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Biomedical subjects

F Robinson

Publications and source records attributed to F Robinson.

At least 19 recordsLinked to original sources
PubMed2005

Regulation of alternative splicing by PTB and associated factors.

PTB (polypyrimidine tract-binding protein) is a repressive regulator of alternative splicing. We have investigated the role of PTB in three model alternative splicing systems. In the alpha-actinin gene, PTB represses the SM (smooth muscle) exon by binding to key sites in the polypyrimidine tract. Repressive binding to these sites is assisted by co-operative binding to additional downstream sites. SM exon splicing can be activated by CELF proteins, which also bind co-operatively to interspersed sites and displace PTB from the pyrimidine tract. Exon 11 of PTB pre-mRNA is repressed by PTB in an autoregulatory feedback loop. Exon 11-skipped RNA gets degraded through nonsense-mediated decay. Less than 1% of steady-state PTB mRNA is represented by this isoform, but inhibition of nonsense-mediated decay by RNA interference against Upf1 shows that at least 20% of PTB RNA is consumed by this pathway. This represents a widespread but under-appreciated role of alternative splicing in the quantitative regulation of gene expression, an important addition to its role as a generator of protein isoform diversity. Repression of alpha-tropomyosin exon 3 is an exceptional example of PTB regulation, because repression only occurs at high levels in SM cells, despite the fact that PTB is widely expressed. In this case, a PTB-interacting cofactor, raver1, appears to play an important role. By the use of 'tethering' assays, we have identified discrete domains within both PTB and raver1 that mediate their repressive activities on this splicing event.

Actinin↗
PubMed2003

INTERMAP: the dietary data--process and quality control.

The aim of this report is to describe INTERMAP standardized procedures for assessing dietary intake of 4680 individuals from 17 population samples in China, Japan, UK and USA: Based on a common Protocol and Manuals of Operations, standardized collection by centrally trained certified staff of four 24 h dietary recalls, two timed 24-h urines, two 7-day histories of daily alcohol intake per participant; tape recording of all dietary interviews, and use of multiple methods for ongoing quality control of dietary data collection and processing (local, national, and international); one central laboratory for urine analyses; review, update, expansion of available databases for four countries to produce comparable data on 76 nutrients for all reported foods; use of these databases at international coordinating centres to compute nutrient composition. Chinese participants reported 2257 foods; Japanese, 2931; and UK, 3963. In US, use was made of 17,000 food items in the online automated Nutrition Data System. Average time/recall ranged from 22 min for China to 31 min for UK. Among indicators of dietary data quality, coding error rates (from recoding 10% random samples of recalls) were 2.3% for China, 1.4% for Japan, and UK; an analogous US procedure (re-entry of recalls into computer from tape recordings) also yielded low discrepancy rates. Average scores on assessment of taped dietary interviews were high, 40.4 (Japan) to 45.3 (China) (highest possible score: 48); correlations between urinary and dietary nutrient values--similar for men and women--were, for all 4680 participants, 0.51 for total protein, range across countries 0.40-0.52; 0.55 for potassium, range 0.30-0.58; 0.42 for sodium, range 0.33-0.46. The updated dietary databases are valuable international resources. Dietary quality control procedures yielded data generally indicative of high quality performance in the four countries. These procedures were time consuming. Ongoing recoding of random samples of recalls is deemed essential. Use of tape recorded dietary interviews contributed to quality control, despite feasibility problems, deemed remediable by protocol modification. For quality assessment, use of correlation data on dietary and urinary nutrient values yielded meaningful findings, including evidence of special difficulties in assessing sodium intake by dietary methods.

Adult↗
PubMed2002

Changing from a mixed to self-selected vegetarian diet--influence on blood lipids.

OBJECTIVE: To observe any changes in serum concentrations of lipids, when UK meat-eaters switch to a self selected vegetarian diet for 6 months. DESIGN: Observational study using capillary blood samples and 3-day estimated dietary diary. SETTING: Free-living subjects in the North-West of England. SUBJECTS: Twelve male and 31 female adult volunteers aged between 18 and 42 years. OUTCOME MEASURES: Serum lipids; nutrient intake and anthropometric measurements at baseline and 6 months after switching to a self-selected vegetarian diet. RESULTS: Total energy intake and amount of energy derived from saturated fatty acids decreased significantly after changing to a vegetarian diet (P < 0.05) whereas energy derived from carbohydrate, and intakes of nonstarch polysaccharide intake increased. On switching to a vegetarian diet, total cholesterol and triacylglycerol concentrations were not significantly changed, but HDL-C was 21% higher than at baseline (1.21 mmol L(-1) vs. 1.47 mmol L(-1); P = 0.001). CONCLUSIONS: These results suggest that beneficial changes to diet occurred on changing to a self-selected vegetarian diet. Changing to a self-selected vegetarian diet appears to be one way of achieving a better blood lipid profile.

Adolescent↗
PubMed2001

Differential alternative splicing activity of isoforms of polypyrimidine tract binding protein (PTB).

Polypyrimidine tract binding protein (PTB) is an RNA-binding protein that regulates splicing by repressing specific splicing events. It also has roles in 3'-end processing, internal initiation of translation, and RNA localization. PTB exists in three alternatively spliced isoforms, PTB1, PTB2, and PTB4, which differ by the insertion of 19 or 26 amino acids, respectively, between the second and third RNA recognition motif domains. Here we show that the PTB isoforms have distinct activities upon alpha-tropomyosin (TM) alternative splicing. PTB1 reduced the repression of TM exon 3 in transfected smooth muscle cells, whereas PTB4 enhanced TM exon 3 skipping in vivo and in vitro. PTB2 had an intermediate effect. The PTB4 > PTB2 > PTB1 repressive hierarchy was observed in all in vivo and in vitro assays with TM, but the isoforms were equally active in inducing skipping of alpha-actinin exons and showed the opposite hierarchy of activity when tested for activation of IRES-driven translation. These findings establish that the ratio of PTB isoforms could form part of a cellular code that in turn controls the splicing of various other pre-mRNAs.

Alternative Splicing↗
PubMed2001

MAP kinases.

Explore the source record for details and available documents.

Mitogen-Activated Protein Kinases↗
PubMed2001

Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.

Mitogen-activated protein (MAP) kinases comprise a family of ubiquitous proline-directed, protein-serine/threonine kinases, which participate in signal transduction pathways that control intracellular events including acute responses to hormones and major developmental changes in organisms. MAP kinases lie in protein kinase cascades. This review discusses the regulation and functions of mammalian MAP kinases. Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted. Particular emphasis is on ERK1/2.

Animals↗
PubMed2001

Disseminating nutrition research findings to health professionals.

Good nutrition is the basis of good health and poor nutrition is directly linked with certain illnesses, such as heart disease. A great deal of research on nutrition is carried out every year, but little may actually be read by health staff. A project aimed at ensuring that the latest information reaches those who need it is now running in 24 European countries.

Europe↗
PubMed2000

Positive and negative selection to reduce tumour contamination in peripheral blood stem cell harvests.

Peripheral blood progenitor cells used during high dose treatments for malignancy may be contaminated with tumour cells that could later contribute to recurrence. CD34+ selected harvests still contain tumour cells and an additional negative selection may be capable of reducing this contamination. We have assessed a two-stage technique in which a CD34+ selection is followed by a tumour specific depletion stage using a B cell or breast cancer specific antibody panel. Initial small-scale selections on 11 patients with NHL and breast cancer showed that cell loss was greatest following the CD34+ selection with a median yield of 38.8 per cent (range 17. 2-56.4 per cent). The addition of the depletion stage resulted in a minimal loss of CD34+ cells with a yield for this step of 94.2 per cent (range 77.5-99.3 per cent). Clinical scale selections were performed on seven patients with CLL and a median of 2.8x10(6)/kg CD34+ cells (range 1.5-6.1x10(6)/kg) were collected. Cell recovery was 53.3 per cent following CD34+ selection and 76.9 per cent following the tumour specific depletion stage, resulting in a final product containing a median of 1.0x10(6)/kg CD34+ cells (range 0. 55-2.0x10(6)/kg). All unmanipulated harvests were heavily contaminated with tumour cells (median contamination 10.2 per cent, range 2.0-83.1 per cent) as measured by flow cytometry and a median 4.7 log (range 3-5 log) tumour cell purge was produced following two-stage selection. Six of the patients have received cells manipulated in this way with median engraftment times of neutrophils>0.5x10(9)/l=16 days (range 13-20 days) and platelets>20x10(9)/l=16.5 days (range 11-42 days). At a median follow-up of 25 months, these transplanted patients remain well and in molecular complete remission.

Adult↗
PubMed2000

Effect of visual background on saccade adaptation in monkeys.

The brain maintains saccade accuracy by modifying saccades that are consistently inaccurate (e.g. hypermetric). To determine whether this adaptation is influenced by the visual background we used several different target and background movements to elicit changes in saccade gain. In almost all cases, the target spot drove gain changes. The background had no effect on, or slightly reduced, adaptation. We conclude that the saccade adaptation mechanism is driven almost entirely by stimuli on or near the fovea and is affected very little by visual stimuli falling more peripherally.

Adaptation, Physiological↗
PubMed1999

Orbital position dependency is different for the gain of externally and internally triggered saccades.

The gain of visually triggered saccades depends on orbital position. Centrifugal saccades have smaller gains and are slower than centripetal saccades elicited by the same target amplitude. We determined whether internally triggered saccades, e.g. scanning or memory saccades, exhibit the orbital position dependency evident in visually guided saccades. The search coil technique was used to record eye movements of healthy subjects while they performed horizontal 12.5 degree saccades under three paradigms (gap, scanning and memory saccades). Orbital position influenced externally triggered gap saccades but not the gain or peak eye velocity of scanning or memory saccades. These findings do not support the idea that position dependency caused by orbital mechanics is compensated for at the level of the common brainstem burst generator. Instead our results are consistent with the view that cortical output reflects the differences evident in the gain of visually triggered centrifugal and centripetal saccades.

Adult↗
PubMed1999

Width/length ratios of normal clinical crowns of the maxillary anterior dentition in man.

The purpose of this investigation was to analyze the clinical crown of the 3 tooth groups of the maxillary anterior sextant of the permanent dentition of normal subjects with respect to (i) width, length and the width/length ratios and (ii) determine if there is a correlation between tooth dimensions or tooth group ratios and subject height. Subjects (> or = 20 y.o.) were recruited for this study if (i) the free gingival margin on the facial surface of teeth in the maxillary sextant was positioned apical to the cervical bulge, (ii) there was no evidence of attachment loss; as determined by lack of a detectable CEJ and (iii) the marginal tissue was knife edged in form, firm in consistency and coral pink in color. Teeth were excluded if (i) there was evidence of gingival alteration, i.e., gingival overgrowth/hyperplasia, inflammation, altered passive eruption, attachment loss, gingival recession or history of periodontal surgery, or (ii) there was evidence or history of incisal edge/proximal tooth alteration as in, i.e., restorative intervention, traumatic injury or occlusal wear into dentin. At least 1 suitable tooth from each tooth group of the maxillary anterior dentition had to be present. A maxillary impression was taken and poured in yellow die stone. The widest mesial-distal portion and the longest apical-coronal portion of the test teeth were measured. Gender, ethnicity and subject height (SH) were recorded for each participant. Due to a limited ethnic diversity only data from the Caucasian group were analyzed. The mean coronal tooth width (mm) of males versus females was CI: 8.59 versus 8.06, LI: 6.59 versus 6.13 and CA: 7.64 versus 07.15. The mean coronal tooth length (mm) of males versus females was CI: 10.19 versus 9.39, LI: 8.70 versus 7.79 and CA: 10.06 versus 8.89. All width and length measures were significantly greater for males than for females. The mean coronal tooth width/length ratios for males versus females was CI: 0.85 versus 0.86, LI: 0.76 versus 0.79 and CA: 0.77 versus 0.81. A comparison between genders of the width/length ratios of the CI and LI were found not to differ, however the CA ratio for females was significantly greater than for males. A statistically significant difference was found to exist between the mean (cm) SH for males versus females: 181.2 versus 164.0. A positive correlation (p < or = 0.0001 to 0.0691) was found to exist between tooth group width/height ratios within genders. No significant correlation was found between any of the tooth dimensions or tooth group ratios and SH. The results of this study indicate that within male and female Caucasians, the mean width/length ratio of the maxillary 3 anterior tooth groups is 0.81. As well, within both genders there is a positive correlation between tooth group width/length ratios. The significance of these findings with respect to periodontal mucogingival plastic surgical procedures is discussed.

Adult↗
PubMed1998

Larynx synchronised stroboscopy--a new tool for outcome measures in the voice clinic.

Direct vocal fold synchronised stroboscopy is a new technique for obtaining useful images of pathological voice, with reduced requirements for both vocal fold cycle regularity and the duration of sustained phonation. Precise synchronisation of the firing of the stroboscope from the Laryngograph waveform, and the capture of images and waveforms into a computer, allows inspection of short periods of phonation (less than one second) as a continuous replay of the images. Replay can be continued indefinitely, automatically repeating the short period of image capture, eliminating the need to rewind a video-tape repetitively. This in turn avoids the need for the lengthy phonation otherwise required when clinical examination is based on the use of conventional live or video-taped stroboscopy. Since the LxStrobe system is based on digital processing, archiving and retrieval of images is much enhanced. A demonstration of the system, called the LxStrobe, is available on the world-wide-web at www.laryngograph.com.

Electrodiagnosis↗
PubMed1997

Out to tender--the nurses' role in awarding the contract for therapeutic bed/mattress hire.

AIM: A project group was established to award the contract for hire of therapeutic beds and mattresses for a large hospital Trust within the United Kingdom National Health Service (NHS). BACKGROUND: No structure existed for awarding or evaluating such a contract. Involving nurses in the process was intended to bring the decision-making nearer the patient. METHOD: The project group consisted of volunteers from a range of clinical nursing grades. They were highly motivated with an interest in pressure sore management. Expertise from NHS Supplies was also involved. RESULTS: The project group successfully awarded the contract, producing a robust operational tool through an objective process. Awareness was raised regarding control of expenditure and a commitment to education. Ongoing evaluation of the contract has also been the responsibility of this group. CONCLUSION: The project group achieved its aim of awarding a contract that best met the needs of the Trust and continues to monitor that contract. The systematic approach, comprehensive documentation and collaboration with NHS Supplies are felt to contribute to its success. Explicit criteria within the contract provides a clear framework for its monitoring and evaluation.

Beds↗