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Biomedical subjects

A Edwards

Publications and source records attributed to A Edwards.

At least 181 records · Page 10Linked to original sources
PubMed1995

Immunogenic HIV variant peptides that bind to HLA-B8 can fail to stimulate cytotoxic T lymphocyte responses.

Cytotoxic T lymphocyte responses in HIV infection can be impaired through variation in the epitope regions of viral proteins such as a gag. We report here an analysis of variant epitope peptides in three gag epitopes presented by HLA B8. Fifteen variant peptides were examined for their binding to HLA-B8; all but one bound at concentrations comparable to known epitopes. All except two of those that bound could be recognized by CTL from an HLA-B8 positive HIV-1-infected patient and were therefore immunogenic. However, in a hemophiliac patient studied in detail, there was a failure to respond to two immunogenic peptide epitopes representing virus present as provirus in the patient's peripheral blood. In one case, the patient's CTL had previously responded to the peptide; in the other case, there was a good response to a peptide of closely related sequence. Thus there was a selective failure of the CTL response to some proviral epitopes. This impaired reaction to new variants could contribute to the loss of immune control of the infection.

Animals↗
PubMed1995

Biochemical and molecular characterization of a novel starch synthase from potato tubers.

An isoform of starch synthase from potato tubers which is present both in the stroma of the plastid and tightly bound to starch granules has been identified biochemically and a cDNA has been isolated. The protein encoded by the cDNA is 79.9 kDa and has a putative transit peptide and a distinct N-terminal domain which is predicted to be highly flexible. It is similar in both amino acid sequence and predicted structure to the granule-bound starch synthase II (GBSSII) of pea embryos. When expressed in Escherichia coli, the mature protein has starch synthase activity. The importance of the isoform has been assessed by biochemical measurements and antisense transformation experiments in which the amount of the isoform in the tuber is severely and specifically reduced. Both approaches indicate that the isoform contributes a maximum of 15% of the total starch synthase activity of the tuber. It is suggested that this isoform and the GBSSII of pea embryos represent a widely distributed class of isoforms of starch synthase. The contribution to total starch synthase activity of members of this class probably varies considerably from one type of storage organ to another.

Amino Acid Sequence↗
PubMed1995

Error propagation in the estimation of glomerular pressure from macromolecule sieving data.

The theoretical effects of the glomerular transmural hydraulic pressure difference (delta P) on the sieving coefficients (theta i) of macromolecules of varying size have led to a number of attempts to use sieving curves to estimate delta P noninvasively, with inconsistent results. The objective of this study was to determine the extent to which experimental errors and imperfections in the theoretical models limit the ability to obtain reliable estimates of delta P using this method. Our approach was to generate many sets of synthetic "experimental data" using computer simulations of glomerular sieving and to compute values of delta P by fitting models to those data in the presence of various types and magnitudes of errors. Unbiased experimental errors were simulated by adding random amounts to individual values of theta i, and systematic errors were investigated by using a model based on one type of pore-size distribution to fit "data" generated using a model of a different type. We found that with random errors in theta i only, the estimate of delta P was accurate to within +/- 4 mmHg nearly all of the time, provided that the standard deviation, sigma i, was < or = 5% of theta i. When there were also systematic errors arising from the use of an "incorrect" form of pore-size distribution, a useful predictor of success was the probability P that the residuals, the differences between the measured and predicted sieving coefficients, were randomly distributed. A value of P > 0.2, as calculated from the algebraic signs of the residuals, indicated a high likelihood that the pressure estimate was accurate, provided that the random errors were sufficiently small. When P > 0.2, the fitted value of delta P was within +/- 4 mmHg of the true value in about 90%, 80%, and 70% of the cases examined when sigma i was < or = 2%, 5%, or 10% of theta i, respectively. An analysis of published data from a number of experimental studies indicated, however, that the favorable conditions of small sigma i and large P are extremely difficult to achieve, making it unlikely that an accurate group-mean value of delta P will be estimated from any given set of sieving data. Significant experimental and theoretical advances will be needed to make this a reliable method for estimating glomerular pressure.

Animals↗
PubMed1995

Development of a microporous compliant small bore vascular graft.

PURPOSE: To produce biodurable small diameter microporous vascular grafts with self-sealing properties for vascular access, for peripheral vascular and potentially for coronary artery bypass. The prosthesis should retain compliance and pulsatile flow in situ using a unique modus operandi permitting wall compression which accommodates changes in volume. METHOD: We have utilized efficient low temperature coagulation technology to develop a unique range of small diameter microporous vascular grafts using ChronoFlex, a biodurable polycarbonate urethane. RESULTS: Grafts have been subjected to a range of in vitro and in vivo testing, demonstrating excellent physical and mechanical characteristics, self-sealing, maintenance of compliance and pulsatile flow in situ and patency up to twenty-two weeks.

Animals↗
PubMed1995

The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults.

GH deficiency is associated with increased cardiovascular morbidity, which may be determined by alterations in vascular risk factors. We report the effect of partially treated hypopituitarism and subsequent GH replacement (mean dose, 0.2 IU/kg.week) on putative cardiovascular risk factors in 22 nondiabetic hypopituitary subjects in a 6-month, double blind, controlled study (active/placebo ratio, 11:11). All patients were subsequently treated with GH for a further 6 months. Total fat, percent body fat, and central fat were measured by dual energy x-ray absorptiometry. The hypopituitary patients had increased percent fat (P = 0.03) and central fat (P < 0.01) compared with body mass index-matched controls. Before GH treatment, fasting (total) and specific insulin positively correlated with body mass index (P = 0.02 and P < 0.001, respectively), waist/hip ratio (P = 0.05 and P = 0.01), and central fat (P = 0.03 and P = 0.003). Specific insulin and insulin sensitivity (IS), calculated by homeostatic model of assessment, were related to total fat (P < 0.001 and P = 0.02). GH treatment for 6 months led to a reduction in total fat (P < 0.02), percent fat (P = 0.002), central fat (P = 0.012), waist/hip ratio (P < 0.05), total cholesterol (P = 0.03), and apolipoprotein-B (P = 00001), as well as a decrease in the IS from 36.9% (range, 12-100%) to 25% (range, 2.5-55%; P = 0.0002). This was paralleled by a rise in fasting (total) and specific insulin (P = 0.016 and P = 0.002). The degree of correlation among indices of IS, body composition, and fat distribution increased after GH treatment. Fasting plasma glucose rose significantly, but was within the reference range. During 12 months of GH therapy, a significant increase in serum lipoprotein-(a) was observed (P < 0.05). Although GH has beneficial effects on central adiposity and lipid fractions, it is also associated with a decrease in IS; these effects may vary between individuals.

Adipose Tissue↗
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↗