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Biomedical subjects

J G Evans

Publications and source records attributed to J G Evans.

At least 19 recordsLinked to original sources

Studies on the disposition, metabolism and hepatotoxicity of coumarin in the rat and Syrian hamster.

The hepatotoxicity, metabolism and disposition of coumarin has been compared in male Sprague-Dawley rats and Syrian hamsters. The treatment of rats for 12, 24 and 42 weeks with diets containing 0.2 and 0.5% coumarin resulted in hepatotoxicity and increased relative liver weights. While levels of cytochrome P450 (CYP) and CYP-dependent enzymes were decreased, levels of reduced glutathione (GSH) and activities of UDP glucuronosyltransferase, gamma-glutamyltransferase and GSH S-transferase were increased. In contrast, coumarin produced few hepatic changes in the Syrian hamster. Following a single oral dose of 25 mg/kg [3-14C]coumarin, radioactivity was rapidly excreted by the rat and Syrian hamster with the urine containing 63.5 and 89.9%, respectively, and the faeces 38.0 and 12.4%, respectively, of the administered dose after 96 h. The biliary excretion of radioactivity was greater in the rat than in the Syrian hamster. Analysis of 0-24-h urine samples revealed that both species were poor 7-hydroxylators of coumarin. In the rat, treatment with 0.5% coumarin in the diet for 24 weeks was found to increase the urinary excretion of single oral gavage doses of 25 and 300 mg/kg [3-14C]coumarin. The marked species difference in hepatotoxicity between the rat and Syrian hamster observed in this study may be at least partially attributable to differences in coumarin disposition. However, additional studies are required to elucidate the metabolic pathways of coumarin in both species.

Animals↗

Alzheimer disease is not associated with polymorphisms in the angiotensinogen and renin genes.

Hypertension has been implicated as a risk factor for Alzheimer disease (AD) and dementia in epidemiological studies of humans. It is thus possible that there are common genetic determinants for hypertension and AD. Epidemiological, clinical, and experimental data suggest that the renin-angiotensin-aldosterone system is a critical regulator of blood pressure. The presence of an MboI site in an RFLP in the renin gene and the Thr at the Met/Thr polymorphism at codon 235 (M235T) of the angiotensinogen gene have been reported to be associated with hypertension. These variants were studied in autopsy-confirmed AD cases and matched controls from the U.K. While no association was detected with the renin polymorphism, a weak deleterious effect was observed in cases homozygous for the angiotensinogen Thr allele. However, this association was not observed in a French cohort of clinically diagnosed AD cases and controls, suggesting that the initial observation was a type I error. Thus, these polymorphisms are unlikely to be associated with AD risk.

Aged↗

The BACE gene: genomic structure and candidate gene study in late-onset Alzheimer's disease.

Alzheimer's disease (AD) pathology is characterized by beta-amyloid plaques and neurofibrillary tangles. Studies of autosomal dominant early-onset AD mutations suggest that beta-amyloid overproduction is sufficient to cause AD. Recently, the BACE gene, which encodes beta-secretase, the rate limiting enzyme in beta-amyloid formation, has been identified. Since this gene is a strong candidate gene for late-onset AD because of its function, we have characterized its genomic organization and identified two polymorphisms. Neither of these polymorphisms were associated with AD risk in genetic association studies comparing autopsy-confirmed late-onset AD cases and age-matched non-demented controls. Thus, we find no evidence that this locus influences risk for late-onset AD.

3' Untranslated Regions↗

Ethanol vapour-fixation of rat lung for immunocytochemistry investigations.

Ethanol-vapour fixation of rat lung has been successfully employed in the immunocytochemical detection of the gastrin mucin antigen termed mucin 5AC without the need of additional antigen retrieval steps. This procedure gives good morphological preservation and provides all the benefits associated with the microscopic examination of inflated lung tissue. This simple fixation technique provides another option for use in immunocytochemical investigations of rodent lung and could be adapted for other species.

Animals↗

Manipulating the in vivo mRNA expression profile of FSH beta to resemble that of LH beta does not promote a concomitant increase in intracellular storage of follicle-stimulating hormone.

The beta-subunits of luteinizing hormone (LH beta) and follicle-stimulating hormone (FSH beta) are differentially expressed, and this may contribute to the unique expression and storage patterns of LH and FSH. Therefore, to determine if the in vivo expression profile of FSH beta could be altered to that of LH beta, a truncated ovine FSH beta (oFSH beta) gene, which would encode a mRNA lacking the putative destabilizing 3' untranslated region, was fused downstream of the ovine LH beta (oLH beta) promoter and expressed in transgenic mice. In two independent lines, line 16 and 17, we measured oFSH beta, mouse LH beta (mLHbeta) and mouse FSH beta (mFSH beta) mRNA levels: (i) after castration in males; (ii) after administering inhibin to ovariectomized mice; and (iii) during the oestrous cycle. In each experiment, the expression profile of oFSH beta mRNA mimicked mLH beta and not mFSH beta mRNA. In addition, after actinomycin D treatment of pituitary cultures, while mFSH beta mRNA did decay, there was no measurable decay of the oFSH beta mRNA transcript. These differences increased total FSH beta steady-state mRNA expression levels in male transgenics. However, there was no detectable increase in pituitary FSH by either radioimmunoassay or western blotting analysis of pituitary extracts. Subsequent analysis revealed that pituitary FSH beta in line 16 was heavily glycosylated; in contrast, pituitary FSH beta in line 17 was largely unmodified. These differences in post-translational modification of the beta-subunit, and the lack of intracellular storage, contributed to increased plasma FSH levels and ovulation rate in line 16, but not line 17. In conclusion, the expression profile of oFSH beta mRNA was manipulated to mimic mLH beta mRNA and this increased FSH beta mRNA expression levels, but did not increase storage of FSH. This suggests that, regardless of the levels of synthesis, post-translational sorting preferentially promotes FSH secretion from the pituitary.

Animals↗

Genetic association of an LBP-1c/CP2/LSF gene polymorphism with late onset Alzheimer's disease.

OBJECTIVES: The only locus unequivocally associated with late onset Alzheimer's disease (AD) risk is APOE. However, this locus accounts for less than half the genetic variance. A recent study suggested that the A allele of the 3'UTR biallelic polymorphism in the LBP-1c/CP2/LSF gene was associated with reduced AD risk. Samples were diagnosed predominantly by clinical rather than pathological criteria. We have sought to replicate this finding in a series of necropsy confirmed, late onset AD cases and non-demented controls. METHODS: The 3'UTR polymorphism in the LBP-1c/CP2/LSF gene was typed in 216 necropsy confirmed AD cases and 301 non-demented controls aged >73 years. RESULTS: We found different LBP-1c/CP2/LSF allele distributions in our AD cases and controls (p=0.048); the A allele was associated with reduced AD risk. The allele and genotype frequencies observed in our cases and controls were similar to those previously reported. No significant effects emerged when the data were adjusted for age, sex, or apoE epsilon4 carrier status. CONCLUSIONS: Our data support LBP-1c/CP2/LSF as a candidate gene/risk factor for AD and provide justification for future studies to investigate the role of this gene in Alzheimer's disease.

Age of Onset↗

Relationships of admissions data and measurements of psychological constructs with psychomotor performance of dental technology students.

Abstract: The psychomotor skills required in dental laboratory technology and dentistry are similar. Dental educators have recognized the problems in selecting from among dental school applicants those with potential psychomotor skills. The purpose of this study was to examine the relationships of admissions data and measurements of psychological constructs of dental technology students with their psychomotor performance in first-semester dental laboratory courses. The dependent variables selected for the study were grades from three laboratory courses. Significant positive correlations (p<.05) were noted between all laboratory grades and previous college hours, previous college GPA, interview scores, field dependence-independence scores, block counting, trust, straightforwardness, and dutifulness. These data indicate that individual differentiation in learning ability, visual or spatial perception, and personality do affect psychomotor learning and should be taken into consideration in the design and execution of teaching and training curricula.

Adult↗

The ACE gene and Alzheimer's disease susceptibility.

A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimer's disease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significantly different ACE genotype distributions in the case and control groups (p=0.007). Homozygotes for both the I and D alleles were associated with a higher risk compared to DI heterozygotes. While the APOE epsilon4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between the APOE and ACE loci. In addition, no interactions were observed between ACE and gender or age at death of the AD cases. A meta-analysis of all published reports (12 case-control series in total) suggested that both the II and ID ACE genotypes are associated with increased AD risk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.63, OR for DI v DD 1.33, 95% CI=1.14-1.53, p=0.0002).

Aged↗

[Innovative teaching, a successful invention: the European Academy for Medicine of Ageing (EAMA). The viewpoint of teachers and students].

INTRODUCTION: The origins of the EAMA (European Academy for Medicine of Aging) course are described in this paper by the Scientific Committee of this new post-graduate teaching activity. CURRENT KNOWLEDGE AND KEY POINTS: Innovations are constantly introduced to improve training methodology so as to enable the students to update their knowledge, help them improve their skills in data gathering and in the critical interpretation of information, and exchange geriatric experience and know-how. To reach such goals, an interactive teaching method is implemented by the professors, with world experts being called in to ensure scientific soundness and quality. Evaluations by students and teachers are regularly carried out with the aim of perfectly adjusting their training methodologies and increasing the scientific level of exchanges. FUTURE PROSPECTS AND PROJECTS: If the students progress, so do the teachers....

Academies and Institutes↗

Measurement of impact force, simulation of fall and hip fracture.

It has been shown that the incidence of hip fracture in the elderly may be influenced by the type of floor covering commonly used in homes for the elderly. This study describes the development of a method for modelling a fall during a hip fracture event, to examine the influence of different floors on impact force. An impact transducer is dropped in free fall through a smooth plastic tube. The impactor nose of the transducer models the curvature of the greater trochanter, and a steel spring is used to simulate the compliance of the skeletal structure. A weight, which corresponds to one-sixteenth of average body mass, compresses the spring and applies force to the impactor nose on striking the floor. The temporal variation in the force of impact with the floor is measured by the transducer to within 0.41 percent (SD = 0.63%, n = 10). Five common floor coverings were tested over a concrete floor slab (vinyl, loop carpet and pile carpet--both with and without underpad). ANOVA analysis showed that the differences between mean forces for each floor covering were highly significant (p > 0.001), with the thicker coverings producing 7 percent lower forces. The transducer may be used to examine the correlation between impact force and fracture incidence for a variety of different floors in homes for the elderly.

Accidental Falls↗

The NHS at fifty.

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Health Care Costs↗

Removable partial dentures: the altered-cast technique.

The altered-cast technique, also known as the corrected-cast technique, for distal extension removable partial dentures (RPD), is not routinely utilized by dentists. Although the technique requires an additional step for both the dentist and dental technician, it offers several advantages--maximum stability, minimal stress on abutment teeth, and more predictable occlusion. The following article describes the altered-cast technique, as well as some advantages and disadvantages of the technique. A quick and easy procedure for constructing an altered-cast is also presented.

Dental Casting Technique↗