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Biomedical subjects

A Edwards

Publications and source records attributed to A Edwards.

At least 163 records · Page 9Linked to original sources
PubMed1994

Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants.

Most asymptomatic individuals infected with HIV-1 have a cytotoxic T lymphocyte (CTL) response to the virus Gag proteins which can be demonstrated in vitro. Epitopes have been mapped in p17 Gag and p24 Gag restricted by HLA-B8 (p17-3 and p24-13) and -B27 (p24-14). Viruses isolated from patients who make CTL responses to these peptides vary within the genetic sequences encoding these epitopes and some mutations lead to reduction in killing activity in vitro. This was attributed to either failure of the variant epitope to bind major histocompatibility complex class I or failure of T-cell receptors to bind the presented peptide. But peptide variants of class I-restricted epitopes cause 'antagonism', that is, the presence of a variant epitope (in the form of peptide) inhibits normal lysis of targets presenting the original epitope. This mirrors similar findings in class II-restricted systems. Here we report that naturally occurring variant forms of p17-3, p24-13 and p24-14 may cause antagonism of CTL lines derived from the same individuals. The effect is present if the epitopes are derived from synthetic peptides and when they are processed from full-length proteins expressed by either recombinant vaccinia constructs or replicating HIV.

Amino Acid Sequence↗
PubMed1994

Transvaginal embryo transfer during the zygote intrafallopian tube transfer procedure.

OBJECTIVE: Our purpose was to evaluate a tactile non-ultrasonographically directed approach to transvaginal tubal cannulation and embryo transfer during the zygote intrafallopian tube transfer procedure. STUDY DESIGN: We studied the application of the tactile approach to transvaginal tubal cannulation and embryo transfer in 68 consecutive zygote intrafallopian tube transfer cycles. RESULTS: The tactile approach to transvaginal tubal cannulation and subsequent embryo transfer was successful in 93% of couples. Pregnancy occurred in 16 of the 63 (25%) women undergoing a successful transvaginal embryo transfer. CONCLUSION: The tactile approach to transvaginal tubal cannulation was found to be easily learned and provided a safe and convenient method of tubal embryo transfer. This low-cost approach, which has application to transfer of both embryos and gametes, deserves further study.

Catheterization↗
PubMed1994

Heterosexual transmission of human immunodeficiency virus type 1 variants associated with zidovudine resistance.

During zidovudine therapy, human immunodeficiency virus type 1 (HIV-1) acquires a distinctive set of mutations that diminish the sensitivity of the virus to this drug in vitro. An AIDS patient is described who, while being treated with zidovudine, transmitted HIV-1 bearing a drug resistance mutation to a young woman who had never received zidovudine treatment. DNA sequencing of HIV-1 proviruses confirmed that these 2 persons shared HIV genetic variants, including a mutation at codon 70 in the reverse transcriptase gene associated with reduced in vitro sensitivity to zidovudine. This mutation persisted in the woman > 1 year in the absence of antiretroviral therapy. HIV-1 with genetic markers of zidovudine resistance can be transmitted heterosexually, but it is uncertain whether dissemination of drug-resistant virus will substantially reduce the usefulness of this drug.

Adult↗
PubMed1994

The autogenous latissimus breast reconstruction.

The autogenous latissimus flap is an alternative to tissue expansion and is the standard latissimus flap in reconstruction of the modified mastectomy defect. It is a useful autogenous reconstruction for partial mastectomy defects, and it serves as an alternative to the TRAM flap. The donor site is acceptable to patients, and the overall results are above average.

Back↗
PubMed1993

Large loop excision of the transformation zone (LLETZ) as an alternative to both local ablative and cone biopsy treatment: a series of 1000 patients.

One thousand patients, referred to the Oxford Colposcopy Clinic, were treated with either large loop excision of the transformation zone (LLETZ, 891 cases) or LLETZ cone (109 cases). Forty-five LLETZ cones were performed empirically, 64 under microcolposcopic guidance. Over 98% of patients were managed as outpatients under local anaesthesia, and 87% of new patients treated with LLETZ had treatment at their first visit. Ninety percent of patients had at least cervical intraepithelial neoplasia grade one (CIN I) and 73% had CIN II or worse. Seventeen cases of invasive or possibly invasive disease were detected, 6 of them unsuspected. The overall rate of complete excision of CIN or worse was 72%. Follow-up was cytologic with or without colposcopy depending on lesion severity. Ninety-one percent of 967 treated patients were free of dyskaryosis at a mean follow-up of 23 months, with complete excision of CIN or worse at LLETZ a significant predictive factor. No cases of invasive carcinoma have developed following treatment. Major morbidity was uncommon, with 3.8% severe hemorrhage. Stenosis was noted in 3.8% cases, mostly after LLETZ cone. One patient (0.1%) has reduced fertility possibly attributable to LLETZ. Questionnaire assessment revealed a very high degree of acceptability of the treatment to patients. LLETZ and LLETZ cone have proved highly acceptable and effective outpatient diagnostic and treatment alternatives to both local ablation and cone biopsy in the Oxford Colposcopy Clinic.

Adolescent↗
PubMed1993

The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years.

A 3-year placebo-controlled trial of sulphasalazine (SASP) in 89 patients with established AS (including radiological sacroiliitis) showed a reduced frequency of peripheral arthritis in the treated group but did not show any definite benefit in the maintenance of spinal mobility. Adverse effects causing treatment withdrawal occurred in five placebo-treated patients and eight SASP-treated patients, but 22 patients preferred to stop taking daily medication of unproven benefit for the full 3 years. The natural history of established AS suggested two groups of patients: the majority with principally spinal symptoms and infrequent peripheral arthritis or iritis, and a minority who tend to have recurrent extra-spinal problems.

Adult↗
PubMed1993

Direct detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction and DNA hybridization.

A polymerase chain reaction (PCR) assay for the rapid diagnosis of pulmonary tuberculosis was developed by using oligonucleotide primers to amplify a fragment of IS6110, an insertion sequence repeated multiple times in the chromosome of Mycobacterium tuberculosis. Sediment obtained from sputa processed by the N-acetyl-L-cysteine-NaOH method was suspended in a simple lysis buffer and was heated at 100 degrees C for 30 min prior to amplification. A dUTP-uracil N-glycosylase PCR protocol was used to prevent false-positive test results because of the carryover of products from previous amplification reactions. The 317-bp amplicon was detected by direct gel analysis and Southern blotting and then hybridization with a biotin-labeled internal probe. Hybrid molecules were detected by using a commercially available avidin-alkaline phosphatase-chemiluminescent substrate system (Tropix, Inc., Bedford, Mass.). The analytical sensitivity of the assay was 10 fg of purified mycobacterial DNA. The limits of detection by culture (Middlebrook 7H11 agar and Lowenstein-Jensen medium) and by PCR were equivalent in terminal dilution experiments for organism suspensions and positive sputa. An internal control was used to detect the presence of amplification inhibitors in each negative reaction mixture. DNA was purified from inhibitory specimens by phenol-chloroform extraction and ethanol precipitation. PCR results were compared with results of microscopy and conventional culture for the detection of M. tuberculosis in 313 sputum specimens. There were 124 specimens that were positive for M. tuberculosis by conventional methods and 113 (91%) that were positive by PCR. PCR detected 105 of 110 (95%) of the smear-positive and 8 of 14 (57%) of the smear-negative specimens. There were no false-positive results by PCR (specificity, 100%). This PCR assay innovations that make application of this new technology feasible in clinical microbiology laboratories.

Bacteriological Techniques↗
PubMed1993

Dual energy X-ray absorptiometry versus skinfold measurements in the assessment of total body fat in renal transplant recipients.

Traditional methods for estimating total body fat rely on the assumption that body fat distribution and bone mineral content are constant. However, in patients undergoing renal transplantation rapid changes in body composition occur, with variations in fat distribution and bone mineral content. In order to determine the reliability of skinfold measurement (SFM) in these patients, we compared it with dual energy X-ray absorptiometry (DEXA), which estimates body composition without reliance on assumptions of constant fat distribution and bone mineral content. Thirty-four adult renal transplant recipients were studied at the time of transplantation and again after 3 and 6 months. The correlation coefficients of DEXA vs SFM at the three time points were 0.84, 0.78, 0.85, respectively (P = 0.0001). In 34 healthy adults serving as controls, the correlation coefficient was 0.95 (P = 0.0001). Total body fat increased progressively following renal transplantation (P < 0.03 by 6 months) with SFM showing considerable disagreement with DEXA measurements of percentage total body fat. Thus skinfold measurements underestimated changes in total body fat following renal transplantation, especially in those gaining substantial amounts of body fat, and DEXA appeared to be a more appropriate technique.

Absorptiometry, Photon↗
PubMed1992

Canadian heart health surveys: a profile of cardiovascular risk. Survey methods and data analysis. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To describe the methods used in nine provincial surveys carried out as part of the Canadian Heart Health Initiative. DESIGN: Population-based cross-sectional surveys, following a core standardized protocol, implemented by provincial departments of health in collaboration with Health and Welfare Canada. Data were obtained through a home interview and a clinic visit. A standard manual of field operations and standardized training procedures were used in all provinces. SETTING: Nine Canadian provinces during the period 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registries in each province. Over 30% of the participants had post-secondary education. About 50% were 18 to 34 years old. OUTCOME MEASURES: Data on sociodemographic characteristics, hypertensive and diabetic status, knowledge and awareness of the causes and consequences of cardiovascular disease and two blood pressure measurements were obtained in a home interview. During a clinic visit, data were collected on height, weight (waist and hip circumferences in four provinces), two blood pressure measures and a blood sample. Total plasma cholesterol, triglycerides and high- and low-density lipoprotein cholesterol were measured in the Lipid Research Laboratory, University of Toronto and St. Michael's Hospital. MAIN RESULTS: Of the subjects invited to participate in the survey, 78% were interviewed, 69% attended the clinic and 64% provided a fasting specimen (8 hours or more). The response rates were slightly lower for men aged 18 to 34, for women aged 65 to 74 and for those with fewer years of education. Data from the provincial surveys (Ontario will complete the survey in 1992) are being compiled in the Canadian Heart Health Database. CONCLUSION: The process followed in the implementation of the provincial heart health surveys is a model of how provincial departments of health may carry out epidemiologic investigations in support of their mandate. The approach illustrates how a country-wide database can be built through partnerships among different levels of government. The use of community health nurses was instrumental in the efficient implementation of the surveys and in the realization of the relatively high rates of response attained.

Adult↗
PubMed1992

Genetic variation at five trimeric and tetrameric tandem repeat loci in four human population groups.

Trimeric and tetrameric short tandem repeats (STRs) represent a rich source of highly polymorphic markers in the human genome that may be studied with the polymerase chain reaction (PCR). We report the analysis of a multilocus genotype survey of 97-380 chromosomes in U.S. Black, White, Mexican-American, and Asian populations at five STR loci located on chromosomes 1, 4, 11, and X. The heterozygote frequencies of the loci ranged from 0.36 to 0.91 and the number of alleles from 6 to 20 for the 20 population and locus combinations. Relative allele frequencies exhibited differences between populations and unimodal, bimodal, and complex distributions. Although deviations were noted at some locus-population test combinations, genotype data from the loci were consistent overall with Hardy-Weinberg equilibrium by three tests. Population subheterogeneity within each ethnic group was not detected by two additional tests. No mutations were detected in a total of 860 meioses for two loci studied in the CEPH kindreds and five loci studied in other families. An indirect estimate of the mutation rates gave values from 2.3 x 10(-5) to 15.9 x 10(-5) for the five loci. Higher mutation rates appear to be associated with greater numbers of tandem repeats in the core motif. The most frequent genotype for all five loci combined appears to have a frequency of 7.59 x 10(-4). Together, these results suggest that trimeric and tetrameric STR loci are useful markers for the study of new mutations and genetic linkage analysis and for application to personal identification in the medical and forensic sciences.

Alleles↗
PubMed1992

Characterization of cDNAs encoding two isoforms of granule-bound starch synthase which show differential expression in developing storage organs of pea and potato.

We have isolated cDNA clones to two isoforms of granule-bound starch synthase (GBSS) from pea embryos and potato tubers. The sequences of both isoforms are related to that of glycogen synthase from E. coli and one, GBSSI, is very similar to the waxy protein of maize and other species. In pea, GBSSII carries a novel 203-amino-acid domain at its N-terminus. Genes encoding both proteins are expressed during pea embryo development, but GBSSII is most highly expressed earlier in development than GBSSI. Similarly, GBSSI and GBSSII are differentially expressed in developing potato tubers. Expression of both isoforms is much lower in other organs of pea than in embryos. GBSSII is expressed in every organ tested while GBSSI is not expressed in roots, stipules or flowers. The possible consequences of this differential use of GBSS isoforms are discussed.

Amino Acid Sequence↗