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Biomedical subjects

R Edwards

Publications and source records attributed to R Edwards.

At least 145 records · Page 8Linked to original sources
PubMed1998

Thy-1 is a component common to multiple populations of synaptic vesicles.

Thy-1, a glycosylphosphatidylinositol-linked integral membrane protein of the immunoglobulin superfamily, is a component of both large dense-core and small clear vesicles in PC12 cells. A majority of this protein, formerly recognized only on the plasma membrane of neurons, is localized to regulated secretory vesicles. Thy-1 is also present in synaptic vesicles in rat central nervous system. Experiments on permeabilized PC12 cells demonstrate that antibodies against Thy-1 inhibit the regulated release of neurotransmitter; this inhibition appears to be independent of any effect on the Ca2+ channel. These findings suggest Thy-1 is an integral component of many types of regulated secretory vesicles, and plays an important role in the regulated vesicular release of neurotransmitter at the synapse.

Animals↗
PubMed1998

Heavy metals in antarctic ice from Law Dome: initial results.

Pb, Cd, Cu, and Zn have been measured using ultraclean procedures in eight sections taken from two well-dated ice cores from Law Dome, an independent small size ice cap with high accumulation rate situated in the coastal area of East Antarctica. Seven sections were dated from the 1830s to 1940s and one was dated from three millennia ago. The data show that there are strong seasonal variations in the concentrations of Pb and Cd, with values approximately tow-to fourfold higher in winter than in spring-summer. Evaluation of the contributions from the different sources suggests that contribution from sea salt spray is relatively important, especially for Cd. Contribution from marine biogenic emissions could also be very significant. The importance of marine contributions is consistent with strong intrusions of marine air masses at this coastal site, especially during wintertime.

Aluminum↗
PubMed1998

Speed-dependent motion-sensitive responses in V5: an fMRI study.

This fMRI study examined motion-sensitive responses in human area V5 as a function of stimulus speed. Consistent with electrophysiological findings, we observed optimal responses at intermediate speeds of around 7 degrees/s to 30 degrees/s. The results are consistent with a nonlinear (inverted "U") dependency on speed that was also observed in V3a. V1 activation was observed to decrease linearly as speed increased. This is consistent with the fact that speed-sensitive cells in V1 have been shown to be tuned to much slower speeds than in V5.

Brain↗
PubMed1998

Expression of xenobiotic-metabolizing cytochrome P450s in human pulmonary tissues.

The purpose of the study was to obtain a comprehensive picture of the expression of cytochrome P450s (CYP) in the human lung, broncho-alveolar macrophages (BAM), and peripheral blood lymphocytes. The methods used were reverse transcriptase-polymerase chain reaction (RT-PCR) with gene-specific primers and immunohistochemistry with specific anti-peptide antibodies. In RT-PCR, CYPs 1A1, 2B6/7, 2E1, 2F1, 3A5 and 4B1 were detected in cDNA prepared from whole lung tissue. BAMs expressed CYPs 1B1, 2B6/7, 2C, 2E1, 2F1, 3A5 and 4B1. These tissues lacked CYPs 1A2, 2A6, 2D6, and 3A7. In peripheral blood lymphocytes, only CYP1B1 and CYP2E1 mRNAs were consistently detected. In immunohistochemistry with anti-CYP3A antibodies, epithelial staining of CYP3A5 was observed in 100% of individuals, while only about 20% exhibited CYP3A4 staining. CYP3A5 protein was localized in the bronchial wall, bronchial glands, bronchiolar epithelium, alveolar epithelium, vascular endothelium and alveolar macrophages. The results indicate that several different xenobiotic-metabolizing CYPs are present in the human lung, possibly contributing to in situ activation of pulmonary procarcinogens.

Cytochrome P-450 Enzyme System↗
PubMed1998

Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients.

BACKGROUND: There is a hypothesis that lack of n-3 polyunsaturated fatty acids (PUFAs) is of aetiological importance in depression. Docosahexaenoic acid, a member of the n-3 PUFA family, is a crucial component of synaptic cell membranes. The aim of this study was to measure RBC membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. METHOD: Red blood cell (RBC) membrane levels, and dietary PUFA intake were measured in 10 depressed patients and 14 matched healthy control subjects. RESULTS: There was a significant depletion of RBC membrane n-3 PUFAs in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with RBC membrane levels and with dietary intake of n-3 PUFAs. CONCLUSION: Lower RBC membrane n-3 PUFAs are associated with the severity of depression. LIMITATIONS: Although patient numbers were small, confounding factors were well controlled for and the results were highly significant. Results of the dietary data would tend to be weakened due to the limitations associated with dietary assessment. CLINICAL RELEVANCE: The findings raise the possibility that depressive symptoms may be alleviated by n-3 PUFA supplementation.

Adult↗
PubMed1998

Glutathione-mediated detoxification systems in plants.

Recent work has highlighted the presence of diverse glutathione-dependent enzymes in plants with potential roles in the detoxification of both xenobiotic and endogenous compounds. In particular, studies on glutathione transferases are further characterising their role in xenobiotic metabolism, and also raising intriguing possible roles in endogenous metabolism. The solution of their three-dimensional structures together with studies on their molecular diversity and substrate specificity is providing new insights into the function and classification of these enigmatic enzymes.

Formaldehyde↗
PubMed1998

Purification, regulation and cloning of a glutathione transferase (GST) from maize resembling the auxin-inducible type-III GSTs.

The glutathione transferases (GSTs) from maize (Zea mays L.) with activities toward the chloroacetanilide herbicide metolachlor and the diphenyl ether herbicide fluorodifen were fractionated into two pools based on binding to affinity columns. Pool 1 GSTs were retained on Orange A agarose and were identified as isoenzymes Zea mays (Zm) GST I-I, Zm GST I-II and Zm GST I-III, which have been described previously. Pool 2 GSTs selectively bound to S-hexyl-glutathione-Sepharose and were distinct from the pool 1 GSTs, being composed of a homodimer of 28.5 kDa subunits, termed Zm GST V-V, and a heterodimer of the 28.5 kDa polypeptide and a 27.5 kDa subunit, termed Zm GST V-VI. Using an antibody raised to Zm GST V-VI, a cDNA expression library was screened and a Zm GST V clone identified showing sequence similarity to the type-III auxin-inducible GSTs previously identified in tobacco and other dicotyledenous species. Recombinant Zm GST V-V showed high GST activity towards the diphenyl ether herbicide fluorodifen, detoxified toxic alkenal derivatives and reduced organic hydroperoxides. Antibodies raised to Zm GST I-II and Zm GST V-VI were used to monitor the expression of GST subunits in maize seedlings. Over a 24 h period the Zm GST I subunit was unresponsive to chemical treatment, while expression of Zm GST II was enhanced by auxins, herbicides, the herbicide safener dichlormid and glutathione. The Zm GST V subunit was more selective in its induction, only accumulating significantly in response to dichlormid treatment. During development Zm GST I and Zm GST V were expressed more in roots than in shoots, with Zm GST II expression limited to the roots.

Amino Acid Sequence↗
PubMed1998

Randomised comparison of percutaneous angioplasty vs continued medical therapy for hypertensive patients with atheromatous renal artery stenosis. Scottish and Newcastle Renal Artery Stenosis Collaborative Group.

BACKGROUND: Data from randomised studies are lacking on the value of interventional procedures in the management of atheromatous renal artery stenosis. This randomised prospective trial compared the effects on blood pressure (BP) and renal function of percutaneous transluminal angioplasty vs medical therapy in hypertensive patients with both unilateral and bilateral disease. METHODS: A total of 135 eligible patients were identified, of whom 55 (44%) were randomised. Eligible patients had sustained hypertension, with a minimum diastolic BP of 95 mm Hg on at least two anti-hypertensive drugs. Renal artery stenosis was defined by renal angiography as at least 50% stenosis in the affected vessel. All patients were observed during an initial 4-week run-in period on a fixed drug regimen and subsequent changes measured from this 4-week baseline. RESULTS: Blood pressure fell during the run-in period in all groups. In patients with bilateral renal artery stenosis randomised to angioplasty, a statistically significant (P<0.05) fall in BP was observed at latest follow-up (range 3-54 months). The mean fall in BP at latest follow-up in the angioplasty group, corrected for the medical group response, was 26/10 mm Hg. In patients with unilateral renal artery stenosis, no statistically significant or clinically important differences in outcome were observed between the two groups. No significant differences or trends in serum creatinine were observed between or within any group during follow-up. Major outcome events (death, myocardial infarction, heart failure, stroke, dialysis) were similar in the angioplasty and medical groups during follow-up. In the 40/135 patients undergoing angioplasty, serious or potentially serious complications attributable to the procedure were observed in 11 patients, bleeding at the arterial site (8 patients) being the most frequent. CONCLUSIONS: In hypertensive patients with atheromatous renal artery stenosis, percutaneous renal angioplasty results in a modest improvement in systolic BP compared with medical therapy alone. This benefit was confined to patients with bilateral disease. No patient was 'cured', renal function did not improve, and intervention was accompanied by a significant complication rate.

Adult↗
PubMed1998

Serotype distribution and prevalence of resistance to benzylpenicillin in three representative populations of Streptococcus pneumoniae isolates from the coast of Kenya.

As surveillance data from sub-Saharan Africa are few, three representative populations of Streptococcus pneumoniae isolates were examined in Kenya for serotype distribution and Etest minimum inhibitory concentrations (MICs) of benzylpenicillin: (1) 75 lung aspirate or blood culture isolates from 301 consecutive adult patients with pneumonia, (2) 112 invasive isolates from continuous pediatric inpatient surveillance over 4 years, and (3) 97 nasopharyngeal isolates from systematically selected sick children. The proportions with benzylpenicillin MICs of > or = 0.1 microgram/mL were 0.27, 0.29, and 0.47, respectively. Vaccine-related serotypes accounted for 96% of invasive isolates from children and 90% of those from human immunodeficiency virus (HIV)-seropositive adults. Serotype 1 accounted for 44% of pneumococci from HIV-seronegative patients but only 5% of those from HIV-seropositive patients (P = .0002). Of serotype 1 isolates, 98% were susceptible to benzylpenicillin, but serogroups 13, 14, 19, and 23 were strongly associated with an MIC of > or = 0.1 microgram/mL.

Adult↗
PubMed1998

The outpatient experience: results of a patient feedback survey.

Patient surveys can be used to enable hospital management to evaluate the services they provide. This study shows high levels of patient satisfaction with the quality of their consultations and the attitude shown to them by medical staff. Patient feedback shows that despite the introduction of the Patients' Charter, waiting times from referral to appointment and delays in clinics are still identified as the main areas for improvement. Findings show that patients are, however, remarkably tolerant and understanding of the pressures and demands placed upon outpatient staff.

Appointments and Schedules↗
PubMed1998

Safety of mefloquine and other antimalarial agents in the first trimester of pregnancy.

BACKGROUND: Safe and effective antimalarials are required to protect pregnant women from the harmful effects of malaria. METHODS: Data were collected from two separate prospective cohorts to ascertain the safety of chloroquine-proguanil, sulfadoxine-pyrimethamine (SP), and mefloquine taken in the first trimester of pregnancy. RESULTS: In a traveler cohort of 236 pregnant women, spontaneous abortions were reported in 7.6% of 99 women taking chloroquine-proquanil, 0% of 19 taking sulfadoxine-pyrimethamine, and 9.1% of 118 women taking mefloquine. Anomalies were identified in 1.7%, 0% and 0% of the same cohort, respectively. Differences in rates of adverse outcomes between the three groups were not statistically significant. In a pharmaceutical database of 331 and 153 women exposed to mefloquine and SP, respectively, the overall rate of abnormal outcomes (spontaneous abortions plus fetal anomalies) was not significantly different (p=.29). Spontaneous abortions were significantly higher with mefloquine than SP (9.1% and 2.6%, respectively; p=.01), but the higher rate was comparable to background rates (7%-11%). Fetal anomalies in the mefloquine group (4.8%) were lower than the SP group (7.8%), but this was statistically not significant (p=.19), and was comparable with the background rate of 4.6% (p=.84). However, mefloquine exposure resulted in a significantly higher rate of therapeutically induced abortions, undertaken for perceived risk to the fetus, compared with SP (p<.0001). CONCLUSION: From the clinical data available, there is no indication that the risk of taking mefloquine in the first trimester of pregnancy is greater than that from any of the other antimalarials studied and the risk is considerably lower than that associated with falciparum malaria.

Abnormalities, Drug-Induced↗
PubMed1998

Interaction between iron metabolism and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice with variants of the Ahr gene: a hepatic oxidative mechanism.

The binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with the aryl hydrocarbon (AH) receptor and subsequent changes in gene expression have been studied intensively, but the mechanisms by which these lead to toxicity are unclear. We investigated the influence of iron, previously implicated in TCDD-induced hepatic porphyria, in mice with alleles of Ahr that encode receptors with varied affinity for TCDD. The administration of iron to Ahrb-1 C57BL/6J (AH-responsive) mice before a single dose of TCDD (75 micrograms/kg) markedly potentiated not only the hepatic porphyria but also general hepatocellular damage and elevation of plasma hepatic enzymes. The formation of hydroxylated and peroxylated derivatives of uroporphyrins formed from uroporphyrinogen and the induction of a mu-glutathione transferase (GST) were consistent with the operation of an oxidative mechanism. In a comparison of C57BL/6J mice with Ahrb-2 BALB/c (AH-responsive) and Ahrd SWR and DBA/2 (AH-nonresponsive) mice, iron overcame the weak hepatic porphyria and toxicity responses in BALB/c and SWR strains but not in DBA/2. CYP1A isoforms are strongly implicated in the mechanism of porphyria, but activities were lowered by 20-30% with iron treatment, and a comparison of levels between strains did not fully account for the resistance of DBA/2 mice. Studies with the use of gel shift assays and cytosolic aconitase of the capacity of the iron regulatory protein controlling the translation of some iron metabolism proteins showed a significant difference between C57BL/6J and DBA/2 mice after the administration of TCDD. We conclude that iron potentiates both the hepatic porphyria and toxicity of TCDD in susceptible mice in an oxidative process with disturbance of iron regulatory protein capacity. Iron even overcomes the AH-nonresponsive Ahrd allele in the SWR strain but not in DBA/2 mice, which remain resistant.

Alleles↗
PubMed1998

Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening.

BACKGROUND: A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. AIMS: To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. SUBJECTS: A total of 3540 subjects aged 55-64 years in Welwyn Garden City (WGC) and 19,706 in Leicester (LE). METHODS: Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. RESULTS: In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. CONCLUSIONS: Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention.

Adenoma↗