Another sniffer dog for the clinic?
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
H Williams
Publications and source records attributed to H Williams.
Use of fluorescent Ca2+ dyes with green fluorescent protein and its variants: problems and solutions.
We have studied the degree to which fluorescent Ca(2+) indicator dyes, and green fluorescent protein and its variants, can be used together. We find that the most commonly used fluorescent protein, enhanced green fluorescent protein (EGFP), seriously contaminates fura 2 signals. We suggest two alternative combinations for which there is no detectable contamination of the Ca(2+) indicator signal by the fluorescent protein. Blue fluorescent protein can be used with the Ca(2+) indicator Fura Red; EGFP can be used with the Ca(2+) indicator X-Rhod 1. The use of these combinations will permit the accurate measurement of Ca(2+) signals in cells transfected with fluorescent proteins.
Animals↗
Localization of the gene for distal hereditary motor neuronopathy VII (dHMN-VII) to chromosome 2q14.
Distal hereditary motor neuronopathy type VII (dHMN-VII) is an autosomal dominant disorder characterized by distal muscular atrophy and vocal cord paralysis. We performed a genomewide linkage search in a large Welsh pedigree with dHMN-VII and established linkage to chromosome 2q14. Analyses of a second family with dHMN-VII confirmed the location of the gene and provided evidence for a founder mutation segregating in both pedigrees. The maximum three-point LOD score in the combined pedigree was 7.49 at D2S274. Expansion of a polyalanine tract in Engrailed-1, a transcription factor strongly expressed in the spinal cord, was excluded as the cause of dHMN-VII.
Chromosome Mapping↗
Association of tumour necrosis factor alpha and interleukin 6 levels with cytomegalovirus DNA detection and disease after renal transplantation.
Cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are thought to be important in the pathogenesis of post-transplant cytomegalovirus (CMV) disease. CMV infection increases the production of TNF-alpha and IL-6. Conversely, TNF-alpha switches on the replication of CMV. To study the association of these two cytokines with CMV activity and disease, TNF-alpha and IL-6 levels were assayed in plasma samples taken serially from three groups of renal transplant recipients. Group A (n = 12) had CMV disease and syndrome; Group B (n = 11) had detectable CMV DNA in plasma or peripheral blood leucocytes without disease, i.e., presumed asymptomatic CMV infection, and Group C (n = 11) had no detectable CMV DNA nor disease. The median peak TNF-alpha levels in patients with CMV disease (Group A) were significantly higher than that in Group B or Group C (P < 0.02) whereas the median peak IL-6 levels in group C patients were significantly lower than that in group A (P < 0.04) or group B (P < 0.03). A TNF-alpha level of above 100 pg/ml was significantly associated with CMV disease and high plasma CMV load (> 10,000 copies/ml). IL-6 levels above 15 pg/ml were significantly associated with CMV DNA detection, but not with CMV disease or elevated CMV load. High levels of TNF-alpha or IL-6 were not associated with CMV donor/recipient serostatus, HHV-6 or HHV-7 DNA detection, immunosuppressive regimen or rejection episodes. The role of TNF-alpha in the pathogenesis of CMV disease deserves further investigation.
Adult↗
Glutamate-loading stimulates metabolic flux and improves cell recovery following chemical hypoxia in isolated cardiomyocytes.
The amino acid glutamate is used in cardioplegic solutions, yet evidence is conflicting as to whether or not exogenous glutamate is indeed cardioprotective. This controversy may be because increasing extracellular glutamate does not necessarily lead to an increase in intracellular glutamate. In this study we aimed to determine whether isolation of myocytes in the presence of glutamate resulted in glutamate-loading of the cells, and, if so, whether such loading protected myocytes from simulated (chemical) hypoxia. Single ventricular myocytes were isolated from rat hearts in the presence and absence of 6.4 mM glutamate. Levels of glutamate and ATP were determined using HPLC, and NADH/NAD(+) was determined from cell autofluorescence. Chemical hypoxia was induced by superfusion with a solution containing 2.5 mM cyanide and no glucose. Intracellular [Ca(2+)] was measured by loading cells with indo-1, and cell length was measured using an edge-tracking device. Isolation of myocytes in the presence of glutamate resulted in increased intracellular glutamate levels compared with cells isolated in the absence of glutamate, 1324+/-108 v 948+/-124 pmol/mg protein, respectively (P<0.05). Cells loaded with glutamate showed increased NADH/NAD(+), (0.384+/-0.032 v 0.281+/-0.029, P<0.05) and greater ATP levels (36.031+/-1.633 nmol/mg protein v 19.279+/-3.327 nmol/mg protein, P<0.005) compared to control cells. When subjected to chemical hypoxia, cells underwent rigor-contracture at various timepoints, and were then reperfused following 5 min in rigor. Cells loaded with glutamate showed better recovery of diastolic [Ca(2+)], Ca(2+) transient amplitude, and improved contractile function compared with cells isolated in absence of glutamate. This study demonstrates an efficient method for loading myocytes with glutamate during cell isolation, and myocytes loaded with glutamate showed increased metabolic flux, as indexed by a higher NADH/NAD(+) and ATP content. Myocytes also exhibited better recovery from chemical hypoxia in terms of both Ca(2+) handling and cell contraction.
Adenosine Triphosphate↗
Characteristics of L-aspartate transport and expression of EAAC-1 in sarcolemmal vesicles and isolated cells from rat heart.
OBJECTIVE: L-Aspartate is an important intermediary metabolite in the heart and has also been implicated in myocardial protection, but little is known about its transport across the cardiac sarcolemma. In this study we have tested the hypothesis that the high affinity sodium-dependent aspartate transporter, EAAC-1 is expressed in heart and have also characterised aspartate transport into the myocardium. METHODS: Characteristics of L-[14C]aspartate uptake into rat heart were investigated using sarcolemmal vesicles and isolated myocytes. The expression of EAAC-1 in the two preparations was also investigated by western blotting. RESULTS: The K(m) and V(max) of L-aspartate uptake was 9.78+/-0.7 microM and 1.17+/-0.27 pmol/mg/s in vesicles compared to 6.53+/-1.24 microM and 13.65+/-1.0 pmol/microl/s in cells. In vesicles, L-aspartate uptake was dependent on external sodium and internal potassium, and was rheogenic. In cells, L-aspartate uptake was also dependent on external sodium. Addition of unlabelled L- and D-aspartate and L-glutamate significantly inhibited L-[14C]aspartate uptake in both preparations but D-glutamate had no effect. An antibody to the aspartate transporter, EAAC-1 recognised a protein of appropriate size in both vesicles and cells. CONCLUSIONS: L-aspartate uptake in heart is mediated by a high affinity sodium-dependent transporter. This is accompanied by the expression in heart of EAAC-1. The physiological significance of this transporter with respect to aspartate utilisation in the heart is discussed.
Amino Acid Transport System X-AG↗
Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls.
A genetic association between NOTCH4 and schizophrenia has previously been proposed. Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observation. These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia.
Case-Control Studies↗
Mutation screening of the KCNN3 gene reveals a rare frameshift mutation.
Explore the source record for details and available documents.
DNA Mutational Analysis↗
Psychosocial factors and adherence to treatment advice in childhood atopic dermatitis.
Poor adherence to maintenance treatment for atopic dermatitis and anxiety about using topical steroids are common features seen among children with atopic dermatitis and their mothers. No systematic study exploring factors associated with adherence to treatment advice on atopic dermatitis has been carried out to date. This study seeks to generate hypotheses regarding the relationship between a range of psychosocial factors and adherence to treatment advice on atopic dermatitis. An anonymous self-completed questionnaire containing adherence items, psychosocial items, some demographic items, and attitudes to steroid use was given to 258 mothers of atopic dermatitis follow-up patients who attended the National Children's Hospital, Tokyo. Responses from 205 families (80%) with complete data were then analyzed to explore the correlation between each factor and to build a structure equation model. The strongest predictor of adherence to skin-care treatment was a good doctor-patient (mother) relationship, followed by the severity of the disease as perceived by the mother. Surprisingly, the mother's anxiety about using topical steroids had no significant influence on reported use of topical steroids nor on adherence to skin-care treatment. This may have been overcome by the well-established doctor-patient (mother) relationship. Maternal personality, husband's cooperation, and social support were indirectly correlated with adherence via the doctor-patient relationship. Maternal self-efficacy of treatment was strengthened by good doctor-patient (mother) relationship.
Adolescent↗
Jet ventilation via a Univent tube for sleeve pneumonectomy.
A 51-year-old man presented with a right upper lobe adenocarcinoma with carinal extension. He underwent a right sleeve pneumonectomy, which involved a carinal resection with anastomosis between the trachea and left main bronchus. This report describes the successful use of jet ventilation, administered via the lumen of the bronchial blocker of a Univent tube. During 15 min of carinal resection, oxygenation of his left lung was maintained with the bronchial blocker bridging the airway discontinuity.
Adenocarcinoma↗
Dowling Oration 2001. Evidence-based dermatology--a bridge too far?
Explore the source record for details and available documents.
Dermatology↗
Disease definition and measures of disease frequency.
Explore the source record for details and available documents.
Dermatitis, Atopic↗
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↗
In vitro and in vivo (SCID mice) effects of phytosterols on the growth and dissemination of human prostate cancer PC-3 cells.
The dietary effect of phytosterols (PS) versus cholesterol on the growth and metastasis of the PC-3 human prostate cancer cells in SCID mice was studied. Also, their direct effect on the growth and migration of these cells in vitro was analysed. In the in vivo experiment, SCID mice were fed a diet containing 2% of either PS mixture or cholesterol plus 0.2% cholic acid and implanted with 2 x 10(6) tumour cells per mouse. Tumour growth was monitored for 8 weeks post inoculation. Animals fed the PS diet had tumours 40-43% smaller than those fed the cholesterol diet. Furthermore, the number of mice with lymph node and lung metastasis was almost one-half that of the cholesterol-fed group. In the in vitro studies, both beta-sitosterol and campesterol inhibited the growth of PC-3 cells by 70% and 14%, respectively, while cholesterol supplementation increased the growth by 18% when compared with controls. PS inhibited the invasion of PC-3 cells into Matrigel-coated membranes by 78% while cholesterol increased it by 43% as compared with the cells in the control media. Migration of tumour cells through 8 microm pore membranes was reduced by 60-93% when the PC-3 cells were in PS media, as compared with a 67% increase after cholesterol supplementation. PS supplementation reduced the binding of PC-3 cells to laminin by 15-38% and fibronectin by 23% while cholesterol increased binding to type IV collagen by 36%. It was concluded that PS indirectly (in vivo as a dietary supplement) and directly (in tissue culture media) inhibited the growth and metastasis of PC-3 cells. beta-Sitosterol was more effective than campesterol in offering this protection in most of the parameters studied.
Animals↗
Clinical standards for specialist community rehabilitation services in the UK.
OBJECTIVE: To develop a set of clinical standards for specialist community rehabilitation services in the UK and to undertake a preliminary survey of consultants who provide those services. DESIGN AND METHODS: The proposed set of standards was adapted from the previously published standards for inpatient services, by a working party of the British Society for Rehabilitation Medicine (BSRM). Consensus was then achieved by an iterative consultation process in five rounds. A postal survey was conducted on behalf of the BSRM amongst its consultant members providing community rehabilitation services in the UK, who were asked to assess their services in relation to these standards, and to comment on the standards themselves, their usefulness and applicability. RESULTS: Fifty consultants who ran specialist community rehabilitation services agreed to participate, of whom 29 (58%) actually responded. Overall, the standards appeared to be acceptable to most, and mainly struck the right level, being attained by the majority of services. Twenty-five (89%) felt the standards were helpful and 26 (93%) felt that they covered the main aspects of specialist community rehabilitation services: 23 (79%) found them at least partially applicable to their own service. CONCLUSIONS: Proposed clinical standards have been developed for specialist community rehabilitation services in the UK. It is likely that they will require further refinement with time, and modification is required to adapt them to different subspecialities and settings.
Community Health Services↗
Phytosterols reduce in vitro metastatic ability of MDA-MB-231 human breast cancer cells.
Metastasis plays a major role in morbidity and mortality from breast cancer. Differences in the incidence and mortality of breast cancer between societies suggest that environmental factors such as diet may play a role in the disease. Previous work from this laboratory suggests that dietary phytosterols (PS) may offer protection from breast cancer by inhibiting growth of the tumor and its metastasis in severe combined immunodeficient mice. Because metastasis is a multistep process, the aim of the present study was to investigate the effect of PS on some steps of the metastatic process: tumor cell invasion, adhesion, and migration. In addition, cell growth and cell cycle progression were evaluated. MDA-MB-231 cells were supplemented with cholesterol, beta-sitosterol, and campesterol. Cells were treated for 3 days with 16 microM sterol that was loaded on 5 mM cyclodextrin. beta-Sitosterol inhibited tumor cell invasion through Matrigel and adhesion of cells to plates coated with collagen I, collagen IV, fibronectin, and laminin compared with cholesterol treatments and controls. Cholesterol treatment resulted in increased adhesion to laminin and collagen IV, two basement membrane (BM) components that are implicated in signaling tumor cell invasion in this cell line. Only cholesterol treatment increased cellular migration. beta-Sitosterol inhibited cell growth by 70% compared with controls and induced cell cycle arrest at the G2/M phase. It is concluded that, among PS, beta-sitosterol may offer protection from breast cancer metastasis by inhibiting cell invasion of the BM, which may be mediated by its ability to limit the adhesive interaction of the tumor cell and the BM.
Breast Neoplasms↗
Choreography of song, dance and beak movements in the zebra finch (Taeniopygia guttata).
As do many songbirds, zebra finches sing their learned songs while performing a courtship display that includes movements of the body, head and beak. The coordination of these display components was assessed by analyzing video recordings of courting males. All birds changed beak aperture frequently within a single song, and each individual's pattern of beak movements was consistent from song to song. Birds that copied their father's songs reproduced many of the changes in beak aperture associated with particular syllables. The acoustic consequences of opening the beak were increases in amplitude and peak frequency, but not in fundamental frequency, of song syllables. The change in peak frequency is consistent with the hypothesis that an open beak results in a shortened vocal tract and thus a higher resonance frequency. Dance movements (hops and changes in body or head position) were less frequent, and the distribution of dance movements within the song was not as strongly patterned as were changes in beak aperture, nor were the peaks in the distribution as strongly marked. However, the correlation between the positioning of dance movements within fathers' and sons' songs was striking, suggesting that the choreography of dance patterns is transmitted from tutor to pupil together with the song.
Animals↗
Thermal capsular shrinkage for shoulder instability. Mid-term longitudinal outcome study.
We present the short- and medium-term clinical results of thermal shrinkage in selected groups of patients with multidirectional or capsular stretch-type instability. We treated 56 patients (61 shoulders) by laser-assisted capsular shrinkage (LACS) and 34 patients (38 shoulders) by radiofrequency (RF) capsular shrinkage. The two groups were followed for mean periods of 40 months and 23 months, respectively. In the LACS group the mean Walch-Duplay score improved to 90 points 18 months after the operation, but then declined to a plateau of about 80 points; 59% of patients considered their shoulders to be 'much better' or 'better' but there was a failure rate of 36.1%. For the RF group the mean Walch-Duplay and Constant scores were 80 points at the various follow-up times; 76.3% of patients considered their shoulder to be 'much better' or 'better'. RF failed in nine shoulders (23.7%). These results match some clinical series of patients with multidirectional instability, undergoing open inferior capsular shift, with a similar rate of failure. We believe that the minimal morbidity involved makes thermal shrinkage a viable alternative to open capsular shift in this difficult group of patients.
Adolescent↗