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Biomedical subjects

E Watson

Publications and source records attributed to E Watson.

At least 73 records · Page 4Linked to original sources
PubMed1987

Expectancy, redefinition and reported pain.

Three groups of subjects were administered a redefinition strategy which asked them to focus on sensations during noxious stimulation. Those in one group were informed that the strategy would reduce pain (positive expectancy), those in a second were informed that it would augment pain (negative expectancy), and those in a third were given no information on expectancy. Subjects in a fourth group received neither redefinition nor instructions on expectancy. The four groups did not differ either in expectancy of pain reduction or in reduction of reported pain. Subjects in all groups expected more pain than they reported, and expectations for pain reduction showed only a small correlation with degree of reported pain reduction. In all groups, men reported less pain than women.

Adult↗
PubMed1986

First-trimester prenatal diagnosis of cystic fibrosis with linked DNA probes.

Linkage analysis with cloned gene probes has shown that the mutation causing cystic fibrosis is located in the middle of the long arm of chromosome 7. First-trimester diagnosis of cystic fibrosis is reported in four informative families and second-trimester diagnosis in one family with fetal DNA prepared from chorionic villi, hybridised with the tightly linked DNA probes, pJ3.11 and met. Risk calculations show that the expected false-negative and false-positive rates are approximately 2% and 6%, respectively, for typical nuclear families with one affected living child. Existing probes are sufficiently informative to allow full diagnosis in about two-thirds of couples presenting with at least one affected child. In half of the remainder, the inheritance of one parental mutant chromosome can be deduced.

Biopsy↗
PubMed1986

Isolation of a further anonymous informative DNA sequence from chromosome seven closely linked to cystic fibrosis.

A library prepared from flow-sorted chromosomes was used to isolate single-copy sequences from chromosome seven. One such sequence 7C22 has been shown to be polymorphic for an EcoRI restriction site and to be informative for the study of CF in approximately 35% of matings. The segregation of the 7C22 alleles was followed through nineteen informative families with more than one child affected by cystic fibrosis. We report that the locus for 7C22 is linked to the locus for cystic fibrosis at a recombination fraction of 0.045. This marker will prove useful in improving the accuracy and informativeness of prenatal diagnosis and in constructing a fine genetic map around the cystic fibrosis gene.

Chromosomes, Human, 6-12 and X↗
PubMed1986

Identification of new metabolites of phosphoramide and nor-nitrogen mustards and cyclophosphamide in rat urine using ion cluster techniques.

The metabolism of nor-nitrogen (NNM) and phosphoramide mustards (PM) and cyclophosphamide (CP) was investigated in the Sprague-Dawley rat using chemical ionization mass spectrometry and ion cluster techniques. Following administrations of a 1:1 mixture of the non-labeled and the corresponding side-chain deuterium-labeled compounds to separate rats, the urinary extracts were screened for cluster ions which were characteristic of the administered compounds and their derived metabolites, and on this basis, tentative identifications of known and new metabolites were accomplished. Combining derivatization, deuterium labeling on strategic locations, gas chromatography/mass spectrometry, and chemical synthesis in some cases, 3-(2-chloroethyl)-1,3-oxazolidin-2-one was identified as a major metabolite for NNM, PM and CP and 3-(2-chloroethyl)-4-hydroxy-1,3-oxazolidin-2-one was identified as a major metabolite for NNM and PM, but a minor metabolite for CP. A new dechlorinated metabolite for CP, 3-(2-hydroxyethyl)-1,3-oxazolidin-2-one, was also identified.

Amides↗
PubMed1986

An example of cross-cultural measurement of psychological symptoms in post-partum mothers.

As one of the components of a longitudinal study of the use made of child health services by mothers resident in Tower Hamlets an attempt was made to assess psychiatric morbidity across cultures using three measures, Goldberg's General Health Questionnaire, the interviewer's assessment of distress and the mothers' own opinion; and secondly to see whether mothers from varying cultures differ from the indigenous population in the psychological symptoms they experienced in the year following their infants' birth. There was a reasonable agreement between the three measures suggesting that it is possible to compare psychiatric morbidity across cultures; in addition there seemed to be little difference in the psychological symptoms experienced in the year following their infant's birth by mothers in the varying cultures.

Bangladesh↗
PubMed1986

The development of performance and cost indicators for preschool immunisation.

The organisation, premises, and staffing of three child health clinics of different types in an inner city area have been studied and related to information on immunisation derived from their computerised child register and other returns, together with some simple estimates of cost. Differences were found between overall uptake of different antigens, consent rate, compliance after consent had been given, and the median age at immunisation for children allocated to each clinic. Thus consent to pertussis immunisation varied from 90% in one clinic to 69% in the other two. In the clinic with the high consent rate, however, only 66% of those whose parents had consented actually received all three doses compared with 82% and 85% in the other clinics. The median age of immunisation also showed pronounced differences between the clinics--314, 351, and 375 days, respectively, for the third dose of the triple course. There were differences in characteristics of the clientele served by each clinic and in staffing and facilities, which led to differences in costs, as well as contributing towards the variable patterns of uptake. We suggest that indicators such as these, largely available from the child health computer system, are used systematically to identify ways of improving uptake and increasing cost effectiveness.

Ambulatory Care Facilities↗
PubMed1986

A model system for the analysis of gene exclusion: cystic fibrosis and chromosome 19.

We have used multilocus analysis to exclude the cystic fibrosis locus from six polymorphic DNA markers covering most of chromosome 19. A substantial increase in the confidence for exclusion was obtained using the computer programme LINKAGE compared to analysis of pairwise lod scores. A structured approach to the analysis of linkage to autosomal recessive inherited diseases where the biochemical defect is not known is described.

Child↗
PubMed1986

Further data supporting linkage between cystic fibrosis and the met oncogene and haplotype analysis with met and pJ3.11.

The linkage of cystic fibrosis (CF) and the polymorphic DNA markers pJ3.11, met, 7C22, DOCR1-917, COL1A2, and TCRB have jointly localized the mutation causing CF to chromosome 7q2.1-3.1. We report further linkage data with two polymorphic markers at the met oncogene locus, pmetH and pmetD, which supports the tight linkage found by White et al. between CF and met. One family shows evidence for meiotic recombination between CF and met. Analysis of haplotypes in CF pedigrees collected for linkage studies combined with data from single affected families requesting prenatal diagnosis (Farrall et al., Lancet i:1402-1404, 1986) shows CF and met to be in linkage equilibrium in our population while pJ3.11-CF haplotypes show a deviation from the equilibrium frequencies.

Cystic Fibrosis↗
PubMed1986

Parameters for the evaluation of IL-2 stability.

Recombinant DNA derived interleukin-2 stability in accelerated and long term studies was evaluated using biological and protein chemical methods. Various biophysical parameters were investigated for their correlation with bioassay results and for their accuracy and utility as quantitative indicators of change. Biochemically distinguishable forms of the molecule exhibited different levels of IL-2 activity in vitro. Of the methods evaluated, SDS-PAGE and, to a greater extent, reverse phase and TSK based HPLC analyses have been found to measure relevant changes in the structure of human interleukin-2. Those test systems detect covalent and non-covalent aggregates, degradation products, and inappropriately oxidized forms of human interleukin-2 all of which contribute to an overall loss of IL-2 biological activity. Such measures provide sensitive and reproducible indications of changes relative to the standard bioassay. These studies have led to the development of an analog of interleukin-2 which is biologically active and shows improved long term stability.

Biological Assay↗
PubMed1985

Kinetics of phosphoramide mustard hydrolysis in aqueous solution.

Hydrolysis of phosphoramide mustard was investigated using HPLC, 31P NMR, and GC-MS with specific deuterium labels. The hydrolysis of phosphoramide mustard in sodium phosphate buffers was found to follow apparent first-order kinetics. The rate of hydrolysis was temperature and pH dependent, being slower under acidic conditions. The hydrolysis was not catalyzed by hydroxyl ion, and its pH dependence appeared to be the result of a change in the mechanism of hydrolysis at different pH values. At a pH value approximately above the pKa of the phosphoramide mustard nitrogen, the major hydrolytic pathway of phosphoramide mustard was via the formation of the aziridinium ion, followed by nucleophilic attack. At pH values below its pKa, cleavage of the P-N bond predominated. At pH 7.4, the formation of an aziridinium ion was followed by a rapid hydrolysis to yield the monohydroxy and, subsequently, the dihydroxy products. The hydrolysis at this pH was adequately described by consecutive first-order kinetics. Seven species in the hydrolytic mixture have been identified as intact phosphoramide mustard, N-(2-chloroethyl)-N-(2-hydroxyethyl)phosphorodiamidic acid, N,N-bis-(2-hydroxyethyl)phosphorodiamidic acid, phosphoramidic acid, phosphoric acid, N,N-bis-(2-chloroethyl)amine, and N-(2-chloroethyl)-N-(2-hydroxyethyl)amine by GC-MS with the aid of deuterium labels. Phosphoramide mustard was found to be stabilized by chloride ion. The stabilization was linearly related to the chloride ion concentration, and the mechanism was found to be via the formation of phosphoramide mustard from the aziridinium and chloride ions. Phosphoramide mustard was significantly more stable in human plasma and in 5% human serum albumin as compared to aqueous buffers, an observation that may be important in vivo.

Bromides↗
PubMed1984

Reserpinization: effects on parotid gland function.

Chronic reserpinization of mice and rabbits affected parotid gland function; cholinergic and beta-adrenergic-stimulated amylase release were significantly reduced, and cyclic-AMP and cyclic-GMP levels were significantly elevated above control-stimulated levels. Amylase released by dibutyryl-c-AMP was also reduced, suggesting a defect in stimulus-secretion coupling subsequent to c-AMP formation.

Amylases↗
PubMed1984

Calcium pyrophosphate deposition in nonhuman primates.

Naturally occurring deposition of calcium pyrophosphate has been identified in six rhesus monkeys following acute episodes of trauma and various septicemias. Scanning electron microscopy with energy-dispersive X-ray analytical system and single crystal electron diffraction studies were used to identify the crystals within the articular cartilage. The osteoarthritis grading system was used to determine the degree of cartilage degenerative changes.

Animals↗
PubMed1984

Isoproterenol-induced amylase release in rabbit parotid acini: relation of protein phosphorylation, cyclic AMP and related kinase activity to changes in secretory rate.

Isoproterenol-induced amylase release from rabbit parotid acini was examined in relation to cyclic AMP (cAMP) concentrations, cAMP-dependent protein kinase (cAMP-PK) activity ratios and protein phosphorylation. Initial stimulation of amylase release by isoproterenol was preceded by increases in cAMP, cAMP-PK activity ratios and phosphorylation of a 34,000 MW (major) and a 30,000 MW (minor) protein in the microsomal fraction. When propranolol was added, decreases in cAMP concentrations and cAMP-PK activity ratios preceded the reduction in amylase release. Detailed analysis was performed on the 34,000 MW protein. The relation of dephosphorylation of protein 34 and reduction in amylase release was complex. Slight dephosphorylation occurred before or concurrently with the decrease in amylase release; however, maximal dephosphorylation was preceded by maximal inhibition of amylase release. When secretion of amylase was reinstituted by isoproterenol or forskolin, increases in cAMP and cAMP-PK activity ratios occurred before or in concert with amylase release but rephosphorylation of protein 34 occurred after the start of amylase release. Photoaffinity labeling studies using [32P]-8-azidoadenosine-3',5'-cyclic monophosphate indicated that proteins 34 and 30 were not regulatory subunits of cAMP-PK or their breakdown products. Although these data are consistent with phosphorylation of proteins 34 or 30 being required for triggering initial secretion, maximum dephosphorylation was not essential for inhibition of secretion. Furthermore, initiation of amylase release by the gland after a short period of quiescence did not depend on prior phosphorylation of protein 34. These data may indicate the absence of a requirement of amylase release for phosphorylation of protein 34.

Adenosine Triphosphate↗