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Biomedical subjects

A Stevens

Publications and source records attributed to A Stevens.

At least 217 records · Page 12Linked to original sources

HIV testing in antenatal clinics: the impact on women.

One hundred and fifty-five women attending antenatal clinics in an inner city area where the rate of AIDS reporting is high were interviewed to examine the acceptability of different modes and purposes of antenatal HIV testing. Eighty-two per cent of women felt the test should be available in antenatal clinics, but only 48% reported that they themselves would take the test. Seventy-four per cent would accept anonymous testing. Potential anxiety levels surrounding the HIV test were significantly higher than for other (currently routine) tests in antenatal clinics. The implications of these findings for policy are discussed.

AIDS Serodiagnosis↗

Drugs affecting postural stability and other risk factors in the hip fracture epidemic--case-control study.

A parallel rise in hip fracture incidence and the rate of prescription of drugs affecting postural stability have been investigated by a case-control study. Other risk factors were also considered. One hundred and seventy-three cases and 134 hospital emergency surgical controls were interviewed and briefly examined, and drug data were corroborated by letter to general practitioners. The analysis revealed no significant difference between consumption of benzodiazepines in cases and controls, major tranquillizers, diuretics or other anti-hypertensives. However, they differed significantly in their average body weight and incidence of stroke. It is suggested that hip fractures on the whole occur in a particularly frail group of elderly people and that the increased fracture incidence over the last 20 years results from the survival of a more frail or less active group than hitherto.

Age Factors↗

Priorities in a London teaching hospital: a health services research approach to gynaecology provision.

In late 1987, as part of the response to an overspend of pounds 3.2 million, the health authority of an inner London teaching district, Paddington and North Kensington, proposed to close urgently 16 of the 56 gynaecology beds at the Samaritan hospital. They did so on the assumption that the hospital often served women who were neither local nor required the special expertise of a teaching hospital. To test this assumption, we reviewed the functions and funding of the hospital, how its activity level and size compared with other districts, and the nature of the workload, i.e. the extent to which the patients were local or non-local, or needed routine or specialist care. It was agreed that non-local routine patients are the district's lowest priority, and we demonstrated that such patients account for no more than six to 11 beds. This information helped to resolve negotiations over the bed numbers. This study demonstrates that it was possible to defuse a potential confrontation by using routinely available and additional survey data to inform the debate.

Catchment Area, Health↗

The measurement of osteoporosis in clinical practice. Comparison of histological and radiological methods.

In a prospective study of the measurement of osteoporosis in patients with fracture of the femoral neck, we compared a histological with a radiological method. We found no significant correlation between histological planimetry and the radiological six metacarpal hand index in patients with either cervical or trochanteric fractures. This demonstrates that metacarpal morphometry cannot predict histological osteoporosis of the iliac crest.

Aged↗

Specific dissociation of alpha B subunits from alpha-crystallin.

Exposure of bovine alpha-crystallin to 0.1 M glycine at pH 7 decreases the average molar mass of the protein from 700 to 420 kDa. When the pH is lowered to 2.5, in the same buffer, the alpha B chains specifically dissociate from the aggregates, leaving a particle of 290 kDa containing only alpha A chains. The decrease in the molar mass corresponds to the mass of the alpha B chains in the original aggregate. The pH-dependent dissociation is fully reversible. Similar changes were observed with rat and kangaroo alpha-crystallins but the dogfish protein was not affected. Sedimentation velocity analyses and fluorescence spectroscopy yielded a pK, for the dissociation, of 3.7 for alpha-crystallin and 4.0 for a homopolymer constructed from purified alpha B2 polypeptides. An alpha A2 homopolymer was virtually unaffected by the lowering of pH. The products from the dissociation were isolated and their properties studied by sedimentation analysis and acrylamide quenching of tryptophan fluorescence. The alpha B chains were found to be completely denatured, whereas the structure of the alpha A chains, in the 290 kDa, particle, were only slightly altered. Comparisons of the sequences of the various proteins examined suggested that decreased ionization of aspartic acid 127 in the alpha B chain was responsible for the specific dissociation of this polypeptide.

Animals↗

Cloning of authentic human epidermal growth factor as a bacterial secretory protein and its initial structure-function analysis by site-directed mutagenesis.

A synthetic chimeric gene, coding for the human epidermal growth factor fused to the signal peptide of Escherichia coli alkaline phosphatase, was cloned into E. coli under the transcriptional control of the trp-lac (tac) promoter. Following induction with isopropylthiogalactoside, the secretion of the correctly processed protein product into the bacterial periplasm was detected and quantitated by its specific binding to the epidermal growth factor receptor. The purified protein was identical to authentic human epidermal growth factor in size, amino acid composition, primary sequence, receptor binding, and stimulation of receptor protein-tyrosine kinase activity. Based on interspecies homologies, structural considerations, and reported studies with peptide fragments, structure-function analysis was initiated with alterations of targeted amino acid residues by oligonucleotide-directed mutagenesis. The receptor binding affinity of each mutant, relative to the wild type, was measured by both radioreceptor competition and receptor tyrosine kinase stimulation assays. In general, the values obtained by the two methods were in agreement for each species of epidermal growth factor and followed the order: wild type greater than Glu24----Gly greater than Asp27----Gly much greater than Pro7----Thr greater than Tyr29----Gly greater than Leu47----His. The relatively low values obtained with the last two mutants suggest that Tyr29 and Leu47 may be important for the biological activity of human epidermal growth factor.

Alkaline Phosphatase↗

Inflammatory infiltrates and natural killer cell presence in human brain tumors.

Immunohistochemical analysis of subpopulations of inflammatory cells in 81 primary and secondary human brain tumors was done. Natural killer (NK) cells, representing non-major histocompatibility complex-restricted, spontaneous cytotoxicity and monocytic cells are virtually absent in infiltrates of gliomas and account only for a minor percentage of inflammatory cells in brain metastases of carcinoma and in craniopharyngeomas. Infiltrates in gliomas consist almost exclusively of T-cells of the suppressor/cytotoxic type whereas infiltrates in carcinoma metastases and craniopharyngeomas contain considerable numbers of T-helper/inducer cells and B-cells. From this the authors conclude (1) that NK cells do not play a major role in tumor rejection, and (2) that the kind of inflammatory reaction does not depend upon the tumor site but more likely on the tumor type. No correlation between tumor differentiation and infiltrate composition is evident.

Antibodies, Monoclonal↗

Demyelination of sciatic nerve in acute experimental allergic neuritis of the rat. A gel electrophoresis investigation.

Acute experimental allergic neuritis (EAN) of Lewis rats was monitored by clinical and electrophysiological tests for 60 days. Sciatic nerve myelin proteins were analyzed by quantitative microgel electrophoresis and electroimmunoblotting at different clinical stages of the disease. The clinical severity of EAN and the demyelination as measured by electrophysiological tests and myelin protein concentrations in sciatic nerve did not correspond during the course of the disease. Demyelination reached its peak after partial clinical recovery and was still present on day 60. The major peripheral nervous system (PNS) myelin proteins P0, P1 and P2 decreased at different rates during the course of the disease, indicating possible differences in their proteolytic degradation. Treatment with Freund's complete adjuvant (CFA) alone resulted in alterations of membrane and myelin protein patterns challenging the widely held belief that pure CFA is inert with regard to demyelination.

Animals↗

Isolation of alpha-crystallin and its subunits by affinity chromatography on immobilized monoclonal antibodies.

Use has been made of the specific interactions between monoclonal antibodies and the alpha A or alpha B subunits of alpha-crystallin to devise methods for the purification of the intact protein or its subunits. alpha A and alpha B subunits were separated by affinity chromatography on an immobilized monoclonal antibody specific for alpha A chains, using a pH gradient. Use of an antibody which binds both subunits has enabled the isolation of intact alpha-crystallin aggregates. Gel electrophoresis, conformational probing and size analysis showed that the affinity purified proteins were purer but otherwise indistinguishable from the alpha-crystallins isolated by other methods.

Animals↗

Characterization of a benzyladenine binding-site peptide isolated from a wheat cytokinin-binding protein: sequence analysis and identification of a single affinity-labeled histidine residue by mass spectrometry.

A wheat embryo cytokinin-binding protein was covalently modified with the radiolabeled photoaffinity ligand 2-azido-N6-[14C]benzyladenine. A single labeled peptide was obtained after proteolytic digestion and isolation by reversed-phase and anion-exchange HPLC. Sequencing by classical Edman degradation identified 11 of the 12 residues but failed to identify the labeled amino acid. Analysis by laser photodissociation Fourier-transform mass spectrometry of 10 pmol of the peptide independently confirmed the Edman data and also demonstrated that the histidine residue nearest the C terminus (underlined) was modified by the reagent in the sequence Ala-Phe-Leu-Gln-Pro-Ser-His-His-Asp-Ala-Asp-Glu.

Adenine↗

mRNA-decapping enzyme from Saccharomyces cerevisiae: purification and unique specificity for long RNA chains.

An enzyme that hydrolyzes one PPi bond of the cap structure of mRNA, yielding m7GDP and 5'-p RNA was purified from Saccharomyces cerevisiae to a stage suitable for characterization. The specificity of the enzyme was studied, using both yeast mRNA and synthetic RNAs labeled in the cap structure. A synthetic capped RNA (540 nucleotides) was not reduced in size, while as much as 80% was decapped. Yeast mRNA treated with high concentrations of RNase A, nuclease P1, or micrococcal nuclease was inactive as a substrate. The use of synthetic capped RNAs of different sizes (50 to 540 nucleotides) as substrates showed that the larger RNA can be a better substrate by as much as 10-fold. GpppG-RNA was hydrolyzed at a rate similar to that at which 5'-triphosphate end group were not hydrolyzed.

Fungal Proteins↗

Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres.

A retrospective cohort of 823 patients with ulcerative colitis who resided at the time of diagnosis in one of three defined geographical areas (West Midlands region, Oxford region, England and Stockholm County, Sweden) was assembled. The patients were first seen at named hospitals in these areas and the diagnosis of ulcerative colitis established within five years of onset of symptoms between 1945-1965. All patients were 15 years of age or more at onset of disease and were followed for a minimum of 17 years and a maximum of 38 years. Ninety seven per cent completeness of follow up was achieved. Examining the colorectal cancer risk in the series relative to the risk in the general population by standardised morbidity ratios, there was an eight fold increased risk of cancer in the series as a whole. Dividing the series by extent of colitis, extensive colitis patients showed a 19 fold increase in risk. A four fold increased risk was shown in the remainder of the series (left sided colitis, proctitis and extent unknown). Life table analyses in extensive colitis gave cumulative risks of 7.2% (CI 3.6-10.8) at 20 years from onset of disease and 16.5% (CI 9.0-24.0) at 30 years from onset. No significant effect of age at onset, sex or referral centre could be detected. Examination of the data by interval from onset to cancer and by actual age at development of cancer suggests that patients who develop colorectal cancer will do so in a distribution around 50 years of age independent of duration of disease in adult onset ulcerative colitis (greater than 15 years at onset of disease). An inverse relationship was shown between age at onset of disease and interval from onset of disease to cancer. Further age specific rates for cancer increased up to 50 years and decreased thereafter. These results suggest that extensive colitis patients have a genetic predisposition to colorectal cancer and that longstanding inflammation is not of primary importance in the initiation/promotion of cancer in this disease.

Actuarial Analysis↗

A 5'----3' exoribonuclease of Saccharomyces cerevisiae: size and novel substrate specificity.

The purification scheme for a 5'----3' exoribonuclease of Saccharomyces cerevisiae has been modified to facilitate purification of larger amounts of enzyme and further extended to yield highly purified enzyme by use of poly(A)-agarose chromatography. As determined by either sodium dodecyl sulfate-polyacrylamide gel electrophoresis or physical characterization, the enzyme has a molecular weight of about 160,000. Further studies of its substrate specificity show that poly(C) and poly(U) preparations require 5' phosphorylation for activity and that poly(A) with a 5'-triphosphate end group is hydrolyzed at only 12% of the rate of poly(A) with a 5'-monophosphate end group. DNA is not hydrolyzed, but synthetic polydeoxyribonucleotides are strong competitive inhibitors of the hydrolysis of noncomplementary ribopolymers. Poly(A).poly(U) and poly(A).poly(dT) are hydrolyzed at 60 and 50%, respectively, of the rate of poly(A) at 37 degrees C. The RNase H activity of the enzyme can also be demonstrated using an RNA X M13 DNA hybrid as a substrate. When poly(dT).poly(dA) with a 5'-terminal poly(A) segment on the poly(dA) is used as a substrate, the enzyme hydrolyzes the poly(A) "tail," removing the last ribonucleotide, but does not hydrolyze the poly(dA).

Exoribonucleases↗