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Biomedical subjects

J Lightfoot

Publications and source records attributed to J Lightfoot.

At least 19 recordsLinked to original sources
PubMed2004

Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome.

Approximately 10% of newborns with Down syndrome develop Transient Leukemia (TL), a disorder that is unique to infants with constitutional trisomy 21 (or trisomy 21 mosaicism). TL blasts disappear spontaneously within the first 3 months of life in the majority of cases. Despite the resolution of TL, 20-30% of these newborns will go on to develop acute megakaryoblastic leukemia (AMKL) later in life. In this study, samples from both TL and AMKL patients were examined using cDNA microarrays to study the pathogenic progression from TL to AMKL. TL and AMKL samples partition separately by cluster analysis, and AMKL samples had substantial increases in apolipoprotein C-I, transporter 1, myosin alkali light chain 4, and spermidine/spermine N-acetyltransferase, compared to TL samples. Although these findings will require validation in an independent series of TL and AMKL samples, they indicate that TL and AMKL have distinct gene signatures, and provide a basis for studies of the different mechanisms underlying either the resolution of TL or its progression to AMKL.

Adolescent↗
PubMed2003

Involving disabled and chronically ill children and young people in health service development.

AIM: To investigate the extent and nature of involvement of physically disabled or chronically ill children and young people in local health service development. METHODS: A postal survey of all health authorities (n = 99) and NHS Trusts (n = 410) in England. RESULTS: Seventy-six per cent of health authorities and 59% of Trusts responded. Twenty-seven initiatives involving chronically ill or disabled children and young people in consultation regarding service development were identified. Over half of these were carried out in partnership between health services and other agencies, usually local authorities and/or voluntary organizations. A variety of methods was used for consultation, including child-friendly methods such as drawing, drama and making a video. Seventeen initiatives reported that children's involvement had resulted in service changes, but only 11 went beyond consultation to involve children and young people in decision making about service development. Only a third of the organizations had someone with designated responsibility for children's involvement. DISCUSSION: The involvement of this group of children and young people in service development in the NHS is at an early stage. The failure of policy documents on user involvement to identify children and young people as a group for whom methods of consultation need to be developed, and the lack of people with designated responsibility for developing children's involvement may be a reason for slow progress in this area. The initiatives identified show that such involvement is possible and can have a positive impact on services.

Adolescent↗
PubMed2003

How well do fourth year Wits dental students place resin composite restorations?

OBJECTIVES: To evaluate, by means of a scanning electron microscope (SEM) the quality of resin composite restorations, placed as a first attempt by fourth-year dental students. METHODS: Ten Class IV direct composite restorations, placed in plaster-mounted extracted incisor teeth as part of pre-clinical course requirements, were selected. Specimens were evaluated and graded on a two-point scale by a staff member according to departmental clinical evaluation criteria. Five restored teeth were prepared for surface evaluation of marginal integrity, surface roughness and contour using SEM. The remaining specimens were embedded in resin and ground down transversely, parallel to the incisal edge until a dentine core was apparent. The ground surfaces were polished, prepared for SEM and assessed for etched layer, placement of bonding agent, composite adaptation and overall consistency. RESULTS: Clinical assessment and SEM surface evaluation correlated favourably for all criteria, except contour, indicating that students were reasonably competent in finishing techniques. Ground samples revealed acceptable etched enamel layers and marginal adaptation. Bonding agent thickness varied between 0 and 200 microns casting doubt on procedural accuracy. Porosities and voids were apparent within the resin composite. Internal features were the main reason for unsatisfactory grades. CONCLUSIONS: Students placed restoration satisfactorily. They would benefit if able to examine sectioned restorations to understand critical placement techniques which would contribute to resin composite restoration success. A research component can be introduced into the dental undergraduate curriculum by way of similar projects linked to didactic course-work.

Clinical Competence↗
PubMed2002

Communicating about pupils in mainstream school with special health needs: the NHS perspective.

AIM: To add to previous research carried out with young people, parents and teachers, by investigating health staff's perspectives on the difficulties, and possibilities for, achieving good communication with school staff with regard to children in mainstream school with a chronic illness or physical disability. RESEARCH DESIGN AND METHODS: A qualitative research study was carried out in one NHS Trust. Twenty semi-structured interviews were carried out with a purposive sample of health staff to cover the spectrum of professionals who have responsibility for meeting the needs of children with a chronic illness or physical disability in mainstream schools (paediatricians, school doctors, school nurses, specialist nurses, health visitors, GPs, speech and language therapists, paediatric occupational therapists, paediatric physiotherapists, clinical psychologists and psychiatrists). RESULTS: The extent to which health professionals communicated with school staff, and the way in which they went about it, varied widely. Communication was facilitated by joint meetings, shared documentation, and local policy development. Sources of difficulty in communication between health and education staff were: the parent as a conduit of information; the practical difficulties of arranging meetings; and lack of knowledge about other professionals' roles. The ethos of the school with regard to health matters, and the flow of information within health services, also had an impact on the communication process. Participants' recommendations focused on two key issues: clarification of the roles of health and education staff with regard to this group of pupils; and how information should flow from health to school staff. DISCUSSION: Many of the findings parallel the previous research with teachers, indicating agreement between professionals from different agencies about aspects of the communication process which are problematic and require attention. The findings suggest that improving communication requires both joint work between health and education staff, and improvements to practice within each agency.

Child↗
PubMed2001

Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1.

The Fanconi anemia group C protein (FANCC) plays an important role in hematopoiesis by ensuring the survival of hematopoietic progenitor cells through an unknown mechanism. We investigated the function of FANCC by identifying FANCC-binding proteins in hematopoietic cells. Here we show that glutathione S-transferase P1-1 (GSTP1) interacts with FANCC, and that overexpression of both proteins in a myeloid progenitor cell line prevents apoptosis following factor deprivation. FANCC increases GSTP1 activity after the induction of apoptosis. GSTP1 is an enzyme that catalyzes the detoxification of xenobiotics and by-products of oxidative stress, and it is frequently upregulated in neoplastic cells. Although FANCC lacks homology with conventional disulfide reductases, it functions by preventing the formation of inactivating disulfide bonds within GSTP1 during apoptosis. The prevention of protein oxidation by FANCC reveals a novel mechanism of enzyme regulation during apoptosis and has implications for the treatment of degenerative diseases with thiol reducing agents.

Apoptosis↗
PubMed2000

Isolation of a cDNA representing the Fanconi anemia complementation group E gene.

Fanconi anemia (FA) is an autosomal recessive chromosomal instability syndrome with at least seven different complementation groups. Four FA genes (FANCA, FANCC, FANCF, and FANCG) have been identified, and two other FA genes (FANCD and FANCE) have been mapped. Here we report the identification, by complementation cloning, of the gene mutated in FA complementation group E (FANCE). FANCE has 10 exons and encodes a novel 536-amino acid protein with two potential nuclear localization signals.

Alternative Splicing↗
PubMed2000

Working to keep school children healthy: the complementary roles of school staff and school nurses.

BACKGROUND: Against a background of future uncertainty for school nursing and little previous research, this study aimed to identify and describe the distinctive role of the school nurse in working to keep school children healthy. Particular attention was paid to the 'interface' between nursing and the health-related work of teachers. The research was carried out in four health authority areas in England. METHODS: Seventy-eight semi-structured interviews were carried out with a range of respondents: school nurses, school Heads and teachers, health authority purchasers and NHS Trust managers. Seven focus group discussions were held with parents and eight with young people of secondary school age. RESULTS: Four key elements of the school nurse role were identified: safeguarding the health and welfare of children; health promotion; a pupils' confidante; and family support. In each of these aspects of work, nurses and teachers had shared or complementary roles. An over-arching role for the school nurse as 'health adviser' to pupils, parents and teachers was also identified. Despite these common elements, emphasis in the practice of individual school nurses varied widely. Difficulties for school nurses in developing their role were identified. Parents and young people saw school as an appropriate setting for health-related work. CONCLUSION: The research identified key components of the school nursing role and the complementary roles of nurses and school staff. To optimize school nurses' contribution to child health, a more strategic approach is required, in partnership with education, along with research into the effectiveness of school nursing interventions.

Adolescent↗
PubMed2000

Relationship of organizational culture and readiness for change to employee commitment to the organization.

OBJECTIVES: A study was undertaken to determine the relationships among organizational culture, organizational commitment, and organizational readiness in a sample of employees participating in a hospital-wide redesign process. METHODS: Employees of an organization undergoing patient-focused redesign were surveyed after a 6-month period of preparation and before the initiation of the new care delivery model. RESULTS: Organizational readiness, a variable rarely described in organizational change literature, was the strongest predictor of employee commitment to the organization. Constructive culture also was predictive, but less so than readiness for change. CONCLUSIONS: Additional research is needed to clarify how an organization's history and culture of change contribute to employee willingness to work for the goals of the organization. Findings suggest that when change is seen as a positive characteristic of the environment, employees are more likely to commit to the work of the institution.

Adult↗
PubMed1999

Supporting pupils in mainstream school with an illness or disability: young people's views.

To date, little research has focused directly on health-related support in school for children with a chronic illness or physical disability, yet these children are known to be at increased risk for psychosocial and academic problems. In addition, few studies have sought the views of pupils directly: those which have report a wide range of problems with school life. The increasing numbers of children surviving and managing their health conditions, together with UK policy for inclusive education, means that a growing proportion of pupils in mainstream schools require understanding of their special health needs and may need service support from education and health professionals. This paper presents findings from semistructured interviews with 33 mainstream secondary school pupils with a variety of illnesses and disabilities on the impact of their health condition on school life. Results show that young people valued school and were actively managing the effects of their condition, but needed support from others. Informal support was most frequently cited, including parents--particularly mothers--teachers and close friends. The main difficulties were implications of school absence, exclusion from school life, teachers' reactions to the illness or disability, and peer relationships. The discussion focuses on ways in which health professionals can play a part in supporting pupils both directly and indirectly, through helping others in school understand the condition and its impact on school life.

Attitude↗
PubMed1999

Characterization of regions functional in the nuclear localization of the Fanconi anemia group A protein.

Fanconi anemia (FA) is an autosomal recessive disease characterized by a variety of congenital abnormalities. Cells from FA patients show chromosomal instability and are hypersensitive to DNA cross-linking agents, though the basic cellular defect in FA is not known. The FANCA gene encodes a protein with an Mr of 162 kDa and with unknown function. The cellular localization of the FANCA protein has been controversial, and has been shown in different reports to be exclusively cytoplasmic and predominantly nuclear. In the present study, we further confirm that FANCA localizes primarily to the nucleus. Fusions of FANCA with the green fluorescent protein (GFP) showed a strong nuclear signal and a weak cytoplasmic signal in several cell types. Confocal laser microscopy confirmed that FANCA is evenly distributed throughout the nucleus. We also examined regions in FANCA that participate in its nuclear import. FANCA contains two bipartite nuclear localization signal (NLS) motifs at the extreme N-terminus. Deletion of amino acids N-terminal to the NLS motifs had no effect on the nuclear localization of FANCA or on its ability to correct mitomycin C sensitivity in an FA-A cell line, while deletion of both motifs impeded but did not prevent nuclear import. Deletions of 75, 90 and 150 residues from the N-terminus yielded a mixture of cells with only a cytoplasmic signal, and with both a nuclear and cytoplasmic signal. Deletion of the N-terminal 250 amino acids was required to block nuclear localization completely. Fusion of GFP to the N-terminal 250 amino acids showed a localization pattern similar to FANCA. Mutant forms of FANCA with deletions of the C-terminal 70 or 260 residues localized to the cytoplasm, although the C-terminal 260 amino acids alone lacked NLS activity. The results show that nuclear localization of FANCA involves several functional regions.

3T3 Cells↗
PubMed1999

Working gases in thermoacoustic engines.

The best working gases for thermoacoustic refrigeration have high ratios of specific heats and low Prandtl numbers. These properties can be optimized by the use of a mixture of light and heavy noble gases. In this paper it is shown that light noble gas-heavy polyatomic gas mixtures can result in useful working gases. In addition, it is demonstrated that the onset temperature of a heat driven prime mover can be minimized with a gas with large Prandtl number and small ratio of specific heats. The gas properties must be optimized for the particular application of thermoacoustics; it cannot be assumed that high specific heat ratio and low Prandtl number are always desirable.

Acoustics↗
PubMed1996

Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA.

Fanconi anaemia (FA) is an autosomal recessive disorder characterized by a diversity of clinical symptoms including skeletal abnormalities, progressive bone marrow failure and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC). Five complementation groups (A-E) have been distinguished on the basis of somatic cell hybridization experiments, with group FA-A accounting for over 65% of the cases analysed. A cDNA for the group C gene (FAC) was reported and localized to chromosome 9q22.3 (ref.8). Genetic map positions were recently reported for two more FA genes, FAA (16q24.3) and FAD (3p22-26). Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization.

Amino Acid Sequence↗
PubMed1995

Prevalence of gca, a gene involved in synthesis of A-band common antigen polysaccharide in Pseudomonas aeruginosa.

Two distinct forms of lipopolysaccharide are expressed by Pseudomonas aeruginosa. These forms are known as the A band and the B band. In an attempt to obtain a better understanding of A-band lipopolysaccharide synthesis, a previously isolated A-band gene known as the gca gene (GDP-D-mannose conversion protein for A-band common antigen polysaccharide) was sequenced and analyzed. Previous protein expression data from our laboratory, along with nucleotide sequence analysis from the present study, suggest that the Gca protein is encoded by the open reading frame ORF36.5. Amino acid homology reveals that this protein may be functioning as a dehydratase or as a bifunctional enzyme, facilitating the conversion of GDP-D-mannose to GDP-D-rhamnose. The distribution of this gca gene among the 20 P. aeruginosa O serotypes, clinical isolates, and other Pseudomonas species was also examined. Southern hybridization results revealed that the gca gene is present and conserved on a 1.6-kb KpnI fragment among all 20 O serotypes with the exception of serotype O12. In addition, the gca gene is not universally found among all pseudomonads; however, probe-reactive profiles are similar to that of P. aeruginosa when the gca gene is present. Primers were designed from the gca nucleotide sequence, and PCR amplification of a 700-bp product was found with each of the 20 O serotypes. Because of the conservation of this gene, gca may be useful as a diagnostic tool for detecting the presence of P. aeruginosa as well as other Pseudomonas species.

Amino Acid Sequence↗
PubMed1994

Demonstrating the value of health visiting.

Concern over levels of public expenditure, introduction of private sector ideology and the accompanying push for improved value for money mean that NHS professionals are having to demonstrate their worth against substitution by lesser-skilled--and lower paid--staff, writes Jane Lightfoot. Here she examines the heated debates over skill mix and suggests ways in which health visiting could demonstrate the added value trained, qualified practitioners offer NHS community health care services.

Community Health Nursing↗
PubMed1993

Nursing by numbers.

Explore the source record for details and available documents.

Community Health Nursing↗
PubMed1993

Chromosomal mapping, expression and synthesis of lipopolysaccharide in Pseudomonas aeruginosa: a role for guanosine diphospho (GDP)-D-mannose.

Pseudomonas aeruginosa can express two distinct forms of lipopolysaccharide (LPS), called A-band and B-band. As an attempt to understand the molecular biology of the synthesis and regulation of these LPS antigens, a recombinant plasmid, pFV3, containing genes for A-band expression was isolated previously. In the present study, P. aeruginosa strain PAO1 was mutagenized with transposon Tn5-751 and yielded a B-band-deficient mutant, called ge6. This mutant was mated with a PAO1 genomic library, and transconjugants were screened for complementation of B-band using B-band-specific monoclonal antibody MF15-4. Recombinant plasmid pFV100 was subsequently isolated by its ability to complement B-band expression in ge6. SDS-PAGE analysis of LPS from ge6 and ge6(pFV100) revealed that ge6 was deficient in expression of B-band, while ge6(pFV100) had an LPS profile similar to that of the parent strain PAO1. With A-band and B-band genes cloned in separate plasmids, pFV3 and pFV100 respectively, we were able to determine the map location of these LPS genes on the P. aeruginosa PAO1 chromosome using pulsed-field gel electrophoresis. A-band genes mapped at 5.75 to 5.89 Mbp (SpeI fragment SpK; DpnI fragment DpF2), while genes involved with expression of B-band LPS mapped at 1.9 Mbp (SpeI fragments SpC, SpI and SpAI; DpnI fragment DpD) on the 5.9 Mbp chromosome. We also performed initial characterization of a gene involved with synthesis of A-band present on pFV3. We previously reported that recombinant plasmid pFV3 and subcloned plasmid pFV36 complemented A-band synthesis in rd7513, an A- mutant derived from A+ strain AK1401. pFV36 was mutagenized with transposon Tn1000 to reveal a one-kilobase region capable of complementing the expression of A-band in the A- strain rd7513. This region was subcloned as a 1.6 kb KpnI fragment into plasmid vector pAK1900 and the resulting clone named pFV39. Labelling of proteins encoded by pAK1900 and pFV39 in Escherichia coli maxicells revealed a single unique polypeptide of approximately 37 kDa expressed by pFV39. Supernatants from disrupted cells of rd7513(pFV39) and AK1401 converted 14C-labelled-guanosine diphospho (GDP)-D-mannose to GDP-rhamnose, while supernatants from rd7513 did not show synthesis of GDP-rhamnose. The data therefore suggest that conversion of GDP-D-mannose to GDP-rhamnose is required for synthesis of A-band LPS, and that a 37 kDa protein is involved in this conversion.

Chromosome Mapping↗
PubMed1992

Ultrastructural examination of the lipopolysaccharides of Pseudomonas aeruginosa strains and their isogenic rough mutants by freeze-substitution.

The majority of Pseudomonas aeruginosa strains synthesize two antigenically distinct types of lipopolysaccharide (LPS), namely, a serotype-specific B-band LPS and a common antigen A-band LPS. A-band LPS consists of uncharged poly-D-rhamnan, which does not bind uranyl ions and is difficult to stain for electron microscopy; the highly charged B-band LPS is more easily visualized. We selected two wild-type strains, PAO1 (serotype O5) and IATS O6 (serotype O6), generated isogenic mutants from them, and examined the distribution of LPS on the surface of these organisms by freeze-substitution and electron microscopy. On PAO1 cells, which express both A-band and B-band LPSs, a 31- to 36-nm-wide fringe extending perpendicularly from the outer membrane was observed. A fine fibrous material was also observed on the surface of serotype O6 (A+ B+) cells, although this material did not form a uniform layer. When the LPS-deficient mutants, strains AK1401 (A+ B-), AK 1012 (A- B-), rd7513 (A- B-), and R5 (an IATS O6-derived rough mutant; A- B-), were examined, no extraneous material was apparent above the bilayer. However, an asymmetrical staining pattern was observed on the outer leaflet of the outer membrane of each of these mutants, presumably conforming to the anionic charge distribution of the core region of the rough LPS. In all cases, expression of the LPS types was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. When optical densitometry on electron microscopy negatives was used to analyze the outer membrane staining profiles, subtle differences in the degrees of core deficiency among rough mutants were detectable. This is the first time an electron microscopy technique has preserved the infrastructure produced in the outer membrane by its constituent macromolecules. We conclude that freeze-substitution electron microscopy is effective in the visualization of LPS morphotypes.

Cell Membrane↗