Potassium ferrate as a DNA chemical sequencing reagent and probe of secondary structure.
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Biomedical subjects
Publications and source records attributed to C Stevenson.
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Between 1968 and 1991, the number of deaths from non-malignant oesophageal disease (NMOD) (International Classification of Diseases code 530), recorded by the Office of Population Censuses and Surveys (OPCS) in England and Wales, trebled in women, from 118 to 340 (5 to 13 per million) and doubled in men, from 131 to 251 (5.5 to 10 per million). Calculation of age specific death rates, shows the increase to result from a rise in mortality in those over 75 years and age standardised mortality confirms a rise in overall frequency from 2.9 to 7.0 deaths per million men and 5.2 to 13.1 per million women. Between 1974 and 1988 when specific diagnoses were coded, deaths from oesophageal ulcer rose from 1.5 to 2.5 per million. In men, the death rate from oesophageal stricture increased from 2.5 to 3 per million and in women from 3.5 to 6 per million. Mortality from oesophageal perforation did not change (1 per million). Some of these changes reflect the increasing age of the population in general, but further explanations are required. Review of 84 sets of case notes from a total of 281 inpatients whose coded diagnoses had included NMOD and who had died suggested that in 28 (33%) death was actually due to NMOD, and in seven of these endoscopic intervention was responsible. The certified underlying cause of death was compared with that suggested from case note review in 62 cases; death from NMOD was substantially underestimated. This study concludes that a rising death rate attributed to NMOD is underestimated on death certificates and that endoscopic intervention explains only a few of the cases.
Methicillin-resistant Staphylococcus aureus (MRSA) has been detected in nursing homes and long-term care facilities. Studies disagree about the risk of infection with MRSA in colonized patients. MRSA colonization and infection were tracked for one year in all admissions to a 60-bed ward at the Philadelphia VA Nursing Home Care Unit (NHCU) from the time of its opening in June, 1990. Patients and staff were blinded to culture results, and the NHCU followed universal precautions for all patients. Of the first 72 patients, 7 were found to be colonized with MRSA; only one of them was known to have had MRSA prior to NHCU transfer. Three patients died (2 had negative cultures prior to death), and 1 was discharged home. Three patients spontaneously cleared MRSA colonization and lived to the end of the study. Three patients appeared to be colonized by MRSA after admission; subsequent cultures were negative. No patients were infected by MRSA in the NHCU. At the close of the study, one year after the nursing home opened, no patient in the nursing home had a culture positive for MRSA. In conclusion, colonization with MRSA at the time of admission to the nursing home is not uncommon, but patients can spontaneously clear it. Besides, nursing homes that pre-screen only those patients with classic risk factors may be admitting many MRSA-colonized patients. Nonetheless, universal precautions appear to be effective in limiting transmission of MRSA in the nursing home; in this study, MRSA acquisition was sporadic and brief.
Gel sequencing experiments with the 5'- and 3'-end-labeled oligonucleotides d(A3GA4GA5GA6GA3G) and d(AT)10 have demonstrated that dimeric adenine photoproducts and thymine-adenine photoadducts constitute alkali-labile lesions in UV-irradiated DNA. On treatment with hot piperidine, DNA strand breakage occurs predominantly at the sites of 5'-adenines in the dimeric photoproducts and of 3'-adenines in the thymine-adenine photoadducts. With 5'-end-labeled oligonucleotides of mixed sequence, major UV-induced loci for alkaline cleavage map to purine bases flanked on their 5'-side by two pyrimidines. This behavior does not arise from enhanced photoreactivity of purines in this sequence context as has been inferred from photofootprinting studies. Instead, as shown by 3'-labeling and selective substitution with 5-methylcytosine, it results from the anomalous electrophoretic mobility of 5'-end-labeled fragments produced by alkaline cleavage of DNA at adjacent pyrimidine (6-4) pyrimidone photoproducts.
The purpose of this research was to estimate the cost-effectiveness of mammographic screening to supplement the results of the National Evaluation of Breast Cancer Screening which identified the mortality benefit as the most sensitive parameter. This appraisal used a different computer model, MISCAN, which models the effects of introducing a national screening program into a previously unscreened population, rather than basing estimates on the assumption of a fully established program. For the 40 to 49 age group a mortality reduction of 8 per cent was assumed, rather than the 30 per cent estimate utilised in the National Evaluation. The revised estimate is based on the two Swedish trials (Malmo and WE). New estimates for treatment costs were also incorporated into the MISCAN model. The cost-effectiveness of the policy recommended in the National Evaluation Report, $11,000 per life year saved with two-yearly screening of women over 40, is estimated by the MISCAN model to be $20,300. These differences arise partly from the difference in mortality effects for the 40 to 49 age group, but also from differences inherent in the steady-state and dynamic population approaches to modelling premature deaths averted. The MISCAN results confirm that screening for women over 50 is more cost-effective than screening women under 50. Screening all women aged 50 to 69 every two to three years is reasonable value for money. For women aged 40 to 49 the mortality benefit and cost-effectiveness is less clear, and it would be prudent to allow screening in this group until further evidence is available.
The aim of this study was to determine whether a mass media campaign about diabetes would increase public awareness and knowledge of diabetes, leading to an increased rate of detection of previously undiagnosed cases. A telephone questionnaire was administered to two groups of randomly selected members of the public before and after a 1-week mass media campaign. Cases of newly diagnosed diabetes were monitored by general practitioners. The median knowledge score rose from 5 (range 0-10) before the campaign to 6 (0-10) afterwards, p < 0.001. The knowledge score for a control group, questioned post-campaign only, was also 6 (1-10). The increase in the median knowledge score was mainly as a result of more people being able to define diabetes and give two presenting symptoms. This increased awareness did not however result in an increase in detection of new cases.
One approach to the diagnosis and therapy of T cell-mediated diseases is to develop reagents specific for T cell receptor (TcR) variable (V) regions. To date, however, TcR expressed on the surface of antigen-specific T lymphocytes have proven to be poorly immunogenic. As a result, few monoclonal antibodies (mAb) recognizing human variable regions are available. In this report, we have used the "phosphatidylinositol linkage" strategy to generate soluble forms of two human allogeneic TcR derived from human cytotoxic T lymphocytes (CTL) known to be specific for HLA-A2 and HLA-Aw68/HLA-Aw69, respectively. Monomeric TcR alpha and beta chains from the HLA-A2-specific CTL were purified in large quantities from CHO cells and each was used to immunize mice to generate mAb. In particular, the anti-beta chain mAb, denoted anti-V beta 13, stain a significant (approximately 5%) fraction of human peripheral blood alpha/beta T lymphocytes, immunoprecipitate native anti-A2 TcR molecules, and activate T cells transfected with the relevant alpha and beta chain cDNA. Anti-alpha chain mAb were also obtained against a constant region determinant which can immunoprecipitate detergent-solubilized polypeptides. In general, we find that immunizations with soluble protein are far superior to those with cells bearing TcR chimeras or in combination with the purified protein.
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From gel sequencing experiments with 32P-end-labelled oligodeoxyribonucleotides, it is shown that treatment of DNA with the powerful oxidant dimethyldioxirane, followed by heating in piperidine, causes selective strand scission at the sites of guanine bases. The same specificity for cleavage at guanine was observed with a 45-mer labelled at either the 3'- or 5'-end and with a single and double stranded 34-mer. On account of its speed and operational simplicity, modification with dimethyldioxirane is proposed as a practicable alternative to conventional chemical sequencing procedures for locating guanine bases in DNA.
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UNLABELLED: The relationships between nutritional factors, calcium regulating hormones, and bone density were evaluated in three groups of normal subjects in rural southeast Kansas. Dietary intake of calcium (Ca), phosphorous (P), protein, and vitamin D; and serum 25OHD, Ca, P, parathyroid hormone (iPTH), and bone density (distal 1/3 radius) were measured in 29 elderly women, 35 elderly men, and 50 perimenopausal women. Measurements were repeated 5 years and 4 years later respectively in 16 elderly women and 15 elderly men. The r values for significant regression correlations for each group were as follows: perimenopausal: bone density and dietary Ca:P--r = .29, iPTH and 25OHD--r = -.38; elderly women: 25OHD and dietary Vitamin D(D)--r = .58, change in bone density (delta BD) and initial bone density (BDI)--r = -.71, delta BD and serum 25OHD--r = -.60, serum calcium and age--r = -.42; elderly men: Serum 25OHD and D--r = .61, iPTH and 25OHD--r = -.43, iPTH and serum phosphorous--r = .59. CONCLUSIONS: The more adequate the state of vitamin D nutriture, the lower the serum iPTH in perimenopausal women and elderly men and the less bone loss in elderly women. The Ca:P ratio in the diet may be important in maintaining bone density in perimenopausal women.
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Forty-one women with oligo-menorrhoea and/or galactorrhoea were subjected to hypothalamic pituitary-thyroid testing in an attempt to establish the presence or absence of an underlying pituitary microadenoma. They were divided into two groups in accordance with the serum level of prolactin (PRL): Group I (N = 25, mean +/- SE 17.6 +/- 1.5 ng/ml) and Group II (N = 16, 102.8 +/- 29.7 ng/ml). The dynamic tests performed were a TRH test, a stimulation test with metoclopramide (MCP) and a suppression test with bromocriptine. The results of these tests were compared with those obtained in nine normal women and eleven patients with surgically proved pituitary microadenoma. Radiologically abnormal pituitary fossas were found in ten subjects from Group I and in fourteen from Group II. All patients were euthyroid. A persistently elevated serum TSH in response to TRH was observed in patients of Group II suggesting an hypothalamic abnormality and a progressive decrease in the 120-min use of serum T3 was noted with increasing evidence of the existence of a pituitary tumour. A negative correlation was found between the basal serum PRL and the rise of serum PRL with TRH. Patients from Group II showed a lower PRL response to MCP when compared to Group I and again a negative correlation between basal level of serum PRL and the change after MCP was observed. No clear difference in the 4-h response to bromocriptine was found between the different groups of subjects. In conclusion, none of the three tests analysed permitted us to establish which of the patients had an underlying pituitary microadenoma.
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