conditions. The immunity induced by vaccination, therefore, represents another example of vaccination against a hematophagous parasite with "concealed" Ags.

Amino Acid Sequence↗

Segmental framework matrix: master cast verification, corrected cast guide, and analog transfer template for implant-supported prostheses.

A procedure is presented whereby a sectioned acrylic resin framework pattern for an implant-supported prosthesis is used for multiple purposes. It captures the three-dimensional spacial relationship of a dental implant. It acts as an analog transfer template, corrected cast guide, and a rigid scaffolding for the actual sculpting of the framework pattern.

Acrylic Resins↗

Genetic mutations in the K1 and K10 genes of patients with epidermolytic hyperkeratosis. Correlation between location and disease severity.

Epidermolytic hyperkeratosis (EH) is a skin disease caused by mutations in the genes encoding K1 and K10, the differentiation-specific keratins of epidermis. To explore the heterogeneity of mutations and to assess whether a correlation exists between disease severity and the extent to which a mutation interferes with keratin network formation, we determined the genetic bases of four severe incidences of EH and one unusually mild case. Two severe cases have the same mutation, K10-R156:C, at a conserved arginine that we previously showed was mutated to a histidine in two unrelated EH families. An additional severe case has a mutation six residues away, still within the amino end of the alpha-helical rod domain of K10. The other severe case has a mutation in the conserved carboxy end of the K1 rod. In contrast, affected members of the atypically mild family have a mutation just proximal to the conserved carboxy end of the K10 rod. By genetic engineering and gene transfection, we demonstrate that each mutation is functionally responsible for the keratin filament aberrations that are typical of keratinocytes cultured from these patients. Moreover, we show that the mild EH mutation less severely affects filament network formation. Taken together, our studies strengthen the link between filament perturbations, cell fragility, and degeneration.

Amino Acid Sequence↗

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↗

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↗

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↗