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Biomedical subjects

C Wilkinson

Publications and source records attributed to C Wilkinson.

At least 19 recordsLinked to original sources

The Pad1+ gene encodes a subunit of the 26 S proteasome in fission yeast.

We have isolated a fission yeast mutant, mts5-1, in a screen for mutations that confer both methyl 2-benzimidazolecarbamate resistance (MBCR) and temperature sensitivity (ts) on Schizosaccharomyces pombe. This screen has previously isolated mutations in the 26 S proteasome subunits Mts2, Mts3, and Mts4. We show that the mutation in the mts5-1 strain occurs in the pad1(+) gene. pad1(+) was originally isolated on a multicopy plasmid that was capable of conferring staurosporine resistance on a wild type strain. mts5-1/pad1-1 has a similar phenotype to 26 S proteasome mutants previously isolated in the same screen and we show that Pad1 interacts genetically with two of these subunits, Mts3 and Mts4. In this study we describe the identification of Pad1 as a subunit of the 26 S proteasome in fission yeast.

Amino Acid Sequence

Can primary prevention or selective screening for melanoma be more precisely targeted through general practice? A prospective study to validate a self administered risk score.

OBJECTIVES: To establish whether a questionnaire incorporating MacKie's risk factor flow chart can identify patients at high risk for melanoma so that they can be targeted for primary and secondary prevention. To validate the risk score derived from the questionnaire and test the feasibility of self completion by comparing patients' self reported skin characteristics with a skin examination performed by an experienced general practitioner. DESIGN: Prospective questionnaire survey followed by a comparative study. SETTING: 16 randomly selected group practices in a health district in Cheshire, United Kingdom. SUBJECTS: Questionnaire survey--3105 consecutive patients aged 16 years and over attending for a primary care consultation; comparative study--a self selected subsample of 388 of the 3,105 patients. MAIN OUTCOME MEASURES: MacKie risk group for melanoma. Comparison of high risk skin characteristics reported by patients and those noted during a skin examination by a doctor (kappa statistic). RESULTS: 4.3% of patients (87% women) were in the highest risk group and 4.4% (79% men) were in the second highest risk group, as defined by the MacKie score. Agreement between patients' self appraisal of skin characteristics and clinical skin examinations was reflected in kappa values of 0.67 for freckles, 0.60 for moles, and 0.43 for atypical naevi. CONCLUSION: This questionnaire helped to identify a group at high risk for melanoma. Furthermore, good agreement was found when the patient's risk scores were compared with results of the clinical skin examination. This risk score is potentially useful in targeting primary and secondary prevention of melanoma through general practice.

Age Distribution

'Being there': learning through active participation.

Students engagement in learning is predicated not only on interest but on the perception of relevance to their needs. A hermeneutic interpretation of narrative student evaluation data from an introduction to nursing lecture course that was taught by means of a practice-based phenomenological approach revealed a pattern of student learning in which students moved from detachment to active participation in their learning. The stories shared by nurses in the practice setting were instrumental in introducing students to the world of nursing and facilitating a sense of belonging. Once engaged in the experience, students looked for opportunities to become active participants in their learning. A practice-based phenomenological approach to a theory course maximizes opportunities for student participation. Active reflection and integration allow students to make their own connections between theory and practice.

Curriculum

Do bereaved children consult the primary health care team more frequently?

It is known that 2% of all children are bereaved of a parent before the age of 18, but there is little support available for these bereaved children in the community. It is not known if these children consult the primary health care team more frequently than their non-bereaved peers. A record-based, case-controlled pilot study of 13 bereaved children over a 2-year period was carried out in a group general practice. All children had been bereaved of a father through malignant disease, and were from seven families. Children who had been bereaved of a parent attended the surgery more frequently than their age/sex-matched controls. There was an observed increase in the frequency of consultations both in the year preceding and following the bereavement. Post-bereavement, over one-third of consultations were for symptoms for which no organic cause could be found. The support needs of these bereaved children did not appear to be addressed. Further research is required to investigate the optimum means of providing support by the primary health care team for the small but significant number of children who are bereaved each year.

Adolescent

Is a rising caesarean section rate inevitable?

OBJECTIVE: To determine the indications for singleton caesarean sections in Scotland in 1994. DESIGN: Prospective survey of singleton caesarean sections using information provided by clinicians entering data onto a computer in labour wards. SETTING: Twenty-three consultant-led obstetric units in Scotland. POPULATION: Women undergoing caesarean section in participating Scottish maternity units during 1994. RESULTS: Using routinely collected data it was found that the caesarean section rate varied by maternal age, parity, gestation, history of previous section and hospital of delivery, but there was no difference by area of deprivation. 87.4% (8369/9573) of Scottish caesarean sections were included in the survey of which 8098 were in women with singleton pregnancies. Most singleton caesarean sections were undertaken in primiparae (50.5%), 31.2% were in women with a history of previous section and 18.3% were in multiparous women who had not had a previous section; 38.9% of the operations were elective, 13.9% were emergencies before labour and 47.2% were emergencies during labour. Four main indications--elective section for breech presentation (10.7% of all sections); emergency caesarean section before labour because of fetal problems (2.8%); emergency caesarean section during labour for fetal distress and/or failure to progress (30.3%); repeat section for reasons other than above (16.2%) accounted for 60% of all caesarean sections in women with no other recorded complications. 7.7% of all singleton caesarean sections (19.8% of elective operations) were associated with maternal request for the operation. DISCUSSION: The survey has identified why caesarean sections are performed by Scottish obstetricians and highlighted some areas where there would be scope to increase the vaginal delivery rate. Before this can be attempted, agreement must be reached by clinicians about effective management of particular problems. Women also need to have ready access to evidenced-based information about caesarean section.

Algorithms

Topographical control of cells.

We review the literature on the reaction of cells to their surrounding topography. The topography may be that of surrounding cells, intercellular materials or biomaterials. The reactions include cell orientation, rates of movement, and activations of the cells. We concentrate on those papers where quantitative measurements of the reactions have been made and largely ignore those on subjective impressions. A wide range of topographies are considered but special attention is given to results on groove-ridge topographies. The question of whether the cells are reacting to the topography directly or to patterned substratum chemistry formed on the topography is discussed. The review ends with a summary of the types of prosthesis where advantage has been taken of the ability to fabricate topography.

Animals

Neutron Laue diffractometry with an imaging plate provides an effective data collection regime for neutron protein crystallography.

Neutron quasi-Laue diffraction data (2 A resolution) from tetragonal hen egg-white lysozyme were collected in ten days with neutron imaging plates. The data processing Laue software, LAUEGEN, developed for X-ray Laue diffractometry, was adapted for neutron diffractometry with a cylindrical detector. The data analysis software, X-PLOR, was modified and used for the refinement of hydrogen atoms, and the positions of 960 hydrogen atoms in the protein and 157 bound water molecules, were determined. Several examples are given of the methods used to identify hydrogen atoms and water molecules.

Animals

Do the homeless get a fair deal from general practitioners?

Many studies have indicated the health status of homeless people to be typically poorer than that of the general population, with various studies indicating a high prevalence of psychiatric illness, drug or alcohol misuse and associated socio-medical problems. The Bristol Primary Healthcare Project is an agency which was established to provide a local health care service tailored to the needs of people who are homeless. The present study was carried out as part of an evaluation of the service offered locally to homeless people by General Practitioners (GPs). A postal questionnaire survey of 155 general practices within the Avon FHSA area was carried out. Both fundholding and non-fundholding practices were included, within an area including inner city, urban and rural/semi-rural locations. One hundred and seventeen completed questionnaires were returned, providing a response rate of 75%. Twenty-seven percent of practices would fully register a homeless person who seeks to register at the practice, 24% would treat as immediate and necessary and 33% would treat as a temporary resident. Four percent of fundholding practices surveyed would fully register homeless persons and 55% of inner city practices would do so. Seventy-nine percent of doctors indicated that homeless patients were more difficult to treat than other patients. The most frequent problems associated with registering homeless persons were perceived to be the associated social problems (90% of respondents agreed), the lack of medical records (88% agreed), the complex health problems (79% agreed) and the associated alcohol or substance misuse (78% agreed). The study has highlighted a need for government to consider providing incentives to GPs to register homeless people without resulting in adverse effects on their contract targets. The reluctance of some practices to register these patients varied by area and type of practice with doctors at fundholding practices being the most reluctant. There is an identified need for further health education and promotion work and initiatives exemplified by the Bristol Primary Healthcare Project for people who are homeless.

Attitude of Health Personnel

Synergistic and hierarchical adhesive and topographic guidance of BHK cells.

Guided cell movement is a fundamental process in development and regeneration. We have used microengineered culture substrates to study the interaction between model topographic and adhesive guidance cues in steering BHK cell orientation. Grooves 0.1, 0.5, 1.0, 3.0, and 6.0 microm deep together with pitch-matched aminosilane tracks 5, 12, 25, 50, and 100 microm wide were fabricated on fused silica substrates using photolithographic and dry-etching techniques. The cues were presented to the cells individually, simultaneously in parallel and orthogonally opposed. Cells aligned most strongly to 25-microm-wide adhesive tracks and to 5-microm-wide, 6-microm-deep grooves. Stress fibers and vinculin were found to align with the adhesive tracks and to the grooves and ridges. Cell alignment was profoundly enhanced on all surfaces that presented both cues in parallel. Cells were able to switch alignment from ridges to grooves, and vice versa, depending on the location of superimposed adhesive tracks. Cells aligned preferentially to adhesive tracks superimposed orthogonally over grooves of matched pitch, traversing numerous grooves and ridges. The strength of the cues was more closely matched on narrower 3- and 6-microm-deep gratings with cells showing evidence of alignment to both cues. Confocal fluorescence microscopy revealed two groups of mutually opposed f-actin stress fibers within the same cell, one oriented with the topographic cues and the other with the adhesive cues. However, the adhesive response was consistently dominant. We conclude that cells are able to detect and respond to multiple guidance cues simultaneously. The adhesive and topographic guidance cues modeled here were capable of interacting both synergistically and hierarchically to guide cell orientation.

Animals

Group discussions in nursing education: a learning process.

This article offers advice on how to obtain the most from group work by taking personal responsibility for learning. The authors consider the components of successful group work and how both students and teachers can take full advantage of this popular educational strategy.

Education, Nursing

Guidelines on how to prepare and present a seminar.

The seminar is a popular teaching method in pre- and post-registration nursing courses. This article explores the values and limitations of this approach and offers guidelines to optimise its usefulness as both a teaching and learning strategy.

Adult

Guidance and activation of murine macrophages by nanometric scale topography.

We studied the guidance and activation of macrophages from the P388D1 cell line and rat peritoneum by topographic features on a nanometric scale. Cells were plated on plain fused silica substrata or substrata with microfabricated grooves and steps, 30-282 nm deep. The contact of cells with the patterned surface activated cell spreading and adhesion and increased the number of protrusions of the cell membrane. These changes were accompanied by an increase in the amount of F-actin in cells. The accumulation of F-actin and vinculin in cells was observed along the edges of single steps or grooves. Formation of focal contacts along discontinuities in the substratum was accompanied by the phosphorylation of tyrosine colocalized with F-actin and vinculin. A similar pattern of staining was seen in cells stained for vitronectin receptor, alphaV integrin, but not for integrins alpha5beta1 or alpha3beta1. Cells cultured on nanogrooves showed a higher phagocytotic activity than cells cultured on plain substrata. We show that macrophages can react to ultrafine features of topography of a size comparable to that of a single collagen fiber and become activated by the contact with topographic features.

Animals

A neutron image plate quasi-Laue diffractometer for protein crystallography.

An instrument which is based on image plate technology has been constructed to perform cold neutron Laue crystallography on protein structures. The crystal is mounted at the center of a cylindrical detector which is 400mm long and has a circumference of 1000mm, with gadolinium oxide-containing image plates mounted on its exterior surface. Laue images registered on the plate are read out by rotating the drum and translating a laser read head parallel to the cylinder axis, giving a pixel size of 200 microm x 200 microm and a total read time of 5 minutes. Preliminary results indicate that it should be possible to obtain a complete data set from a protein crystal to atomic resolution in about two weeks.

Animals

Bone density change and biochemical indices of skeletal turnover.

Although biochemical markers of skeletal turnover cannot replace bone density scanning for the diagnosis of osteoporosis, it is thought that they may help add to prediction of fracture risk and help determine adequacy of osteoporosis therapy. Nevertheless, whether biochemical markers in the serum or urine can predict individual rates of bone loss in the spine or hip region is unknown. We studied a heterogeneous group of women (n = 81) who were premenopausal, untreated postmenopausal, and estrogen-treated postmenopausal with baseline determination of body mass index (BMI), calcium intake, biochemical measurements, and serial bone densitometry over 3 years. Serum assays included bone Gla protein (BGP), total and bone-specific alkaline phosphatase (AP, BSAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). Urine assays included hydroxyproline (OHP), calcium, total pyridinoline, and total deoxypyridinoline. Individual biochemical markers and calcium intake were modestly correlated with bone density changes but were inconsistent regarding the spine versus the hip. All of the formation variables were significantly correlated to spine density change (r = -0.24 to -0.49) whereas the only resorption variable that correlated was urine OHp/Cr (r = -0.31). The only formation variable that correlated with hip density change was serum PICP whereas all of the resorption variables except serum TRAP were correlated (r = -0.23 to -0.35). "High turnover" individuals were defined at those with levels of biochemical variables at least 1 SD above the mean young normal for each variable. Higher bone loss rates were seen in this group for several of the turnover markers compared with bone loss rates in all other individuals. However, the sensitivity of this "high turnover" status for identifying high bone losers did not exceed 60% for any of the variables. In untreated postmenopausal women, a model using urine OHp, serum ICTP, serum BSAP, and calcium intake was able to predict 42% of the variance of change in BMD of the lumbar spine. A model using BMI, serum ICTP, and serum BGP could predict 32% of the variance of change in BMD of the femoral neck. No combination of markers could predict variance in bone density change at either site in estrogenized women (premenopausal and estrogen-treated postmenopausal). We conclude that measuring individual serum and urine markers of bone turnover cannot accurately predict bone loss rates in the spine and hip; however, combinations of demographic and biochemical variables could predict some of the variance in untreated postmenopausal women. Biochemical markers cannot replace serial bone densitometry for accurate determination of change in bone mass at the most clinically relevant sites.

Adult