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Biomedical subjects

R Graves

Publications and source records attributed to R Graves.

At least 19 recordsLinked to original sources

Combined IV-intra-arterial thrombolysis: a color-coded duplex pilot study.

The authors compared the transcranial color-coded duplex pattern of the middle cerebral arteries (MCAs) before and after IV and combined IV-intra-arterial (IV-IA) thrombolysis in consecutive first-ever stroke patients. Patients receiving combined IV-IA thrombolysis showed greater improvement in flow signal and higher incidence of complete MCA recanalization vs those receiving IV thrombolysis, especially when the MCA was occluded or had only minimal flow.

Aged↗

Miniaturization of a hepatitis C virus RNA polymerase assay using a -102 degrees C cooled CCD camera-based imaging system.

Innovations in detection technologies have allowed us to develop a novel assay in 1536-well plate format and assess the advantages of screen miniaturization compared with conventional high-throughput compound screening in 96- or 384-well plates. An HCV RNA polymerase assay has been miniaturized in 1536-well plates by using a new detection technology known as LEADseeker homogeneous imaging system. It uses a -102 degrees C cooled charge-coupled device (CCD) camera and newly designed scintillation proximity microparticles. The miniaturized assay used europium-doped streptavidin-coated yttrium oxide (YO(x)) or polystyrene (PS) microspheres to capture biotin-labeled [(3)H]RNA product transcripts. Beads in proximity to the radioisotope convert the emitted beta(-) particles into photons having wavelengths in the red region of the visible spectrum, optimal for detection by the CCD camera. Because the camera collects light from all wells of the plate simultaneously, 1536-well plates are imaged as rapidly as 384-well plates, on the order of 10 min per plate. The assay has a signal to background of approximately 20-fold, satisfactory for high-throughput robotics screening. The enzyme kinetics and potency of a known inhibitor were similar to those obtained from the conventional assay using scintillation proximity assay (SPA) beads and a scintillation plate counter. Furthermore, the newly developed microbeads (emitting at 610 to 620 nm) are less prone to quenching effects caused by yellow-colored compounds, than conventional SPA beads or scintillation fluid (emitting at 400 to 480 nm region). Thus, the LEADseeker imaging system is a useful new tool for miniaturization of assays for high-throughput screening.

Cold Temperature↗

Statistical power and effect sizes of clinical neuropsychology research.

Cohen, in a now classic paper on statistical power, reviewed articles in the 1960 issue of one psychology journal and determined that the majority of studies had less than a 50-50 chance of detecting an effect that truly exists in the population, and thus of obtaining statistically significant results. Such low statistical power, Cohen concluded, was largely due to inadequate sample sizes. Subsequent reviews of research published in other experimental psychology journals found similar results. We provide a statistical power analysis of clinical neuropsychological research by reviewing a representative sample of 66 articles from the Journal of Clinical and Experimental Neuropsychology, the Journal of the International Neuropsychology Society, and Neuropsychology. The results show inadequate power, similar to that for experimental research, when Cohen's criterion for effect size is used. However, the results are encouraging in also showing that the field of clinical neuropsychology deals with larger effect sizes than are usually observed in experimental psychology and that the reviewed clinical neuropsychology research does have adequate power to detect these larger effect sizes. This review also reveals a prevailing failure to heed Cohen's recommendations that researchers should routinely report a priori power analyses, effect sizes and confidence intervals, and conduct fewer statistical tests.

Data Interpretation, Statistical↗

Electrochemical characteristics of high-Pd alloys in relation to Pd-allergy.

OBJECTIVE: The aim of this study was to determine whether the Pd-Cu-based dental ceramic alloys possess any electrochemical characteristics distinguishable from that of other Pd-containing alloys. Of all Pd-containing alloys, this particular alloy group has been linked to frequent incidence of allergy and hypersensitivity reactions. Electrochemical corrosion may instigate these reactions. METHODS: Four groups of alloys, Pd-Cu, Pd-Ga-(with and without Ag), Pd-Ag, and Au-Pd, were evaluated by traditional corrosion measurement techniques in a phosphated buffer saline solution at 20 degrees C. The electrochemical characteristics measured were: (1) 20 h open circuit potential (OCP); (2) 20 h corrosion rate (Icorr); and (3) anodic polarization (E-i) curves. RESULTS: The OCP values (232 +/- 25 mV) of the Ag-free Pd-Ga and Pd-Cu-based alloys were higher than and distinctly different from that (144 +/- 52 mV) of the Ag-containing alloys. The Icorr values of different alloys, despite varied compositions, were indistinguishable from one another. The E-i curves of all alloys were essentially similar, with the Ag-containing (> 5 wt%) alloys showing a subtle difference in their anodic slope within 100 mV above their corrosion potentials. SIGNIFICANCE: The OCP values of Pd-Cu alloys and the Ag-free Pd-Ga alloy are comparable to that reported for pure Pd (239 +/- 21 mV), which indicates that during corrosion these alloys undergo dealloying and consequent Pd-enrichment on their surface. Such a condition is conducive to the release of allergenic Pd++ ions and offers a plausible explanation for the frequent incidence of hypersensitivity reactions associated with the Pd-Cu alloys. The OCP values in other alloys are attributed to dealloying followed by surface enrichment with Ag and/or Au and the possible formation of an insoluble AgCl surface film on the respective alloy surfaces. These events have the potential to suppress or prevent Pd++ ion release. Alloys showing these characteristics have seldom been linked to allergic reactions.

Allergens↗

Measurement of calcium flux through ionotropic glutamate receptors using Cytostar-T scintillating microplates.

Human embryonic kidney cells (HEK293), expressing the human GluR4 receptor sub-unit of 2-amino-3-hydroxy-methylisoxazol-4-ylpropionic acid (AMPA) type non-NMDA receptors were used, in combination with Cytostar-T scintillating microplates, to develop an assay system for the screening of novel compounds with potential AMPA antagonistic characteristics. Agonist dose responses were measured using the agonists: AMPA; quisqualic acid; L-glutamic acid and kainic acid (KA), and EC50 values of 40, 10, 100 and 100 microM were estimated for each of the agonists, respectively. The AMPA receptor antagonists LY293558 and GYK152466 were tested and shown to inhibit agonist induced [45Ca] influx into the cells. An IC50 value of 600 microM was estimated for the competitive antagonist LY293558 and a value of 100 microM estimated for the non-competitive antagonist GYK152466. The developed assay system is homogeneous, allowing increased assay precision and speed. This allows the potential for automation of the assay and it may be used for screening large numbers of novel compounds.

Calcium↗

A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis.

Adaptive thermogenesis is an important component of energy homeostasis and a metabolic defense against obesity. We have cloned a novel transcriptional coactivator of nuclear receptors, termed PGC-1, from a brown fat cDNA library. PGC-1 mRNA expression is dramatically elevated upon cold exposure of mice in both brown fat and skeletal muscle, key thermogenic tissues. PGC-1 greatly increases the transcriptional activity of PPARgamma and the thyroid hormone receptor on the uncoupling protein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose cells activates expression of UCP-1 and key mitochondrial enzymes of the respiratory chain, and increases the cellular content of mitochondrial DNA. These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis.

Adaptation, Physiological↗

An homogeneous assay for measuring the uptake and efflux of radiolabelled drugs in adherent cells.

We have developed an homogeneous assay to measure the uptake and efflux of [14C]adriamycin (doxorubicin hydrochloride) in human squamous lung carcinoma cells (SKMES-1), using 96 well scintillating microplates. The assay was also used to examine the effect of inhibitors of multidrug resistance in adriamycin resistant cells (SKMES-1/ADR). The effect of adriamycin on cell growth and viability was examined by continuous monitoring of the uptake of [14C]thymidine. The non-invasive nature of these assays, and the ease of use of the microplates, suggests a role in screens for, and characterisation of, novel chemotherapeutic or chemosensitizing agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Noninvasive, real-time method for the examination of thymidine uptake events--application of the method to V-79 cell synchrony studies.

[14C]Thymidine uptake into V-79 hamster lung fibroblasts has been successfully demonstrated using a noninvasive, real-time method utilizing Cytostar-T scintillating microplates. These plates are standard format, tissue culture-treated, 96-well microplates with an integral scintillating base. The microplates permit the culture and observation of adherent cell monolayers. Biological activities of the cells can be studied by the provision of specific radiolabeled compounds. The biological activities of the adherent monolayer bring the specific radiolabel into proximity with the scintillating base and a scintillation signal is thereby generated. [14C]Thymidine incorporation on the microplates can be used to examine cell proliferation and cell cycle events. Using a combined mitotic shake-off/aphidicolin treatment to achieve synchronization, the thymidine incorporation activities of V-79 cells have been examined on Cytostar-T plates and correlated to traditional methods of determining incorporation. The method was further used to examine the effects of colcemid and olomoucine, both chemical inhibitors of cell proliferation, on synchronous populations of cells. The homogeneous detection format and the microplate nature of the method suggest a role for scintillating microplates in cell biology research and drug discovery.

Animals↗

Sequence specificity of DNA repair by Escherichia coli Fpg protein.

The sequence specificity of guanine methylation in DNA by N-methyl-N-nitrosourea and the subsequent repair of ring-opened N7-methylguanine was studied using oligonucleotides of defined sequence. It was found that the methylation of TAGGGGCCCCTA was less than 2-fold greater than that occurring in TAGAGATCTCTA or TATGTGCACATA and 6-fold greater than in TACGCGCGCGTA. This is consistent with the concept that guanine methylation is least when the 5' preceding base is a pyrimidine and greatest when the 5' base is another guanine. These dodecamers were used to study repair by the Escherichia coli Fpg protein (formamidopyrimidine-DNA glycosylase) after the 7-methyl-guanine present in them was converted to the ring-opened form by alkaline treatment. The repair of ring-opened 7-methylguanine was much faster in self-complementary double-stranded 12mer substrates and was twice as rapid at 37 degrees C in TAGGGGCCCCTA compared with TACGCGCGCGTA. However, at 15 degrees C, the relative rates were reversed since TACGCGCGCGTA was repaired at the same rate as at 37 degrees C, whereas the repair of TAGGGGCCCCTA was much slower at 15 degrees C. The repair of TAGGGGCCCCTA at 37 degrees C was also much faster than the repair of TAGAGATCTCTA and was slightly more rapid than repair of TATGTGCACATA. Ligation of the dodecamer substrates to form 24mers or 36mers slightly reduced the initial rates of repair but did not abolish these differences. These results indicate that under physiological conditions, the Fpg protein is more active against adducts in guanine-rich regions and such regions may be the most likely sites of adduct formation at the N7-position of guanine which can then give rise to derivatives attacked by this enzyme.

Base Sequence↗

Dissociated hemispheric and stimulus effects upon affective choice and recognition.

Following lateralized tachistoscopic presentations of faces and pronounceable nonsense words, subjects made two kinds of choices, affective (AFF) and recognition (REC). Subliminal presentations influenced later affective choices for faces (but not for nonsense words), while recognition was not influenced. Liminal presentations produced no effects. Supraliminal presentations influenced later affective choices for nonsense words (but not for faces), while recognition choices showed the expected LVF advantage for faces and a RVF advantage for nonsense words. Affective and recognition judgments appeared to be competing processes since only one or the other but not both differed significantly from chance in a visual field for a given stimulus type and exposure duration.

Adult↗

Clinical periodontal status of regularly attending patients in general dental practices.

Periodontal status of regular patients of general practitioners in the United States is unknown. A project assessing the effectiveness of continuing professional education in altering provider behavior and patient periodontal health provided the opportunity to clinically examine 1092 patients in the offices of 36 general practitioners. These regularly attending patients were selected by a random start systematic sample of patient records. The examination included recording missing teeth and assessing plaque, gingivitis, calculus, probing depth, and attachment loss on the facial and facial-mesial surfaces of the Ramfjord teeth (PDI). The mean patient age was 48 years, and 63% were female. The mean number of missing teeth, not including third molars, was 3.9. Almost 78% of the patients had no sites with a P1I score greater than 1, but 52% of the patients had at least one site with bleeding. Calculus was present in 62% of the patients. Deepest pocket depth was 4 mm or greater in 9% of patients and 3.8% had sites with 4 mm or greater attachment loss. Mean attachment loss was 1.6 mm across all sites. Although the majority of these regular patients had plaque, calculus, and gingivitis, only a minority exhibited periodontitis at the index sites.

Adult↗

Effect of ventricular function on the exercise hemodynamics of variable rate pacing.

To determine the effect of ventricular function on the exercise hemodynamics of variable rate pacing, 16 selected patients underwent paired, double-blind, randomized exercise tests in single rate demand (VVI) or variable rate (VVIR) pacing modes. Ejection fraction and cardiac index were determined by two-dimensional and Doppler echocardiography at baseline and during peak exercise. Baseline ejection fraction ranged from 14 to 73% and was less than 40% in 6 patients (Group 1) and greater than or equal to 40% in 10 patients (Group 2). Duration of exercise was longer during the VVIR mode (502 s) than during the VVI mode (449 s) (p less than 0.01) and unrelated to baseline ejection fraction. Heart rate during exercise increased 9% in the VVI mode and 35% in the VVIR mode (p less than 0.005). Cardiac index increased 49% in the VVI mode and 83% in the VVIR mode. Analysis of variance for repeated measures showed a significant effect of pacing mode (p less than 0.01) and exercise (p less than 0.001), but not baseline ejection fraction, on cardiac index. Baseline ejection fraction did not correlate with the increase in cardiac index in either pacing mode or with the difference in increase between modes. There was no significant difference between Groups 1 and 2 in exercise duration, peak heart rate-blood pressure (rate-pressure) product, baseline or peak heart rate or baseline or peak cardiac index. Therefore, in selected patients, VVIR pacing during exercise results in an increase in heart rate, duration of exercise and cardiac index that is unrelated to the degree of baseline left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cognitive task influence on relative hemispheric motor control: mouth asymmetry and lateral eye movements.

While strictly verbal cognitive tasks showed a strong left-hemisphere dominance, the presence of visualization and emotion in cognitive tasks resulted in increased involvement of the right hemisphere in motor control of speech as measured by mouth asymmetry. Spontaneous smiles showed right-hemisphere dominance. Lateral eye movements showed an unexpected shift to left gaze during speech which may suggest a dual task interference between speech and gaze motor control.

Adolescent↗

Hemispheric control of speech expression in aphasia. A mouth asymmetry study.

Clinical observation of aphasic patients often shows a dissociation between impaired propositional speech and preserved automatic speech. The question of differing hemispheric control between these speech tasks was examined by measuring asymmetry in facial muscle activity. In spite of right-sided facial palsy, greater opening of the right side of the mouth was seen for spontaneous speech, repetition, and word list generation, suggesting that the damaged left hemisphere still controlled motor output in these propositional tasks. However, greater opening of the left side of the mouth for serial speech and singing indicated at least a relatively greater role of the right hemisphere in these "automatic" tasks.

Adult↗

Dissociated hemispheric superiorities for reading stenography vs print.

In two lateralized tachistoscopic lexical decision experiments at different exposure durations, we found for high-frequency function words written in stenography a shift from a RVF advantage at long exposures to a LVF advantage at short exposures, while for the same words written in print a strong RVF effect persisted. We suggest that a reduction of exposure duration, together with the strong visuo-spatial features in stenography, activate right-hemispheric word recognition. Stenography, a non-orthographic and syllabic-ideographic writing system, could be a model to investigate different hemispheric reading processes in Western subjects.

Adult↗