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M Hutton

Publications and source records attributed to M Hutton.

At least 127 records · Page 7Linked to original sources

Kinetic resolution of the reaction catalysed by proton-translocating transhydrogenase from Escherichia coli as revealed by experiments with analogues of the nucleotide substrates.

The mechanism, by which transhydrogenase couples transfer of H- equivalents between NAD(H) and NADP(H) to the translocation of protons across a membrane, has been investigated in the solubilised, purified enzyme from Escherichia coli using analogues of the nucleotide substrates. The key observation was that, at low pH and ionic strength, solubilised transhydrogenase catalysed the very rapid reduction of acetylpyridine adenine dinucleotide (an analogue of NAD+) by NADH, but only in the presence of either NADP+ or NADPH. This indicates that the rates of release of NADP+ and NADPH from their binary complexes with the enzyme are slow. The dependences on pH and salt concentration suggest that (a) release of both NADP+ and NADPH are accompanied by the release of H+ from the enzyme and (b) increased ionic strength decreases the value of the pKa of the group responsible for H+ release. Modification of the enzyme with N,N1-dicyclohexylcarbodiimide led to inhibition of the rate of release of NADP+ and NADPH from the enzyme, but had a much smaller effect on the binding and release of NAD+, NADH and their analogues and on the interconversion of the ternary complexes of the enzyme with its substrates. It is considered that the binding and release of H+, which accompany the binding and release of NADP+/NADPH, might be central to the mechanism of proton translocation by the enzyme in its membrane-bound state.

Binding Sites↗

Duplication of inferior vena cava: its importance in retroperitoneal surgery.

Anomalies of the inferior vena cava arise infrequently. Knowledge of their presence can be established preoperatively with a variety of radiologic studies. This knowledge can prevent hemorrhagic complications from occurring during surgery. We present a case report of a patient with renal cell carcinoma and duplication of the inferior vena cava.

Carcinoma, Renal Cell↗

Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis.

The short chain fatty acids, acetate, propionate, and butyrate are produced by colonic bacterial fermentation of non-starch polysaccharides. Butyrate is the major fuel source for the colonic epithelium and there is evidence to suggest that its oxidation is impaired in ulcerative colitis. Triplicate biopsy specimens were taken at colonoscopy from five regions of the large bowel in 15 sufferers of ulcerative colitis. These patients all had mild or quiescent colitis as assessed by clinical condition, mucosal endoscopic and histological appearance. The rate of oxidation of glucose, glutamine, and butyrate through to carbon dioxide was compared with that in biopsy specimens from 28 patients who had no mucosal abnormality. Butyrate (272 (199-368)) was the preferred fuel source for the colitic mucosa followed by glutamine (33 (24-62)) then glucose (7.2 (5.3-15)) pmol/micrograms/hour; medians and 95% confidence intervals, p < 0.01. There was no regional difference in the rate of utilisation of these metabolites. In the group with colitis the rate of butyrate oxidation to carbon dioxide was significantly impaired compared with that in normal mucosa decreasing from 472 (351-637) pmol/micrograms/hour to 272 (199-368) pmol/micrograms/hour; median and 95% confidence intervals, p = 0.016. The rate of glucose and glutamine utilisation were not significantly different between normal and colitic mucosa. These data confirm that in quiescent ulcerative colitis there is an impairment of butyrate oxidation.

Adult↗

New technique to measure mucosal metabolism and its use to map substrate utilization in the healthy human large bowel.

A new method of assessing substrate utilization in gastrointestinal mucosal specimens is described. Small human endoscopic biopsy specimens with wet weights ranging between 1.4 and 12.2 mg were used to quantify the oxidation of three metabolic substrates, glucose, glutamine and butyrate, through to carbon dioxide over a 2-h period. The technique proved to be reproducible and capable of distinguishing variations in mucosal metabolism between individuals (P < 0.0001 for each substrate). Results were similar to those obtained previously using human and rat colonocytes. To characterize the metabolism of the healthy large bowel, specimens were obtained from five regions in 15 patients who had a normal colonoscopic examination. The results show that butyrate is the preferred fuel source of large bowel mucosa, followed by glutamine, then glucose (P < 0.01). There was no significant regional variation in utilization of the three substrates between the five regions; with respect to glutamine, this is contrary to previous findings.

Adult↗

Carotid endarterectomy in a metropolitan community: the early results after 8535 operations.

Several retrospective community surveys have provoked speculation concerning the safety of carotid endarterectomy (CEA) throughout the United States. To address this serious issue, surgical outcome was calculated for 8535 CEAs entered prospectively into a computer registry by 51 trained vascular surgeons in a large metropolitan area from 1973 to 1985. A total of 7480 procedures (88%) were performed for symptomatic lesions and 1055 (12%) were performed for asymptomatic stenosis or ulceration. There were 178 operative strokes (2.1%) and 135 early deaths (1.6%), for a combined morbidity-mortality rate of 3.2%. Fatal events were attributed to cardiac disease in 0.7%, neurologic complications in 0.6%, and other causes in 0.3%. The stroke rate (n = 148; 2.0%) in symptomatic patients was better than that in asymptomatic patients (n = 30; 2.8%) (chi 2 = 5.2; p less than 0.025), but the combined morbidity-mortality rates (2.9% and 3.7%) were not statistically different. The incidence of stroke reported by surgeons who performed more than 5 CEAs annually (1.7%) was statistically superior to the stroke rate (3.4%) among those with less experience (chi 2 = 37.1; p less than 0.0001). Nevertheless, both groups had acceptable results that were consistent with their training and continued interest in vascular surgery.

Aged↗

The cadmium and lead content of suspended particulate matter emitted from a U.K. refuse incinerator.

Suspended particulate matter (SPM), sampled from the stack of a large refuse incinerator in the U.K., contained markedly elevated levels of Cd (approximately 1600 micrograms g-1) and Pb (approximately 3%). These values were similar to those previously reported for several other incinerators in Europe, but the Pb concentrations were lower than in the SPM from three American incinerators. Calculation of the metal concentration ratio SPM/fly ash for the U.K. incinerator revealed a three-fold enrichment of the two metals on the SPM. Similar ratios were obtained for several other European incinerators; this correspondence in metal partitioning was linked to the use of electrostatic precipitators in these facilities. The SPM metal data obtained in this study were used to estimate atmospheric emissions of 0.5 t Cd year-1 and 11 t Pb year-1 from the incinerator. Extrapolation of the Cd and Pb emission factors derived from this study to the quantity of refuse incinerated in the U.K. results in atmospheric discharges of 6 t Cd year-1 and 115 t Pb year-1. These estimates are in good agreement with those previously reported by an emissions inventory which identified incineration as the single largest source of airborne Cd in the U.K.

Air Pollutants↗

The leachability and chemical speciation of selected trace elements in fly ash from coal combustion and refuse incineration.

A laboratory leaching test has been used to predict the potential mobility of As, Se, Pb and Cd in landfilled fly ash produced by coal combustion and refuse incineration. These waste residues also formed the basis of a speciation study in which the valency states of As and Se and the chemical forms of Pb and Cd have been determined. Selenium displayed the greatest leachability in each ash type, despite being present at relatively low concentrations in both materials. Substantial amounts of other trace elements were also leached, particularly Pb and Cd from refuse ash and As from coal ash. Chemical associations of Pb and Cd were examined by a sequential extraction procedure. In coal fly ash, both elements were mostly present in the residual fraction, while in refuse ash these elements were mainly associated with the exchangeable fraction. Water-soluble extracts of coal fly ash contained As exclusively as As(V); high background interference prevented the detection of water-soluble As in refuse ash. Selenium was present largely as Se(IV) in aqueous extracts of both ash types. The value of speciation techniques and leaching tests as predictors of environmental behaviour is discussed in conjunction with results of routine trace element determinations and plant uptake studies.

Journal Article↗

The quantities of cadmium, lead, mercury and arsenic entering the U.K. environment from human activities.

This paper presents an estimate of the quantities of cadmium, lead, mercury and arsenic entering the U.K. environment from human activities. Discharges are divided into three source categories: the production and use of the elements, inadvertent sources and various waste disposal practices. The major atmospheric sources of cadmium and mercury include refuse incineration, nonferrous metal production, iron and steel production, fossil fuel combustion and, for mercury alone, the chlor-alkali industry. In contrast, lead and arsenic each have only one major atmospheric source: petrol and coal combustion, respectively. The largest inputs of cadmium, lead and mercury to landfill arise from the disposal of municipal wastes; for arsenic, ash disposal from coal combustion is more important. Industrial activities represent the major sources of trace element input to the U.K. sewage system but domestic sources are important for lead and cadmium, while road run-off makes a considerable lead input. In U.K. coastal waters the major sources of cadmium are the direct discharge of sewage and industrial effluents. For the other elements, the dumping of solid wastes is of more significance. The largest inputs of lead, mercury and arsenic to U.K. agricultural land arise from atmospheric deposition; for cadmium the application of phosphate fertilizers is a more important source, while sewage sludge can be of local significance.

Air Pollutants, Occupational↗

A prospective atmospheric emission inventory for cadmium--the European community as a study area.

The quantities of cadmium emitted to the atmosphere from natural and human sources have been estimated for the member states of the European Community, allowing the construction of an atmospheric emission inventory for cadmium at the regional level. A survey of the available emission data was used to calculate an emission factor (g cadmium emitted tonne -1 material consumed or produced) for each source. This value was applied to the most recent consumption or production data for the region to obtain an annual discharge estimate. Predictions of future trends in cadmium emissions from human sources over the next two decades were based on economic forecasts for the process in question. The iron and steel industries and refuse incineration are the two largest sources of airborne cadmium in the region, followed by volcanic action and zinc production. It is forecast that there will be an increase in cadmium emissions over the next two decades due mainly to the iron and steel industries and zinc production. A comparison of the emission estimates obtained in this study with those given in previously published inventories reveal disparities in the source strengths for some processes. In particular, it would appear that cadmium emissions from coal combustion and non-ferrous metal production have been overestimated in some past studies.

Air Pollutants↗

Sources of cadmium in the environment.

This paper is concerned with quantifying the major sources of cadmium in the European Community and assessing the relative significance of such inputs to the environmental compartments, air, land, and water. The methodology involved identification of potential sources of cadmium, including natural processes, as well as those associated with human activities. This was followed by a review of any emission studies of these processes and subsequent estimation of an emission factor for each source. The emission factor was applied to the most recent production or consumption data for the process in question to obtain an estimate of the annual discharge. The steel industry and waste incineration, followed by volcanic action and zinc production, are estimated to account for the largest emissions of atmospheric cadmium in the region. Waste disposal results in the single largest input of cadmium to land; the quantity of cadmium associated with this source is greater than the total from the four other major sources--coal combustion, iron and steel production, phosphate fertilizer manufacture and use, and zinc production. The characterization of cadmium inputs to aquatic systems is incomplete but of the sources considered, the manufacture of cadmium-containing articles accounts for the largest discharge, followed by phosphate fertilizer manufacture and zinc production.

Cadmium↗

The effects of environmental lead exposure and in vitro zinc on tissue delta-aminolevulinic acid dehydratase in urban pigeons.

1. Elevated lead burdens in three urban pigeon populations caused ALAD inhibition, in blood, kidney and liver, the degree of inhibition generally corresponding to the lead content of each tissue. The values obtained are compared with those given by studies of lead exposure in mammals. 2. The usefulness of blood ALAD as an index of lead exposure is discussed. 3. The pH activity profile of ALAD in blood and kidney of urban pigeons was also changed. 4. In vitro zinc additions partially restored lead-inhibited ALAD. 5. These findings are discussed in terms of the possible manner in which lead inhibits ALAD.

Animals↗

The role of wildlife species in the assessment of biological impact from chronic exposure to persistent chemicals.

Assessments of chemical toxicity have regularly placed reliance upon experimental studies which employ environmentally unrealistic exposure regimes. This approach ignores the long-term low-level nature of environmental exposure which facilitates the development of factors which modify the toxicity of such chemicals. Examples of such adaptive mechanisms will be taken from the author's own studies. Factors discussed include the development of protective trace element interactions in target organs, the induction of specific metal-binding proteins, and the alteration of the distribution of chemicals at the organ and organelle level. Exposure-response investigations in wildlife are not restricted to the organism level and the impact of an environmentally released chemical upon breeding success and population dynamics can also be investigated. Disadvantages and problems associated with this kind of study, such as multiple pollutant exposure and variability in response, will also be considered.

Animal Population Groups↗

Effect of metoclopramide on interdigestive myoelectric activity in the conscious dog.

The effect of two-hour infusions of metoclopramide at five different doses on interdigestive intestinal electrical activity was studied in four conscious fasting dogs. Spike activity during the infusions was quantitatively compared with activity during preceding and following periods of saline infusion. The effect of the drug was the enhancement of spike activity during migrating myoelectric complexes (MMC) without disruption of the fasting pattern; the effect was most marked in the proximal small intestinal and diminished distally. As in other published studies with metoclopramide, its effects were variable and not dose dependent. The enhancement of the MMC by an exogenous stimulus, not previously reported, provides indirect evidence for cholinergic mediation of cyclical motor activity, and also suggests a rational basis for therapy.

Animals↗