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Biomedical subjects

J McEvoy

Publications and source records attributed to J McEvoy.

At least 19 recordsLinked to original sources
PubMed2001

Investigations of cholesterol transformation during sewage treatment: relevance to estrogen formation pathways?

There is currently a great deal of concern over the observation of so-called estrogenic effects (specifically increases in the concentrations of the egg yolk precursor, vitellogenin) in male fish living in some UK rivers. The effects have been attributed to chemicals, including estrogenic steroids, which enter the rivers via sewage effluents. The origins of these estrogenic steroids in sewage may include contributions from the influents and possibly in situ transformation processes of other steroids occurring during sewage treatment. The present study examined the latter possibility. The bacterial metabolism of radiolabelled cholesterol during laboratory-simulated aerobic sewage treatment was studied by reverse phase radio-high performance liquid chromatography (rHPLC) and radio-gas chromatography (rGC) to examine the hypothesis that cholesterol could undergo A-ring aromatisation to form first, 19-norcholest-1,3,5(10)-trien-3-ol (NCT) and hence, by known bacterial pathways, the estrogenic steroid, estrone. The results showed that, to the contrary, much of the cholesterol (approx. 50% in 96 h) underwent rapid mineralisation to carbon dioxide, consistent with A-ring rupture (rather than aromatisation) and beta-oxidation of the alkyl side chain as major transformation routes. Some polar (early-eluting) rHPLC products were observed, possibly steroidal conjugates and/or fatty acids. Among the minor metabolites detected by rGC and GC-mass spectrometry (GC-MS) were cholest-3,5-diene and a second cholestadiene isomer. However, since alkenes were unexpected in this rHPLC fraction, they may arise as artefacts from thermal decomposition of cholesteryl esters, indicating that some cholesterol esterification had also occurred. In the alcohol rHPLC fractions, cholestadienol was identified by GC and GC-MS but neither NCT or estrone were detected. This suggests that, at least under these simulated conditions, in situ aromatisation of cholesterol to NCT and formation of estrone from NCT were not major processes.

Animals↗
PubMed2001

Seasonal variation and estradiol-dependent elevation of Thames estuary eel Anguilla anguilla plasma vitellogenin levels and comparisons with other United Kingdom estuaries.

Eel Anguilla anguilla plasma vitellogenin was investigated as a biomarker of exposure to environmental compounds with estrogenic activity, along the tidal course of the Thames Estuary, UK. A. anguilla was chosen as a sentinel species because of their wide distribution, robustness in field and laboratory studies and also because they have a characterised normal intersex' condition where the gonad contains both developing male and female gonadal cells termed a Syrski organ. Following laboratory exposure to 17beta-estradiol (intraperitoneal injection), a plasma protein (approx. 211 kDa apparent molecular weight) was detected by monoclonal antibodies to vitellogenin of striped bass (Morone saxatilis). Western and dot blot analyses were developed and vitellogenin was isolated from 17beta-estradiol-treated fish to calibrate the quantification of the blots by image analysis. The limits of sensitivity for the Western and dot blots were 100 and 10 ng vitellogenin/ml, respectively. Levels of vitellogenin in Thames estuary samples were below the detection limits of the Western but not the dot blot, and showed no statistically significant site-specific (10 sites) and seasonal-specific (May, August, November) differences. Values were observed to be low, between 11 and 165 ng/ml, compared with 17-50 mg/ml for 17beta-estradiol-treated eels. Similar low levels of plasma vitellogenin were determined in fish sampled along the Tyne, Wear, Tees or Humber estuaries, or the Weston canal Liverpool, with mean plasma vitellogenin levels varying between 44 and 82 ng/ml. These levels of vitellogenin in A. anguilla plasma were observed to be consistent with the known biology of the eel. Immature females, or fish with syrski organs, reported both lower levels and smaller variation of plasma vitellogenin concentrations whereas the highest plasma vitellogenin concentrations were determined in fish above 45 cm consistent with female fish. These results indicate inter-species variation between the plasma vitellogenin concentrations of A. anguilla and other published fish studies undertaken along the same estuaries.

Anguilla↗
PubMed2001

Analysis of estrogens in river water and effluents using solid-phase extraction and gas chromatography-negative chemical ionisation mass spectrometry of the pentafluorobenzoyl derivatives.

A procedure was developed for the analysis of estrogens in environmental water and effluents. Samples were extracted by passing through polymer-impregnated solid-phase extraction discs or C18 cartridges, followed by gas chromatography-negative chemical ionisation mass spectrometry of the pentafluorobenzoyl derivatives. The derivatives were stable and gave diagnostic negative molecular ions as the base peak for each of the major estrogens studied. The absolute recovery of estrogens spiked into clean groundwater using the disc procedure was 84-116% at the 10 ng l(-1) level (calculation not based on use of internal standards). Using doubly deuterated estradiol as internal standard added prior to extraction, the % relative standard deviation of estrogen extraction and analysis in spiked groundwater at the 10 ng(-1) level was 2.6-9.8%. Detection limits were 0.2 ng l(-1) or below for the major estrogens, based on a 2.5 litre sample. The most abundant estrogen was estrone, with concentrations over the range 6.4-29 ng l(-1) in effluents, and 0.2 to 17 ng l(-1) in water from the River Thames.

Estrogens↗
PubMed2001

Seasonal export of phosphorus from a lowland catchment: upper River Cherwell in Oxfordshire, England.

The export of phosphorus from a lowland catchment, the River Cherwell in southern England, was measured over a period of 1 year. The results describe total phosphorus concentrations in the water and river discharge at 4-day intervals. These were used to estimate the load of total phosphorus exported from the catchment. These annual loads were compared with exports estimated from sewage inputs and diffuse inputs calculated from land-coverage data, with assigned phosphorus export coefficients for particular land uses. The method was further developed to examine seasonal changes in phosphorus exports by predicting monthly losses using annual export coefficients normalised with respect to the relative hydraulic runoff for a particular month. The results show a strong seasonal dependence of total exports, with retention of phosphorus in the river system in the spring to early autumn and release of stored material during the winter. This pattern remained true, even with 50% increase in the main land-cover export and a similar increase in treated sewage exports.

Agriculture↗
PubMed2001

Investigations of the origins of estrogenic A-ring aromatic steroids in UK sewage treatment works effluents.

The present preliminary study describes an investigation of a putative aromatisation pathway in sewage from cholesterol through the corresponding A-ring aromatic steroid, norcholest-1,3,5(10)-trienol (NCT) to estrone. The synthesis and analytical characterisation of NCT and of the trimethyl silyl ether by gas chromatography-mass spectrometry, is described. The analytical properties of synthetic NCT were used to direct a search for the compound over several months in 1998 in the effluents of two sewage treatment works (STW; Deephams and Harpenden, north London). The study was prompted by the earlier findings that increased vitellogenin concentrations in the plasma of caged male rainbow trout held in the STW effluents (so-called fish 'feminisation') could be attributed to the presence of A-ring steroids such as estrone. Until now it has been assumed that these steroids originate from the STW influents and it is not clear to what extent, if at all, aromatisation of steroids might occur during STW operation. NCT was only detected in the solid particles associated with the effluents on one occasion in 8 months. This suggests that the hypothesised pathway is not a major one. Confirmation of previous reports of estrone and 17 beta-estradiol was also obtained using a published analytical method and by a simple modification of the method these reports were extended to include a regular occurrence of the weaker estrogen, 16 alpha-estriol in the case of Harpenden STW effluents in 1998.

Environmental Monitoring↗
PubMed2001

Replacement of fish oil with rapeseed oil in diets of Atlantic salmon (Salmo salar) affects tissue lipid compositions and hepatocyte fatty acid metabolism.

Duplicate groups of Atlantic salmon post-smolts were fed five practical-type diets in which the added lipid was 100% fish oil [FO; 0% rapeseed oil (0% RO)], 90% FO + 10% RO (10% RO), 75% FO + 25% RO (25% RO), 50% FO + 50% RO (50% RO) or 100% RO, for a period of 17 wk. There were no effects of diet on growth rate or feed conversion nor were any histopathological lesions found in liver, heart, muscle or kidney. The greatest accumulation of muscle lipid was in fish fed 0% RO, which corresponded to significantly lower muscle protein in this group. The highest lipid levels in liver were found in fish fed 100% RO. Fatty acid compositions of muscle lipid correlated with RO inclusion in that the proportions of 18:1(n-9), 18:2(n-6) and 18:3(n-3) all increased with increasing dietary RO (r = 0.98-1.00, P < 0.013). The concentrations of eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)] in muscle lipid were significantly reduced (P < 0.05), along with total saturated fatty acids, with increasing dietary RO. Diet-induced changes in liver fatty acid compositions were broadly similar to those in muscle. Hepatic fatty acid desaturation and elongation activities, measured using [1-(14)C] 18:3(n-3), were increased with increasing dietary RO. Limited supplies of marine fish oils require that substitutes be found if growth in aquaculture is to be maintained such that fish health and product quality are not compromised. Thus, RO can be used successfully as a substitute for fish oil in the culture of Atlantic salmon in sea water although at levels of RO >50% of dietary lipid, substantial reductions occur in muscle 20:5(n-3), 22:6(n-3) and the (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio, which will result in reduced availability of the (n-3) highly unsaturated fatty acids that are beneficial for human health.

Animals↗
PubMed2001

Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia.

OBJECTIVE: This study compared the specific antiaggressive effects of clozapine with those of olanzapine, risperidone, and haloperidol. METHODS: A total of 157 inpatients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were randomly assigned to receive clozapine, olanzapine, risperidone, or haloperidol in a double-blind 14-week trial. The trial was divided into two periods: eight weeks during which the dosage was escalated and then fixed, and six weeks during which variable dosages were used. The hostility item of the Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure. Covariates included the items that reflect positive symptoms of schizophrenia (delusions, suspiciousness or feelings of persecution, grandiosity, unusual thought content, conceptual disorganization, and hallucinations) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation (NOSIE). RESULTS: Patients differed in their treatment response as measured by the hostility item of the PANSS. The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone. The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking, a formal thought disorder, or hallucinations and independent of sedation as measured by the NOSIE. Neither risperidone nor olanzapine showed superiority to haloperidol. CONCLUSION: Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent.

Adult↗
PubMed2000

Depletion of alpha-tocopherol and astaxanthin in Atlantic salmon (Salmo salar) affects autoxidative defense and fatty acid metabolism.

Duplicate groups of Atlantic salmon post-smolts were fed four purified diets supplemented with both vitamin E and the carotenoid astaxanthin (Ax) (+E, +Ax), or supplemented with either vitamin E or Ax (-E, +Ax and +E, -Ax) or deficient in both vitamin E and Ax (-E, -Ax) for 22 wk. There were no effects of diet on growth rate, but an extensive lipoid liver degenerative lesion was observed in 15% of fish fed diets deficient in vitamin E. Tissue vitamin E concentrations varied in accordance with dietary vitamin E in liver, muscle, heart, plasma, brain and eye; levels were reduced to approximately 3% in liver but only to 40% in eye of fish fed diets deficient in vitamin E compared with those fed diets supplemented with vitamin E. An interactive sparing of Ax supplementation on tissue vitamin E concentration was observed, but only in brain. Dietary deficiency of both vitamin E and Ax significantly increased the recovery of desaturated and elongated products of both [1-(14)C] 18:3(n-3) and [1-(14)C] 20:5(n-3) in isolated hepatocytes, suggesting that conversion of fatty acids to their long-chain highly unsaturated products can be stimulated by a deficiency of lipid-soluble antioxidants. The antioxidant synergism of vitamin E and Ax was supported by their ability to reduce malondialdehyde formation in an in vitro stimulation of microsomal lipid peroxidation and to reduce plasma levels of 8-isoprostane. The results of this study suggest that both vitamin E and the carotenoid Ax have antioxidant functions in Atlantic salmon.

Animal Feed↗
PubMed1998

Flesh Lipid and Carotenoid Composition of Scottish Farmed Atlantic Salmon (Salmo salar).

Samples of steaks from market-size salmon (2.5-5 kg), produced under the requirements of the Product Certification Scheme for Scottish Quality Farmed Salmon, were obtained from five Scottish salmon producers on a weekly basis for over 2 years. Samples were assayed for total lipid content, lipid class composition, fatty acid composition, vitamin E content, and carotenoid pigment [astaxanthin (AX) and canthaxanthin (CX)] content. In addition, samples were obtained from the same producers to assess loss of carotenoid pigment in the period up to 120 h post-harvest and to measure lipid and pigment content of different body regions. The analyses showed a positive correlation between dietary lipid and deposition of lipid in flesh, although there was great variation in flesh lipid content within each dietary lipid level. The average lipid content of Scottish salmon was 10.1 +/- 2.9% (n = 495). Salmon flesh was rich in the n-3 highly unsaturated fatty acids, 22:6n-3 and 20:5n-3, with average values of 11.3 and 5.4% of total fatty acids or 10.2 and 4.8 g/kg flesh, respectively. Vitamin E content of salmon flesh was around 30 mg/kg but was significantly higher in fish fed the lowest dietary lipid level. Studies investigating changes in carotenoid pigmentation up to 120 h post-harvest suggested that fish fed AX alone showed a loss of pigment over time that did not occur in fish fed either CX alone or a combination of AX and CX. Measurement of lipid content of different body regions showed that the highest levels were found in the region immediately in front of the dorsal fin and that the lowest lipid levels were in the tail region. Total lipid content of all five body zones was positively correlated with dietary lipid. Carotenoid pigment levels were the same across all body zones and were not affected by dietary lipid.

Journal Article↗
PubMed1997

The second finger of Urbs1 is required for iron-mediated repression of sid1 in Ustilago maydis.

The urbs1 gene encodes a transcriptional regulator of siderophore biosynthesis in Ustilago maydis. Biological and DNA-binding activities of the two putative zinc-finger motifs of Urbs1 were studied by analyzing mutants containing altered finger domains. The mutated urbs1 alleles from three previously described N'-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutants were mapped and cloned by a gap-repair procedure. Sequence analyses revealed single amino acid substitutions in two of the NTG mutants. Both mutations (G-507 to D in urbs1-1 and P-491 to L in urbs1-3), which are located in the Urbs1 C-terminal finger domain, reduced DNA-binding activity by 10-fold and were sufficient to confer a urbs1-minus phenotype. The third NTG urbs1 mutant (urbs1-2) also contained a mutation in one of the conserved amino acids (P-518 to S) in the C-terminal finger domain, but this mutation alone was not sufficient to confer a urbs1-minus phenotype. A second frame shift mutation was identified in urbs1-2 and is necessary for the urbs1-minus phenotype. In an analysis of the function of the N-terminal finger of Urbs1, the conserved amino acid Arg-350 was mutated to leucine. A Urbs1 protein with this mutation complemented a urbs1 null mutant strain. By contrast, a similar mutation in the C-terminal domain abolished the ability of Urbs1 to regulate siderophore biosynthesis and greatly reduced its ability to bind target DNA.

Amino Acid Sequence↗
PubMed1996

Nicotine-haloperidol interactions and cognitive performance in schizophrenics.

Nearly 90% of schizophrenics smoke cigarettes, considerably higher than the general population's rate of 25%. There is some indication that schizophrenics may smoke as a form of self-medication. Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs. In the current study, we assessed the interactions of haloperidol and nicotine on cognitive performance of a group of schizophrenics. These patients were in a double-blind study, randomly assigning them to low, moderate, and high dose levels of haloperidol. The subjects, all smokers, came to the laboratory on four different mornings after overnight deprivation from cigarettes. In a double-blind fashion, they were administered placebo, low (7 mg/day), medium (14 mg/day), or high (21 mg/day) dose nicotine skin patches. Three hours after administration of the skin patch, the subjects were given a computerized cognitive test battery including: simple reaction time, complex reaction time (spatial rotation), delayed matching to sample, the Sternberg memory test, and the Conners continuous performance test (CPT). With the placebo nicotine patch, there was a haloperidol dose-related impairment in delayed matching to sample choice accuracy and an increase in response time on the complex reaction time task. Nicotine caused a dose-related reversal of the haloperidol-induced impairments in memory performance and complex reaction time. In the CPT, nicotine reduced the variability in response that is associated with attentional deficit. These results demonstrate the effects of nicotine in reversing some of the adverse side effects of haloperidol and improving cognitive performance in schizophrenia.

Adult↗
PubMed1991

The performance of children with a moderate mental handicap on simple counting tasks.

This study examines both oral and object counting, and the ability to read numerals in a group of 51 children with a moderate degree of mental handicap. The findings indicate deficiencies in basic counting competencies across a wide spread of ability. There is also evidence for a distinction between oral and object counting on a cognitive skills basis. The findings are discussed within a remediation context.

Achievement↗
PubMed1989

An integrated team approach to the management of patients with oropharyngeal dysphagia.

This paper describes a team approach to the assessment and management of patients with oropharyngeal dysphagia of neurologic origin. The team's major focus was to determine the need for adjustments to the patient's diet to maintain or restore the safety of oral feeding. This involved the development of a detailed radiographic examination and a series of dysphagia diets, in addition to comprehensive evaluations by an occupational therapist, physiotherapist, and speech pathologist. The effects of deteriorating swallowing ability on the physical, cognitive, and emotional status of the patient are discussed in the context of a multidisciplinary approach.

Aged↗
PubMed1983

Vasectomy and nonfatal myocardial infarction: continued observation indicates no elevation of risk.

The incidence of nonfatal myocardial infarction among 4,733 vasectomized men followed for 33,969 man-years was 1.3 cases per 1,000 man-years. This incidence was nearly identical in a 5-fold larger series of comparable nonvasectomized men. These data represent a substantially increased long-term followup over that reported previously for these groups and provide continued assurance of the lack of an association between vasectomy and myocardial infarction, particularly 10 or more years after vasectomy.

Adult↗