Search PubMed⌕ Search

Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 415 records · Page 23Linked to original sources
PubMed1992

Analysis of the contraceptive potential of antibodies against native and deglycosylated porcine ZP3 in vivo and in vitro.

We have undertaken a comparative analysis of the contraceptive activity of antibodies directed against the porcine sperm receptor zona pellucida antigen (ZP3) and its Mr = 32,000 polypeptide core (DGZP-32). The strategies employed for this analysis included the induction of active immunity in a primate, the common marmoset, and an in vitro fertilization protocol involving the use of viable human ova. In both experimental situations, antibodies against ZP3 were shown to exhibit contraceptive activity, leading respectively to the induction of long-term infertility in the primate model and to the complete inhibition of human fertilization in vitro. The in vivo studies also revealed that the induction of high titer antibodies against ZP3 was inevitably associated with the appearance of an ovarian pathology characterized by the progressive depletion of the primordial follicle pool within one to two years. This side effect could not be alleviated by the use of DGZP-32 as antigen since the induction of immunity against this polypeptide was also associated with the eventual appearance of an ovarian pathology identical to that observed with ZP3. Furthermore, the DGZP-32 peptide was less effective than ZP3 in inducing the formation of antibodies capable of inhibiting the fertilization of human ova in vitro. We conclude that significant problems remain with the use of deglycosylated zona peptides for the development of contraceptive vaccines and that their potential will not be realized until the epitopes responsible for the induction of infertility and the primordial follicle depletion have been identified and segregated.

Animals↗
PubMed1992

Demonstration of the intracellular production of tissue-destructive protease by Legionella pneumophila multiplying within guinea-pig and human alveolar macrophages.

The major extracellular enzyme of Legionella pneumophila, a metalloprotease, has been proposed as a pathogenic factor in Legionnaires' disease due to its cytotoxic, tissue-destructive, and phagocyte-inhibitory properties. The relevance of these activities depends on the production of the protease during infection, i.e. by L. pneumophila multiplying intracellularly. In this study, L. pneumophila was demonstrated to produce protease in guinea-pig and human alveolar macrophages infected in vitro. After 24 h infection, approximately 0.1 to 0.2 micrograms of protease per 10(6) bacteria was measured by ELISA in culture supernatants and lysates of the infected cells, whereas no protease could be detected immediately after infection. Immunogold labelling using anti-protease antibody showed the enzyme to be located within phagosomes and distributed throughout the macrophages. Recent observations have shown that this protease could modify host defence mechanisms through inhibition of bacterial killing by neutrophils and monocytes. The intracellular production of the enzyme in infected macrophages demonstrated here further supports a role for the protease in the pathogenesis of Legionnaires' disease.

Animals↗
PubMed1992

Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.

Acute-Phase Reaction↗
PubMed1992

Cost-effectiveness analysis: is it ethical?

Many clinicians believe that allowing costs to influence clinical decisions is unethical. They are mistaken in this belief, because it cannot be ethical to ignore the adverse consequences upon others of the decisions you make, which is what 'costs' represent. There are, however, some important ethical issues in deciding what costs to count, and how to count them. But these dilemmas are equally strong with respect to what benefits to count and how to count them, some of which expose ethically untenable assumptions about such widely-used clinical criteria as survival rates. One of the advantages of systematic cost-effectiveness analysis is that it exposes these hidden assumptions, and requires explicit judgements to be made about which ethical position is appropriate in a particular policy context. This should have the important incidental benefit of improving the accountability of policy-makers to the community they are serving.

Cost Control↗
PubMed1992

Intergenerational talk and communication with older people.

A program of research conducted within an anti-agism paradigm demonstrates that young people process and respond to the speech of older people in stereotypical ways. Such conclusions result from studies using a variety of research methods. Experimental studies demonstrate that older-sounding speech triggers age schematic responses and that young people tend to use agist strategies of information seeking and compliance gaining from older people, while interactive studies explore how stereotypes and age identities are co-produced by young and old people in conversation. We use lifespan and intercultural perspectives to argue that the communicative patterns we observe in our studies are in some senses and contexts counterproductive in both the long and short term, in that they can reproduce negative attitudes toward aging as well as inhibit successful aging.

Adult↗
PubMed1992

Communication skills training in undergraduate medicine: attitudes and attitude change.

The importance of communication skills training in undergraduate medical education is now widely accepted. However little is known about student attitudes towards their own communication skills and whether their attitudes changes as a result of participating in communication skills courses. The aim of the present study was to identify these attitudes prior to commencing such a course and to further evaluate changes in these attitudes on completion of the course. Results demonstrated an improvement in perceived confidence regarding a number of specific communication skills. The study provides further evidence of the value of such courses in undergraduate medical training.

Attitude↗
PubMed1992

Models of healthcare delivery in cancer pain management.

The delivery of pain management services to patients with cancer varies across healthcare settings. Identification of areas common to successful programs would be helpful to healthcare professionals developing or restructuring their own programs. The delivery of pain management services in six different systems is described with respect to organizational structure, service process, and essential components. Three elements common to successful programs are identified: (1) team effort and coordination, (2) provision of education, and (3) accountability and administrative support. The authors conclude that these three elements are critical to the delivery of pain management services across healthcare settings.

Health Personnel↗
PubMed1992

General practitioners' confidence in diagnosing and managing eye conditions: a survey in south Devon.

In order to open dialogue aimed at increasing eye care in general practice and reduce waiting times for ophthalmic outpatient appointments general practitioners in the Torbay health district were asked about their levels of confidence in ophthalmology as a subject, and in the diagnosis and management of specific eye conditions. They were also asked about ophthalmic equipment available to them, their management policies for 34 specific eye conditions, and their perceived need for further training in this subject. A total of 75% of the general practitioners responded to the questionnaire. Despite more than half of the general practitioners indicating that they did not feel confident with ophthalmology generally, most expressed confidence in diagnosing and managing common eye conditions. Basic equipment for examining the eye was available to most doctors. Referral policies varied considerably, and these have resource implications. Seventy eight per cent of respondents were prepared to take on more eye care in general practice, and over 80% of general practitioners requested informal teaching sessions in ophthalmology. Support must be forthcoming if general practitioners are to provide eye care in general practice.

Clinical Competence↗
PubMed1992

Time-course of medial and intimal thickening in pig venous arterial grafts: relationship to endothelial injury and cholesterol accumulation.

With use of an established model of pig saphenous vein grafts in the carotid artery, the time-course of the following changes was related: (1) medial and intimal size by morphometry of transverse sections, (2) cell number by deoxyribonucleic acid concentration, (3) cell density by deoxyribonucleic acid concentration per milligram wet weight and by counting nuclei in transverse sections, (4) endothelial morphology by scanning electron microscopy, and (5) cholesterol concentration. In the first week after grafting, medial and intimal thickening occurred associated with an increase in cell number. Between 1 and 4 weeks after grafting, further rapid medial and intimal thickening occurred with no further increase in cell number but with a reduction in cell density, which suggested that cell migration, hypertrophy, and the laying down of extracellular matrix were responsible. Between 4 and 39 weeks after grafting, a slower increase in medial and intimal size occurred, associated with a parallel increase in cell number and no further change in cell density. The endothelium of grafts showed only localized abnormalities, including loss of cells and leukocyte adhesion, either 1 or 4 weeks after grafting. Cholesterol concentration was slightly elevated 1 week after grafting but returned to values similar to those in vein by 4 weeks after grafting. Distention to 600 mm Hg during surgical preparation of vein for grafting resulted in lower graft patency after either 1 or 4 weeks and caused significant medial and endothelial injury. Distention did not, however, affect changes in medial or intimal size, deoxyribonucleic acid, or cholesterol concentration caused by grafting. We conclude that three processes contribute to medial and intimal thickening, namely: (1) an initial phase of rapid smooth muscle cell proliferation, (2) smooth muscle cell migration, hypertrophy, and synthesis of extracellular matrix, and (3) a late phase of slower smooth muscle cell proliferation. The incomplete late suppression of smooth muscle cell proliferation occurs despite regeneration of a morphologically intact endothelium and in the absence of progressive cholesterol accumulation.

Anastomosis, Surgical↗
PubMed1991

Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1.

Endothelial-leukocyte adhesion molecule 1 is a cell surface glycoprotein expressed by cytokine-activated endothelium that mediates the adhesion of blood neutrophils. Endothelial-leukocyte adhesion molecule 1 is a member of the selectin family of cell adhesion molecules each of which contain an amino-terminal lectin-like domain, followed by an epidermal growth factor-like domain and a variable number of short consensus repeats similar to those found in complement binding proteins. Genomic clones encoding the ELAM gene were isolated and the organization of the ELAM gene was determined. The gene, which is present in a single copy in the human genome, contains 14 exons spanning about 13 kilobases of DNA. The positions of exon-intron boundaries correlate with the putative functional subdivisions of the protein. Introns are found at similar positions in all of the six complement regulatory repeats, suggesting that these elements arose by internal gene duplication. A consensus TATAA element is located upstream of the transcriptional start site. The ELAM promoter contains an inverted CCAAT box and consensus NF-kappa B- and AP-1-binding sites. The ELAM gene was assigned to the q12 greater than qter region of human chromosome 1 by analysis of human-mouse hybrid cell lines. Two other members of the selectin gene family, the leukocyte adhesion molecule 1 (LAM-1, TQ1, LEC-CAM 1, or Leu-8) and the granule membrane protein 140 (GMP-140, PADGEM, or CD62) have been localized to the long arm of chromosome 1, as have the structurally related complement binding proteins, suggesting that these genes may share a common evolutionary history.

Amino Acid Sequence↗
PubMed1991

Magnetic resonance imaging of the head and spine: effective for the clinician or the patient?

OBJECTIVES: To test how the results of magnetic resonance imaging influence clinicians' diagnoses and management plans for patients with cranial and spinal problems and to assess changes in the quality of life of these patients. DESIGN: Survey of patients undergoing cranial and spinal magnetic resonance imaging with questionnaires about diagnoses and intended management plans before and after imaging and quality of life questionnaires at the time of imaging and again four months later. SETTING: Regional magnetic resonance imaging and spectroscopy unit. SUBJECTS: 100 consecutive patients referred for cranial imaging in early 1989; 100 similar patients referred for spinal imaging. MAIN OUTCOME MEASURES: Changes in clinicians' leading diagnoses after magnetic resonance imaging and their confidence in these diagnoses; changes in intended management plans; assessment of the contribution to the future management of the patient; changes in patients' quality of life. RESULTS: Magnetic resonance imaging altered the clinicians' leading diagnoses in 35 of 169 (21%) cases. The clinicians became more confident about their leading diagnoses in 90 of 167 (54%). There was a change in management plan in 113 of 182 (62%). The clinicians considered that magnetic resonance imaging made an important contribution to management in 119 of 162 (73%) patients. Overall, the patients' quality of life was unchanged at the four month assessment. CONCLUSIONS: Magnetic resonance imaging of patients with cranial and spinal problems influences clinicians' diagnoses and management plans, but the quality of life of these patients remains unchanged.

Adolescent↗
PubMed1991

New monoclonal antibodies reacting with bile ducts: further insights into the pathogenesis of bile ductular proliferation in biliary diseases.

We have produced a range of monoclonal antibodies which stain human intrahepatic bile ducts of different sizes. Amongst 26 monoclonal antibodies produced, five clones reacted specifically with bile ducts of different sizes, of which three have been maintained in culture and their viability following freezing and thawing confirmed. Staining patterns varied between normal adult liver tissue, normal fetal liver tissue and a variety of hepatobiliary diseases. The antibodies provide further evidence of the immunological heterogeneity of the human intrahepatic biliary tree and support the hypothesis that proliferating bile ductules are derived from periseptal hepatocytes. The preparation of the antibodies, their staining reactions in normal adult, normal fetal and a variety of liver diseases are described.

Adult↗