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Biomedical subjects

B Evans

Publications and source records attributed to B Evans.

At least 19 recordsLinked to original sources
PubMed1992

Bending-incompetent variants of Flp recombinase mediate strand transfer in half-site recombinations: role of DNA bending in recombination.

One key feature of the interaction of Flp recombinase with its target site (FRT) is the large bend introduced in the substrate as a result of protein binding. The extent of bending was found to depend on the phasing and spacing of the Flp monomers occupying the two Flp-binding elements (FBE) bordering the strand-exchange region (spacer) of the substrate. The relative mobilities of the Flp complexes formed by the two permuted substrate fragments, containing the FRT site near the end or in the middle, corresponded to a DNA bend of approx. 140 degrees when each of the two FBEs flanking the spacer was occupied by a protein monomer. The estimated bend angle was the same when the reference DNA fragment with the FRT site at the end was substituted by one with the site in the middle, but containing a 4-bp insertion within the spacer. We used a combination of wild-type Flp and Flp variants that were competent or incompetent in DNA bending, together with full, or half FRT sites, to ask whether bending is a conformational requirement for catalysis, namely cleavage and exchange of strands. We obtained the following results: in full-site (FRT) vs. full-site recombinations or in full-site vs. half-site (half FRT) recombinations, there was a large difference in the reactivity between Flp and a bending-incompetent Flp variant. This difference virtually disappeared when reactions were done with half-FRT sites. We conclude that bending is not a prerequisite for catalysis, but represents the manner in which the substrate accommodates the Flp protomer-protomer interactions that are pertinent to catalysis.

Base Sequence↗
PubMed1992

A population-wide profile of prescription drug use in Saskatchewan, 1989.

OBJECTIVE: To measure the prevalence of prescription drug use in Saskatchewan in 1989. DESIGN: Retrospective study. PARTICIPANTS: A total of 961,203 Saskatchewan residents (including those who died or were born during the study year) who were eligible for coverage under the Saskatchewan Prescription Drug Plan. The study population represented 94% of the province's total population; those excluded were mostly status Indians (for whom a federal plan is available). MAIN RESULTS: At least one prescription was received by 66.0% of the study population in 1989. The mean number of prescriptions per patient was 8.2, and the mean cost of drug material per prescription was $13.95. Females received substantially more prescriptions than males; the difference was particularly notable for cardiovascular agents, antidepressants and benzodiazepines. In the senior population 80.8% received at least one prescription; the mean number of prescriptions per patient was 18.4. The most commonly dispensed drug for the entire study population was amoxicillin (290 prescriptions per 1000 people); triazolam was the most frequently dispensed central nervous system drug (74 prescriptions per 1000 people). Regional variation in overall drug use was remarkably small, although it increased at the drug-class level, especially for tranquillizers. The use of cardiovascular drugs was 27% to 32% higher (depending on how use was measured) per Regina resident than per Saskatoon resident. Benzodiazepines were commonly used on a long-term basis, despite recommendations to the contrary. CONCLUSIONS: The results quantify the prevalence of prescription drug use, underscore the importance of careful management of drug therapy by physicians and pharmacists (especially for seniors), illustrate substantial variation in drug therapy strategies and raise questions about utilization of benzodiazepines and cardiovascular drugs.

Age Factors↗
PubMed1992

The effect of cyclosporin A on cationized bovine serum albumin-induced nephropathy in NZW rabbits.

The effect of cyclosporin A (CyA) was studied on the morphology and protein excretion of a rabbit chronic serum sickness nephritis using cationized bovine serum albumin (cBSA). One group of rabbits was given intravenous (i.v.) immunizing doses of cBSA and Escherichia coli endotoxin. One week later, these animals began a 6-week i.v. injection schedule of cBSA only. A second group followed the same injection protocol, but was given intramuscular (i.m.) CyA for 3 days prior to the immunizing dose of cBSA/endotoxin and throughout the subsequent cBSA schedule. A third group was given i.m. CyA only. Regular blood samples for CyA levels were taken from animals given the drug. Two 24-h urine samples were obtained from all animals in the study. Analysis of the blood samples showed that immunosuppressive levels of CyA were achieved after two i.m. doses of CyA. These levels were maintained during the course of the schedule. Morphologically, all rabbits completing the cBSA only injection schedule showed evidence of an immune-mediated glomerulopathy with variably severe membranous and endocapillary proliferative change. Less than half the rabbits in the cBSA/CyA group showed any evidence of membranous change. The glomeruli of animals given CyA only were normal. No morphological evidence of CyA toxicity was seen in any animal given the drug. The proteinuria profiles, however, suggested that as well as reducing protein excretion in rabbits given cBSA, CyA may interact with the immunizing dose of cBSA to produce an early, reversible, nephrotoxic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Auditing AIDS reporting. Experience from a central London district 1982-1991.

OBJECTIVE: To evaluate completeness of reporting of cases of AIDS to the Communicable Disease Surveillance Centre (CDSC) between 1982-1991. SETTING: Southside of the Bloomsbury and Islington District Health Authority. DESIGN: Reconciliation exercise with CDSC of cases reported with those known to have received treatment in the district from 1982 to March 1990. Case note review of unreported cases and follow-up at March 1991. MAIN OUTCOME MEASURES: Delayed and non-reporting of cases. RESULTS: Cumulatively 13% (46/351) of patients whose initial AIDS illness was diagnosed in the District remained unreported by March 1991. Non-reporting increased from 9% (2/23) of cases diagnosed prior to 1985 to 28% (26/92) of cases diagnosed between 1989 and 1990. After September 1987 the proportion of patients with a diagnosis of Pneumocystis carinii pneumonia or Kaposi's sarcoma was significantly higher in the reported group than in the non-reported group: 78% (124/158) v 51% (24/49) p < 0.001. Nine of 19 (47%) cases of AIDS transferring their care into the district had not been reported by their previous District Health Authority. CONCLUSIONS: Within the district non-reporting of cases of AIDS has risen over time as the numbers of patients treated has increased. The physician must be aware of the full AIDS case definition for surveillance purposes and the implications of non-reporting for the allocation of special "ring-fenced" resources for AIDS care. Adequate investment in information and reporting systems would seem essential.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Glomerular epithelial cell endocytosis in puromycin-induced glomerulopathy.

Glomerulopathy and nephrotic syndrome were induced in rats by intravenous puromycin aminonucleoside. Ten days after the injection of puromycin, the animals have developed heavy proteinuria. During this phase, glomerular epithelial cell endocytosis was studied by injecting a conjugate of horseradish peroxidase and poly-L-lysine. This conjugate has been shown to be endocytosed by glomerular epithelial cells. The rats were serially sacrificed from 1 min to 24 h after this injection. Peroxidase was localised cytochemically and observed at light and electron microscopy. The early events of endocytosis in glomerulopathy (namely the binding to the plasma membrane, the membrane invagination and the formation of the early vesicles) were qualitatively similar to those in the normal. The later events (the fusion of the vesicles and their movement within the cells) were inhibited. The results show that puromycin aminonucleoside damages epithelial cell endocytotic activity and affects the later processing of the conjugate within the cells.

Animals↗
PubMed1992

Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.

Ornithine transcarbamylase is a mitochondrial urea cycle enzyme. Women with heterozygous ornithine transcarbamylase deficiency may have no symptoms or have episodic, symptomatic hyperammonemia, which can be fatal. We report a previously undiagnosed heterozygote ornithine transcarbamylase-deficient patient who had symptomatic hyperammonemia during initiation of valproate therapy. This is the second such patient reported. Symptomatic hyperammonemia during valproate therapy may indicate ornithine transcarbamylase deficiency. Since valproate inhibits ureagenesis and can be toxic to mitochondria, it should be used extremely cautiously, or not at all, in ornithine transcarbamylase-deficient patients.

Adult↗
PubMed1991

Is risk of Kaposi's sarcoma in AIDS patients in Britain increased if sexual partners came from United States or Africa?

OBJECTIVE: To determine whether the risk of Kaposi's sarcoma in patients with AIDS is increased by sexual contact with groups from abroad with a high incidence of Kaposi's sarcoma. DESIGN: Analysis of risk of Kaposi's sarcoma in patients with AIDS, according to country of origin of their sexual partners. SETTING: United Kingdom. PATIENTS: 2830 patients with AIDS reported to the Communicable Disease Surveillance Centre and the Communicable Disease (Scotland) Unit up to March 1990, of whom 566 had Kaposi's sarcoma. MAIN OUTCOME MEASURES: Percentage of patients with AIDS who had Kaposi's sarcoma. RESULTS: 537 of 2291 homosexual or bisexual men (23%) with AIDS had Kaposi's sarcoma; 10% (14/135) of the men and women who acquired HIV by heterosexual contact had Kaposi's sarcoma. None of the 316 subjects who acquired HIV through non-sexual routes had Kaposi's sarcoma. Kaposi's sarcoma was more common among homosexual men whose likely source of infection included the United States (171/551, 31%) or Africa (9/34, 26%) than among those infected in the United Kingdom (119/625, 19%) (p less than 0.05). CONCLUSION: The data suggest that Kaposi's sarcoma is caused by a sexually transmissible agent which was introduced into the British homosexual population mainly from the United States [corrected].

Acquired Immunodeficiency Syndrome↗
PubMed1991

Determinants of somatization in primary care.

This study explores possible determinants of somatization in primary care. Hypotheses were tested on samples of 'somatizers', 'psychologizers' and controls recruited by epidemiological procedures. Although 'somatizers' were found to be similar to 'psychologizers' in many respects, they were (i) less depressed; (ii) reported lower levels of social dissatisfaction, social stress and less dependence on their relatives; (iii) more likely to have an unsympathetic attitude towards mental illness and less likely to consult a doctor about psychological symptoms, and (iv) more likely to have received medical in-patient care as an adult before they had consulted their doctor with their current illness. These findings are discussed in the context of previous research.

Adaptation, Psychological↗
PubMed1991

A systematic consideration of the neoplastic spectrum of AIDS: registry linkage in Illinois.

To examine unexplored aspects of the association between AIDS and neoplasia, the Illinois AIDS and Cancer Registries were linked. The method integrated use of a personal computer to find exact matches on names and dates of birth with manual review to assure satisfaction of a match definition. Of the factors examined, white race and homosexuality predicted Kaposi's sarcoma (KS) among people with AIDS (PWAs), and white race predicted non-Hodgkin's lymphoma (NHL). Earlier reports of a declining proportion of PWAs with KS were confirmed. Lymphoma (mixed lymphocytic/histiocytic type), while not currently diagnostic of AIDS, occurred more frequently among PWAs than in the Illinois population. For the first time, rates of cancers other than KS and NHL were demonstrated to be significantly increased among PWAs compared with general populations. In the light of these findings, reconsideration of current neoplastic definitions may be useful.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Effect of calcium phosphate coating characteristics on early post-operative bone tissue ingrowth.

The synthesis of model porous metal-CPC materials, and their use in one-parametric studies of bone tissue ingrowth enhancement were considered. By using the same starting calcium-deficient hydroxyapatite powder, three different coatings, CAP1, CAP2 and CAP3, were obtained of thicknesses 50 +/- 5, 75 +/- 5 and 75 +/- 5 microns, respectively. CAP1 and 2 were either the starting powder mixed in a 3:1 ratio CPC: poly(lactic acid) or the powder by itself. The CAP3 coating was the result of a thermal treatment producing a mixture of oxyhydroxyapatite, alpha- and beta-tricalcium phosphate. Orderly oriented wire mesh porous coated specimens were implanted, along with the same specimens lined with CAP 1, 2 or 3. Subsequently, the total of 156 specimens was retrieved at 2, 4 or 6 wk, and tested mechanically and processed for histomorphometry. The data produced considerable evidence for the CPC-dependent enhancement of bone tissue ingrowth in porous metals immediately after implantation. They prove that the materials processing of CPC coatings influences the resulting biological behaviour substantially. Furthermore, they support the hypothesis that ceramic dissolution is a causative factor on the bone tissue growth enhancement mechanisms.

Animals↗
PubMed1990

Training trainers: a new approach for community medicine.

During 1985, two separate one-day seminars for trainees and trainers in South East Thames Regional Health Authority highlighted the need for a 'training the trainers' course to be run for trainers throughout the Region. This was held during 1987 and this paper gives a descriptive account of the course, highlights the lessons learnt, and summarises the evaluation obtained from participants. Thirteen trainers started the course, one changed jobs and left the Region, leaving twelve completing the course. Spread over nine months, the course included an initial weekend but was mainly run on a day release basis. The facilitators for the course, a psychologist and sociologist, had teaching experience in running similar courses for GP trainers. The course emphasised an adult learning model in which the trainer enabled the trainee to identify and meet their learning needs through appropriate support and facilitation. Although the career change from clinical work to public health medicine is likely to be more traumatic than other transitions within clinical medicine, the approach is applicable on a much wider basis.

Adult↗
PubMed1990

Effect of fructose 1,6-diphosphate on exercise capacity in patients with peripheral vascular disease.

Exogenous fructose 1,6-diphosphate (FDP), a glycolytic intermediate, increases blood ATP and 2,3 diphosphoglycerate levels, facilitates the dissociation of oxygen from hemoglobin, and increases red blood cell flexibility. These mechanisms explain why it has been effective in enhancing energy production in a variety of ischemic conditions. The present study was undertaken to determine whether FDP could enhance oxygen supply and thus improve exercise performance in patients with peripheral vascular disease. Ten male patients (mean age 63 +/- 5 years) with peripheral vascular disease performed symptom-limited exercise testing after randomized, double blind infusion of either 200 mg/kg body weight FDP or placebo. Data were evaluated at rest, at a matched submaximal workload (2-3 MPH/0% grade), and at peak exercise, defined as the occurrence of moderately severe claudication. No differences were observed in heart rate, blood pressure, gas exchange data, time to the onset of claudication or peak exercise, or lactate and 2,3 diphosphoglycerate levels. In contrast to previous studies performed among patients with peripheral vascular disease and other studies using more severe hypoxic conditions, FDP did not affect the respiratory gas exchange or exercise capacity of patients with exertional claudication.

Aged↗
PubMed1990

Glomerular epithelial-cell endocytosis of horseradish peroxidase-polylysine conjugate in immune-complex glomerulonephritis.

Glomerulonephritis was induced in rats by daily intravenous cationised bovine serum albumin. The conjugate of horseradish peroxidase with poly-L-lysine was injected as a tracer of endocytosis by glomerular epithelial cells. The rats were sacrificed serially from 1 min to 24 h after the injection of the conjugate. The cytochemical localisation of peroxidase was observed by light- and electron-microscopy. Peroxidase was detectable in the GBM and immune deposits from 1 min after the injection but was cleared by 2 h. Cellular membrane staining by the conjugate and the membrane invaginations containing concentrated peroxidase were prominent adjacent to the subepithelial immune deposits. Peroxidase was initially localised intracellularly in membrane-bound vesicles adjacent to the subepithelial deposits. They subsequently moved towards the cell centre and became larger, some having the characteristics of lysosomes. Peroxidase activity significantly diminished within the cells by 16 h. The results show that glomerular epithelial-cell endocytosis in immune-complex glomerulonephritis is similar to that observed in the normal, but cellular membrane binding and invagination are more prominent adjacent to immune deposits. The trapping of the tracer in the deposits did not seem to alter its property of being taken up by the epithelial cells.

Animals↗