Protamine sulphate used in combination with thrombin to remove fibrinogen prior to electrophoresis of heparinised plasma.
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Biomedical subjects
Publications and source records attributed to S Maguire.
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Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.
We have isolated a major protein constituent from a highly enriched fraction of yeast nuclear pore complexes (NPCs). The gene encoding this protein, Nup188p, was cloned, sequenced, and found to be nonessential upon deletion. Nup188p cofractionates with yeast NPCs and gives an immunofluorescent staining pattern typical of nucleoporins. Using immunoelectron microscopy, Nup188p was shown to localize to both the cytoplasmic and nucleoplasmic faces of the NPC core. There, Nup188p interacts with an integral protein of the pore membrane domain, Pom152p, and another abundant nucleoporin, Nic96p. The effects of various mutations in the NUP188 gene on the structure of the nuclear envelope and the function of the NPC were examined. While null mutants of NUP188 appear normal, other mutants allelic to NUP188 exhibit a dominant effect leading to the formation of NPC-associated nuclear envelope herniations and growth inhibition at 37 degrees C. In addition, depletion of the interacting protein Pom152p in cells lacking Nup188p resulted in severe deformations of the nuclear envelope. We suggest that Nup188p is one of a group of proteins that form the octagonal core structure of the NPC and thus functions in the structural organization of the NPC and nuclear envelope.
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Discusses the NHS Executive's information management and technology (IM&T) strategy and its relationship to the 1991 reforms. Examines the recommendation for large acute hospitals to adopt integrated hospital information support systems (HISS). Reports that a recent census of these hospitals, undertaken by the authors, suggests that the implementation of the strategy's recommendations has been slow at the local level. Attempts to diagnose the factors that are impeding implementation, using the evidence provided by the census. Identifies four main problem areas: the lack of success of past IM&T initiatives undermines confidence in the current strategy; the strategy is poorly aligned with other policy initiatives; the legacy of discrete, proprietary information systems within hospitals makes the creation of an integrative information environment difficult to accomplish without massive investment in new systems; and there are implicit contradictions between the following: the absence of a comprehensive post-implementation evaluation of the economic, technological and cultural feasibility of HISS at any of the three HISS pilot sites; the strategy's advocacy of HISS as the way forward for large acute hospitals; the requirement for a comprehensive business case to support any substantial investment in IM&T. Concludes that a massive rethink of policy is required, with a much greater emphasis on research, development and independent evaluation.
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A detailed comparison of the severity of chest disease with mutational status was carried out by cross sectional study of 127 cystic fibrosis patients, aged 1 to 31 years, living in Wales. Lung disease was classified according to severity, depending on pulmonary function tests (carried out on 76 patients) and chest radiograph status; information was obtained also on age at diagnosis in relation to severity of chest disease and colonisation with Pseudomonas species. Genotypes were determined by analysis for the mutations delta F508, delta I507, G551D, R553X, G542X, R117H, R560T, 1717--IG > A, and 621 + 1G > T. CF patients homozygous positive and heterozygous for the delta F508 deletion showed a significant decline of lung function with age. Unlike other studies, we did not find patients homozygous positive for the delta F508 deletion to have poorer lung function compared with heterozygous patients. Patients with the genotype 621 + IG > T/delta F508 tended to have more severe chest disease than the delta F508 homozygous patients in the same age group. There was some evidence that four patients heterozygous for R117H have mild chest disease.
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Recent evidence has suggested that the levels of Apolipoprotein A-1 and B in plasma are better indicators of the risk of atherosclerotic artery disease than plasma lipids. This study describes the measurement of plasma Apolipoprotein A-1 and B by immunoturbidimetry in patients with atherosclerotic artery disease and in normal controls. Apoprotein B and the ratio of Apoprotein A-1/Apoprotein B were found to be the best discriminators between the two groups.
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ATPase-deficient foci in rat liver, considered to be clonal in origin and possible precursors of hepatocellular carcinomas, were induced by injecting male Wistar AF/Han (200-220 g) rats with N-methyl-N-nitrosourea (MNU) (25 mg/kg) 16 or 22 h after partial hepatectomy and feeding for 80 days with a diet containing phenobarbital. The animals were killed after 90 days and the intralobular distribution of the preneoplastic foci was analysed quantitatively. The locations of 48 foci in the 16-h group and 22 foci in the 22-h group were determined from serial sections and blocks of liver from five animals. The mean distance of the foci from the portal vein in the 16-h group (385 microns) was 30% less than the distance of randomly selected points (546 microns), while the mean distance of the foci in the 22-h group (450 microns) was 16% less than the random points (535 microns). The mean diameter of the foci (235 microns) was 17% greater in the 22-h group than in the 16-h group (196 microns). We suggest that the cells in early S phase which are periportally situated 16 h after partial hepatectomy and occupy an intermediary position at 22 h represent the sensitive target population for initiation.
Allergic bronchopulmonary aspergillosis has been recognized in association with cystic fibrosis in children since 1965. Since then, however, there have been a paucity of reports of pediatric cystic fibrosis complicated by allergic bronchopulmonary aspergillosis, and, in most cases, these have been diagnosed retrospectively. A cluster of five acute cases seen during a 4-month period in a single cystic fibrosis center with a systemic illness and deterioration in respiratory status are described. In all five patients, reversible bronchoconstriction and infiltrative changes on x-ray films suggested the diagnosis. This was confirmed by the presence of (1) peripheral blood eosinophilia, (2) elevated total IgE and Aspergillus fumigatus-specific IgE, and (3) circulating serum precipitins against A fumigatus in all cases. All children tested had positive type 1 immediate hypersensitivity to skin tests for A fumigatus, in sputum eosinophilia, and Aspergillus cultured from sputum. Only three of five children were previously noted to be atopic and none had severe advanced suppurative lung disease. All children had previously received bronchodilator therapy and appropriate antibiotics. Following treatment with corticosteroids, acute symptoms and radiologic changes resolved for 1 to 5 months. To date, no children have had recurrence of their allergic bronchopulmonary aspergillosis while receiving alternate-day steroid treatment for 6 months.
Changes in the transformation sensitivity of hepatocytes during the cell cycle were in relation to clonogenicity investigated in partially resected rat liver. The hourly rate of the G1-S transit was measured in a control group by means of tritium-labelled thymidine (3H-TdR). At defined periods after partial hepatectomy the animals were injected with a single dose of N-methyl-N-nitrosourea (MNU) (25 mg/kg) and subsequently exposed to phenobarbital (0.05% in the diet) for 80 days. ATPase-deficient cell populations which arise by clonal growth (Rabes et al., 1982) were determined in the liver 90 days after MNU treatment and served as a marker for the initiating action of the carcinogen. The number of foci appeared to be related to the hourly rate of influx of hepatocytes into DNA synthesis at the time of MNU administration. Few foci were observed after MNU exposure in G1 and their frequency increased steeply when MNU treatment coincided with the first peak of cellular G1-S transit. As the rate of influx into S-phase decreased, so did the number of foci, despite the proportion of cells in S-phase still being at a maximum. The possibility of a gradient of clonogenicity existing within the cells of the liver lobule is envisaged. It is suggested that proliferative cells of the peri-portal region, which begin DNA synthesis early after partial hepatectomy, have the greatest ability to form clones of ATPase-deficient putative pre-neoplastic foci after initiation by a carcinogen and might thus represent, if exposed to carcinogen in early S-phase, the effective target cell population for the induction of hepatocellular carcinomas.
Cyclosporin A (CyA) was assayed by high performance liquid chromatography (HPLC) following extraction of the whole blood or plasma with diethyl ether and chromatography on a Sep-Pak Silica cartridge. Using carefully chosen volumes and ratios of ethyl acetate and hexane in the eluting sequences on the Sep-Pak, the major interferent present in normal blood and serum was eliminated.