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Biomedical subjects

N J Taylor

Publications and source records attributed to N J Taylor.

At least 19 recordsLinked to original sources

Dynamic contrast-enhanced magnetic resonance imaging is a poor measure of rectal cancer angiogenesis.

BACKGROUND: The aim of this study was to investigate the use of magnetic resonance imaging (MRI) for non-invasive measurement of rectal cancer angiogenesis and hypoxia. METHODS: Fifteen patients with rectal adenocarcinoma underwent preoperative dynamic contrast-enhanced (DCE) and blood oxygenation level-dependent (BOLD) MRI. Microvessel density (CD31 level), and expression of vascular endothelial growth factor (VEGF) and carbonic anhydrase (CA) 9 were measured immunohistochemically in histological tumour sections from 12 patients. Serum VEGF levels were also measured in 14 patients. Correlations between quantitative imaging indices and immunohistochemical variables were examined. RESULTS: There was good correlation between circulating VEGF and CD31 expression (r(S) = 0.88, P < 0.001). CD31 expression did not correlate with any dynamic MRI parameter, except transfer constant, with which it correlated inversely (r(S) = -0.65, P = 0.022). Tissue and circulating VEGF levels did not correlate, and neither correlated with any tumour DCE MRI parameter. No relationship was seen between BOLD MRI and CA-9 expression. CONCLUSION: The negative correlation between transfer constant (reflecting tumour blood flow and microvessel permeability) with CD31 expression is paradoxical. DCE MRI methods for assessing tissue vascularity correlate poorly with histological markers of angiogenesis and hypoxia, suggesting that DCE MRI does not simply reflect static histological vascular properties in patients with rectal cancer.

Adenocarcinoma↗

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI.

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4-24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (K(trans)) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in K(trans) or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in K(trans). Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy.

Adult↗

5,5'-Bridged bis(1,2,3-dithiazoles): spin states and charge-transfer chemistry.

Bifunctional 1,2,3-dithiazoles bridged with azine and phenylenediamine spacers have been prepared, with a view to determining the extent of communication between the two dithiazole rings as a function of the electronic and steric demands of the bridge. The crystal structure of the closed-shell diazine derivative [S(2)NClC(2)=NN=C(2)ClNS(2)] is rigorously planar. Cyclic voltammetry on this compound indicates two reversible one-electron oxidations. The radical cation state has been characterized by EPR spectroscopy and by crystal structure determination of its 1:1 PF(6)(-) salt. The latter reveals little interaction between neighboring radical cations; consistently, the material exhibits a conductivity of sigma < 10(-5) S cm(-1). Insertion of a phenylene group into the diazine bridge to afford [S(2)NClC(2)=NC(6)H(4)N=C(2)ClNS(2)] leads to significant torsional motion between the phenylene ring and the two end groups, as a result of which the two DTA rings are electronically independent; no radical cation state has been observed for this species. Crystal data for Cl(2)S(4)N(4)C(4): a = 5.1469(15), b = 13.343(2), c = 14.2031(17), orthorhombic, Pbca, Z = 4. Crystal data for Cl(2)S(4)N(4)C(4)PF(6): a = 11.699(4), b = 12.753(5), c = 10.461(4), beta = 112.17(1) degrees, monoclinic, C2/c, Z = 4. Crystal data for C(l2)S(4)N(4)C(10)H(4): a = 3.9477(6), b = 23.790(3), c = 7.3769(9), beta =90.793(12) degrees, monoclinic, P2(1)/c, Z = 2.

Journal Article↗

BOLD MRI of human tumor oxygenation during carbogen breathing.

An MRI method is described for demonstrating improved oxygenation of human tumors and normal tissues during carbogen inhalation (95% O2, 5% CO2). T2*-weighted gradient-echo imaging was performed before, during, and after carbogen breathing in 47 tumor patients and 13 male volunteers. Analysis of artifacts and signal intensity was performed. Thirty-six successful tumor examinations were obtained. Twenty showed significant whole-tumor signal increases (mean 21.0%, range 6.5-82.4%), and one decreased (-26.5 +/- 8.0%). Patterns of signal change were heterogeneous in responding tumors. Five of 13 normal prostate glands (four volunteers and nine patients with nonprostatic tumors) showed significant enhancement (mean 11.4%, range 8.4-14.0%). An increase in brain signal was seen in 11 of 13 assessable patients (mean 8.0 +/- 3.7%, range 5.0-11.7%). T2*-weighted tumor MRI during carbogen breathing is possible in humans. High failure rates occurred due to respiratory distress. Significant enhancement was seen in 56%, suggesting improved tissue oxygenation and blood flow, which could identify these patients as more likely to benefit from carbogen radiosensitization.

Aged↗

Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures.

The gas mixture carbogen may be breathed by patients to enhance the oxygenation level and therefore the radiosensitivity of tumours. However, owing to the high CO2 content, its inhalation is associated with patient intolerance. Our aim was to determine a suitable carbon dioxide and oxygen gas mixture with similar enhancement of arterial oxygenation to 5% carbogen and with improved patient tolerance. 14 patients entered the study; of those 14, 8 were able to tolerate 2%, 3.5% and 5% carbogen mixtures as well as a control gas for sufficient time to allow successful arterial blood gas sampling. Gas exchange parameters were measured using a carbon dioxide monitor and a blood gas analyser. Arterial carbon dioxide tension ranged from 2.9 kPa to 6.82 kPa whilst breathing the carbogen mixtures, and arterial oxygen tension increased at least three-fold from basal values. There were no significant changes in the respiratory rate, heart rate and blood pH. The results suggest that 2% CO2 in O2 enhances arterial oxygen levels to a similar extent as 3.5% and 5% CO2 and that it is well tolerated.

Aged↗

Dynamic contrast enhanced magnetic resonance scanning as a predictor of response to accelerated radiotherapy for advanced head and neck cancer.

Tumour perfusion has been assessed in patients with advanced head and neck cancer using dynamic contrast enhanced MRI prior to and at completion of accelerated radiotherapy, and related to local tumour control. Sequential MRI scans, at 3 s intervals after intravenous injection of gadolinium using a dynamic scan sequence through a tumour region of interest (ROI), were performed in 13 patients with advanced head and neck cancer before and on completion of radiotherapy. The scans have been analysed in terms of maximum tumour enhancement (E), slope of the enhancement versus time curve and the time taken to reach maximum tumour enhancement (Tmax), and these parameters related to tumour outcome after radiotherapy. Local tumour control was related to the value of E on a post-radiotherapy scan and the difference in Tmax between a pre- and post-radiotherapy scan. Durable local control was seen in those tumours with a post-radiotherapy value for E of less than 8 and a mean fall in Tmax of 27.3 s. These results imply that tumours with diminished tumour perfusion at the end of radiotherapy are those most sensitive to treatment and that those tumours which show greater tumour enhancement after accelerated radiotherapy are likely to fail locally. This may reflect the persistence of viable perfused tumour at completion of radiotherapy.

Contrast Media↗

Do general practitioners use prostate-specific antigen as a screening test for early prostate cancer?

OBJECTIVE: To assess the proportion of prostate-specific antigen (PSA) tests being ordered for prostate cancer screening. PARTICIPANTS AND SETTING: General practitioners (GPs) in central Sydney, New South Wales, ordering PSA tests during a seven-week period. DESIGN AND METHODS: Self-administered questionnaire, attached to 179 consecutive PSA test results returned to the ordering GPs. The questionnaire assessed reasons for ordering the test, associated patient morbidity and physical findings, and intended management. RESULTS: 66% response rate with no evidence of response bias. Of 118 PSA tests, 67 (57%) were defined as screening tests on men aged 39-84 years, not otherwise indicated for clinical reasons consistent with NHMRC guidelines. "Patient request" was the sole reason for nine (13%) of the screening tests and a factor in seven others (10%). "Routine test for age" was the reason for 25 (37%) of the screening tests, on men aged 49-78 years. Results of 59 (88%) of the screening tests were normal. CONCLUSION: More than half of the PSA tests ordered during the study period were screening tests. Our method could be used to monitor the impact of guidelines and strategies for reducing PSA screening.

Adult↗

A simple phantom to locate the origin of MRI ghost artefacts.

A simple pyramidal tube phantom has been designed to allow accurate location of a selected slice along the desired axis of a magnetic resonance scanner and to provide a check of the quality of slice selection. It is particularly helpful in locating the origin of any out-of-slice ghost artefacts. The geometry of the phantom allows the slice positions to be calculated readily.

Artifacts↗

Expression and inheritance of multiple transgenes in rice plants.

The ability to control integration, inheritance, and expression of multiple transgenes is a prerequisite for manipulating biosynthetic pathways and complex agronomic characteristics in plants. One hundred and twenty-five independent transgenic rice plants were regenerated after cobombarding embryogenic tissues with a mixture of 14 different pUC-based plasmids. Eighty-five percent of the R0 plants contained more than two, and 17% more than nine, of the target genes. Plants containing multiple transgenes displayed normal morphologies and 63% set viable seed. Multigene cotransformation efficiency was correlated with the ratio in which the plasmids were mixed with respect to the selectable marker. All target genes had an equal chance of integration, indicating that the nature of the coding region had no effect on the efficiency of integration. Three plant lines containing 11, 10, and 9 transgenes, respectively, were analyzed for patterns of integration and inheritance until the R3 generation. Integration of multiple transgenes occurred at either one or two genetic loci, with inheritance conforming to a 3:1 Mendelian ratio. Coexpression of four marker genes was investigated until the R2 generation.

Acetyltransferases↗

The response of human tumors to carbogen breathing, monitored by Gradient-Recalled Echo Magnetic Resonance Imaging.

PURPOSE: Gradient-Recalled Echo (GRE) Magnetic Resonance Imaging (MRI), which detects changes in blood vessel deoxyhaemoglobin content, has been investigated as a noninvasive monitor of changes in human tumor oxygenation and blood flow, in response to carbogen (95% O2, 5% CO2) breathing. METHODS AND MATERIALS: GRE images (TE = 60 ms, TR = 200 ms, alpha = 40 degrees, 256[2] matrix) were acquired from 31 patients with primary and metastatic disease, prior to and during carbogen breathing. Three patients underwent a follow-up examination after radiotherapy. RESULTS: Seventeen out of 34 tumors showed enhanced image intensity, consistent with an improvement in tumor oxygenation and blood flow, while 11 showed no response; 6 studies were technical failures. In one patient a metastatic node that had eluded orthodox investigation was visualized. A reduction in response was observed in the three patients studied postradiotherapy. CONCLUSION: This method, which can be performed on a standard clinical MRI instrument, provides a noninvasive measurement of tumor response to oxygenation/blood flow modification. In principle, this should enable the clinician to optimize treatment protocols, such as carbogen breathing, for individual radiotherapy patients.

Administration, Inhalation↗

Development of friable embryogenic callus and embryogenic suspension culture systems in cassava (Manihot esculenta Crantz)

Procedures for the production of a new and highly prolific embryogenic culture system have been developed in cassava. The importance of the basal salts and type of auxin in controlling the development of cassava embryogenic tissues has been demonstrated, with culture on Gresshoff and Doy basal medium in the presence of 4-amino-3,5,6,trichloro-picolinic acid (picloram) inducing the formation of friable embryogenic callus from which highly totipotent embryogenic suspension cultures could be established. Plants have been regenerated from these cultures. The availability of embryogenic suspension cultures is considered to have important implications for the application of genetic transformation and other biotechnologies in the agronomic improvement of cassava.

Culture Techniques↗

A 3-amino-4-hydroxy-3-cyclobutene-1,2-dione-containing glutamate analogue exhibiting high affinity to excitatory amino acid receptors.

The syntheses of several novel N-(hydroxydioxocyclobutenyl)-containing analogues of gamma-amino-butyric acid and L-glutamate were undertaken to test the hypothesis that derivatives of 3,4-dihydroxy-3-cyclobutene-1,2-dione (squaric acid), such as 3-amino-4-hydroxy-3-cyclobutene-1,2-dione, could serve as a replacement for the carboxylate moiety in neurochemically interesting molecules. The syntheses were successfully accomplished by preparation of a suitably protected diamine or diamino acid followed by reaction with diethyl squarate. Subsequent deprotection resulted in the isolation of the corresponding N-(hydroxydioxocyclobutenyl)-containing analogues 13, 14, and 18. These analogues were screened as displacers in various neurochemical binding site assays. The L-glutamate analogue 18, which showed high affinity as a displacer for kainate and AMPA binding, was also examined for agonist potency for CA1 pyramidal neurons of the rat hippocampal slice preparation. It rivaled AMPA as one of the most potent agonists for depolarizing pyramidal neurons in medium containing 2.4 mM Mg+2 ions in which kainate/AMPA receptors are active but NMDA receptors are inhibited (IC50 = 1.1 microM). It was 1 order of magnitude less potent for depolarizing pyramidal neurons under conditions in which kainate/AMPA receptors were inhibited by 10 microM CNQX but NMDA receptors were active in 0.1 mM Mg(+2)-containing medium (IC50 = 10 microM). Compound 18 did not induce sensitization of CA1 pyramidal cells to depolarization by phosphonate analogues of glutamate (the QUIS-effect).

Animals↗

A rapid interleaved method for measuring signal intensity curves in both blood and tissue during contrast agent administration.

A method has been developed that uses dynamic MR imaging to measure simultaneously the changes in signal intensity due to paramagnetic contrast agent in blood and tissue, using interleaved single-angle projection and imaging sequences. The basic projection/image sequence has a projection time resolution of 50 ms and can measure rapid changes in the blood signal intensity. Variants with a tissue suppression slab have time resolutions of 57 or 75 ms. Orientation of the projection and image planes can be defined independently. This technique will facilitate functional measurements using MR contrast agents, allowing the blood input function to be determined with excellent time resolution.

Animals↗

Response to isoantigens and mitogens in the cat: effects of cyclosporin A.

Growing interest in the use of domesticated cats to study immune-mediated disease and in the research and clinical application of organ and tissue transplantation provided the need for in vitro assays estimating histocompatibility and cell-mediated immunity. In the present study, a whole-blood lymphocyte-stimulation microassay and mixed lymphocyte-response assay were adapted and used to measure significant responses from feline lymphocytes to mitogen and lymphocyte-defined histocompatibility antigens. The addition of cyclosporin A to whole-blood lymphocyte-stimulation microassay and mixed lymphocyte-response assay produced similar non-cytotoxic decrease in lymphocyte responses seen in other species.

Animals↗

Effect of trace elements found in coal fly ash, on lymphocyte blastogenesis.

To evaluate the potential health effects of coal fly ash, a byproduct of coal combustion for electrical energy production, on the immune system, we studied the effects of trace elements found in fly ash on lymphocyte blastogenesis. Of the sixteen trace elements studied, seven inhibited lectin-induced lymphocyte division, six showed no inhibition and three produced inconsistent effects. The ranking of the toxicity of the elements is Mn, V, As (III), Cu, Cd, Se, and Be. Our data indicate that whole blood lectin-induced lymphocyte blastogenesis is a sensitive and reproducible test for in vitro screening of trace elements affecting the immune system.

Carbon↗

Equivalence of 'non-IgG binding' and 'acrosomeless' sperm populations from the female genital tract of the rabbit.

Spermatozoa were recovered from the ejaculate, vagina, uteri and oviducts of mated does between 2.5 and 14 h p.c. For each sample, the proportion of spermatozoa exhibiting no binding of IgG from normal serum, after air drying and acetone fixation, was compared with the proportion of acrosomeless spermatozoa as assessed by staining with eosin and fast green. The correlation was excellent (r = 0.97; P less than 0.001) suggesting that failure of acetone-fixed spermatozoa to bind IgG from normal serum may reflect acrosome absence rather than 'acrosomal uncoatibility'. Usually the proportion of immunofluorescence negative or acrosomeless spermatozoa was about 10% in the ejaculate; 15% in the vagina; 25% in the uterus and 70-100% in the oviducts. This phenomenon is not an air-drying artefact, and seems to be independent of flushing medium.

Acrosome↗

Investigation of sperm-induced cervical leucocytosis by a double mating study in rabbits.

The cervices of 2 normally mated does at 1 h post coitum were examined for the presence of leucocytes and compared with the cervix of an unmated doe. Cervical leucocytosis (50 x 10(6) leucocytes) was demonstrated following mating with either of 2 bucks, but not in the unmated doe. Each of 16 does was single-mated with 2 bucks whose offspring could be distinguished clearly. The interval between first and second mating was 0, 0.5, 1 or 4 h. One buck produced 68 offspring, the other buck produced 37. Cervical leucocytosis did not impair the fertility of the second buck even if it was the inferior buck; so fertilizing spermatozoa may traverse the cervices, even through large numbers of leucocytes. The differences in fertility between spermatozoa from different bucks during competitive fertilization may reflect different capacitation times of these spermatozoa.

Animals↗