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Biomedical subjects

A R Taylor

Publications and source records attributed to A R Taylor.

At least 19 recordsLinked to original sources

Male breast cancer in World War II aviation: a case report and review.

Increased incidence of malignancies within aviators is well documented. Commercial female flyers have been found to have a higher risk of developing breast cancer. However, there has not been any report of male breast cancer related to flying either alone or where malignant melanoma and other primary cancers are also associated. We report two male World War II, British Royal Air Force pilots with primary breast carcinoma associated with two other primary cancer sites.

Aged↗

Apparent absence of a redox requirement for blue light activation of pump current in broad bean guard cells.

In guard cells, membrane hyperpolarization in response to a blue light (BL) stimulus is achieved by the activation of a plasma membrane H(+)-ATPase. Using the patch clamp technique on broad bean (Vicia faba) guard cells we demonstrate that both steady-state- and BL-induced pump currents require ATP and are blocked by vanadate perfused into the guard cell during patch clamp recording. Background-pump current and BL-activated currents are voltage independent over a wide range of membrane potentials. During BL-activated responses significant hyperpolarization is achieved that is sufficient to promote K(+) uptake. BL activation of pump current becomes desensitized by three or four pulses of 30 s x 100 micromol m(-2) s(-1) BL. This desensitization is not a result of pump inhibition as maximal responses to fusicoccin are observed after full BL desensitization. BL treatments prior to whole cell recording show that BL desensitization is not due to washout of a secondary messenger by whole cell perfusion, but appears to be an important feature of the BL-stimulated pump response. We found no evidence for an electrogenic BL-stimulated redox chain in the plasma membrane of guard cells as no steady-state- or BL-activated currents are detected with NADH or NADPH added to the cytosol in the absence of ATP. Steady-state- nor BL-activated currents are affected by the inclusion along with ATP of 1 mM NADH in the pipette under saturating red light or by including NADPH in the pipette under darkness or saturating red light. These data suggest that reduced products of photosynthesis do not significantly modulate plasma membrane pump currents and are unlikely to be critical regulators in BL-stimulation of the plasma membrane H(+)-ATPase in guard cells.

Cell Membrane↗

The use of the latissimus dorsi musculocutaneous flap for immediate correction of the deformity resulting from breast conservation surgery.

Breast conservation surgery is now widely accepted as the treatment of choice in early breast cancer. Randomised controlled trials have shown comparable recurrence and survival rates following breast conservation when compared to mastectomy, with the perceived advantage that it should leave a cosmetically acceptable result without reconstruction. It is our experience that an adequate local excision may result in a poor cosmetic result with distortion of the nipple position, especially in women with small breasts. Between January 1994 and July 1996, we have performed 30 procedures, combining a wide local excision and axillary lymph node clearance for breast cancer with immediate reconstruction of the defect with a latissimus dorsi musculocutaneous flap. All patients had postoperative radiotherapy to the residual breast and, where appropriate, to the axilla. Adjuvant hormonal therapy or chemotherapy was prescribed where indicated. Patient's ages ranged from 36 to 72 years. All tumours were in the lateral, superior or inferior quadrants. The mean combined operating time was 120 min. Two patients required postoperative blood transfusion. Mean hospital stay was 8 days. Histology confirmed tumour clearance in all cases and six patients had axillary lymph node metastases. There were two cases of minor wound infection and six cases of seroma at the donor site. We conclude that breast cancers are ideally treated by a multidisciplinary team and that an immediate latissimus dorsi musculocutaneous flap may correct the deformities often seen after breast conservation surgery.

Adult↗

Overview and initial results of the very long baseline interferometry space observatory programme

High angular resolution images of extragalactic radio sources are being made with the Highly Advanced Laboratory for Communications and Astronomy (HALCA) satellite and ground-based radio telescopes as part of the Very Long Baseline Interferometry (VLBI) Space Observatory Programme (VSOP). VSOP observations at 1.6 and 5 gigahertz of the milli-arc-second-scale structure of radio quasars enable the quasar core size and the corresponding brightness temperature to be determined, and they enable the motions of jet components that are close to the core to be studied. Here, VSOP images of the gamma-ray source 1156+295, the quasar 1548+056, the ultraluminous quasar 0014+813, and the superluminal quasar 0212+735 are presented and discussed.

Journal Article↗

Seal-promoting solutions and pipette perfusion for patch clamping plant cells.

Patch-clamp technology has greatly increased our knowledge of plant membrane transport. However, the success of patch clamping crucially relies on establishing a high resistance (G omega) seal between the membrane and the patch-clamp pipette. This can prove problematic in many plant-cell preparations. It is therefore of great importance to develop protocols for protoplast isolation, maintenance and seal formation that improve seal rate. This study investigated whether the pH and the K+ and the Cl(-)concentration of the pipette solution had an effect on the seal formation. High pH and absence of K+ significantly promoted membrane sealing, whereas the concentration of Cl- had no effect. To reap the benefit of seal-promoting pipette solutions and yet retain the option to adjust this solution to experimental requirements, a pipette perfusion apparatus was implemented. The perfusion system was successfully applied in cell-attached patch, excised-patch and whole-cell configurations, using plasma membrane and tonoplast of three different species. The system enables complete solution exchange within minutes and is potentially of great benefit in the study of channel selectivity, the application of (cytoplasmic) channel blockers and the study of primary and secondary transport.

Arabidopsis↗

A galactic chimney in the Perseus arm of the Milky Way.

Galaxies are surrounded by large haloes of hot gas which must be replenished as the gas cools. This has led to the concept of galactic 'chimneys'--cavities in the interstellar medium, created by multiple supernova explosions, that can act as conduits for the efficient transport of hot gas from a galaxy's disk to its halo. Here we present a high-resolution map of atomic hydrogen in the Perseus arm of our galaxy, which shows clear evidence for the existence of such a chimney. This chimney appears to have been formed by the energetic winds from a cluster of young massive stars, and may currently have reached the stage of bowing out into the halo.

Astronomical Phenomena↗

A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer.

139 peri- and postmenopausal women with advanced or recurrent breast cancer who had not received prior hormonal therapy were randomised in an open, cross-over study comparing the synthetic progestogen megestrol acetate with tamoxifen. The response rate (CR/PR) to megestrol acetate (25%; 95% confidence interval (CI) 15-35%) was not significantly different from that produced by tamoxifen (33%, CI 22-44%). Time-to-treatment failure was also similar in the two groups. Cross-over treatment was given on progression in 76 cases. Cross-over response (CR/PR) was seen in 3 of 35 patients (9%) receiving megestrol acetate as second-line therapy and in 6 of 41 patients (15%) receiving tamoxifen second-line. There was no significant difference in survival between the groups (P = 0.17) with median survival times of 24 and 32 months for the megestrol acetate and tamoxifen groups, respectively. The toxicity profile of the two drugs was different, although significant toxicity was rare with either agent. Megestrol acetate is an effective treatment for advanced breast cancer in older women when used either as first- or second-line treatment. Cross-over response is seen following both treatments. Given that most patients now receive tamoxifen as adjuvant treatment, megestrol acetate would appear to be one of the logical choices for patients who find the side-effects of tamoxifen unacceptable and for those who relapse on tamoxifen with further hormone therapy being clinically indicated.

Adult↗

Laser microsurgery of higher plant cell walls permits patch-clamp access.

Plasma membranes of guard cells in epidermal peels of Vicia faba and Commelina communis can be made accessible to a patch-clamp pipet by removing a small portion (1-3 micrometers in diameter) of the guard cell wall using a microbeam of ultraviolet light generated by a nitrogen laser. Using this laser microsurgical technique, we have measured channel activity across plasma membranes of V. faba guard cells in both cell-attached and isolated patch configurations. Measurements made in the inside-out patch configuration revealed two distinct K(+)-selective channels. Major advantages of the laser microsurgical technique include the avoidance of enzymatic protoplast isolation, the ability to study cell types that have been difficult to isolate as protoplasts or for which enzymatic isolation protocols result in protoplasts not amenable to patch-clamp studies, the maintenance of positional information in single-channel measurements, reduced disruption of cell-wall-mediated signaling pathways, and the ability to investigate intercellular signaling through studies of cells remaining situated within tissue.

Cell Membrane↗

Identification of trimetazidine metabolites in human urine and plasma.

1. The objective was to use modern mass spectrometric techniques to update current information on the metabolism of trimetazidine in human subjects found by previous studies. 2. Urine and plasma samples were taken from four healthy human volunteers taking part in a larger kinetic study. Each subject received an oral dose of 80-mg trimetazidine daily for 4 days. 3. Identification and quantitation of trimetazidine and its metabolites in urine and plasma were achieved using modern liquid chromatography-mass spectrometric methods. 4. The major drug-related component observed in urine and plasma was unchanged trimetazidine. In addition to the parent drug, 10 metabolites were detected in urine in concentrations ranging from 0.008 (0.01% dose) to 1.094 micrograms.ml-1 (1.4% dose). Metabolic profiles following acute and chronic doses of trimetazidine were qualitatively similar.

Adult↗

Synthesis of putative metabolites and investigation of the metabolic fate of gliclazide, [1-(3-azabicyclo(3,3,0)oct-3-yl)-3-(4-methylphenylsulfonyl) urea], in diabetic patients.

Synthesis of postulated hydroxylated metabolites of gliclazide is described together with their detailed structural analysis using 1H-NMR, two-dimensional 1H-NMR, and MS to characterize the products. Metabolism of gliclazide has been investigated in the urine of nine patients of different ethnic origins receiving gliclazide therapy for the treatment of diabetes. Urine extracts were analyzed by GC/MS to quantify and identify the metabolites excreted in urine and the metabolites compared with the synthesized products. Metabolic profiles in all diabetic patients were very similar and comparable with those reported for healthy human volunteers. In addition to the expected metabolites arising from oxidation of the 4-methylphenyl ring, four isomeric hydroxylated products of the azabicyclooctyl ring were identified and the structure of a fifth isomer postulated.

Adult↗

Transfection of metastatic capability with total genomic DNA from human and mouse metastatic tumour cell lines.

From a large series of experiments involving transfer of high molecular weight total genomic DNA from highly metastatic human and mouse tumour cell lines to other mouse tumour cell lines we have derived a few cell lines with greatly augmented metastatic properties. In one of these experiments the transfected cell line (designated AH8 Test) not only colonised the lungs but also formed secondary tumour colonies in several extrapulmonary sites including the skin, skeletal muscles, bone, liver diaphragm, spleen and heart. There were no qualitative and quantitative effects of this magnitude when we used DNA from several non-metastatic or non-tumourigenic sources. Secondary transfection of metastatic capability with DNA obtained from a metastasis formed by one of the primary transfectant lines (AH8 Test) has also been accomplished. Concomitant transfer of human DNA through both transfection cycles in this experiment was confirmed by a variety of methods including Southern blot analysis, in situ hybridisation and polymerase chain reaction (PCR) amplification of DNA using primers recognising human-specific Alu repeat sequences. The findings offer opportunities for the isolation of sequences programming metastatic behaviour and we have cloned and sequenced a fragment of human DNA, which has not been previously characterised, from the transfected cells.

Animals↗

Localized Patch Clamping of Plasma Membrane of a Polarized Plant Cell : Laser Microsurgery of the Fucus spiralis Rhizoid Cell Wall.

We used an ultraviolet laser to rupture a small region of cell wall of a polarized Fucus spiralis rhizoid cell and gained localized access to the plasma membrane at the growing apex. Careful control of cell turgor enabled a small portion of plasma membrane-bound cytoplasm to be exposed. Gigaohm seals allowing single-channel recordings were obtained with a high success rate using this method with conventional patch clamp techniques.

Journal Article↗

Comparative biodisposition and metabolism of 14C-(+/-)-fenfluramine in mouse, rat, dog and man.

1. The comparative metabolism of fenfluramine was investigated in mouse, rat, dog and man following a single oral dose of 14C-(+/-)-fenfluramine hydrochloride (1 mg/kg), and also in rat after eight consecutive 12-h subcutaneous doses (24 mg/kg). 2. Main route of excretion of radioactivity in all species and at all doses was into urine (> 80%), with only minor amounts of radioactivity found in faeces. 3. From all species examined a total of 11 metabolites were observed in urine and plasma by t.l.c. and h.p.l.c. analysis and no metabolite was present in the plasma which was not present in urine. 4. All species dealkylate fenfluramine to the active metabolite norfenfluramine, to a relative greater or lesser extent, with plasma metabolic ratios (norfenfluramine/fenfluramine) showing inter-animal variation (rat >> dog >> mouse = man). 5. These differences are due to the efficient deamination of both compounds to polar inactive metabolites in man, with less dealkylation and lower plasma levels of norfenfluramine compared with the other species studied. 6. In conclusion, major species differences in the metabolism of (+/-)-fenfluramine, both qualitative and quantitative were observed, and no one species had a similar metabolic profile to that found in man.

Animals↗

An immunohistochemical study of papillary tumors in the central nervous system.

An immunohistochemical study was performed on the paraffin sections of 25 tumors in the central nervous system (CNS) with prominent papillary configurations. These tumors included seven metastatic papillary carcinomas, six choroid plexus tumors, four papillary ependymomas, two myxopapillary ependymomas, two papillary pituitary adenomas, two astroblastomas, one papillary meningioma, and one anaplastic astrocytoma with significant papillary changes. The panel of antibodies applied included anti-glial fibrillary acidic protein (GFAP), anti-carcinoembryonic antigen (CEA), anti-vimentin (VM), anti-S-100 protein (S-100 P), anti-cytokeratin, and anti-prealbumin antisera. All ependymomas and astroblastomas examined expressed both VM and GFAP, which were either absent or focally expressed in choroid plexus tumors. In contrast, all choroid plexus tumors showed anti-cytokeratin immunoreactivity that was absent in the ependymomas and astroblastomas. Five choroid plexus tumors also expressed S-100 P, thus differentiating them from metastatic carcinoma that showed negative immunostaining. Anti-CEA antisera immunoreactivity was seen in six metastatic tumors, whereas none of the primary CNS tumors expressed CEA. Prealbumin was expressed in four choroid plexus tumors and two metastatic tumors. Immunohistochemical typing using a panel of antibodies has allowed the differentiation of most of the papillary tumors in the CNS examined in this study.

Astrocytoma↗

Arabinosylcytosine-induced accumulation of DNA nicks in myotube nuclei detected by in situ nick translation.

This laboratory has recently reported the occurrence of DNA nicking at the onset of terminal skeletal myogenesis by using the technique of in situ nick translation (Dawson and Lough: Dev. Biol., 127:362-367, 1988). Because 1-beta-D-arabinofuranosylcytosine (araC), a cytocidal agent that is routinely used to removed dividing fibroblasts from myogenic cultures, inhibits DNA repair, it was of interest to determine whether araC treatment resulted in an accumulation of the endogenously created nicks. Thus, we have assessed the accumulation of DNA nicks in myotube cells during a 20 hour araC treatment period at the onset of terminal myogenesis (44-64 hours in vitro) by using three techniques: alkaline sucrose gradient density centrifugation, kinetic in situ nick translation, and cellular in situ nick translation. Although alkaline sucrose gradient centrifugation revealed no detectable nicking after 20 hours, kinetic in situ nick translation analysis revealed subtle but significant increases in DNA nicks caused by araC within 7 hours of drug application, and a 1.5-fold increase in DNA repair sites after 20 hours of drug treatment. That these observations reflected nicking specifically in myotube nuclei was determined by immunocytochemical localization of nicked sites after repair with a biotinylated nucleotide analog (biotin-11-dUTP). The effects of araC were only incompletely reversible, whether or not the drug was removed from the cultures, within 2 days of the treatment period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗