Search PubMed⌕ Search

Biomedical subjects

P Stephenson

Publications and source records attributed to P Stephenson.

At least 19 recordsLinked to original sources

Development and genetic mapping of sequence-tagged microsatellites (STMs) in bread wheat (Triticum aestivum L.).

The density of SSRs on the published genetic map of bread wheat (Triticum aestivum L.) has steadily increased over the last few years. This has improved the efficiency of marker-assisted breeding and certain types of genetic research by providing more choice in the quality of SSRs and a greater chance of finding polymorphic markers in any cross for a chromosomal region of interest. Increased SSR density on the published wheat genetic map will further enhance breeding and research efforts. Here, sequence-tagged microsatellite profiling (STMP) is demonstrated as a rapid technique for the economical development of anonymous genomic SSRs to increase marker density on the wheat genetic map. A total of 684 polymorphic sequence-tagged microsatellites (STMs) were developed, and 380 were genetically mapped in three mapping populations, with 296 being mapped in the International Triticeae Mapping Initiative W7984 x Opata85 recombinant inbred cross. Across the three populations, a total of 479 STM loci were mapped. Several technological advantages of STMs over conventional SSRs were also observed. These include reduced marker deployment costs for fluorescent-based SSR analysis, and increased genotyping throughput by more efficient electrophoretic separation of STMs and a high amenability to multiplex PCR.

Chromosome Mapping↗

High levels of genetic diversity throughout the range of the Portuguese wheat landrace 'Barbela'.

BACKGROUND AND AIMS: Landrace populations represent an important intra-crop reservoir of biodiversity and source of novel gene alleles for use in breeding programmes. Here the aim was to measure the diversity of a wheat landrace, 'Barbela', from the north of Portugal. METHODS: DNA was extracted from 59 accessions of Barbela collected across its geographical range. Diversity was measured by microsatellite length polymorphisms using 27 primer pairs amplifying 34 polymorphic microsatellite loci. KEY RESULTS: High levels of polymorphism were found, with an average polymorphism information content of 0.52; an average of 4.77 alleles (range 2-11) were present at each locus, and half of these loci showed an additional allele in the reference variety 'Chinese Spring'. CONCLUSIONS: 'Barbela' is maintained from seeds collected by farmers, but it maintains high allelic variation, and no groupings of accessions were detected when analysed by geographical region, farm or climate, indicating that the wheat landrace is a homogeneous entity. The diversity within the farmer-maintained landrace demonstrates the importance of characterization and maintenance of landrace collections before valuable genetic combinations are lost as uniform commercial crops are introduced.

Alleles↗

A new approach to extending the wheat marker pool by anchored PCR amplification of compound SSRs.

A study was undertaken to determine the utility in bread wheat of anchored PCR for the development of single locus SSR markers targeted at compound repeat motifs. In anchored PCR, microsatellite amplification is achieved using a single primer complementary to the flanking sequence, and one which anchors to the repeat junction of the compound SSR. The recovery rate of useable markers was found to be similar (43%) to that reported for conventionally generated SSRs. Thus, anchored PCR can be used to reduce the costs of marker development, since it requires that only half the number of primers be synthesised. Where fluorescence-based platforms are used, marker deployment costs are lower, since only the anchoring primers need to be labelled. In addition, anchored PCR improves the recovery of useful markers, as it allows assays to be generated from microsatellite clones with repeat sequences located close to their ends, a situation where conventional PCR amplification fails as two flanking primers cannot be designed. Strategies to permit the large-scale development of compound SSR markers amplified by anchored PCR are discussed.

Alleles↗

A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).

BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.

Adult↗

Modelling femoral curvature in the sagittal plane: a cadaveric study.

This study examined the possibility of representing the mid third of the human femur with two straight sections. This portion of the femur visually has a distinct curvature, which can potentially present problems when considering implant stem designs to be introduced in this region. Sixteen femora were sectioned at 10 mm intervals along the femoral shaft in the mid third region (35-65 per cent of femoral length). Photographic records were obtained of each section against a consistent axis system to which all coordinates were referenced. The position of the centre of the medullary canal cross-sectional area along the femur, in relation to fixed orthogonal planes, has been analysed; the outer anterior cortex was also modelled. The results showed that the medullary centre of area plots and the anterior cortex coordinates are suitably modelled as two straight lines. For each bone it was possible to define the intersection point between the two straight sections (point of angulation), and the subtended angle between these sections (angle of incidence). The average point of angulation for the medullary plots occurred at 57 per cent along the femur, while the mean angle of incidence was 6.5 degrees. The anterior surface had an average point of angulation at 58 per cent along the femur with the mean angle of incidence being 22.2 degrees. The centre-line of the medulla was also found to be almost parallel to the outer anterior surface for sections distal to the point of angulation. It is proposed therefore, that this difference in angulation is the result of medullary expansion/cortical thinning towards the proximal extremity of the femur, causing the straight-line model of the medulla to angulate less than the outer anterior cortex.

Cadaver↗

Towards rice genome scanning by map-based AFLP fingerprinting.

Map-based DNA fingerprinting with AFLP markers provides a fast method for scanning the rice genome. Three hundred AFLP markers identified with ten primer combinations were mapped in two rice populations. The genetic maps were aligned and almost full coverage of the rice genome was obtained. The transferability of AFLP markers between indica x japonica and indica x indica crosses was tested. The chromosomes were divided into DNA Fingerprint Linkage Blocks (DFLBs) defined by specific AFLP markers. Using these blocks, the degree of similarity or divergence within specific chromosome regions was calculated for nine varieties. Applications of map-based fingerprinting for biodiversity studies and maker-assisted selection are discussed.

Chromosome Mapping↗

Cross-sectional geometry of the human femur in the mid-third region.

The design of a medical implant requires that the geometry and anatomy of the host region is fully understood. For any prosthesis to be located in the mid-third of the human femur it is therefore vitally important that an in-depth understanding of this region is obtained. This study focuses on the geometry of the medulla and the cortex and the relationship between them in the diaphyseal region of the human femur. Sixteen femora obtained from the Human Biology Department of the University of Leeds were sectioned at 10 mm intervals along the shaft and scaled photographs of each section were taken. These photographs then provided the raw data to enable the variation in long bone cross-sectional geometry to be evaluated. The results show that the medulla is almost cylindrical in the mid-third region, being most cylindrical between 35 and 50 per cent of the total bone length. The medullary width is found to be greater in the antero-posterior direction (> 90 per cent maximum diameter) than in the medio-lateral direction (78-88 per cent maximum diameter) along the studied femoral length. The cortex is also analysed and it is found that the mean cortical thickness on the anterior side is significantly smaller than the medial cortex and the lateral cortex, with the posterior cortex being the thickest. All the above findings suggest that the medulla does not lie centrally within the femur but is positioned slightly anteriorly. Anatomical characteristics such as this can have profound effects on the design of prostheses to be implanted in this region.

Aged↗

Using remote sensing to predict outbreaks of Oestrus ovis in Namibia.

The Directorate of Veterinary Services of the Ministry of Agriculture, Water and Rural Development of Namibia issues warnings to farmers in the south of the country about the likelihood of infestation of small-stock by the nasal bot fly, Oestrus ovis. Farmers can then treat their stock at the most appropriate time. The O. ovis puparia develop at shallow depths in the soil and the timing of emergence is directly dependent on climate conditions, specifically the number of degree-days above a particular threshold soil temperature. Based on temperature measurements from only a few stations scattered throughout the country, the veterinary department warnings lack precision in space and time. This paper presents an attempt to support the programme of warnings with accumulated temperature information from Meteosat satellite images, in order to strengthen predictions of the time of emergence in specific places, and to improve the precision and reliability of warnings given to farmers.

Animals↗

Inhibition of bacteriophage T7 RNA polymerase in vitro transcription by DNA-binding pyrrolo[2,1-c][1,4]benzodiazepines.

The interactions of several pyrrolo[2, 1-c][1,4]benzodiazepine (PBD) antitumor antibiotics with linearized plasmid pGEM-2-N-ras DNA have been analyzed by quantitative in vitro transcription (QIVT) and in vitro transcription footprinting (IVTF) methods. A concentration-dependent inhibitory effect of the PBDs on transcription is observed using both techniques. The rank order for overall inhibition of transcription by the QIVT method is found to be: sibiromycin > tomaymycin > anthramycin > DC-81 > neothramycin, whereas the IVTF experiments show a different ranking: sibiromycin > anthramycin > neothramycin > tomaymycin. In addition, stimulation of transcription was observed at low PBD concentrations in both the QIVT and IVTF experiments. These results demonstrate unequivocally that the formation of PBD-DNA adducts at AGA-5' base sequences on the transcribed strand results in transcription blockage for all PBDs examined. Furthermore, the sequence of flanking base pairs appears to influence the degree of blocking, with the sequences ACAGAAA-5', AAAGATG-5', AGAGATA-5', and CAAGAAC-5' providing the most pronounced blocks for all PBDs studied in this system. Neothramycin and tomaymycin cause additional blocks at some GGA-5' and TGA-5' sequences. Parallel MPE-Fe(II) footprinting studies have revealed PBD binding sites on both the transcribing and nontranscribing strands, although all transcription blocks determined from the IVTF assays are due to drug bound on the transcribing DNA template strand.

Anthramycin↗

Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.

OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people.

Adult↗

Reducing maternal mortality in St Petersburg.

Following the entry of St Petersburg into Europe's Healthy Cities Project in 1991 it was decided that the highest priority should be given to reducing the city's maternal mortality ratio, then standing at approximately 70 deaths per 100,000 live births. Preventing deaths from unsafe, illegal abortion became the main focus of attention. The use of modern contraceptive methods was promoted, information was disseminated to improve the utilization of family planning services, special outreach services for teenagers were established, and providers were given opportunities for education and training. The maternal mortality ratio and the abortion rate have now declined and contraceptive use appears to be increasing. These achievements are attributable in large measure to the commitment of a broad spectrum of St Petersburg society as well as to outside support.

Adolescent↗

Agreement between the Takeda UA-731 automatic blood pressure measuring device and the manual mercury sphygmomanometer: an assessment under field conditions in Newcastle upon Tyne, UK.

STUDY OBJECTIVE: To assess agreement between two Takeda UA-731 automatic blood pressure measuring devices (referred to as machines A and B) and two manual mercury sphygmomanometers. DESIGN: A 'Y' connector attached each Takeda UA-731 to a manual mercury sphygmomanometer. Simultaneous measurements were made on adult subjects. SETTING: A population based cardiovascular disease survey in Newcastle upon Tyne, UK. PARTICIPANTS: Measurements on machine A were compared in 71 individuals (all women), and on machine B in 75 individuals (9 men, 66 women). The age range of subjects was 28 to 76 years and median ages were 59 years for machine A and 50 years for machine B. MAIN RESULTS: Blood pressure (mmHg) ranged from 72 to 212 systolic and 44 to 102 diastolic. Both Takedas gave significantly lower readings than the manual devices for systolic and diastolic pressures: differences were mean (SD: 95% CI) 3.7 mmHg (6.5: 2.2, 5.2) for machine A systolic, 2.3 mmHg (4.5: 1.3, 3.4) machine A diastolic; 1.8 mmHg (6.2: 0.4, 3.3) machine B systolic, and 1.8 (4.4: 0.8, 2.8) machine B diastolic. On the British Hypertension Society criteria, machine A was graded C on systolic measurements and B on diastolic; machine B was graded B on both systolic and diastolic measurements. CONCLUSIONS: The performance of these machines compares favourably with the Dinamap 8100, recently adopted for survey work by the Department of Health. The Takeda UA-731 looks promising for epidemiological survey work but before it can be fully recommended further evaluations are needed.

Adult↗

Cytotoxic and clastogenic effects of benzyl isothiocyanate towards cultured mammalian cells.

Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables present in the human diet, has previously been shown to induce chromosome aberrations in an Indian muntjac cell line. The results of this study show that it also induces both chromosome aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence of an exogenous metabolic activation system and induces DNA strand breaks as measured by the single-cell gel electrophoresis assay. However, whereas it increased the number of aberrations four-fold, it was not able to raise SCE levels by more than 50% and there was a levelling-off in the dose-response curve. Whereas the survival curve of CHO cells exposed to BITC was linear in shape, that of the human colorectal adenocarcinoma cell line HT29 was found to fit the exponential model (with an alpha equivalent of 0.28 and a beta equivalent of 2.80, where the concentration of BITC is measured in micrograms/ml). This pattern of clastogenic and cytotoxic activities is reminiscent of that generated by ionizing radiation and certain radiomimetic chemotherapeutic agents.

Adenocarcinoma↗

Selective toxicity of compounds naturally present in food toward the transformed phenotype of human colorectal cell line HT29.

It has previously been observed that allyl isothiocyanate, a compound naturally present in the diet, is more cytotoxic toward the human colorectal adenocarcinoma cell line HT29 in its control transformed state than after exposure to sodium butyrate or to dimethylformamide, which slow growth and induce differentiation (detransformation). In the present study, a range of other dietary compounds were assayed for such selective toxicity. These compounds were chosen as constituents of foodstuffs that have been identified from epidemiologic studies as being potentially antitumorigenic and also as having anticarcinogenic activity in experimental models. Benzyl and phenethyl isothiocyanate, benzyl thiocyanate, and quercetin showed decreased toxicity towards HT29 after detransformation of the cells by one or both treatments, whereas no change was observed in the sensitivity to diallyl sulfide or diallyl disulfide. It is proposed that the presence of such selectively toxic compounds in the diet may inhibit the development of tumors by interfering with the growth of preneoplastic lesions while having little effect on normal cells. The cumulative effects of these inhibitions may contribute to the chemopreventive properties of the parent foodstuffs observed in epidemiologic studies.

Adenocarcinoma↗

Changes in locus-of-control attitudes about drug misuse in a self-help group in a methadone maintenance clinic.

Clients of a methadone-maintenance clinic in Brooklyn, New York participating in a clinically-guided self-help (CGSH) program plus standard treatment (methadone maintenance plus individual counseling) demonstrated statistically significant changes in locus-of-control beliefs, from external to internal causation, about personal responsibility for drug misuse. Members of two control groups--one participating in a didactic lecture program plus standard treatment and the other receiving only standard treatment--failed to demonstrate similar changes. This increase in internal locus of control in the CGSH group suggests the potential efficacy of CGSH as a relapse-prevention therapeutic technique.

Acquired Immunodeficiency Syndrome↗

Careprovider and obstetrical interventions--a comparative study of four European countries.

The purpose of this study was to compare the treatment recommendations of obstetricians and midwives in four European countries: the Czech Republic, Finland, Hungary, and Slovenia. Intervention orientation was examined with six hypothetical patient cases. We wanted to learn whether midwives differ from obstetricians in their choices, and whether there is any variation among countries regarding the willingness of staff to intervene. In Finland the two professions were quite similar in their recommendations for interventions, but in Hungary and Slovenia, midwives and obstetricians differed from each other. There were also differences between the countries in the treatment recommendations, and there was disparity between opinions and actual obstetrical practices. Slovenian obstetrical staff were the most interventionistic in many cases, compared with others, although the actual frequency of interventions was no greater than in other countries. In Finland the staff were the most passive in their opinions, yet the actual proportion of interventions was greatest.

Adult↗

Audit of a system for dealing with a practice's laboratory test results.

In order to improve efficiency in a non-computerized practice of 4700 patients the system for dealing with laboratory test results and communicating them to patients was audited over a two-week period. The audit involved a questionnaire for the practice team, a postal questionnaire to 36 patients, and an analysis of doctors' and receptionists' workload when dealing with laboratory test results. A new system was introduced, with two receptionists logging investigation details into a newly designed results book, and with date/process stamping of results. The new system was re-audited using another practice questionnaire and analysis of doctors' and receptionists' workload and found to be as effective as the old system but less time consuming, largely owing to the layout of the new results book. All members of the practice team were more satisfied with the new system. The function of a results book and its role in doctor-patient communication is discussed.

Diagnostic Services↗