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Biomedical subjects

R Pearson

Publications and source records attributed to R Pearson.

At least 19 recordsLinked to original sources

Antibody-mediated inhibition of the growth of larvae from an insect causing cutaneous myiasis in a mammalian host.

Many insects feed on blood or tissue from mammalian hosts. One potential strategy for the control of these insects is to vaccinate the host with antigens derived from the insect. The larvae of the fly Lucilia cuprina feed on ovine tissue and tissue fluids causing a cutaneous myiasis associated with considerable host morbidity and mortality. A candidate vaccine antigen, peritrophin 95, was purified from the peritrophic membrane, which lines the gut of these larvae. Serum from sheep vaccinated with peritrophin 95 inhibited growth of first-instar L. cuprina larvae that fed on this serum. Growth inhibition was probably caused by antibody-mediated blockage of the normally semipermeable peritrophic membrane and the subsequent development of an impervious layer of undefined composition on the gut lumen side of the peritrophic membrane that restricted access of nutrients to the larvae. The amino acid sequence of peritrophin 95 was determined by cloning the DNA complementary to its mRNA. The deduced amino acid sequence codes for a secreted protein containing a distinct Cys-rich domain of 317 amino acids followed by a mucin-like domain of 139 amino acids. The Cys-rich domain may be involved in binding chitin. This report describes a novel immunological strategy for the potential control of L. cuprina larvae that may have general application to the control of other insect pests.

Amino Acid Sequence

Stabilization investment template for direct casting connection of implant framework segments.

This article presents a procedure whereby a template made of casting investment is used to stabilize a sectioned implant framework that has been adapted in a passive relationship to the implant analogs in a corrected master cast. The joints in the sectioned framework are filled with wax, sprues attached, and the template and sectioned framework are invested in a casting ring. When the casting procedure is completed, the framework will be reconnected by direct metal casting.

Dental Casting Investment

Factors in standardizing automated cholinesterase assays.

A scientific panel assembled by the U.S. Environmental Protection Agency (EPA) determined that variability in cholinesterase (ChE) activities in the agency's pesticide/animal study database likely was due to a lack of accepted guidelines for ChE methodology. A series of trials was held in which participating laboratories measured ChE activity in blood and brain samples from untreated and pesticide-treated rats using a colorimetric assay method. The degree of inhibition of ChE activity in plasma and brain samples compared to controls was consistent among most of the laboratories. The ChE activity in erythrocyte samples differed more between laboratories due to a high blank, low erythrocyte AChE activity and hemoglobin absorption at the wavelength of the assay. Strategies are suggested for minimizing the variability of ChE activity in hemoglobin-rich samples.

Acetylcholinesterase

The entry of mentally disordered people to the criminal justice system.

BACKGROUND: The police are the gatekeepers to the criminal justice system (CJS). It is agreed that where possible mentally ill people should be diverted to psychiatric care. The purpose of this investigation was to determine what factors were associated with the entry of obviously mentally ill people into the CJS. METHOD: The population of all detainees arrested in seven London police stations was observed to determine the presence of obvious mental illness. All detainees regarded as ill or known to have significant psychiatric histories were followed through the CJS to court disposal. Defendants diagnosed as psychotic by court liaison psychiatrists were identified and the circumstances of their arrest and detention examined. RESULTS: Of all police detainees observed, 1.4% were found to be acutely ill. Diversion of obviously ill detainees was common practice. The factor most strongly associated with entry to the CJS was the presence of violence at time of arrest. Other factors were the persistence of (petty) offending and the operation of court warrants issued as a result of the person's failure to appear at court when required to do so. CONCLUSIONS: Both police and courts are well aware of the inappropriateness of custody for acutely ill people and efforts are made to divert such people out of the CJS. Persistent petty offenders are often being recycled from the street to police station to court and back to the street without the benefit of care. A dedicated facility is recommended in central London to meet this need.

Criminal Law

Drunkenness among police detainees.

All detainees at seven police stations within the Metropolitan Police Area were observed by the authors. Continuous 24-hour cover was provided at each station for periods of 3 weeks. The number of people arrested for offences of drunkenness was noted, as was the apparent degree of drunkenness of all detainees, irrespective of arrest offence. Arrest for drunkenness in London was strongly associated with being white and with having been born in Scotland or Ireland. Within the confines of the station, being drunk was associated with aggressiveness, with the need for medical examination and with delays in implementing interview procedures. The physical condition of many chronically drunk people was very poor and evidence of long-term self neglect was common. Formal cautioning of drunkenness offenders has effectively removed such people from the courts; in the present study only 5% of those arrested for drunkenness alone were subsequently charged. Despite this the police in London must continue to arrest and detain the drunk and incapable for want of suitable alternatives.

Adolescent

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