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Biomedical subjects

B Powell

Publications and source records attributed to B Powell.

At least 19 recordsLinked to original sources
PubMed2006

A review of the surgical treatment of vulval lymphangioma and lymphangiectasia: four case reviews.

OBJECTIVE: To evaluate whether surgical management of vulval lymphoedema and/or lymphangiectasia conveys any longstanding patient benefit. PATIENT AND METHODS: A qualitative analysis of signs and symptoms that occurred before and after surgical treatment for vulval lymphoedema and/or lymphangiectasia was performed. This was done by analysis of patient notes and telephone conducted interview. RESULTS: From a hospital database search, four patients were found to have had surgical treatment--three for lymphangioma and one for lymphangiectasia. Overall there was a clear improvement in the signs and symptoms associated with these conditions. In particular, all patients reported an improvement (i.e. a reduction or elimination) in the amount of oedema following surgery. CONCLUSION: Carbon dioxide laser therapy and superficial radiotherapy have been previously described for the management of vulval lymphangioma and lymphangiectasia with limited success, whereas our data suggests surgery offers a more permanent solution. In particular, labial reduction seems to be more successful than methods such as lymphovenous anastomoses and lymphangioplasties. A single operation may provide benefit for up to ten years. This approach has the potential to allow patients to be rehabilitated to normal life and activity.

Adolescent↗
PubMed2004

A review of acid sulfate soil impacts, actions and policies that impact on water quality in Great Barrier Reef catchments, including a case study on remediation at East Trinity.

An estimated 666,000 ha of acid sulfate soils (ASS) occur within the Great Barrier Reef (GBR) catchments of Queensland, Australia. Extensive areas have been drained causing acidification, metal contamination, deoxygenation and iron precipitation in reef receiving waters. The close proximity of ASS to reef waters makes them a substantial threat to water quality. Another important issue linked with ASS is their release of soluble iron, which is known to stimulate nuisance marine algal blooms, in particular Lyngbya majuscula. Known blooms of the cyanobacteria in reef waters have been confirmed at Shoalwater Bay, Corio Bay, the Whitsunday area and Hinchinbrook Channel. Acid sulfate soils are intimately related to coastal wetland landscapes. Where landscapes containing ASS have been disturbed (such as for agriculture, aquaculture, marinas, etc.) the biodiversity of adjacent wetlands can be adversely affected. However, there is no clear knowledge of the real extent of the so-called "hotspot" ASS areas that occur within the GBR catchments. Management of ASS in reef catchments has benefited from the implementation of the Queensland Acid Sulfate Soils Management Strategy through policy development, mapping, training programs, an advisory service, research and community participation. However, major gaps remain in mapping the extent and nature of ASS. Areas of significant acidification (i.e. hotspots) need to be identified and policies developed for their remediation. Research has a critical role to play in understanding ASS risk and finding solutions, to prevent the adverse impacts that may be caused by ASS disturbance. A case study is presented of the East Trinity site near Cairns, a failed sugar cane development that episodically discharges large amounts of acid into Trinity Inlet, resulting in periodic fish kills. Details are presented of scientific investigations, and a lime-assisted tidal exchange strategy that are being undertaken to remediate a serious ASS problem.

Animals↗
PubMed2002

Subungual melanoma in situ: two independent streaks in one nail bed.

We report an unusual case of two nail-bed streaks under one nail, revealing melanoma in situ affecting the nail bed and plate, but not the nail fold. This unusual mode of presentation together with the absence of any nail-fold involvement has not been reported previously. We highlight the need for early histological assessment of nail-bed lesions and discuss subungual melanoma.

Adult↗
PubMed2001

Drought-induced guard cell signal transduction involves sphingosine-1-phosphate.

Stomata form pores on leaf surfaces that regulate the uptake of CO2 for photosynthesis and the loss of water vapour during transpiration. An increase in the cytosolic concentration of free calcium ions ([Ca2+]cyt) is a common intermediate in many of the pathways leading to either opening or closure of the stomatal pore. This observation has prompted investigations into how specificity is controlled in calcium-based signalling systems in plants. One possible explanation is that each stimulus generates a unique increase in [Ca2+]cyt, or 'calcium signature', that dictates the outcome of the final response. It has been suggested that the key to generating a calcium signature, and hence to understanding how specificity is controlled, is the ability to access differentially the cellular machinery controlling calcium influx and release from internal stores. Here we report that sphingosine-1-phosphate is a new calcium-mobilizing molecule in plants. We show that after drought treatment sphingosine-1-phosphate levels increase, and we present evidence that this molecule is involved in the signal-transduction pathway linking the perception of abscisic acid to reductions in guard cell turgor.

Abscisic Acid↗
PubMed2001

The effects of phenolic components of tea on the production of pro- and anti-inflammatory cytokines by human leukocytes in vitro.

Epidemiological evidence suggests protective effects of dietary flavonoids against cardiovascular disease. Tea provides a major source of dietary flavonoids in many countries and its polyphenolic components have well-recognised antioxidant properties. However, scavenging of free radicals may not be the sole mechanism by which tea-derived polyphenols exert their protective effects. This study investigates the effects of four major tea-derived catechins and a black tea extract on the production of pro- and anti-inflammatory cytokines by human leukocytes in vitro. Epicatechin gallate, epigallocatechin and epigallocatechin gallate decreased the production of interleukin 1beta and enhanced the production of interleukin 10, but had no effect on the production of interleukin 6 or tumour necrosis factor-alpha. Although these effects suggest anti-inflammatory properties of the tea-derived catechins, they were observed at concentrations which were unlikely to be achievable in plasma in vivo and are therefore unlikely to contribute to the protective effects of tea-derived flavonoids in inflammatory diseases.

Anti-Inflammatory Agents↗
PubMed2001

Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy.

We examined the cytotoxicity of the immunosuppressant agent rapamycin and its analogue CCI-779 in human brain tumor cell lines in vitro and in vivo as single agents and in combination with standard chemotherapeutic drugs. In the rapamycin-sensitive PNET/MB cell line DAOY, rapamycin exhibited additive cytotoxicity with cisplatin and with camptothecin. In vivo, CCI-779 delayed DAOY xenograft growth by 160% after 1 week and 240% after 2 weeks of systemic treatment, compared with controls. Single high-dose treatment induced 37% regression of tumor solume. Growth inhibition of DAOY xenografts was 1.3 times greater after simultaneous treatment with CCI-779 and cisplatin than after cisplatin alone. Interestingly, CCI-779 also produced growth inhibition of xenografts derived from U251 malignant glioma cells, a human cell line resistant to rapamycin in vitro. These studies suggest that the rapamycin analogue CCI-779 is an important new agent to investigate in the treatment of human brain tumors, particularly PNET/MB.

Animals↗
PubMed2001

Glutamate is a transmitter that mediates inhibition at the rectifying electrical motor giant synapse in the crayfish.

Spike transmission at the electrical synapse between the giant fibres (GFs) and motor giant neurone (MoG) in the crayfish can be blocked by depolarising postsynaptic chemical inhibition, which has previously been shown to be mediated in part by gamma-aminobutyric acid (GABA). The authors show that glutamate applied to the synaptic region of the MoG mimics the depolarisation of the chemical input and can also block spike transmission from the GFs. The glutamate induces an inward current mediated by a conductance increase that is 30-40% of that induced by GABA and that is blocked substantially by picrotoxin. Glutamate has no effect on the presynaptic GF, and the effects in the MoG are maintained in the presence of cadmium, indicating that the glutamate is acting directly on the MoG. Both GABA and glutamate have similar effects on the cell body, where the response reverses 10-20 mV positive to resting potential, is dependent on chloride concentration, and is inhibited by picrotoxin. Joint application of glutamate and GABA induces a nonadditive current under voltage clamp, suggesting that the transmitters can activate the same postsynaptic receptors. Immunocytochemical staining shows that, whereas some synaptic profiles impinging on the MoG contain pleomorphic agranular vesicles and are immunoreactive to GABA and not glutamate (as previously reported), there are at least as many other profiles that contain round, agranular vesicles and that are immunoreactive to glutamate and not to GABA. Thus, the authors conclude that some of the interneurones mediating inhibition of the electrical synapse use glutamate as their neurotransmitter.

Animals↗
PubMed2001

P53 alteration and microsatellite instability have predictive value for survival benefit from chemotherapy in stage III colorectal carcinoma.

PURPOSE: We recently presented evidence for tumor site and gender-specificity in the survival benefit from adjuvant chemotherapy in Stage III colorectal cancer (CRC). In the current study, we examined whether p53 alteration or the microsatellite instability (MSI) phenotype provide additional predictive information in CRC patients. EXPERIMENTAL DESIGN: A retrospective series of 891 Stage III CRC patients with negative surgical margins was investigated. Thirty percent (270 of 891) received postoperative adjuvant chemotherapy with curative intent and comprising of 5-fluorouracil/levamisole. Adjuvant treatment and nontreatment patient groups were well matched for tumor site, grade, p53 alterations, and MSI. Surgical tumor specimens were investigated for p53 overexpression using immunohistochemistry and for p53 mutation and MSI using single-strand conformation polymorphism analysis. The predictive value of these markers was evaluated by comparing the survival of adjuvant-treated and nonadjuvant treated patients. RESULTS: A strong inverse correlation was observed between p53 alteration and MSI (P < 0.0001). In univariate analysis, the factors of sex, site, p53 alteration, and MSI were each strong predictors of a survival benefit from chemotherapy. Multivariate analysis revealed that chemotherapy provided maximal survival benefit for female patients (P = 0.005) and for patients whose tumors contained normal p53 (P = 0.041). Males whose tumors contained a p53 alteration and were negative for MSI appeared not to benefit from chemotherapy. CONCLUSIONS: Our findings suggest that p53 alteration and MSI could be clinically useful molecular predictive markers for the identification of CRC patients who might benefit from 5-fluorouracil-based chemotherapy.

Adult↗
PubMed2000

An approach to analysis of large-scale correlations between genome changes and clinical endpoints in ovarian cancer.

This report describes analyses of associations of genome copy number abnormalities in ovarian cancers with clinical features using genome-wide graphical and analytical procedures. These studies show that tumor grade is a better indicator of the extent of genomic progression than stage, that loss of chromosome 4 occurs preferentially in high-grade tumors, and that gains of 3q26-qter, 8q24-qter, and 20q13-qter occur frequently in low-grade and low-stage tumors and thus may be early events in ovarian cancer development. In addition, loss of chromosome 16q24 and a total number of independent genome copy number aberrations >7 are associated with reduced survival duration. The association of loss of 16q24 (D16S3026) with decreased survival duration was confirmed by quantitative PCR. Regions that frequently are abnormal and associated with altered survival duration are strong candidates for higher resolution analysis and gene discovery and may be useful markers for prediction of clinical outcome.

Chromosome Aberrations↗
PubMed2000

Molecular characterization of the yeast vacuolar H+-ATPase proton pore.

The Saccharomyces cerevisiae vacuolar ATPase (V-ATPase) is composed of at least 13 polypeptides organized into two distinct domains, V(1) and V(0), that are structurally and mechanistically similar to the F(1)-F(0) domains of the F-type ATP synthases. The peripheral V(1) domain is responsible for ATP hydrolysis and is coupled to the mechanism of proton translocation. The integral V(0) domain is responsible for the translocation of protons across the membrane and is composed of five different polypeptides. Unlike the F(0) domain of the F-type ATP synthase, which contains 12 copies of a single 8-kDa proteolipid, the V-ATPase V(0) domain contains three proteolipid species, Vma3p, Vma11p, and Vma16p, with each proteolipid contributing to the mechanism of proton translocation (Hirata, R., Graham, L. A., Takatsuki, A., Stevens, T. H., and Anraku, Y. (1997) J. Biol. Chem. 272, 4795-4803). Experiments with hemagglutinin- and c-Myc epitope-tagged copies of the proteolipids revealed that each V(0) complex contains all three species of proteolipid with only one copy each of Vma11p and Vma16p but multiple copies of Vma3p. Since the proteolipids of the V(0) complex are predicted to possess four membrane-spanning alpha-helices, twice as many as a single F-ATPase proteolipid subunit, only six V-ATPase proteolipids would be required to form a hexameric ring-like structure similar to the F(0) domain. Therefore, each V(0) complex will likely be composed of four copies of the Vma3p proteolipid in addition to Vma11p and Vma16p. Structural differences within the membrane-spanning domains of both V(0) and F(0) may account for the unique properties of the ATP-hydrolyzing V-ATPase compared with the ATP-generating F-type ATP synthase.

Escherichia coli↗
PubMed2000

Identification of lipid-accessible sites on the nephrops 16-kDa proteolipid incorporated into a hybrid vacuolar H(+)-ATPase: site-directed labeling with N-(1-Pyrenyl)cyclohexylcarbodiimide and fluorescence quenching analysis.

Proton translocation by the vacuolar H(+)-ATPase is mediated by a multicopy transmembrane protein, the 16-kDa proteolipid. It is proposed to assemble in the membrane as a hexameric complex, with each polypeptide comprising four transmembrane helices. The fourth helix of the proteolipid contains an intramembrane acidic residue (Glu140) which is essential for proton translocation and is reactive toward N,N'-dicyclohexylcarbodiimide (DCCD). Current theoretical models of proton translocation by the vacuolar ATPase require that Glu140 should be protonated and in contact with the membrane lipid. In this study we present direct support for this hypothesis. Modification with the fluorescent DCCD analogue N-(1-pyrenyl)cyclohexylcarbodiimide, coupled to fluorescence quenching studies and bilayer depth measurements using the parallax method, was used to probe the position of Glu140 with respect to the bilayer. Glutamate residues were also introduced mutagenically as targets for the fluorescent probe in order to map additional lipid-accessible sites on the 16-kDa proteolipid. These data are consistent with a structural model of the 16-kDa proteolipid oligomer in which the key functional residue Glu140 and discrete faces of the second and third transmembrane helices of the 16-kDa proteolipid are exposed at the lipid-protein interface.

Amino Acid Sequence↗
PubMed2000

Can p53 alterations be used to predict tumour response to pre-operative chemo-radiotherapy in locally advanced rectal cancer?

PURPOSE: To examine whether p53 tumour suppressor gene alterations can be used to predict tumour response to pre-operative chemo-radiation in locally advanced rectal cancer in terms of reduction in tumour size and local failure. METHODS: p53 alterations were studied in pre-treatment biopsy specimens of rectal carcinomas from 48 patients by immunohistochemistry (IHC) and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) gene mutation analysis. Pre-operative pelvic radiotherapy was delivered with four fields, 45 Gy to the ICRU point in 25 fractions over 5 weeks. A radio-sensitising dose of 5-fluorouracil (500 mg/m(2)) was delivered concurrently for 6 days of the 5-week schedule (days 1, 2, 3 and days 22, 23 and 24). Total meso-rectal excision was planned 4 to 6 weeks from completion of pre-operative treatment. Response to therapy was assessed by macroscopic measurement of the surgical specimen by a pathologist who was unaware of the pre-treatment tumour size or of the p53 status. RESULTS: IHC evidence of p53 protein accumulation was found in 40% of tumours, p53 gene mutation in 35% and p53 alteration (either or both changes) in 46%. The average reduction in tumour size was 53% in the group with 'wild-type' p53 (IHC-/SSCP-) and 63% in the group with altered p53 (either IHC+ or SSCP+; P=0.18). No significant differences in tumour size reduction or local failure were observed in the groups with p53 overexpression or p53 mutation compared with normal. CONCLUSIONS: p53 alteration detected by IHC or SSCP analysis is not a clinically useful predictor of local response to pre-operative adjuvant therapy in advanced rectal carcinoma.

Adenocarcinoma↗
PubMed2000

Prognostic significance of TP53 gene mutation in 995 cases of colorectal carcinoma. Influence of tumour site, stage, adjuvant chemotherapy and type of mutation.

Previous studies on the prognostic significance of TP53 gene alterations in colorectal cancer (CRC) have led to conflicting results. The present study investigated the prognostic significance of TP53 gene mutation in a very large series of 995 Dukes' B and C CRC patients, the majority of whom did not receive chemotherapy. Mutations were found in 385 (39%) cases and were not associated with tumour stage, histological grade, patient age or sex. Significantly more mutations were found in tumours from the left-sided colon compared with those from the right side (43% versus 34%, P=0.006). TP53 gene mutation had no prognostic value in the overall series or in different site or stage subgroups. None of the different types of TP53 gene mutation showed prognostic value. A trend for association with worse survival was observed in the patient subgroup that received adjuvant chemotherapy (Hazard Ratio (HR) 1.4, 95% confidence interval (CI) 0.89-2.21, P=0.15). These results indicate that mutation of the TP53 gene is not a useful prognostic marker for CRC patients who do not receive adjuvant chemotherapy. Further study is required to determine whether different types of TP53 mutation might be of value in predicting the response of CRC patients to chemotherapy.

Adult↗