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F Crawford

Publications and source records attributed to F Crawford.

At least 19 recordsLinked to original sources
PubMed2006

Elucidation of some Bax conformational changes through crystallization of an antibody-peptide complex.

The Bcl-2 family member Bax plays a critical role in apoptosis. In healthy resting cells, Bax resides in the cytoplasm and loosely attached to the mitochondrial membrane. Apoptotic stimuli induce Bax activation, which is characterized by translocation and multimerization on the mitochondrial membrane surface resulting in exposure of an amino terminal epitope recognized by the monoclonal antibody 6A7. To understand the structural changes that occur during Bax activation, we determined the crystal structure of a Bax peptide bound to the 6A7 Fab fragment to a resolution of 2.3 A. The structure reveals the conformation of the 6A7 peptide epitope on Bax in the activated form and elucidates the extensive structural changes that Bax must undergo during the conversion from its native to its activated conformation.

Antibodies↗
PubMed2005

Clinical trials in dental primary care: what research methods have been used to produce reliable evidence?

OBJECTIVE: To identify controlled clinical trials done exclusively in dental primary care and to classify the research according to design. Details of any procedures used to recruit general dental practitioners and any special organisational arrangements were also collected. DESIGN: A scoping literature review. SETTING: Dental primary care defined as general dental practice, community and school dental settings. PARTICIPANTS: Published randomised controlled trials using randomised or quasi randomised approaches and controlled clinical trials were considered for inclusion in the review. Reports were excluded if they did not describe either a randomised controlled trial or a controlled trial. Studies were excluded if the setting was not primary dental care or the intervention was for non-dental conditions. Conference abstracts without a full report and trials published in a language other than English were also excluded. MAIN OUTCOMES: Experimental and quasi-experimental designs, clinical areas and different kinds of strategies used to recruit dentists, any organisational arrangements made to support research in dental primary care. RESULTS: The search of the Cochrane Oral Health Group Controlled Trials Register found 174 articles. Forty-three randomised controlled trials met the inclusion criteria. Trials to evaluate the effects of interventions for types of anaesthesia, periodontal diseases, smoking cessation techniques, dental materials, organisational aspects of dental care, patient anxiety, post extraction healing rates, antibiotics were identified. All were done in general dental practice. Trials in school and community settings were also included. CONCLUSIONS: Practice-based research needs to be encouraged to provide dental primary care with relevant evidence upon which effective treatment can be based. This review shows there are few trials done in dental primary care to inform clinical practice, most of which have been reported since 1997. The range of trial designs shows that this method of evaluation can be used to evaluate dental primary care interventions and this is promising for those with an interest in improving dental patient outcomes. More research on how to recruit dentists into clinical trial research must be done.

Community Dentistry↗
PubMed2005

Randomised controlled trial of home based motivational interviewing by midwives to help pregnant smokers quit or cut down.

OBJECTIVE: To determine whether motivational interviewing--a behavioural therapy for addictions-provided at home by specially trained midwives helps pregnant smokers to quit. DESIGN: Randomised controlled non-blinded trial analysed by intention to treat. SETTING: Clinics attached to two maternity hospitals in Glasgow. PARTICIPANTS: 762/1684 pregnant women who were regular smokers at antenatal booking: 351 in intervention group and 411 in control group. INTERVENTIONS: All women received standard health promotion information. Women in the intervention group were offered motivational interviewing at home. All interviews were recorded. MAIN OUTCOME MEASURES: Self reported smoking cessation verified by plasma or salivary cotinine concentration. RESULTS: 17/351 (4.8%) women in the intervention group stopped smoking (according to self report and serum cotinine concentration < 13.7 ng/ml) compared with 19/411(4.6%) in the control group. Fifteen (4.2%) women in the intervention group cut down (self report and cotinine concentration less than half that at booking) compared with 26 (6.3%) in the control group. Fewer women in the intervention group reported smoking more (18 (5.1%) v 44 (10.7%); relative risk 0.48, 95% confidence interval 0.28 to 0.81). Birth weight did not differ significantly (mean 3078 g v 3048 g). CONCLUSION: Good quality motivational interviewing did not significantly increase smoking cessation among pregnant women.

Adult↗
PubMed2002

Confirmation of association between D10S583 and Alzheimer's disease in a case--control sample.

Several independent studies have reported that loci on chromosome 10 are associated/linked with Alzheimer's disease (AD), including a family-based study demonstrating an association between the marker D10S583 and AD. We have examined the D10S583 polymorphic marker and apolipoprotein E (APOE) gene in a case-control study. We observed the expected association of the APOE allele varepsilon4 with AD, and an inverse association between the D10S583 allele 209 and AD. These data support the original findings that suggest the presence of a candidate gene for AD in this region of chromosome 10. The nearby insulin degrading enzyme gene has been previously proposed as a candidate gene; however, a number of other putative candidate genes are also located in this region. The ongoing investigation of the genetic source of association and linkage in this region is clearly warranted.

Aged↗
PubMed2002

Oral treatments for fungal infections of the skin of the foot.

BACKGROUND: About 15% of the population have fungal infections of the feet (tinea pedis or athlete's foot). Whilst there are many clinical presentations of tinea pedis the most common are between the toes (interdigital) and on the soles, heels and sides of the foot (plantar) which is known as moccasin foot. Once acquired the infection can spread to other sites including the nails, which can be a source of reinfection. Oral therapy is usually used for chronic conditions or when topical treatment has failed. OBJECTIVES: To assess the effects and costs of oral treatments for fungal infections of the skin of the foot (tinea pedis). SEARCH STRATEGY: Randomised controlled trials were identified from MEDLINE, EMBASE and CINAHL from the beginning of these databases to January 2000. We also searched the Cochrane Controlled trials Register (Cochrane Library issue 1, 2000) the Science Citation Index, BIOSIS, CAB-Health, Health star and Economic databases. Bibliographies were searched, podiatry journals hand searched and the pharmaceutical industry and schools of podiatry contacted. SELECTION CRITERIA: Randomised controlled trials including participants who have a clinically diagnosed tinea pedis, confirmed by microscopy and growth of dermatophytes in culture. DATA COLLECTION AND ANALYSIS: Study selection was done by two independent reviewers. Methodological quality assessment and data collection was also assessed by two independent reviewers. MAIN RESULTS: Twelve trials, involving 700 participants, were included. The two trials comparing terbinafine and griseofulvin produced a pooled risk difference of 52% (95% confidence intervals 33% to 71%) in favour of terbinafine's ability to cure infection. No significant difference was detected between terbinafine and itraconazole; fluconazole and either itraconazole and ketoconazole; or between griseofulvin and ketoconazole, although the trials were generally small. Two trials showed that terbinafine and itraconazole were effective compared with placebo. Adverse effects were reported for all drugs, with gastrointestinal effects most commonly reported. REVIEWER'S CONCLUSIONS: The evidence suggests that terbinafine is more effective than griseofulvin and that terbinafine and itraconazole are more effective than no treatment.

Administration, Oral↗
PubMed2002

"Walk in to Work Out": a randomised controlled trial of a self help intervention to promote active commuting.

STUDY OBJECTIVE: To determine if a self help intervention, delivered via written interactive materials (the "Walk in to Work Out" pack), could increase active commuting behaviour (walking and cycling). DESIGN: Randomised controlled trial. The intervention group received the "Walk in to Work Out" pack, which contained written interactive materials based on the transtheoretical model of behaviour change, local information about distances and routes, and safety information. The control group received the pack six months later. Focus groups were also conducted after six months. SETTING: Three workplaces in the city of Glasgow, Scotland, UK. PARTICIPANTS: 295 employees who had been identified as thinking about, or doing some irregular, walking or cycling to work. MAIN RESULTS: The intervention group was almost twice as likely to increase walking to work as the control group at six months (odds ratio of 1.93, 95% confidence intervals 1.06 to 3.52). The intervention was not successful at increasing cycling. There were no distance travelled to work, gender, or age influences on the results. Twenty five per cent (95% confidence intervals 17% to 32%) of the intervention group, who received the pack at baseline, were regularly actively commuting at the 12 month follow up. CONCLUSION: The "Walk in to Work Out" pack was successful in increasing walking but not cycling. The environment for cycling must be improved before cycling will become a popular option.

Adult↗
PubMed2001

The microtubule associated protein Tau gene and Alzheimer's disease--an association study and meta-analysis.

Several studies have suggested an association between polymorphisms and an extended haplotype of the microtubule associated protein tau gene and Alzheimer's disease (AD) in synergy with apolipoprotein E (APOE) epsilon 4 status. However these findings have not been consistently replicated. We investigated the role of the tau haplotype in AD by conducting an association study as well as a meta-analysis of all the studies conducted to date. We examined six polymorphisms known to be in the extended tau haplotypes, one in exon 7 and five in and around exon 9 in 200 late onset AD and 189 control samples. All the polymorphisms examined fell into the recognised tau haplotypes. There was no statistical significant association with any of the polymorphisms and late onset AD. Stratification of data by APOE epsilon 4 status also produced no strongly significant association. The meta-analysis showed no significant differences between AD cases and controls, however stratification of data by APOE epsilon 4 status showed a small significant decrease in the H1 haplotype in AD before correction for multiple testing.

Aged↗
PubMed2001

TCR-induced transmembrane signaling by peptide/MHC class II via associated Ig-alpha/beta dimers.

Previous findings suggest that during cognate T cell-B cell interactions, major histocompatability complex (MHC) class II molecules transduce signals, leading to Src-family kinase activation, Ca2+ mobilization, and proliferation. Here, we show that antigen stimulation of resting B cells induces MHC class II molecules to associate with Immunoglobulin (Ig)-alpha/Ig-beta (CD79a/CD79b) heterodimers, which function as signal transducers upon MHC class II aggregation by the T cell receptor (TCR). The B cell receptor (BCR) and MHC class II/Ig-alpha/Ig-beta are distinct complexes, yet class II-associated Ig-alpha/beta appears to be derived from BCR. Hence, Ig-alpha/beta are used in a sequential fashion for transduction of antigen and cognate T cell help signals.

Animals↗
PubMed2001

A systematic review of oral treatments for fungal infections of the skin of the feet.

OBJECTIVE: To synthesize the evidence for the effectiveness and cost-effectiveness of oral treatments for fungal infections of the skin of the feet. DESIGN: Systematic review. INTERVENTIONS: Oral treatments for fungal infections. METHODS: Ten electronic databases, four journals and the bibliographies of all review papers identified were searched. The authors also wrote to international pharmaceutical companies and all podiatry schools in the UK. The studies selected were randomized trials of clinically diagnosed fungal skin infections of the foot that confirmed cure by culture and microscopy. Two reviewers independently selected trials and abstracted data using a structured tool including 12 recognized quality criteria. RESULTS: Of 26 trials identified, 12 met the inclusion criteria and evaluated five different treatments. Single placebo-controlled trials showed that terbinafine and itraconazole were both effective. Two trials showed that terbinafine cures 50% more patients than griseofulvin. Four trials compared terbinafine with itraconazole, one showed that terbinafine given for 2 weeks had a better cure rate than 2 weeks of itraconazole, but the other three showed that it was no better than 4 weeks of itraconazole. CONCLUSIONS: There is significant evidence that terbinafine is more effective than griseofulvin, though more costly. There is weak evidence that terbinafine may be more cost-effective than itraconazole. Firm recommendations about the choice between terbinafine and the azoles need further research.

Administration, Oral↗
PubMed2001

Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice.

Mounting evidence suggests that cholesterol may contribute to the pathogenesis of Alzheimer disease (AD). We examined whether cholesterol might be present in senile plaques, a hallmark neuropathological feature of AD. We employed 2 different fluorometric-staining techniques (filipin staining and an enzymatic technique) for the determination of cholesterol in brains of postmortem confirmed AD patients and in nondemented, age-matched histopathologically normal controls. AD patient brains showed abnormal accumulation of cholesterol in congophilic/birefringent dense cores of senile plaques that was essentially absent in histopathologically normal controls. To determine whether increased senile plaque-associated cholesterol occurred generally in all plaques or was restricted to a specific subset, quantitative analysis was performed. Data indicate abnormal accumulation of cholesterol in cores of mature plaques but not in diffuse or immature plaques. Additionally, transgenic mice that overexpress the "Swedish" amyloid precursor protein (Tg APP(SW), line 2576) exhibited a similar pattern of abnormal cholesterol accumulation in mature, congophilic amyloid plaques at 24 months of age that was absent in their control littermates or in 8-month-old Tg APP(SW) mice (an age prior to amyloid deposition). Taken together, our results imply a link between cholesterol and AD pathogenesis and suggest that cholesterol plays an important role in the formation and/or progression of senile plaques.

Aged↗
PubMed2000

T cell receptor (TCR)-mediated repertoire selection and loss of TCR vbeta diversity during the initiation of a CD4(+) T cell response in vivo.

We recently described a novel way to isolate populations of antigen-reactive CD4(+) T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS((R)) sorting by CD4(high) expression. Phenotypic, FACS((R)), functional, antibody inhibition, and major histocompatibility complex-peptide tetramer analyses, as well as T cell receptor Vbeta sequence analyses, of the antigen-specific CD4(high) T cell populations demonstrated that a diverse sperm whale myoglobin 110-121-reactive CD4(+) T cell repertoire was activated at the beginning (day 3 after immunization) of the immune response. Within 6 d of immunization, lower affinity clones were lost from the responding population, leaving an expanded population of oligoclonal, intermediate affinity (and residual high affinity) T cells. This T cell subset persisted for at least 4 wk after immunization and dominated the secondary immune response. These data provide evidence that CD4(+) T cell repertoire selection occurs early in the immune response in vivo and suggest that persistence and expansion of a population of oligoclonal, intermediate affinity T cells is involved in CD4(+) T cell memory.

Animals↗
PubMed2000

CD45 opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase.

Reactive microglia have been suggested to play a role in the Alzheimer's disease (AD) process, and previous studies have shown that expression of CD45, a membrane-bound protein-tyrosine phosphatase (PTP), is elevated in microglia in AD brain compared with controls. To investigate the possible role of CD45 in microglial responsiveness to beta-amyloid (Abeta) peptides, we first co-treated primary cultured microglia with a tyrosine phosphatase inhibitor [potassium bisperoxo (1,10-phenanthroline) oxovanadate (phen), 5 micrometer] and freshly solubilized Abeta peptides (1000 nm). Data show synergistic induction of microglial activation as evidenced by tumor necrosis factor alpha (TNF-alpha) production and nitric oxide (NO) release, both of which we show to be dependent on activation of p44/42 mitogen-activated protein kinase (MAPK). Furthermore, co-treatment with phen and Abeta peptides results in microglia-induced neuronal cell injury. Stimulation of microglial CD45 by anti-CD45 antibody markedly inhibits these effects via inhibition of p44/42 MAPK, suggesting that CD45 is a negative regulator of microglial activation. Accordingly, primary cultured microglia from CD45-deficient mice demonstrate hyper-responsiveness to Abeta, as evidenced by TNF-alpha release, NO production, and neuronal injury after stimulation with Abeta peptides. As a validation of these findings in vivo, brains from a transgenic mouse model of AD [transgenic Swedish APP-overexpressing (Tg APP(sw)) mice] deficient for CD45 demonstrate markedly increased production of TNF-alpha compared with Tg APP(sw) mice. Taken together, these results suggest that therapeutic agents that stimulate the CD45 PTP signaling pathway may be effective in suppressing microglial activation associated with AD.

Alzheimer Disease↗
PubMed2000

Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers.

We characterized antigen-specific CD4(+) T cells in six patients with treatment-resistant Lyme arthritis, using an HLA-DRB1*0401 major histocompatibility complex (MHC) class II tetramer covalently loaded with OspA(164-175), an immunodominant epitope of Borrelia burgdorferi. Direct analysis of OspA-tetramer binding CD4(+) cells in patients expressing the HLA-DRB1*0401 allele revealed frequencies of between <0.005 and 0.1% in peripheral blood (n = 6), and between <0.005 and 3.1% in synovial fluid (n = 3). OspA-tetramer(+)CD4(+) cells were directly cloned at 1 cell per well and expanded by mitogen and IL-2 on allogeneic feeder cells. As measured by [(3)H]thymidine incorporation, 95% of 168 T cell clones from synovial fluid binding the OspA-tetramer were antigen-reactive. Clones generated from peripheral blood revealed a different pattern of responsiveness when compared with clones generated from synovial fluid, as measured by proliferation, IFN-gamma, and IL-13 secretion. These clones, selected on the basis of their peptide binding, also responded to whole protein, but with a different cytokine profile. Our studies demonstrate that MHC class II tetramers can be used in humans to directly identify, isolate, and characterize antigen-reactive T cells from an inflammatory compartment.

Antigens, Surface↗
PubMed2000

Gender-specific association of the angiotensin converting enzyme gene with Alzheimer's disease.

Epidemiological studies have demonstrated that risk factors for vascular disease are also risk factors for Alzheimer's disease (AD). The gene for the angiotensin converting enzyme (ACE) has recently been reported to be associated with risk for AD. We have investigated the possibility of such an association in 98 clinic-based and 73 community-based AD cases versus 175 community-based controls and find a gender-specific association of ACE genotype with AD in the female clinic population. These data suggest that gender may interact with genetic factors to influence risk for AD. Gender-specific risk for AD has been previously reported, and a biological rationale for involvement of ACE in the AD process is supported by studies exploring the relationship between AD and vascular risk factors such as hypertension. However, the results may also be a consequence of the known anomalies that arise in genetic association studies as a consequence of sample selection.

Alzheimer Disease↗
PubMed2000

Use of soluble peptide-DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis.

Considerable evidence indicates that CD4(+) T cells are important in the pathogenesis of rheumatoid arthritis (RA), but the antigens recognized by these T cells in the joints of patients remain unclear. Previous studies have suggested that type II collagen (CII) and human cartilage gp39 (HCgp39) are among the most likely synovial antigens to be involved in T cell stimulation in RA. Furthermore, experiments have defined dominant peptide determinants of these antigens when presented by HLA-DR4, the most important RA-associated HLA type. We used fluorescent, soluble peptide-DR4 complexes (tetramers) to detect synovial CD4(+) T cells reactive with CII and HCgp39 in DR4(+) patients. The CII-DR4 complex bound in a specific manner to CII peptide-reactive T cell hybridomas, but did not stain a detectable fraction of synovial CD4(+) cells. A background percentage of positive cells (<0.2%) was not greater in DR4 (DRB1*0401) patients compared with those without this disease-associated allele. Similar results were obtained with the gp39-DR4 complex for nearly all RA patients. In a small subset of DR4(+) patients, however, the percentage of synovial CD4(+) cells binding this complex was above background and could not be attributed to nonspecific binding. These studies demonstrate the potential for peptide-MHC class II tetramers to be used to track antigen-specific T cells in human autoimmune diseases. Together, the results also suggest that the major oligoclonal CD4(+) T cell expansions present in RA joints are not specific for the dominant CII and HCgp39 determinants.

Adult↗
PubMed2000

Interventions for treating plantar heel pain.

BACKGROUND: Ten percent of people may experience pain under the heel (plantar heel pain) at some time. Injections, insoles, heel pads, strapping and surgery have been common forms of treatment offered. The absolute and relative effectiveness of these interventions are poorly understood. OBJECTIVES: The objective of this review was to identify and evaluate the evidence for effectiveness of treatment in treating plantar heel pain. SEARCH STRATEGY: MEDLINE (from 1966 to December 1997), EMBASE and the Cochrane Library were searched. Three podiatry journals (The Foot, The Chiropodist (later The Journal of British Podiatric Medicine), and The British Journal of Podiatric Medicine) were handsearched. We contacted known investigators in the field to identify unpublished data or research in progress. Non English language reports were excluded from the review. SELECTION CRITERIA: Randomised and quasi randomised trials of interventions for plantar heel pain in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated studies for inclusion, extracted data and assessed study quality. Additional information was obtained by direct contact with investigators. No poolable data were identified. Where measures of variance were available we have calculated the weighted mean differences based on visual analogue scale (VAS) scores. MAIN RESULTS: Eleven randomised trials involving 465 participants were included. Study quality was generally poor, and pooling of data was not possible. All studies measured a reduction in heel pain as the primary outcome. Seven trials evaluated interventions against placebo/dummy or no treatment. There was limited evidence for the effectiveness of topical corticosteroid, administered by iontophoresis in reducing pain. There was no evidence for the effectiveness of injected corticosteroid. There was limited evidence for the effectiveness of low energy extracorporeal shock wave therapy in reducing night pain, resting pain and pressure pain in the short term (12 weeks). In individuals with chronic pain (longer than six months), there was limited evidence for the effectiveness of dorsiflexion night splints in reducing pain. There was no evidence to support the effectiveness of therapeutic ultrasound, low-intensity laser therapy, exposure to an electron generating device or insoles with magnetic foil. No randomised trials evaluating orthotic devices, surgery, or radiotherapy against a control population were identified. There was limited evidence for the superiority of corticosteroid injections over orthotic devices. REVIEWER'S CONCLUSIONS: Although there is limited evidence for the effectiveness of local corticosteroid therapy, the effectiveness of other frequently employed treatments in altering the clinical course of plantar heel pain has not been established in comparative studies. Well designed and conducted randomised studies are required.

Adrenal Cortex Hormones↗
PubMed2000

Topical treatments for fungal infections of the skin and nails of the foot.

OBJECTIVES: The objective of this review is to identify and evaluate the evidence of efficacy for topical treatments for fungal infections of the skin and nails of the human foot. To establish the effectiveness of topical treatments in achieving a cured condition and in preventing recurrence SEARCH STRATEGY: Randomised controlled trials were identified from the MEDLINE, EMBASE and CINHAL databases, from the beginning of these databases to December 1997. Also we screened the Cochrane Controlled Trials Register, the Science Citation Index BIOSIS, CAB - Health, Healthstar and Economic databases. References and unpublished studies were searched, podiatry journals handsearched and the pharmaceutical industry contacted. SELECTION CRITERIA: Only randomised controlled trials (RCTs) using participants who have mycologically diagnosed fungal infections of the skin and nails of the human foot are included in the analysis. DATA COLLECTION AND ANALYSIS: Two reviewers independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool which assessed 12 quality criteria. MAIN RESULTS: Of 126 trials identified in 121 papers, 72 met the inclusion criteria. Placebo-controlled trials yielded the following pooled relative risks of failure to cure (RRFC) for skin infections: allylamines 0.30 (95% confidence interval 0.23 to 0.37); azoles 0.53 (0.42 to 0.68); undecenoic acid 0.28 (0.11 to 0.74); tolnaftate 0.46 (0.17 to 1.22). Though meta-analysis of 11 trials comparing allylamines and azoles showed an RRFC of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidence of language bias. Seven English language reports favoured allylamines (RRFC = 0.79; 0.68 to 0.93) but four foreign language reports showed no difference between the two drugs (RRFC = 1.00; 0.90 to 1.12). The two trials of nail infections did not provide any evidence of benefit for topical treatments compared with placebo. REVIEWER'S CONCLUSIONS CONCLUSIONS: In placebo-controlled trials allylamines, azoles and undecenoic acid were efficacious. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive. The most cost-effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails.

Administration, Topical↗