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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 73 records · Page 4Linked to original sources
PubMed1999

Characterization of replication-competent adenovirus isolates from large-scale production of a recombinant adenoviral vector.

Replication-deficient adenoviral vectors have been developed for the delivery of DNA sequences encoding a variety of proteins intended for the management of disease through gene therapy. One concern is the occurrence of replication-competent adenovirus (RCA) in the population of replication-deficient adenoviral vectors as a result of recombination or contamination. To address this concern, it is necessary to determine the frequency of occurrence and to fully characterize the molecular structure and biological infectivity of RCA. rAd/p53 is a pIX-deleted p53 gene therapy vector that is designed to lower the RCA occurrence and to deliver the tumor suppressor gene p53 for treatment of various cancers. Multiple preparations of the replication-deficient adenoviral vector rAd/p53 were tested for the presence of RCA, employing a sensitive biological assay. Single plaques from RCA-positive preparations of rAd/p53 were isolated for molecular characterization. All of the RCA isolates displayed a single unique structure that contains the complete E1 sequence of adenovirus type 5 but lacks the p53 sequence. The detailed sequence analysis of the RCA suggests that it is most likely generated as a result of recombination events between the rAd/p53 DNA and the 293 host adenoviral sequence. Results from viral infectivity analysis by flow cytometry demonstrate no substantial difference in infectivity of RCA, rAd/p53, and wild-type adenovirus type 5 in 293 cells.

Adenovirus E1A Proteins↗
PubMed1999

Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins.

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.

Adolescent↗
PubMed1999

A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs.

Important risk factors for melanoma are densely clustered melanocytic nevi (common moles) and mutations in the p16 (CDKN2A) gene. Nevi may be subclassified as raised or flat. In our sample, raised nevi were 27% of the total, and the two kinds had a correlation of.33. Correlations for total-nevus count (TNC) in 153 MZ and 199 DZ twin pairs were.94 and.60, respectively, which are compatible with a very-high degree of genetic determination. We hypothesized that some of the genetic variance might be due to variation in the p16 gene. Analysis of linkage to a highly polymorphic marker (D9S942), located close to p16, detected quantitative-trait-loci (QTL) effects accounting for 27% of variance in TNC, rising to 33% if flat but not raised moles were considered. Total heritability was higher for raised (.69) than for flat (.42) moles, but QTL linkage was 0 for raised moles, whereas it accounted for 80% of the heritability of flat moles; additionally, family environment accounted for only 15% of variance in raised versus 46% in flat moles. These findings suggest that raised and flat nevi have very different etiologies. Longer alleles at D9S942 were associated with higher flat-mole counts, and a novel modification to a within-sibship association test showed that this association is genuine and not due to population stratification, although it accounts for only 1% of total variance. Since germline mutations in the exons of CDKN2A are rare, it is likely that variants in the noncoding regions of this gene, or in another gene nearby, are responsible for this major determinant of moliness and, hence, of melanoma risk.

Child↗
PubMed1999

Flumazenil in drug overdose: randomized, placebo-controlled study to assess cost effectiveness.

OBJECTIVE: To investigate cost effectiveness of administration of flumazenil to patients presenting with suspected acute drug overdose. DESIGN: Double-blind, prospective, placebo-controlled randomized study. SETTING: University teaching hospital. PATIENTS: Forty-three adults presenting with suspected drug overdose and having a Glasgow Coma Scale (GCS) score of <13. Patients with known benzodiazepine/tricyclic ingestion were excluded. INTERVENTIONS: Intravenous administration of flumazenil (up to 2 mg) or placebo. MEASUREMENTS AND MAIN RESULTS: Individual patient costs were assessed and data aggregated for each treatment group. Major diagnostic and therapeutic interventions were recorded and between group comparisons performed. Clinical response to study drug administration was assessed by obtaining pre- and post-drug GCS scores and observation of the patient for at least 180 mins for signs of resedation. Aggregate cost or number of major diagnostic and therapeutic interventions were not different between groups. Patients randomized to the flumazenil group showed a marked increase in GCS score (7.4 to 11.8) compared with those in the placebo group (8.2 to 8.6). CONCLUSION: Use of flumazenil in intentional drug overdose of unknown etiology is not cost effective.

Adolescent↗
PubMed1998

Comparison of flow cytometry and laser scanning cytometry for the intracellular evaluation of adenoviral infectivity and p53 protein expression in gene therapy.

The determination of recombinant adenoviral (rAd) infectivity and p53 protein expression is important for the evaluation of rAd vectors containing the p53 gene (rAd-CMV-p53) for gene therapy. We have previously reported that rAd5-CMV-p53 vectors can be assessed for infectivity and concomitant p53 protein expression in single- and two-color assays using intracellular staining methodology and flow cytometric analysis. We have compared the flow cytometry-based assays for rAd infectivity (hexon protein) and p53 protein expression with the new slide-based laser scanning cytometry (LSC). We report that LSC analysis of rAd-CMV-p53-infected human 293 cells correlated very well with flow cytometric analysis across a wide range of viral infectivity for both infectivity assessment (r2 = 0.97) and p53 protein expression (r2 = 0.96). Absolute values for infective titer and p53 protein expression titer from an rAd5-CMV-p53 production batch were similar and within experimental error with the two different analytical methods. Finally, bivariate format analysis of rAd-CMV-p53-infected cells revealed comparable results between LSC and flow cytometric analysis. LSC is a reliable and useful tool for the intracellular staining for adenoviral hexon protein expression for determining infectivity and for p53 protein expression from an expressed p53 transgene.

Adenoviruses, Human↗
PubMed1998

Dentists in the chair.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMed1998

Age limitation on provision of orthopedic therapy and orthognathic surgery.

Canadian orthodontists were surveyed by mail to determine the latest skeletal age at which they would recommend orthopedic therapy and orthognathic surgery and the earliest at which they would recommend orthognathic surgery. For the purposes of this introductory study, orthopedic therapy implied stimulation of physiologic response using appliance force, without specification of appliance type. Response rate from 512 orthodontists was 65% (n = 334), with the response rate by item varying from 92% to 95%. By Greulich and Pyle standards, the latest recommended age for orthopedic therapy was at 97% completion of skeletal growth (females 13.5 years, males 15 years), whereas the earliest recommended age for orthognathic surgery was when skeletal growth is 99% complete (females 14.9 years, males 16.5 years). Surgery would be recommended by 32% of respondents for a patient before the age of 8 years, if deformity is severe. For orthognathic surgery, respondents either perceived no age maximum or recommended 69 years, the maximum age on the questionnaire item. Orthodontists' traits influenced recommendations for timing treatment.

Adolescent↗
PubMed1997

Asking the academics.

Assumptions are no match for real consultation. As part of the MRI, the BDJ conducted a special survey to see if academic dentists could predict the primary care research priorities of general dental practitioners. How would the predictions differ from the priorities of the GDPs themselves?

Attitude of Health Personnel↗