The phosphoinositide 3-kinase inhibitor wortmannin inhibits CD28-mediated T cell co-stimulation.
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Biomedical subjects
Publications and source records attributed to A Wilson.
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We have studied in seven healthy conscious volunteers the correlation between the electromyographic (EMG) and clinical criteria used to identify adequate recovery from sub-paralysing doses of pipecuronium. Pipecuronium (mean dose 1.88 (range 0.92-3.16) mg) was administered to reach a T4/T1 ratio of 0.5; full recovery to 1.0 was produced in a mean time of 25.3 (14-39) min. During recovery from neuromuscular block, we measured tidal volume, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) negative inspiratory pressure (NIP), peak expiratory flow rate (PEFR), mid-expiratory flow rate (MEFR) and 5-s head lift. The assessments were started when the train-of-four (TOF) ratio reached 0.5 +/- 0.001 and repeated at each 0.1 +/- 0.001 increase up to a ratio of 1.0. All volunteers showed ptosis and diplopia after the first dose and difficulty in swallowing with subsequent doses. They also experienced a pleasant, relaxing sedative sensation. All could sustain head lift for 5 s at a TOF ratio of 0.5 and higher, except for one subject who could not lift his head only at a ratio of 0.5. There was a statistically significant decrease in FVC, FEV1 and PEFR with a nonsignificant decrease in other pulmonary measurements, except for NIP which only decreased significantly at a ratio of 0.5. These changes are probably of no clinical importance. All the measured respiratory variables returned to control values at a TOF ratio of 0.9.
BACKGROUND: There has been a major decline in mortality from coronary heart disease (CHD) in Australia from about 1967 through to 1989, occurring across all age groups simultaneously. We have analysed data up until 1992 to examine for trends within age cohorts. METHODS: Death registrations for acute myocardial infarction and CHD were used to construct male and female 5-year age- and cohort-specific mortality rates starting at 1900-1904 for cohorts and 25-29 years for age. Trends within age group and within cohort were compared across time. RESULTS: Across all female and most male birth cohorts there was a decrease in CHD mortality across the time period. In the youngest male cohorts there was a significant flattening in the rate of decline in the most recent periods. Comparison of age-specific mortality across cohorts showed the mortality at any period to be lower in the most recent cohort. CONCLUSIONS: This analysis demonstrates a continuing decline in mortality from CHD among females of all ages in Australia although the rate of decline appears to have slowed or even ceased in younger males.
The mature TCR is composed of a clonotypic heterodimer (alpha beta or gamma delta) associated with the invariant CD3 components (gamma, delta, epsilon and zeta). There is now considerable evidence that more immature forms of the TCR-CD3 complex (consisting of either CD3 alone or CD3 associated with a heterodimer of TCR beta and pre-T alpha) can be expressed at the cell surface on early thymocytes. These pre-TCR complexes are believed to be necessary for the ordered progression of early T cell development. We have analyzed in detail the expression of both the pre-TCR and CD3 complex at various stages of adult thymus development. Our data indicate that all CD3 components are already expressed at the mRNA level by the earliest identifiable (CD4lo) thymic precursor. In contrast, genes encoding the pre-TCR complex (pre-T alpha and fully rearranged TCR beta) are first expressed at the CD44loCD25+CD4-CD8- stage. Detectable surface expression of both CD3 and TCR beta are delayed relative to expression of the corresponding genes, suggesting the existence of other (as yet unidentified) components of the pre-TCR complex.
Tension pneumothorax and hemothorax are life-threatening emergencies that require immediate treatment. Field stabilization of trauma patients often requires rapid surgical drainage of these injuries but inevitably delays departure for hospital. Conventional treatment involves the insertion of a chest drain but we describe a modified technique of simple thoracostomy that is faster and simpler to perform and avoids the risks associated with insertion of the chest drain. Following use of a simple thoracostomy as an alternative to chest drain insertion in 45 patients at the roadside, this technique appears to have important advantages over conventional techniques and warrants further clinical evaluation.
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T cells belong to either the alpha beta+ or gamma delta+ lineage as defined by their antigen receptor. Although both T-cell subsets have been shown to be involved in the immune response to the parasite Leishmania major, very little is known about possible interactions between these two populations. In this study, using a mouse model of infection with L. major, we showed that expansion of a subset of gamma delta+ T cells in vivo is dependent upon the presence of alpha beta+ CD4+ T cells. Moreover, this effect appears to be mediated via the secretion of lymphokines by CD4+ cells with a T-helper 2 (Th2) functional phenotype. Results showing that activation of Th2-type cells in mice treated with anti-immunoglobulin D antibodies or infected with Nippostrongylus brasiliensis also results in gamma delta+ T-cell expansion suggest that this effect of the Th2-type CD4+ cells is a general phenomenon not restricted to infection with L. major.
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OBJECTIVES: To assess the effect of urban deprivation on childhood growth in a modern British society by analysing data from a regional growth survey, the Tayside growth study. SETTING: The Tayside Region in Scotland, which has three districts with distinct socioeconomic status: Dundee (D, urban city), Angus (A, rural), and Perth (P, rural and county town). SUBJECTS AND METHODS: Height and weight of 23,046 children (> 90% of the regional childhood population) were measured as part of a child health surveillance programme, by community health care workers at 3, 5, 7, 9, 11, and 14 years. Height standard deviation score (calculated against Tanner) and body mass index (BMI-weight (kg)/height (m)2) were calculated for each child by a central computer program; mean height standard deviation score and BMI standard deviation score were calculated for each measuring centre (school, health clinic). A deprivation score for each centre was calculated from the prevalence of single parent families; families with more than three children; unemployment rate; the number of social class V individuals; the percentage of council houses. RESULTS: Mean height standard deviation score for Tayside was 0.11. An intraregional difference was demonstrated: mean height standard deviation score (SD) D = 0.04 (1.0); A = 0.14 (1.1); P = 0.21 (1.1); P < 0.002. There was a positive association between short stature and increasing social deprivation seen throughout Tayside (P < 0.05), with a strong association in Dundee primary school children (r = 0.6; P < 0.001). Analysis by district showed that the association was significant only above the age of 8 (P < 0.004). There was no relation between BMI and social deprivation. CONCLUSIONS: In an industrialised developed society, urban deprivation appears to influence height mostly in late childhood, and this association should be taken into consideration in the clinical management of short stature. Height seems to be a better physical indicator of urban deprivation, and hence an index of childhood health, than BMI.
Although alpha-interferons have anti-tumour activity in a variety of solid and haematological malignancies, they are not generally considered to be effective therapy for mature testicular teratomas. We report a case of complete remission in a patient with recurrent mature teratoma following treatment with alpha-interferon.
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Aged memory-impaired (AI) and unimpaired (AU) 24-25-month-old Long-Evans rats were used to investigate the integrity of various cholinergic markers during normal aging and to establish if alterations can possibly relate to cognitive disabilities. AI and AU rats were classified on the basis of their performance in the Morris swim maze task. Choline acetyltransferase activity (ChAT) was not differentially altered in various cortical and hippocampal areas between these two groups. Similarly, quantitative receptor autoradiography did not reveal significant differences in 3H-pirenzepine/muscarinic M1 and 3H-hemicholinium-3/high-affinity choline uptake binding sites in AI versus AU rats. In contrast, 3H-AF-DX 384/putative muscarinic M2 binding was significantly increased in certain cortical and hippocampal areas of the age-impaired animals. These increments were correlated with decreased in vivo acetylcholine (ACh) release capacity in the AI rats. Most interestingly, the muscarinic M2 antagonist BIBN-99 reversed, in a dose-dependent manner, the impaired ACh release as well as the cognitive deficits observed in the AI group. Similarly, BIBN-99 reversed scopolamine-induced amnesia in young animals. The efficacy of BIBN-99 likely relates to its antagonistic properties on negative muscarinic M2 autoreceptors that are apparently increased in the AI animals, leading to altered ACh release. Taken together, these findings strengthen the role of ACh in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic functions, such as Alzheimer's disease.
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A relatively small dose of rocuronium (0.45 mg kg-1) was compared with equipotent doses of atracurium (0.35 mg kg-1) and vecuronium (0.075 mg kg-1) for ease of intubation at 60 s. All patients could be intubated but the proportion with excellent or good conditions was much greater with rocuronium. Mean clinical duration of effect of this dose was 22.2 min. There was no correlation between intubating conditions and the degree of block of the adductor policis.
OBJECTIVE: To investigate the variability in serum pepsinogen levels in an asymptomatic population. DESIGN: Cross-sectional survey of 420 men aged 18-63 years, without symptoms or a history of gastric disease, recruited from four factories in Stoke-on-Trent. METHODS: During an interview, data on history of gastric health, 'lifestyle' and occupation were collected, blood samples were taken for measurement of serum pepsinogen and anti-Helicobacter pylori antibody levels and height and weight were measured. RESULTS: Extreme (low/high) levels of pepsinogens A and C, indicative of chronic gastritis, were found in 24 (5.7%) and 61 (14.5%) of the participants, respectively. Low A-C ratios, indicative of moderate or severe gastric atrophy, were found in 13 (3.1%) participants. Of the variables examined, Helicobacter pylori serology had the strongest influence on serum pepsinogen levels. Serum pepsinogen A and C levels were significantly higher in the 33.6% of participants who were seropositive. The effect was more marked for pepsinogen C; thus, A-C ratios were lower in seropositive individuals. In seronegative participants, both pepsinogen A and pepsinogen C levels increased with increasing age; pepsinogen A levels increased with increasing height and were higher in smokers, but decreased with increasing weight. The effect of smoking on pepsinogen A levels was also detectable in seropositive individuals, but was considerably less marked. Among seronegative participants, those employed on the 'shop-floor' in manual jobs had higher serum pepsinogen C levels and lower A-C ratios than office-based workers. CONCLUSION: H. pylori serology was a major source of variation in serum pepsinogen levels, but causes of gastritis other than H. pylori were indicated. Independent of these effects, serum pepsinogen levels may also vary with age, height and weight. Screening of serum pepsinogen levels in the general population may identify 5-15% who require further investigation. Other 'filters' may be required in conjunction with serum pepsinogen levels to identify those needing investigation for significant gastric pathology.
OBJECTIVE: To determine what proportion of health promotion activities reported by the patient is recorded in the general practice notes and to compare these methods of assessing health promotion with audio tape analysis. DESIGN: Secondary analysis of data obtained in a controlled trial of differing appointment lengths. After each consultation the medical record was examined and the patient invited to completed a questionnaire. A subsample of consultations was audio taped. SETTING: Nottinghamshire. SUBJECTS: 16 general practitioners from 10 practices. This report includes 3324 consultations with patients aged > or = 17, with data on measurement of blood pressure and advice about smoking and alcohol. RESULTS: Data from questionnaire and medical notes were available for 2281 consultations. Advice on smoking was recorded in the notes in 30.9% of cases in which a patient reported it (for alcohol and measurement of blood pressure, 44.4% and 82.7% of cases respectively). In 516 cases analysis of audio tape and review of records was performed. Advice on smoking was recorded in the patient's notes in 28.6% of cases in which it was detected on audio tape (for alcohol, 31.1% of cases). In 335 consultations data from audio tape and questionnaire were available. Advice on smoking was reported by patients in 73.9% of cases in which it was detected on audio tape (for alcohol, 75.0% of cases). CONCLUSIONS: Review of the medical record is a reasonably accurate method of assessing measurement of blood pressure in the consultation but would lead to significant underestimation of advice about smoking and alcohol.
During T cell development in the thymus, T cell receptor (TCR) alpha, beta, gamma, and delta genes are rearranged and expressed. TCR rearrangement strictly depends upon the coordinate activity of two recombinase activating genes, Rag-1 and Rag-2. In this study we have followed the expression of these genes at different stages of intrathymic development. The results indicate that there are two periods of high Rag-1 and Rag-2 mRNA expression. The first wave peaks early at the CD25+CD4-CD8-CD3- stage of development and coincides with the initial appearance of transcripts derived from fully rearranged TCR beta, gamma, and delta genes, whereas the second wave occurs later at the CD4+CD8+ stage coincident with full-length TCR alpha mRNA expression. Active downregulation of Rag-1 and Rag-2 mRNA expression appears to occur in vivo between the two peaks of recombinase activity. This phenomenon can be mimicked in vitro in response to artificial stimuli such as phorbol myristate acetate and calcium ionophore. Collectively our data suggest that recombinase expression is actively regulated during early thymus development independently of cell surface expression of a mature heterodimeric TCR protein complex.