Search PubMed⌕ Search

Biomedical subjects

G Davies

Publications and source records attributed to G Davies.

At least 55 records · Page 3Linked to original sources

Distribution and expression of CD44 isoforms and Ezrin during prostate cancer-endothelium interaction.

CD44 is a multifunctional cell surface adhesion molecule that has been implicated in tumour cell invasion and metastasis. Many cancer cell types as well as their metastases express high levels of CD44. Furthermore, the expression of certain CD44 variants has been linked with metastasis and tumour progression. It is known that ezrin, a member of the ERM family of proteins, can bind to CD44 and thus raises the possibility that it is involved in cell migration and metastasis. Therefore we examined the expression and distribution of CD44, its co-localisation and translocation with ezrin in prostate cancer cell lines as they interact with endothelial cells. Experimental results indicate prostate cancer cells express multiple CD44 isoforms that co-localise with ezrin in DU-145 and PC-3 prostate cancer cells. Treatment with hepatocyte growth factor (HGF/SF) resulted in up-regulation of CD44 and its co-translocation with ezrin during tumour-endothelial cell interactions. In addition, tumour cell adhesion to endothelial cells and their invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. It is concluded that CD44 and ezrin interact in endothelial cells and that they co-localise in the areas of tumour-endothelial contact. The CD44/ezrin complex plays a pivotal role in the capture and invasion of endothelial cells by prostate cancer cells.

Cytoskeletal Proteins↗

The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant.

Hepatocyte growth factor/scatter factor (HGF/SF) plays a crucial role in cancer cell migration, matrix adhesion, invasion, and angiogenesis, via the phosphorylation of the c-met tyrosine kinase. This study examined the ability of NK4, a recently discovered HGF/SF variant, to inhibit the influence of HGF/SF on cell-matrix interaction, paxillin phosphorylation, and invasion of prostate cancer cells. HGF/SF was shown to dramatically enhance tumour cell motility, invasion, cell-matrix adhesion, together with an increase in the degree of paxillin phosphorylation and formation of focal adhesion complexes. However, these HGF/SF-induced effects were suppressed by the presence of NK4. NK4 effectively inhibited the degree of HGF/SF-induced paxillin phosphorylation and matrix adhesion. As a consequence, the matrix invasion of these prostate cancer cells was also suppressed by NK4. In conclusion, this study shows that these HGF/SF-enhanced events, which are critical steps in metastasis, can be inhibited through the addition of NK4, thus warranting further in vivo studies on the implication of NK4 as a potential antimetastasis agent in prostate cancer.

Antineoplastic Agents↗

Sex ratio of nuclear industry employees' children.

Does preconceptional exposure to ionising radiation before conception affect the health of offspring? Some studies have suggested that radiation exposure might influence the sex ratio at birth, potentially indicating genetic damage. We examined the sex ratio of over 46000 children born to UK nuclear industry workers, using information on exposure from the workers' individual employment and dosimetry records. We found no statistically significant alterations of the sex ratio, and no evidence that exposure to low-level ionising radiation at work influences the sex ratio of children conceived after exposure.

Air Pollution, Radioactive↗

The design and evaluation of a simulated-patient teaching programme to develop the consultation skills of undergraduate pharmacy students.

OBJECTIVES: This study aimed to identify the key skills and knowledge required for the delivery of an ideal patient consultation in order to develop a training programme (using simulated-patients) to teach consultation skills to undergraduate pharmacy students. METHODS: Participants included all third year undergraduate Pharmacy students (MPharm, level III) at the School of Pharmacy & Biomolecular Sciences, University of Brighton (from October 1999 to March 2000). Working in groups of 12, students participated in two 4 hour seminars. A structured questionnaire was designed to assess students' perceptions of the difficulty of conducting a consultation and their confidence in delivering a structured consultation. MAIN OUTCOME MEASURES: Questionnaires were administered before and after delivery of the teaching programme to assess changes in students' confidence and ability to consult with patients. RESULTS: Twelve volunteers satisfied the criteria set to serve as simulated patients and then received appropriate training. Six scenarios were developed which focused on the key skills and knowledge identified from the adherence and consultation skills literature. A total of 91 students participated in the programme (mean age = 23 years, SD = 4.5). Following participation in the programme students' perceived 'confidence' for conducting an effective consultation significantly increased (t = -5.9, p < 0.01) while a statistically significant decrease was seen in students' perceived level of 'difficulty' when conducting a consultation (t = 4.0, p < 0.01). CONCLUSION: This study has shown that the use of a structured teaching programme improves students' perceptions of their ability and confidence in conducting an effective consultation. Providing skills training around the consultation process, using simulated patients, provides pharmacists with a good framework around which to practice pharmaceutical care.

Adult↗

Gastric antral vascular ectasia in systemic sclerosis: complete resolution with methylprednisolone and cyclophosphamide.

A case of severe, transfusion dependent anaemia in a 72 year old woman, which on endoscopy was found to be due to gastric antral vascular ectasia (GAVE), is reported. Repeated endoscopic sclerotherapy was ineffective. She subsequently developed Raynaud's phenomenon and on further investigation was found to have classical systemic sclerosis with lung involvement. Treatment with pulses of intravenous methylprednisolone and cyclophosphamide resulted in significant improvement in her pulmonary function tests and skin score. Coincidentally, her haemoglobin stabilised and further endoscopic examinations were normal. This is the first report of cyclophosphamide and methylprednisolone leading to complete and sustained resolution of GAVE in association with systemic sclerosis.

Aged↗

Primary infertility in nuclear industry employees: report from the nuclear industry family study.

OBJECTIVE: To determine whether men and women who are occupationally exposed to ionising radiation are at increased risk of primary infertility. METHODS: A cross sectional analysis of reproductive outcome was reported in an occupational cohort of nuclear industry workers from the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels in the United Kingdom. Data on employment and radiation monitoring supplied by employers were linked to data obtained from self administered questionnaires sent to all current employees and a sample of past workers. A total of 5353 men and 603 women aged 40 years or more at the time of survey whose first pregnancy, or attempt at pregnancy, had occurred after first employment in the nuclear industry were recruited to the study. Primary infertility was defined as consultation with a doctor about the failure to achieve at least one viable (24 weeks gestational age or more) pregnancy. RESULTS: 2.6% Of men and 3.7% of women reported primary infertility. For men, this proportion did not differ by amount of radiation monitored or by dose received. The prevalence of infertility was higher among monitored women than non-monitored women, but not significantly so and the numbers were too small to draw any firm conclusions. CONCLUSIONS: No support was found for a hypothesis linking exposure to low level ionising radiation among men with primary infertility. There was weak evidence of an association in women, but the relatively few monitored women prevented detailed examination of these data.

Adult↗

HGF/SF modifies the interaction between its receptor c-Met, and the E-cadherin/catenin complex in prostate cancer cells.

The effect of HGF/SF on the association between the E-cadherin/catenin complex and the tyrosine kinase receptor c-Met, was examined in prostate cancer cells LNCap FGC. Stimulation by HGF/SF showed E-cadherin and beta-catenin to be co-precipitated and located at areas of cell-cell contact with the HGF/SF receptor c-Met, as detected by immunoprecipitation and immunofluorescence respectively. Furthermore, continued exposure to this motogen increased the level of co-precipitations between the E-cadherin/catenin complex with c-Met, and also increased tyrosine phosphorylation of c-Met. In contrast, continued stimulation by HGF/SF decreased the level of co-localised peripheral staining and increased the level of cytoplasmic staining. In conclusion, the association between the E-cadherin/catenin complex with the HGF/SF receptor c-Met, may influence or regulate intercellular adhesion in prostate cancer following stimulation by HGF/SF.

Cadherins↗

The interaction between beta-catenin, GSK3beta and APC after motogen induced cell-cell dissociation, and their involvement in signal transduction pathways in prostate cancer.

The effect of HGF/SF was examined on the interactions between APC, GSK3beta and beta-catenin in prostate cancer cells LNCapFGC (E-cadherin positive) and PC-3 (E-cadherin negative). Using immunoprecipitation, APC was found to be co-precipitated with either GSK3beta or beta-catenin in both cell lines. Stimulation with HGF/SF showed no change in the co-precipitation status of these protein molecules. In contrast, co-precipitation between GSK3beta and beta-catenin was only observed in LNCapFGC cells, and increased upon continued exposure to the motogen HGF/SF. Furthermore, using immunofluorescence, stimulation with HGF/SF was found to increase the level of co-localised cytoplasmic staining between beta-catenin and GSK3beta, in prostate cancer cells. RT-PCR revealed that there were no mutations within the binding regions between beta-catenin and GSK3beta. It is concluded, that uncomplexed cytoplasmic pools of beta-catenin associate more readily with the Axin complex in the absence of E-cadherin. Whereas, in the presence of E-cadherin, beta-catenin is stabilised by forming tight cell-cell contacts which may influence the invasive potential of cancer cells.

Adenomatous Polyposis Coli Protein↗

Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell-cell dissociation and in vitro invasion.

PURPOSE: The current study examined the effects of hepatocyte growth factor/scatter factor (HGF/SF) on cell-cell dissociation, invasion, and its association with the mediated release of matrix metalloproteinase-7 (Matrilysin) on the extracellular cleavage of E-cadherin in prostate cancer cells. EXPERIMENTAL DESIGN: The effects of HGF/SF on cell-cell dissociation, in vitro invasion, and on the expression of E-cadherin at both protein and mRNA levels were assessed in cells whose expression of Matrilysin was altered by treatment with antisense oligonucleotide. RESULTS: Incubation with HGF/SF mediated the release of active Matrilysin (M(r) 19,000), resulting in extracellular cleavage of E-cadherin from prostate cancer cells. This resultant soluble M(r) 80,000 fragment of E-cadherin was subsequently recognized upon immunoprobing with an anti-E-cadherin antibody. Both recombinant human Matrilysin (rh-Matrilysin) and/or HGF/SF increased the level of soluble E-cadherin and decreased the level of full-length (M(r) 120,000) E-cadherin as detected by Western blotting. The effects of rh-Matrilysin and HGF/SF were inhibited by an antisense oligonucleotide specifically directed toward human Matrilysin. In addition, stimulation with either rh-Matrilysin or HGF/SF resulted in disruption to the E-cadherin/beta-catenin complex, as shown by a significant increase (P < 0.05) in both cell scattering and invasion index. CONCLUSIONS: Treatment with HGF/SF induced Matrilysin-mediated cleavage to the extracellular domain of E-cadherin, resulting in its dissociation from the cadherin/catenin complex. This provides a new mechanism in HGF/SF-induced cell scattering, resulting in a switch to a more invasive phenotype in LNCapFGC cells, as demonstrated by in vitro invasion.

Cadherins↗

Pest insect control in organically-produced crops of field vegetables.

In the UK, the demand for organic vegetable and salad crops is increasing, mainly as a result of the requirements of the multiple retailers. However, approximately 85% of the organic fruit and vegetable produce sold in the UK is imported. A major constraint to growing field vegetable crops, and particularly organically-produced crops, is the reduction in crop yield and quality caused by pest insects. This paper will consider the control techniques currently available to organic growers and other techniques that may become available in the future. Growing plant varieties with complete or even partial resistance to pest insects can be an effective way of reducing crop damage. There are already varieties of carrot, with resistance to carrot fly, and lettuce, with resistance to certain pest aphid species, which are available commercially. Cultural techniques to exclude, deter or avoid pest insects are also being used by some organic growers. Although isolating new crops from sources of infestation can be a highly effective control strategy, many organic growers cannot use it, as the land converted for organic production is still limited. Various crop covers can be used to prevent pest insects from damaging field crops, but to be effective such covers have to be in place before the pests enter the crop. Several researchers have tried to develop techniques to prevent pest insects from finding their host-plants. No technique involving semiochemicals has been sufficiently successful to be used in field vegetable production in the UK. Other studies have shown that the numbers of pest insects found on crop plants are reduced considerably when the crop is allowed to become weedy, is intercropped with another plant species, or is undersown with a living mulch. Hence, work is now needed to select background plant species that will both reduce pest insect numbers and cause the least reduction in yield to the harvested crop plants. There is also a need to obtain a better understanding of "companion planting", a practice used frequently by organic growers. To date, microbial control is the only biological technique that has been used successfully in field vegetable crops in the UK. However, only the toxicant produced by one microbial agent, the bacterium Bacillus thuringiensis, has so far been registered for use. The use of bacteria, fungi and viruses to control pests of field vegetable crops certainly has possibilities. However, in many cases there are still problems to be overcome to select pathogens that are compatible with, or can still be effective in, the wide fluctuations in temperature, humidity and soil moisture that occur under field conditions. Attempts are now being made to use entomopathogenic nematodes and predatory arthropods to control one major pest insect, the cabbage root fly. Techniques developed to improve the timing of application of various crop protection procedures in systems of conventional vegetable production apply equally well to organic production, despite the choice of control options being more limited. In particular, models to forecast the timing of pest insect attacks could be used to great effect, to indicate the best times to plant, protect and harvest a specific crop to minimise pest insect damage.

Agriculture↗

Fetal death and congenital malformation in babies born to nuclear industry employees: report from the nuclear industry family study.

BACKGROUND: There is some concern about the genetic effects of exposure to low-level ionising radiation, but the evidence is sparse and conflicting. Most work has concentrated on cancer in offspring and little has been done on adverse reproductive outcome. We aimed to assess whether the offspring of men and women who are occupationally exposed to ionising radiation are at increased risk of fetal death and congenital malformation. METHODS: We analysed pregnancies reported by an occupational cohort of nuclear industry workers in the UK, employed at establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. Employment and radiation monitoring data supplied by employers was linked to each pregnancy. FINDINGS: 11,697 men and 1903 women reported one or more singleton pregnancy conceived after first employment within the nuclear industry, the men reporting a total of 23,676 singleton pregnancies and the women 3585. The risks of fetal death and congenital malformation were not related to whether the father had been monitored before conception or to the dose of radiation received. Among pregnancies reported by women, the risk of early (<13 weeks of gestation) miscarriage was higher if the mother had been monitored before conception (odds ratio [OR] 1.3, 95% CI 1.0-1.6), but there was no trend with dose. The risk of stillbirth was also higher if the mother had been monitored before conception (OR 2.2, 95% CI 1.0-4.6), but the finding was based on only 29 cases (13 exposed). The risk of any major malformation, or of specific groups of malformations, was not associated with maternal monitoring, or dose received, before conception. INTERPRETATION: We found no evidence of a link between exposure to low-level ionising radiation before conception and increased risk of adverse reproductive outcome in men working in the nuclear industry. Similarly for women there was no evidence of an association between monitoring before conception and malformation in offspring. The findings relating maternal preconceptual monitoring to increased risk of fetal death are equivocal and require further investigation.

Abnormalities, Radiation-Induced↗