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Biomedical subjects

A G Davison

Publications and source records attributed to A G Davison.

At least 37 records · Page 2Linked to original sources
PubMed1992

Evidence for phosphatidylinositol hydrolysis in pancreatic islets stimulated with carbamoylcholine. Kinetic analysis of inositol polyphosphate metabolism.

Anion-exchange h.p.l.c. was used initially to analyse the products formed after addition of either [3H]Ins(1,3,4,5)P4 or [3H]Ins(1,4,5)P3 to homogenates of pancreatic islets. Metabolic routes similar to those of other tissues were established: dephosphorylation of Ins(1,4,5)P3 to Ins(1,4)P2 and then Ins4P; and sequential degradation of Ins(1,3,4,5)P4 to Ins(1,3,4)P3, Ins(3,4)P2 and Ins(3 or 1)P. In addition, there was a limited conversion of Ins(1,3,4)P3 into Ins(1,3)P2. After stimulation of [3H]inositol-prelabelled islets with the muscarinic-receptor agonist carbamoylcholine (carbachol), there was a rapid (10 s) increase in Ins(1,4,5)P3, Ins(1,3,4)P3, Ins(1,4)P2 and Ins4P. In the presence of 10 mM-LiCl, Ins1P was also significantly increased (P less than 0.05) by 5 s, before any increase in Ins4P (10 s), Ins(1,3)P2 (60 s) or Ins(3,4)P2. When carbachol was displaced with atropine, after 1 h pre-stimulation, the maximal decreases in Ins(1,4,5)P3 and Ins1P from the stimulated steady state (5 s) clearly preceded those of the other metabolites. These declines were used to calculate the turnover times and rate of metabolic flux through the various inositol phosphates. These experiments confirmed the relatively minor importance of the Ins(1,3)P2 pathway (less than 10% of the total flux) and demonstrated that Ins(1,4,5)P3 removal was evenly distributed through the Ins(1,4)P2 and Ins(1,3,4,5)P4 routes. They also established that flux through Ins1P was 8-fold greater than that through Ins(1,4,5)P3, indicating that the former could not have been derived from PtdInsP2 hydrolysis. Similarly, in islets pretreated with neomycin, which binds to PtdInsP2 with greater affinity than to PtdIns, the increase in Ins1P caused by 1 min stimulation with carbachol was not affected, despite virtual abolition of the increase in Ins4P, and an overall inhibition of PtdInsP2 hydrolysis by 67%. The results indicate that, in addition to PtdInsP2 breakdown, carbachol also promotes a rapid PtdIns hydrolysis which becomes increasingly predominant with prolonged stimulation.

Animals↗
PubMed1989

Effect of phorbol esters on the distribution and total activity of protein kinase C in the perfused rat heart.

1. The perfused rat heart was treated with the tumour-promoter and protein kinase C activator, phorbol 12-myristate 13-acetate and the distribution of protein kinase C activity between cytosolic and particulate fractions determined. 2. Phorbol ester treatment led to a rapid loss of protein kinase C activity from the cytosol (t0.5 = 2 min) with a corresponding translocation into the particulate fraction. Translocated protein kinase C activity was tightly bound to the particulate fraction, could only be extracted with buffers containing 2% Triton X-100 and could therefore be misinterpreted as being down-regulated. 3. Claims of rapid down-regulation of protein kinase C activity by phorbol esters need to be supported by rigorous procedures for extraction of the particulate material.

Animals↗
PubMed1989

Consequences of occupational asthma.

Seventy-nine patients attending hospital for follow-up of occupational asthma were interviewed, on average 6 years after asthma developed. Although 90% thought their symptoms had improved, 10% had required a hospital admission (apart from for investigation), 72% still took medication and most reported symptoms in the last 3 months. One-third were currently unemployed and 40-73% reported limitation in everyday activities, such as housework or shopping. Symptoms on waking were used as an index of troublesome asthma. Those 31 in whom this occurred at least once a week reported limitation in everyday activities significantly more commonly than others. This relation was more marked in men than women. Limitation in everyday activities was, however, more frequently reported by women than men, who were also more likely than men to be unemployed, suggesting that factors other than impairment of function also contribute to handicap in occupational asthma.

Activities of Daily Living↗
PubMed1989

Pseudo-occupational asthma.

A case is reported in which a pattern of work related asthma in a record of peak expiratory flow was artefactual. The patient had pronounced morning dips, which she recorded on working days, when she made the first recording at 0700 h, but not on holiday, when she stayed in bed longer. The case emphasises the need for clear instructions to patients about peak flow records.

Asthma↗
PubMed1988

Cadmium fume inhalation and emphysema.

Lung function and chest radiographs of 101 men who had worked for 1 or more years manufacturing copper-cadmium alloy were compared with those of a referent group matched for age, sex, and employment status. Cigarette consumption was similar in the two groups. The cadmium workers had an excess of abnormalities of lung function and of radiographic changes consistent with emphysema. Classification of the cadmium workers by exposure categories based on either estimated cumulative cadmium exposure or liver cadmium measured by neutron activation analysis showed that abnormalities of lung function were greatest in those with the highest cumulative cadmium exposure or liver cadmium. The difference in the transfer coefficient (KCO) between cadmium workers and referents increased linearly with increasing cumulative exposure without evidence for a threshold. The estimated mean decrement in KCO for a cadmium worker employed 5 or more years with a cumulative exposure of 2000 yr.microgram.m-3 (exposure to the current UK control limit of 50 micrograms.m-3 for a working lifetime of 40 yr) lies between 0.05 and 0.3 mmol.min-1.kPa-1.l-1 (95% confidence interval). This decrement is consistent with the functional and radiological changes of emphysema observed in this group of workers.

Aged↗
PubMed1988

Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers.

Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Alloys↗
PubMed1987

Meptazinol overdose producing near fatal respiratory depression.

Meptazinol is one of the new powerful opioid analgesic agents, and an oral formulation has recently been marketed. Clinically significant respiratory depression is said to be absent and no overdoses from meptazinol have been reported in the literature. We report a patient who had a respiratory arrest following an overdose of meptazinol.

Azepines↗
PubMed1986

Number of patients required in lung function studies.

Tables are presented showing estimates of the number of subjects which is required to give an 80% or 90% chance of detecting various differences in forced expiratory volume in one second, forced vital capacity, total lung capacity, transfer factor, and residual volume between the mean of two groups by means of Student's t test.

Humans↗
PubMed1985

Occupational asthma due to methyl methacrylate and cyanoacrylates.

Five patients had asthma provoked by cyanoacrylates and one by methyl methacrylate, possibly because of the development of a specific hypersensitivity response. Acrylates have wide domestic as well as industrial uses, and inhalation of vapour emitted during their use can cause asthma.

Adult↗
PubMed1984

Peak flow rate records in surveys: reproducibility of observers' reports.

Records of peak expiratory flow rate (PEFR), commonly used in hospital in the management of asthma, have not been evaluated as a method of identifying cases of asthma in population surveys. Four observers were asked to report on whether asthma was present or absent in 61 graphs of PEFR recorded two hourly for four weeks during surveys of working population. Agreement within individual observers was measured using a subset of 29 graphs which had been copied and distributed at random among the set of 61; agreement was good, from 90% in one observer to 100% in two. Agreement between observers was measured on the basis of all 61 graphs. Agreement occurred between all four observers in 69% of graphs, between at least three out of four in 97%, and, when pairs of observers were examined, between 72% and 93% of graphs. Graphs assessed as showing asthma demonstrated more within day PEFR variability (expressed as the number of days in which the difference between maximum and minimum readings was at least 15%) than graphs assessed as not showing asthma. Some graphs with little within day variability were assessed as showing asthma, apparently because they demonstrated between day PEFR variability.

Asthma↗
PubMed1983

Asthma in merchant seamen and laboratory workers caused by allergy to castor beans: analysis of allergens.

Three merchant seamen and two laboratory workers who developed allergic symptoms following exposure to castor beans have been investigated. Bronchial-provocation testing with castor beans in the merchant seamen demonstrated a late reaction in two. Specific IgE against whole castor-bean extract and ricin, ricinus agglutinin and dericinated extracts of castor bean were found in the patients' sera using radioallergosorbent tests (RAST). RAST inhibition, toxocological and haemagglutination tests suggest that the ricin and dericinated extracts contain distinct allergens.

Adult↗
PubMed1983

Cystic fibrosis mimicking Bartter's syndrome.

A four-month-old female presented with dehydration and an unexplained hypoelectrolytaemia and metabolic alkalosis in association with hyperreninaemia and hyperaldosteronism. These findings suggested Bartter's syndrome. Sweat sodium concentrations were within normal limits. Total skin water loss was estimated and found to be sufficient for the sodium loss in the sweat to exceed the dietary intake. Reinvestigation at three years revealed normal plasma electrolytes, plasma renin activity and aldosterone values but sweat sodium concentrations were in excess of 80 mmol/l, indicating a diagnosis of cystic fibrosis.

Aldosterone↗
PubMed1983

Interstitial lung disease and asthma in hard-metal workers: bronchoalveolar lavage, ultrastructural, and analytical findings and results of bronchial provocation tests.

Five patients with respiratory disorders associated with hard metal exposure are described. In four patients electron microprobe analysis of bronchoalveolar lavage cells or lung tissue was used to show tungsten and other hard-metal components. Three patients had interstitial pneumonia and fibrosis with unusual multinucleate giant cells. Electron microscopy showed that the giant cells comprised both type II alveolar epithelial cells and alveolar macrophages. The multinucleate macrophages formed a distinctive feature of the bronchoalveolar lavage material but the multinucleate alveolar epithelial lining cells were evident only in lung tissue. The other two patients both suffered from work-related asthma, one of whom also had pulmonary opacities. Bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible.

Adult↗