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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 541 records · Page 30Linked to original sources

Improving the validity of the GHO30 by rescoring for chronicity: a failure to replicate.

To replicate the finding by Goodchild and Duncan-Jones (1985), that rescoring the GHQ30 in order to take account of chronicity would improve its validity, a random sample of 244 people completed the GHQ. Of these 102 also took part in a second interview in which they were administered the PSE. There was no evidence that the new scoring scheme improved correlations between the GHQ and other measures of morbidity nor did this improve its sensitivity or specificity when validated agaist the PSE.

Adult↗

Role for the oligodendrocyte cytoskeleton in myelination.

Enriched cultures of rat brain oligodendrocytes were extracted with a buffer that separated the cells into a Triton X-100-soluble fraction and an insoluble cytoskeleton (CSK) residue. The buffer was optimised so that intact microtubules were preserved in the CSK residue. The partition of four myelin proteins between the soluble and the CSK fractions was determined by immunoblotting and immunofluorescence. Immunoblotting showed that two integral membrane proteins of myelin, the proteolipid protein (PLP) and the DM-20 protein, were completely extracted under these conditions. By contrast, a substantial amount of myelin basic protein (MBP) and to a lesser extent 2,3-cyclic nucleotide-3-phosphohydrolase (CNP) remained associated with the CSK residue. The association of these proteins with the CSK was confirmed by immunofluorescence. A remarkable difference in the distribution of microfilaments and microtubules was observed in oligodendrocytes. Immature cells possessed many fine processes that were rich in microfilaments. The cell body of these oligodendrocytes was devoid of microfilaments but did contain microtubules. Furthermore, a close association between CNP and microfilaments and between MBP and microtubules was revealed after detergent lysis. The strong interaction between CNP and filamentous actin was underlined by their concomitant disappearance from the extremities of the cell at a later stage of development when extensive membrane sheets had formed. Mature cells had fewer, thicker processes than younger cells and their processes contained microtubules, not microfilaments. MBP was present throughout the thick processes and the membrane sheets. These observations suggest roles for CNP and MBP at distinct stages of myelin process formation and support a directive role for the oligodendrocyte's CSK in the formation of myelin.

Actin Cytoskeleton↗

Mechanism of 201Tl uptake in tumours.

We have studied the mechanism of tumour uptake of 201Tl by in vivo and in vitro studies. In a series of patients with breast cancer (n = 26), lung cancer (n = 56) and lymphoma (n = 15), the time course of tumour uptake of 201Tl paralleled that in the myocardium with almost identical times of peak uptake being obtained in tumours and myocardium. In a patient with hepatic metastases from colonic cancer undergoing laparotomy, 99mTc labelled microspheres and 201Tl were injected into the hepatic artery and biopsies of metastatic and normal liver tissue obtained. The tumour to normal liver activity ratios for 201Tl were one tenth of those for 99mTc microspheres. In the final part of the study, cells from a lung cancer tissue culture line were incubated for 30 min with 201Tl with and without the addition of cardiac glycoside, which acts a sodium potassium pump blocker. The cells exposed to the cardiac glycoside showed markedly decreased uptake of 201Tl compared to the cells not so exposed (0.6% +/- 0.1% vs 11.8 +/- 0.7.2% of the administered dose). The mechanism of 201Tl uptake of tumours is similar to that in the myocardium. Sodium potassium pump activity appears to be more important than tumour blood flow. 201Tl uptake may provide a useful means of studying tumour viability.

Breast Neoplasms↗

Phase II study of low dose aminoglutethimide 250 mg/day plus hydrocortisone in advanced postmenopausal breast cancer.

Low dose aminoglutethimide 125 mg twice daily plus hydrocortisone 20 mg twice daily was shown to produce oestrogen and androgen suppression in postmenopausal women. A phase II study was carried out in 101 patients with advanced postmenopausal breast cancer. Objective response rates were 4% CR and 21% PR. Fourteen per cent had disease stabilization for more than 6 months (SD). Soft tissue sites showed the best response. Responses occurred in previous tamoxifen failures (28%) including SD. Toxicity was less than reported for higher dose regimens or low dose aminoglutethimide without hydrocortisone, particularly nausea and drowsiness. Survival from first relapse and start of therapy was not significantly different between PR and SD. This dosage regimen appears of comparable efficacy to previously reported higher dosage regimens with reduced toxicity compared to low dose regimens without hydrocortisone.

Aged↗

Coping with political violence in Northern Ireland.

Recent community based research, employing a self-assessed measure of psychological distress, has suggested that people in Northern Ireland may be coping relatively well with the stress of continuing political violence. This paper reports a first direct investigation of coping in Northern Ireland. Using two scales from the Folkman and Lazarus Ways of Coping Questionnaire--Distancing and seeking Social Support--an attempt was made to investigate the role of coping in relation to local levels of violence, the appraisal of violence, gender and trait neutoticism. The results indicated that trait neuroticism was not related to the appraisal of levels of violence, but that appraisal was related to both types of coping. In particular, those who perceived the violence to be more serious reported using less distancing, while they also reported seeking the most social support. In addition more women reported seeking social support compared to men. Finally those who lived in a high violence area were more likely to report using distancing than were those from a less violence prone area. These results were taken to support the contention that some form of denial may be the main form of coping in Northern Ireland, and that coping is related more to the appraisal of violence than to actual violence levels, while the appraisal of violence is in turn not related to trait neuroticism.

Adaptation, Psychological↗

Opsonic requirements and interaction of Haemophilus influenzae with human polymorphonuclear neutrophil leucocytes studied by luminol-enhanced chemiluminescence.

We have used human polymorphonuclear leucocyte (PMNL)-dependent chemiluminescence (CL) to study bacteria opsonised with those factors in serum which are reported to be important in opsonisation of H. influenzae, and to determine whether alteration of various surface characteristics of H. influenzae influence those CL responses by PMNL. Although complement plays a role, immunoglobulin and a heat-labile factor(s) were found to be the principle stimulants of PMNL-dependent CL when H. influenzae was opsonised in pooled normal human serum. Acquisition of capsule (serotype a,b,c,e, or f) by an uncapsulated strain significantly (P less than 0.001) reduced its ability to stimulate PMNL-dependent CL, but the type of capsule did not discriminate between the strains in this regard. Surface-adherent capsule inhibited PMNL-dependent CL stimulation more than capsular material released into the supernatant. Altering the lipooligosaccharide composition of the bacterial cell wall also affected PMNL-dependent CL stimulation independent of capsule. We conclude that, although surface characteristics of H. influenzae influenced its ability to stimulate PMNL-dependent CL, these experiments provide no evidence to support the hypothesis that the increased virulence of serotype b capsulated strains compared with other capsulated types could be explained by any specific ability to avoid opsonisation.

Haemophilus influenzae↗

In vivo and in vitro effects of beta-carotene and algae extracts in murine tumor models.

Phycotene, an algae extract with known antineoplastic activity, was demonstrated to prolong, but not sustain, an increased survival rate in a murine fibrosarcoma model when it was combined with immunotherapy. It was further shown that splenocytes from phycotene and beta-carotene-treated survivors could not confer protection to a fresh tumor cell challenge in virgin mice after adoptive transfer. In a series of cytotoxicity assays, phycotene combined with immunization was demonstrated to enhance cell-mediated and complement-dependent cytotoxicity in the first 14-21 days. However, after 21 days, the phycotene and immunization groups exhibited a decreased ability to mediate immune cytotoxicity compared with immunization-only controls. This may serve to explain the in vivo findings that while survival was increased early on in active immunization and phycotene-treated mice, it eventually dropped to the level of the active immunization controls.

Animals↗

Carnitine and weakness in haemodialysis patients.

Weakness in haemodialysis patients has been attributed to several factors including carnitine deficiency. Malnutrition, neuropathy, uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced muscle power compared with a normal population, and to be malnourished by dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle, with an excess of esterified carnitine in both plasma and muscle and diminished free plasma carnitine. Muscle biopsy showed no features of carnitine deficiency and electromyography showed a non-specific neuropathy with additional myopathic changes in some. Dietary supplementation with L-carnitine (2 g/day) for 6 weeks in a placebo-controlled trial showed a redistribution of carnitine fractions but no subjective or objective improvement in muscle function. There was no improvement in the plasma lipid profile. The weakness of haemodialysis patients is multifactorial. We have not demonstrated total carnitine depletion in either muscle or plasma, and oral supplementation of L-carnitine has no demonstrable effect in this group.

Administration, Oral↗

Free radicals and Graves' disease: the effects of therapy.

Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change. All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red-cell membrane. In addition LSH is a general radical scavenger and SOD a specific O2- scavenger. In Graves' disease the increased oxidative stress and increased general radical scavenging may result from raised free-radical activity. These changes, which have not previously been reported in Graves' patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect.

Adult↗

On the relationship between carcinogenicity and acute toxicity.

Parodi et al. and Zeise et al. found a surprising statistical correlation (or association) between acute toxicity and carcinogenic potency. In order to shed light on the questions of whether or not it is a causal correlation, and whether or not it is a statistical or tautological artifact, we have compared the correlations for the NCI/NTP data set with those for chemicals not in this set. Carcinogenic potencies were taken from the Gold et al. database. We find a weak correlation with an average value of TD50/LD50 = 0.04 for the non-NCI data set, compared with TD50/LD50 = 0.15 for the NCI data set. We conclude that it is not easy to distinguish types of carcinogens on the basis of whether or not they are acutely toxic.

Animals↗

Effect of Streptococcus pneumoniae on human respiratory epithelium in vitro.

A total of 11 of 15 Streptococcus pneumoniae culture filtrates and all five bacterial autolysates produced by cell death in the stationary phase caused slowed ciliary beating and disruption of the surface integrity of human respiratory epithelium in organ culture. This effect was inhibited by cholesterol and was heat labile and reduced by standing at room temperature but was stable at -40 degrees C. The activity was detected at the late stationary phase of culture and was associated with the presence of hemolytic activity. Gel filtration of a concentrated culture filtrate and autolysate both yielded a single fraction of approximately 50 kilodaltons which slowed ciliary beating and were the only fractions with hemolytic activity. Rabbit antiserum to pneumolysin, a sulfhydryl-activated hemolytic cytotoxin released by S. pneumoniae during autolysis, neutralized the effect of the culture filtrate on respiratory epithelium. Both native and recombinant pneumolysin caused ciliary slowing and epithelial disruption. Electron microscopy showed a toxic effect of pneumolysin on epithelial cells: cytoplasmic blebs, mitochondrial swelling, cellular extrusion, and cell death, but no change in ciliary ultrastructure. Recombinant pneumolysin (10 micrograms/ml) caused ciliary slowing in the absence of changes in cell ultrastructure. Release of pneumolysin in the respiratory tract during infection may perturb host defenses, allowing bacterial proliferation and spread.

Autolysis↗

Crystal deposition in hypophosphatasia: a reappraisal.

Six subjects (three female, three male; age range 38-85 years) with adult onset hypophosphatasia are described. Three presented atypically with calcific periarthritis (due to apatite) in the absence of osteopenia; two had classical presentation with osteopenic fracture; and one was the asymptomatic father of one of the patients with calcific periarthritis. All three subjects over age 70 had isolated polyarticular chondrocalcinosis due to calcium pyrophosphate dihydrate crystal deposition; four of the six had spinal hyperostosis, extensive in two (Forestier's disease). The apparent paradoxical association of hypophosphatasia with calcific periarthritis and spinal hyperostosis is discussed in relation to the known effects of inorganic pyrophosphate on apatite crystal nucleation and growth.

Adult↗

Effect of pyocyanin and 1-hydroxyphenazine on in vivo tracheal mucus velocity.

Products of the bacterium Pseudomonas aeruginosa have been shown to slow the beating of human respiratory tract cilia in vitro. We have tested the effects of two of these compounds, pyocyanin and 1-hydroxyphenazine (given as a bolus dose dissolved in 2 microliters Ringer solution), on tracheal mucus velocity of radiolabeled erythrocytes in anesthetized guinea pigs. 1-Hydroxyphenazine (200 ng) caused a rapid slowing of tracheal mucus velocity (maximum fall 47% at 20 min) with recovery by 1 h. The effect of pyocyanin was slower in onset, 600 ng causing 60% reduction in tracheal mucus velocity at 3 h, and no recovery occurred. A combination of pyocyanin and 1-hydroxyphenazine produced an initial rapid slowing equivalent to the same dose of 1-hydroxyphenazine given alone, but the later slowing attributed to pyocyanin was greater than the same dose administered alone. This study demonstrates one mechanism by which products of P. aeruginosa may facilitate its colonization of the respiratory tract.

Animals↗

Serum thyroglobulin--its measurement and clinical use.

Radioimmunoassays (RIA) have been shown to be unreliable in measuring serum thyroglobulin levels in patients with antithyroglobulin antibodies. The aim of this study was twofold. Firstly to compare the abilities of two immunoradiometric assays (IRMA), one commercially available, the other an 'in house' assay, with a conventional RIA. In addition the prognostic value of serum thyroglobulin levels in patients likely to relapse following a course of antithyroid drugs for Graves' disease was examined. The results obtained showed both of the IRMA methods to be unaffected by the presence of antithyroglobulin antibodies. Serum thyroglobulin levels were found to be poor predictors of relapse or remission following a 12 month course of antithyroid drugs.

Animals↗

Hyperemesis gravidarum and thyrotoxicosis--a diagnostic and therapeutic problem.

We report a case of hyperemesis gravidarum complicated by thyrotoxicosis which was managed conservatively during pregnancy. Problems of diagnosing mild thyrotoxicosis in pregnancy are discussed. Although no specific antithyroid therapy was given, the patient had an uneventful pregnancy after the first trimester. Neither she nor her baby exhibited any subsequent features of thyroid dysfunction. This suggests that treatment of thyrotoxicosis in early pregnancy is not always required because of the spontaneous improvement which is likely to occur as pregnancy progresses.

Female↗