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Biomedical subjects

R Wilson

Publications and source records attributed to R Wilson.

At least 577 records · Page 32Linked to original sources

The effect of antithyroid drugs on B and T cell activity in vitro.

This study examined the abilities of methimazole, propylthiouracil (PTU) and propranolol to exert an immunosuppressive effect in vitro. Incubation of peripheral blood lymphocytes (PBL) with propranolol showed the drug to have no effect on either B- or T-cell activity. Methimazole or PTU at concentrations of greater than or equal to 10(-5)M resulted in significantly lower amounts of IgG and IgM being released into the culture medium. Both drugs were also found to have a direct effect on T-cell function as they caused the percentage of total and suppressor cells to increase towards normal levels. The three drugs were all found to have some free radical scavenging ability. These ranked PTU greater than methimazole greater than propranolol. These in-vitro findings would suggest that both methimazole and PTU have some direct effect on the immune system. It would seem more likely however that these effects are mediated via interleukin 2 rather than by their ability to act as free radical scavengers.

Antithyroid Agents↗

Sex-role attributes, perceived competence and the development of depression in adolescence.

Studies are described which investigated the relationship of sex-role traits to age trends and sex differences in depression in adolescents. Psychological masculinity was negatively related to the level of depression in males and females, and evidence which indicates that this relationship is mediated by a link between masculinity and perceived competence is presented. The level of masculinity was stable across the age ranges studied, but was related to an increasingly higher rate of depression in females than males. It is therefore argued that a sex difference in masculinity arises prior to adolescence, but interacts with other factors which influence vulnerability to depression during the teenage years, thus bringing about the sex difference in depression.

Achievement↗

Effects of the myocardial-selective alpha 1-adrenoceptor antagonist UK-52046 and atenolol, alone and in combination, on experimental cardiac arrhythmias in dogs.

1. Adrenaline-induced arrhythmias in anaesthetized dogs respired with halothane were attenuated in 3 groups of 6 dogs by either UK-52046, 3.8 +/- 1.4 micrograms kg-1 (mean +/- s.e.mean), atenolol 14.6 +/- 2.1 micrograms kg-1, or a combination containing equal amounts of the two drugs of 0.36 +/- 0.1 microgram kg-1. The pressor response to adrenaline was reduced (P less than 0.01) by UK-52046 but not by atenolol or the combination of both drugs. 2. In a group of 6 dogs with multiventricular ectopic beats 24 h after coronary artery ligation (CAL), UK-52046, 32 micrograms kg-1, increased the number of sinus beats in each 5 min period from 137 +/- 47 to 662 +/- 99 (P less than 0.01); this was associated with a significant (P less than 0.01) fall in blood pressure. Atenolol in doses of up to 800 micrograms kg-1 had no effect. 3. UK-52046, 3.7 +/- 1.4 micrograms kg-1, prevented adrenaline-induced arrhythmias 3-4 days after CAL in 6/6 conscious dogs; atenolol in doses of up to 100 micrograms kg-1 produced an 84.4 +/- 7.4% reduction in the number of ventricular ectopic beats. A combination containing 3.7 +/- 1.1 micrograms kg-1 of each drug prevented the arrhythmia in 6/6 dogs. The pressor response to adrenaline was attenuated (P less than 0.05) by UK-52046, but resting blood pressure was unaffected by the different treatments. An increase (P less than 0.01) in heart rate was associated with both UK-52046 and the combination. 4. Neither UK-52046 (doses up to 64 micrograms kg-1) nor atenolol (up to 800 micrograms kg-1) had any effect upon ouabain-induced arrhythmias in 2 groups of 6 anaesthetized dogs. 5. In a study of the early (1a/1b) arrhythmias of acute myocardial ischaemia, the total number of ventricular ectopic beats occurring within 30 min of CAL was not reduced by 4 micrograms kg-1 UK-52046 but fell (P less than 0.01 compared with placebo) after 8 micrograms kg-1 [median values with ranges for placebo, 4 micrograms kg-1 and 8 micrograms kg-1 respectively 190 (4-674), 246 (9-1204) and 12 (1-154)]. Both doses of UK-52046 were associated with significant falls in blood pressure. 6. The arrhythmias produced by programmed electrical stimulation were studied in 2 groups of 6 conscious dogs, 7-30 days after CAL. With placebo, 4/6 dogs remained unchanged and 2 died: UK-52046 prevented arrhythmias in 2/6, 2 remained unchanged and 2 died (P = 0.29). Compared with placebo, blood pressure fell with doses greater than 4jg kg- '. 7. These results indicate antiarrhythmic effects of UK-52046 in a number of experimental models and suggest an enhanced role of alpha-receptors in the genesis of ischaemia-related arrhythmias. In several of the models used, UK-52046 produced haemodynamic changes in keeping with peripheral alpha-adrenoceptor antagonism.

Adrenergic alpha-Antagonists↗

Measurement of Pseudomonas aeruginosa phenazine pigments in sputum and assessment of their contribution to sputum sol toxicity for respiratory epithelium.

The phenazine pigments pyocyanin and 1-hydroxyphenazine were resolved by high-pressure liquid chromatography from the sputum sol phase from 9 of 13 patients with cystic fibrosis or bronchiectasis colonized by Pseudomonas aeruginosa. The concentrations measured were each sufficient to inhibit ciliary beating in vitro and contributed a significant proportion of sol phase toxicity for respiratory epithelium.

Cilia↗

Isolation and complementation of mutants of Anabaena sp. strain PCC 7120 unable to grow aerobically on dinitrogen.

Mutants of Anabaena sp. strain PCC 7120 unable to grow aerobically on dinitrogen were isolated by mutagenesis with UV irradiation, followed by a period of incubation in yellow light and then by penicillin enrichment. A cosmid vector, pRL25C, containing replicons functional in Escherichia coli and in Anabaena species was constructed. DNA from wild-type Anabaena sp. strain PCC 7120 was partially digested with Sau3AI, and size-fractionated fragments about 40 kilobases (kb) in length were ligated into the phosphatase-treated unique BamHI site of pRL25C. A library of 1,054 cosmid clones was generated in E. coli DH1 bearing helper plasmid pDS4101. A derivative of conjugative plasmid RP-4 was transferred to this library by conjugation, and the library was replicated to lawns of mutant Anabaena strains with defects in the polysaccharide layer of the envelopes of the heterocysts. Mutant EF116 was complemented by five cosmids, three of which were subjected to detailed restriction mapping; a 2.8-kb fragment of DNA derived from one of the cosmids was found to complement EF116. Mutant EF113 was complemented by a single cosmid, which was also restriction mapped, and was shown to be complemented by a 4.8-kb fragment of DNA derived from this cosmid.

Aerobiosis↗

The effect of bacterial products on ciliary function.

Mucociliary clearance protects the respiratory epithelium against inhaled particles. There is in vitro evidence that some bacteria produce factors that cause ciliary slowing, dyskinesia, and stasis. These changes may predominantly affect ciliary function alone or be associated with epithelial disruption and cell death. Some factors act immediately, while others can take up to a number of days to achieve effect. It is postulated that rapidly acting factors may be involved during bacterial colonization, allowing the bacterium time (by slowing clearance) to penetrate the mucociliary barrier and reach putative receptors on the epithelial surface. The compounds might similarly facilitate contiguous spread through the bronchial tree and augment the tissue damage caused by the host inflammatory response during chronic bronchial sepsis. Future work should define more clearly the in vivo significance of the largely in vitro observations made to date.

Bacterial Infections↗

Absence of gradient of thyrotropin receptor antibody and T cell subset distribution between thyroid and peripheral venous blood in patients with Graves' disease prepared for surgery with carbimazole and potassium iodide.

The aim of the study was to examine tri-iodothyronine, thyroxine, thyroid antibody and thyrotropin receptor antibody levels in thyroid and peripheral venous blood at the time of surgery in patients with Graves' disease. T cell subset patterns in peripheral and thyroidal venous blood were compared to the distribution of T cell subset patterns within the thyroid gland itself. The results showed that at the time of surgery there were no significant differences in any of the parameters measured between thyroidal and peripheral venous samples. T cell subset patterns within the thyroid gland were subjectively similar to those in the venous samples.

Autoantibodies↗

Differential immunosuppressive action of carbimazole and propylthiouracil.

Carbimazole and Propylthiouracil (PTU) are widely used in the treatment of Graves' disease, although controversy still exists as to whether or not they have any direct effect on the immune system. While many previous studies have investigated the possible effects of one or other of these drugs on the immune system only a few have directly compared the effects of equivalent doses of each drug. This study aimed to examine the effects of both drugs, during the initial 8 weeks of treatment, on various biochemical and immunological parameters. The results obtained showed that while thyroid hormone levels fell at similar rates in both treatment groups, TRAb levels and T cell subset abnormalities returned towards normal more rapidly in patients receiving Carbimazole compared to PTU. These results indicate that the effects of Carbimazole on TRAb levels and T cell subset abnormalities are not due solely to its action in controlling the biochemical features of Graves' disease and provide indirect evidence of an action on the immune system in vivo.

Adult↗

Upper respiratory tract involvement in sarcoidosis and its management.

Of some 750 sarcoidosis patients, 27 were found to have involvement of their nasal mucosa. Most had multisystem disease, which was usually chronic. Nasal stuffiness or blockage and crusting were the major symptoms, and were usually present at the first presentation with sarcoidosis. The larynx was involved in five cases. The Kveim test was positive in twelve of the fourteen patients in whom it was performed, serum angiotensin converting enzyme was frequently elevated and sinus radiographs were often abnormal. Topical medication improved symptoms in some patients, but the majority required systemic corticosteroids. It was possible to withdraw medication completely after seven years in only one patient. Relapse was encountered during reduction of dosage in other patients. Random biopsy of macroscopically normal nasal mucosa did not yield histological support for a diagnosis of sarcoidosis in twelve out of thirteen patients, but upper respiratory tract lymphoid tissue may contain granulomas in patients with sarcoidosis.

Adenoids↗

Thyrotrophin receptor antibodies in type 1 (insulin-dependent) diabetes mellitus.

Graves' disease and type 1 (insulin-dependent) diabetes are common autoimmune endocrine disorders which may co-exist. Since the class II HLA-DR3 antigen is associated with both these diseases, and since an association between DR3 and the thyrotrophin receptor antibody (TRAb) has been suggested, we wished to determine whether TRAb levels were increased and were HLA-D related in diabetes mellitus. In 115 clinically euthyroid subjects (33 type 1 diabetics, 82 healthy controls) there was a correlation between age and TRAb levels (r = -0.39, p less than 0.001). TRAb levels were elevated in DR3 subjects (n = 32) compared to an age matched group of non-DR3 (n = 61) subjects [median (range): 18.1 (-1.7 to 47.4) versus 6.7 (-9.8 to 19.1), p less than 0.001]. Diabetic DR3 and control DR3 subjects had similar TRAb levels which were elevated when compared to their respective non-DR3 control group (both p less than 0.001). All but two subjects (both diabetic) had TRAb levels in our normal range. Thus TRAb levels are elevated in the subjects who possess the HLA-DR3 antigen. Since DR3 is found so commonly in type 1 diabetes this phenomenon may partly explain the association with Graves' disease in this patient population.

Adult↗

A visit to Chernobyl.

Details of the accident at the Chernobyl nuclear power plant were given by Soviet experts at a special International Atomic Energy Agency meeting in Vienna, Austria, in August 1986. Several unanswered questions were made much clearer by a visit to the decontaminated and operating power plant at Chernobyl and by discussions with Soviet scientists. The visit gives us insights into the way the Soviets design their technology, the consequences of the accident, and the magnificent way they coped with the disaster. Although there are general conclusions to be drawn for the rest of the world, such as the realization that operators of technological systems can and will deliberately cut out safety systems, the primary specific conclusion is to be grateful that the West did not follow the Soviet route in its development of nuclear power.

Accidents↗

Risk assessment and comparisons: an introduction.

Risk assessment is presented as a way of examining risks so that they may be better avoided, reduced, or otherwise managed. Risk implies uncertainty, so that risk assessment is largely concerned with uncertainty and hence with a concept of probability that is hard to grasp. The results of even the simplest risk assessments need to be compared with similar assessments of commonplace situations to give them some meaning. We compare and contrast some risk estimates to display their similarities and differences.

Accidents↗