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Biomedical subjects

R W Jones

Publications and source records attributed to R W Jones.

At least 55 records · Page 3Linked to original sources
PubMed2000

A new human genetic resource: a DNA bank established as part of the Avon longitudinal study of pregnancy and childhood (ALSPAC).

We describe a unique human DNA resource forming part of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), a longitudinal cohort study involving 14 000 children and their families living in a geographically defined area of England. The DNA bank will underpin the search for associations between genetic polymorphisms and common health outcomes. The opportunities to collect blood samples suitable for DNA extraction are necessarily limited, and the samples themselves have often been treated in different ways and have varied storage histories. With the need to maximise yields, the choice of DNA extraction method is critical to the success of the bank and we have investigated the suitability of various commercial and in-house methods of DNA extraction. Various steps have been taken to minimise errors in sample address and identification, including the use of a pipetting robot for dilution and transfer of samples between 96-well arrays to provide aliquots suitable for PCR. The robot has been programmed to cope with concentrated viscous DNA solutions.

Animals↗
PubMed2000

Trend recognition in clinical signals using template-based methods.

The recognition of clinically significant trends in monitored signals plays an important role in many medical diagnostic applications. A template-based system technique to identify characteristic patterns in time-series data is described, based on fuzzy logic. Fuzzy set theory allows the creation of fuzzy templates from linguistic rules. The resulting fuzzy template system can accommodate multiple time signals, relative or absolute trends, and automatically generates a normalised "goodness of fit" score. The template approach was originally developed for monitoring during anaesthesia but has the potential to be useful in other domains that require temporal pattern recognition.

Artificial Intelligence↗
PubMed2000

Loss of fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease.

Allelic losses involving chromosome 3p are frequently observed in cervical cancers. Deletion mapping studies of primary cervical carcinomas have localized common regions of deletion to 3p14.2 and 3p21. The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Fhit protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas. To expand these observations to preinvasive cervical epithelial lesions and to determine whether loss of Fhit protein expression might be associated with tumor progression, immunohistochemical methods were used to examine Fhit expression in 95 invasive cervical carcinomas, 33 high-grade squamous intraepithelial lesions (HSILs) associated with concurrent invasive cancer, 38 HSILs unassociated with invasive cancer, 24 low-grade squamous intraepithelial lesions, and 22 normal cervix samples. All normal cervical epithelia and low-grade squamous intraepithelial lesions exhibited diffuse cytoplasmic immunostaining of moderate to strong intensity. Fhit protein expression was markedly reduced or absent in 67 of 95 (71%) invasive cancers, 17 of 33 (52%) HSILs associated with invasive cancer, and 8 of 38 (21%) HSILs without associated invasive cancer. The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression. Moreover, absent or reduced Fhit protein is observed at a significantly higher frequency in HSILs associated with progression to invasive cancer than in HSILs with unknown risk for progression (P = 0.012). These findings suggest that loss of Fhit expression in HSILs could serve as a useful marker of high-grade preinvasive lesions that have an increased likelihood of progression to invasive carcinoma.

Acid Anhydride Hydrolases↗
PubMed1999

The -491A/T polymorphism of the Apolipoprotein E gene is associated with the ApoEepsilon4 allele and Alzheimer's disease.

Several studies have attempted to confirm the association between the recently reported polymorphism located at position -491 in the transcriptional regulatory region of the Apolipoprotein E (ApoE) gene and Alzheimer's disease (AD). Results have been inconclusive, possibly due to the use of clinically diagnosed subjects and controls only. In this retrospective case-control study of 149 (96 AD and 53 controls) brain samples we show that homozygosity for the -491A variant is associated with an increased risk of development of AD. The genotype is also strongly associated with the presence of at least one epsilon4 allele (an established risk factor for AD) in women but not in men.

Alzheimer Disease↗
PubMed1999

Sibutramine pharmacokinetics in young and elderly healthy subjects.

OBJECTIVE: To investigate the pharmacokinetics of the pharmacologically active metabolites of sibutramine (metabolites 1 and 2) in healthy young and elderly volunteers following a single oral dose of sibutramine. METHODS: This was an open, parallel-group study completed by 12 young (six male, six female; mean age 24.0 years) and 12 elderly (six male, six female; mean age 70.3 years) healthy volunteers. Blood samples were taken at intervals up to 48 h post-dose. Plasma concentrations of metabolites were determined using HPLC-MS. Model-independent pharmacokinetic parameters of the two metabolites were compared for the two age groups. RESULTS: The similarity of the plasma profiles of the two desmethyl metabolites showed that despite the possibility of reduced hepatic function due to age, the rate and extent of formation of these was the same in both young and elderly, i.e. sibutramine metabolism was not impaired in elderly subjects. There were also no significant differences in elimination of metabolite 2 between groups, although the elderly group showed a slight trend for a reduction in k(el). CONCLUSIONS: The pharmacokinetics of the two pharmacologically active metabolites of sibutramine (metabolites 1 and 2) were not significantly different between the young and elderly groups in this study. Based on this information, a similar dosing regimen would be appropriate for both the young and elderly.

Adult↗
PubMed1999

Diagnostic monitoring in anaesthesia using fuzzy trend templates for matching temporal patterns.

A technique based on the concept of a 'fuzzy trend template' has been developed to identify characteristic patterns in multiple time-series. The method has its foundation in fuzzy logic and allows for the intuitive and transparent description of 'templates', which preserve nuances of vagueness, temporal relationships and quantitative descriptors. Evaluation of fuzzy trend templates can provide both belief and plausibility information for use in diagnostic applications. The technique has been applied to the diagnosis of specific problems in anaesthesia and has demonstrated sensitivity and specificity of 95 and 65%, respectively. Evaluation of fuzzy trend templates is, computationally, relatively efficient and has allowed a real-time implementation. The technique has the potential to be useful in any domain that requires temporal pattern recognition based on linguistic rules.

Anesthesia↗
PubMed1999

Transient infrared spectroscopy for detection of toxigenic fungi in corn: potential for on-line evaluation.

An urgent need for rapid sensors to detect contamination of food grains by toxigenic fungi such as Aspergillus flavus prompted research and development of Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) as a highly sensitive probe for fungi growing on the surfaces of individual corn kernels. However, the photoacoustic technique has limited potential for screening bulk corn because currently available photoacoustic detectors can accommodate only a single intact kernel at a time. Transient infrared spectroscopy (TIRS), on the other hand, is a promising new technique that can acquire analytically useful infrared spectra from a moving mass of solid materials. Therefore, the potential of TIRS for on-line, noncontact detection of A. flavus contamination in a moving bed of corn kernels was explored. Early test results based on visual inspection of TIRS spectral differences predict an 85% or 95% success rate in distinguishing healthy corn from grain infected with A. flavus. Four unique infrared spectral features which identified infected corn in FTIR-PAS were also found to be diagnostic in TIRS. Although the technology is still in its infancy, the preliminary results indicate that TIRS is a potentially effective screening method for bulk quantities of corn grain.

Aflatoxins↗
PubMed1999

Properties of the Macrophomina phaseolina endoglucanase (EGL 1) gene product in bacterial and yeast expression systems.

Functional expression of a beta-D-1,4 glucanase-encoding gene (egl1) from a filamentous fungus was achieved in both Escherichia coli and Saccharomyces cerevisiae using a modified version of pRS413. Optimal activity of the E. coli-expressed enzyme was found at incubation temperatures of 60 degrees C, whereas the enzyme activity was optimal at 40 degrees C when expressed by S. cerevisiae. Enzyme activity at different pH levels was similar for both bacteria and yeast, being highest at 5.0. Yeast expression resulted in a highly glycosylated protein of approx 60 kDa, compared to bacterial expression, which resulted in a protein of 30 kDa. The hyperglycosylated protein had reduced enzyme activity, indicating that E. coli is a preferred vehicle for production scale-up.

Basidiomycota↗
PubMed1999

Analyzing prior clinical events at presentation in 102 women with vulvar carcinoma. Evidence of diagnostic delays.

OBJECTIVE: To evaluate the clinical events preceding the diagnosis of squamous cell carcinoma of the vulva. STUDY DESIGN: One hundred two women presenting with squamous cell carcinoma of the vulva to a gynecologic oncology unit between 1989 and 1996 were prospectively evaluated by a single investigator. History, clinical findings, previous physician contact, investigations and treatment were analyzed. RESULTS: Vulvar symptoms were present for more than six months in 88% and for more than five years in 28% of women. Eighty-five percent of patients had clinical evidence of abnormal skin adjacent to the cancer. Thirty-one percent of women had three or more medical consultations for vulvar symptoms prior to the diagnosis of cancer. Twenty-five percent of women had had a previous diagnostic vulvar biopsy, and 27% gave a history of having applied topical estrogen or corticosteroid to the vulva. Patients with a history of a preceding biopsy were more likely to present with stage 1 disease. CONCLUSION: Avoidable factors appear to be present in many women who present with vulvar cancer. A more active approach to the diagnosis and management of precursor lesions may often prevent the development of vulvar cancer.

Adrenal Cortex Hormones↗
PubMed1999

Teledermatology--UK experience of setting up an integrated teledermatology service.

Telemedicine has traditionally been seen as an all or nothing solution to the problem of providing medical service to remote communities. In the UK, however, the majority of the population lives within easy travelling distance of medical service, and it is inappropriate to apply telemedicine for the same reasons and in the same way. We describe an alternative approach, where telemedicine is used to complement the existing clinical infrastructure of the outreach clinic and hospital visit, and the patient may opt to have any follow up appointments by video conference. We also describe the concept of the virtual consultation that we have developed to support our work.

Dermatology↗
PubMed1999

AIDMAN--advanced informatics distributed medical access network.

We describe AIDMAN, a pilot project in which health clinics in remote areas of Greece are connected with mainland hospitals, to provide routine clinical service for both chronic health care and accident and emergency. Clinical practice is supported through the use of the Virtual Consultation Workstation that is being developed and evaluated specifically for the project and which is based on readily available commercial products and international standards. The communication infrastructure remains a major obstacle to any telemedicine project, and for this reason, satellite communication is used in the AIDMAN project to overcome the current lack of digital links and bandwidth. The proposed system will provide real time video, high definition image, shared applications and data over a link running at 128 kbps. In this paper we discuss the design of the AIDMAN system, the Virtual Consultation Workstation and the communication channel.

Computer Communication Networks↗
PubMed1998

Serotypic characterization of outer capsid spike protein VP4 of vervet monkey rotavirus SA11 strain.

The vervet monkey rotavirus SA11, a prototype strain of group A rotaviruses, has been shown to possess VP7 serotype 3 specificity but its neutralization specificity with regard to the other outer capsid protein VP4 has not been elucidated. We thus determined its VP4 specificity by two-way cross-neutralization with guinea pig antiserum prepared with a single gene substitution reassortant that had only the VP4-encoding gene from the simian rotavirus SA11 strain and remaining ten genes from human rotavirus DS-1 strain (G serotype 2). The SA11 VP4 was related antigenically in a one-way fashion to rhesus monkey rotavirus MMU18006 VP4 (a P5B strain) and marginally to human and canine rotavirus VP4s with P serotype 5A specificity. In addition, the SA11 VP4 was shown to be distinct antigenically from those of other known P serotypes (1-4, and 6-11) as well as those of uncharacterized equine, lapine, and avian rotavirus strains. The SA11 VP4 is thus proposed for classification as a P5B serotype.

Animals↗
PubMed1997

Site-directed mutagenesis of a fungal beta-1,4-endoglucanase increases the minimum size required for the substrate.

Conserved regions within a family-5 beta-1,4,-endoglucanase (Eg11), produced by the fungus Macrophomina phaseolina, have been modified through site-directed mutagenesis, resulting in production of an enzyme with novel substrate requirements. The engineered form was generated through mutagenesis of D232A, which lies within the substrate-binding cleft of Eg11. Wild-type Eg11 requires a minimum substrate size of five glucosyl units, while the engineered form requires a minimum of six glucosyl units. Screening was facilitated by the unique ability to obtain functional expression of the fungal endoglucanase in Escherichia coli. Wild-type and mutated Eg11 have equivalent activity on cellohexaose, and both release cellobiose from the reducing end of the cellodextrin. This is the first example of protein engineering of an endoglucanase that results in a novel minimum substrate requirement for cellohexaose. This substrate specificity has not been reported for any native endoglucanases, thus the modified Eg11 may prove useful in applications requiring specific hydrolysis of complex carbohydrates such as beta-glucans.

Amino Acid Sequence↗
PubMed1997

Trends in squamous cell carcinoma of the vulva: the influence of vulvar intraepithelial neoplasia.

OBJECTIVE: To determine trends in the clinicopathology of vulvar squamous cell carcinoma over the past 2 decades, with particular reference to the possible effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN) during this time. METHODS: Two cohorts of 56 and 57 women with squamous cell carcinoma of the vulva and separated by at least 2 decades were reviewed retrospectively. Pathologic specimens were analyzed concurrently. RESULTS: In the 1965-1974 cohort, only one of 56 patients was younger than 50 years of age at the time of presentation, whereas in the 1990-1994 cohort, 12 of 57 (21%) were younger than 50 years of age (P = .001). Ten of 13 women younger than 50 years of age, compared with 13 of 100 of women 50 years of age or older, had warty or basaloid VIN associated with their invasive carcinoma (P < .001). Cigarette smoking and multiple lower genital tract neoplasia were both significantly more common in women younger than 50 years of age (P < .001). CONCLUSION: Over the past 2 decades, a subset of women younger than 50 years of age with squamous cell carcinoma of the vulva has emerged. Most of these carcinomas appear to arise in a field of warty or basaloid VIN. This suggests that the increasing incidence of VIN seen in young women during the past 2 decades is being reflected now in VIN-associated squamous cell carcinoma of the vulva in younger women.

Adult↗