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Biomedical subjects

J Grainger

Publications and source records attributed to J Grainger.

At least 19 recordsLinked to original sources
PubMed2001

Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels.

1. The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. 2. In endothelium-intact rings precontracted to the thromboxane A(2) mimetic, U46619, anandamide (0.01 - 30 microM) induced slowly developing concentration-dependent relaxations (pEC(50) [negative log of EC(50)]=6.1+/-0.1; R(max) [maximum response]=81+/-4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying R(max). Methanandamide was without effect on U46619-induced tone. 3. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 microM), the vanilloid receptor antagonist, capsazepine (3 and 10 microM) or the nitric oxide synthase inhibitor, L-NAME (100 microM). 4. The cyclo-oxygenase inhibitor, indomethacin (3 and 10 microM) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 microM), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 microM), shifted the anandamide concentration-response curve to the right. 5. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (R(max)=7+/-7%), as did K(+) channel blockade with tetraethylammonium (TEA; 3 microM) or iberiotoxin (100 nM). Blockade of small conductance, Ca(2+)-activated K(+) channels, delayed rectifier K(+) channels, K(ATP) channels or inward rectifier K(+) channels was without effect. 6. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Cross-modal repetition priming of heterographic homophones.

In two cross-modal priming experiments in French, we investigated the effects of auditorily presented heterographic homophones (an English example is /meId/) on the subsequent visual recognition of the dominant (MADE) and subordinate (MAID) printed forms. When only pronounceable, regular nonwords were used as distractor items in the lexical decision task, both dominant and subordinate forms were facilitated by the homophone prime relative to an unrelated word prime. When pseudohomophones were added among the nonword distractors, dominant targets continued to show facilitation while subordinate targets showed an inhibitory trend. These results provide evidence for inhibition-based selection in the processing of ambiguous words in the absence of any biasing context.

Adult↗
PubMed2001

Shared neighborhood effects in masked orthographic priming.

Several studies have found effects of orthographically related masked nonword primes on lexical decisions to target words. These effects have been explained by the neighborhood characteristics of the target word (Forster, 1987), but the neighborhood characteristics of the prime in combination with the target are also found to be important (Hinton, Liversedge, & Underwood, 1998). In this study, we present a new account of masked form-priming effects based on the shared neighborhood of prime and target. Shared neighbors are words that are activated by both prime and target. According to the interactive activation model (McClelland & Rumelhart, 1981), shared neighborhood determines the size of priming effects. This prediction was tested and confirmed in a masked priming experiment that manipulated the shared neighborhood density of complete primes.

Adult↗
PubMed2001

Priming complex words: evidence for supralexical representation of morphology.

Effects of morphologically related primes were examined in two masked prime experiments. Responses to both free root and derived suffixed word targets were facilitated when primes were derived suffixed words containing the target's root, and this facilitation effect showed a time course similar to that for the facilitation effect of repetition primes (though systematically smaller in magnitude). In a control experiment only the longest prime duration of Experiment 1 was used; responses to derived suffixed word targets were facilitated by both free root primes and derived suffixed word primes sharing the target's root (relative to unrelated and form-related control primes). The free root and derived suffixed word prime conditions did not differ significantly. In Experiment 2, only true derived word primes produced facilitation, whereas morphologically simple primes containing a pseudoroot did not influence performance relative to the unrelated prime condition. We argue that this supports a supralexical account of morphological representation.

Adult↗
PubMed2000

Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) can persist through adolescence and adulthood, resulting in significant disability. The use of low-dose oral methotrexate (MTX) for persistent polyarthritis has been shown to be effective by the USA/USSR collaborative study group. However, 2 of the most disabling subgroups of JIA, systemic and extended oligoarthritis, were underrepresented in that study. The present study was therefore conducted to investigate the efficacy of MTX in these 2 subgroups. METHODS: Patients under the age of 16 years who fulfilled the International League of Associations for Rheumatology criteria for systemic or extended oligoarticular arthritis were eligible for this multicenter, double-blind, placebo-controlled crossover trial. Forty-five patients with systemic and 43 with extended oligoarticular arthritis were enrolled. The dosage of MTX or placebo was 15 mg/m2, which could be increased to 20 mg/m2 after 2 months. Core outcome variables were considered as primary measures, giving a final score of "improved" or "not improved." Secondary measures included scores of systemic features and biochemical laboratory measures. Assessment of function was not included since there were no validated functional measures at the start of this trial in 1991. RESULTS: In the extended oligoarticular arthritis group, MTX treatment produced significant improvement in 3 of 5 core variables (erythrocyte sedimentation rate, physician's global assessment of disease activity, and parent's global assessment of disease activity). By the primary improvement criteria, there was significant overall improvement during MTX treatment. In the systemic arthritis group, only 2 of 5 core variables were significantly improved (physician's and parent's global assessment of disease activity). Systemic features were not part of the core variables, but the systemic feature score was not significantly different between MTX and placebo treatment. There was no significant overall improvement in this group during MTX treatment. However, no significant interaction between disease subgroup and treatment effect was demonstrated. When the data from both disease subgroups were combined, there was significant clinical improvement during MTX treatment (P = 0.006). CONCLUSION: MTX 15-20 mg/m2 given orally once a week was found to be an effective treatment for both extended oligoarticular and systemic JIA in this shortterm trial. Long-term efficacy needs to be addressed in future studies.

Adolescent↗
PubMed2000

Visual and phonological codes in letter and word recognition: evidence from incremental priming.

Critical issues in letter and word priming were investigated using the novel incremental priming technique. This technique adds a parametric manipulation of prime duration (or prime intensity) to the traditional design of a fast masked priming study. By doing so, additional information on the time course and nature of priming effects can be obtained. In Experiment 1, cross-case letter priming (a-A) was investigated in both alphabetic decision (letter/non-letter classification) and letter naming. In Experiment 2, cross-case word priming was investigated in lexical decision and naming. Whereas letter priming in alphabetic decision was most strongly determined by visual overlap between prime and target, word priming in lexical decision was facilitated by both orthographic and phonological information. Orthographic activation was stronger and occurred earlier than phonological activation. In letter and word naming, in contrast, priming effects were most strongly determined by phonological/articulatory information. Differences and similarities between letter and word recognition are discussed in the light of the incremental priming data.

Adult↗
PubMed1999

Unconscious semantic priming from pictures.

Three experiments examined the effects of unconsciously presented picture primes on semantic categorization and naming responses to both word and picture targets. Picture naming and word categorization responses to targets were faster and more accurate when the picture primes belonged to the same semantic category as the targets, so called priming effect. No priming was found when subjects performed a word reading task. When priming was evident, no difference was found between responses to targets that were nominally identical to primes (e.g. the picture of a lion followed by either the word LION or the picture of a lion) compared with nominally different targets from the same semantic category as the primes (e.g. the picture of an ELEPHANT followed by either the word LION or the picture of a lion). Responding did not differ significantly from chance when subjects were asked to categorize the primes as natural objects vs. artifacts or as meaningful vs. meaningless objects in three distinct forced-choice unspeeded tasks.

Adult↗
PubMed1999

Evaluation of polymorphisms in the presenilin-1 gene and the butyrylcholinesterase gene as risk factors in sporadic Alzheimer's disease.

The E4 allele of the apolipoprotein E gene (APOE) is a major risk factor for late-onset Alzheimer's disease (LOAD) but is neither necessary nor sufficient to cause the disease. In this study, we investigated polymorphisms in the presenilin-1 (PS-1), and butyrylcholinesterase (BChE) genes, which have been implicated as risk factors for LOAD. Our data-set comprised 177 AD and 118 control patients, all of whom had been histopathologically confirmed following autopsy. We have tested homozygosity for the PS-1 allele 1 and possession of the BChE-K variant in association with APOE epsilon4 as risk factors in LOAD. Our findings support an association between the PS-1 polymorphism and LOAD, finding homozygosity for allele 1 associated with an approximately two-fold increased risk. Our data also show that in subjects greater than 75 years of age possession of both BChE-K and APOE-epsilon4 alleles is associated with an increased risk of LOAD, whilst the risk associated with APOE-epsilon4 allele alone is not significant.

Aged↗
PubMed1999

The role of letter identity and letter position in orthographic priming.

Four experiments are reported investigating orthographic priming effects in French by varying the number and the position of letters shared by prime and target stimuli. Using both standard masked priming and the novel incremental priming technique (Jacobs, Grainger, & Ferrand, 1995), it is shown that net priming effects are affected not only by the number of letters shared by prime and target stimuli but also by the number of letters in the prime not present in the target. Several null results are thus explained as a tradeoff between the facilitation generated by common letters and the inhibition generated by different letters. Inhibition was significantly reduced when different letters were replaced by nonalphabetic symbols. Facilitation effects disappeared when the common letters did not have the same relative position in the prime and target strings, thus supporting a relative-position coding scheme for letters in words.

Adult↗
PubMed1998

Separation of polycyclic aromatic hydrocarbon metabolites by gamma-cyclodextrin-modified micellar electrokinetic chromatography with laser-induced fluorescence detection.

Using a modified micellar buffer consisting of gamma-cyclodextrin (gamma-CD) and sodium dodecyl sulfate (SDS), we have obtained separations of hydroxy-polycyclic aromatic hydrocarbons (hydroxyPAHs). These compounds are oxidative products of mammalian PAH metabolism. The analytes were detected with a commercial laser-induced fluorescence (LIF) detector. A number of hydroxyPAH isomers could be separated by changes in gamma-CD concentration. Baseline resolution of 12 hydroxyPAHs was obtained using 30 mM borate, 60 mM SDS and 40 mM gamma-CD. The particular site substitution of the hydroxy group can produce changes in the hydroxyPAH fluorescence spectrum, and the effect of optical filter selection was studied for the LIF detection. The mass detection limits were in the (0.08-0.5) x 10(-15) mol range. To our knowledge, this is the first report of the separation of metabolic products of PAHs (and several positional isomers) using gamma-CD and micellar electrokinetic chromatography.

Chromatography, Liquid↗
PubMed1997

Effects of orthographic neighborhood in visual word recognition: cross-task comparisons.

Effects of orthographic neighborhood in visual word recognition in Spanish were examined in 5 paradigms: progressive demasking, standard lexical decision, lexical decision with blocking of neighborhood density, naming, and semantic categorization. The results showed inhibitory effects of neighborhood frequency in the progressive-demasking task, in both lexical-decision tasks, as well as for low-density words in the naming task, and for high-density words in the semantic-categorization task. Higher levels of neighborhood density produced an inhibitory trend in the progressive-demasking task, facilitation in lexical decision (significant only when neighborhood density was blocked), and a robust facilitation effect in naming (only for words with higher frequency neighbors). A global analysis across tasks and one simulation study helped outline some of the underlying task-specific and task-independent mechanisms.

Decision Making↗
PubMed1997

Masked orthographic priming in bilingual word recognition.

Two lexical decision experiments tested the influence of briefly presented orthographically related primes on target word recognition in bilinguals. The prime stimuli were high-frequency words either from the same language as that of the target or from the other language known by the bilingual subjects. When the prime and target were from the same language, orthographically related primes systematically inhibited target word recognition, whereas orthographically dissimilar primes did not. When the prime and target were words from different languages, the amount of inhibition increased as a function of subjects' level of proficiency in the prime word's language, with highly proficient bilinguals showing practically equivalent amounts of within and across language inhibitory priming. These results strongly suggest that a printed string of letters can simultaneously activate lexical representations in both of the bilingual's languages (insofar as these share the same alphabet), even when subjects are performing a monolingual task.

Humans↗
PubMed1997

Extensive maternal representation of DNA-binding proteins that interact with regulatory target sites of the Strongylocentrotus purpuratus CyIIIa gene.

Nine different embryonic transcription factors interact at specific target sites in the cis-regulatory domain of the Strongylocentrotus purpuratus CyIIIa gene. We tested eight of these site sequences and show here that for every one a DNA-binding protein was present in unfertilized egg cytoplasm. The concentrations of active DNA-binding proteins per egg were estimated. We also present a new and convenient method for preparation of a material cytoplasmic fraction that retains these factors in active form.

Actins↗
PubMed1996

How initial fixation position influences visual word recognition: a comparison of French and Arabic.

The position the eye initially fixates in a written word influences the ease with which this word is recognized. Prior research has shown that the function relating ease of word recognition and initial fixation position in the word is not symmetric. Word recognition is generally superior when the initial fixation is left rather than right of the center of the word. This asymmetry in the function relating initial fixation position to word identifiability could be due to (a) hemispheric specialization, (b) reading habits, or (c) variations in lexical constraint. The present experiments tested these alternative explanations by comparing the effects of initial fixation position in prefixed and suffixed words in French and Arabic. The results show that, contrary to both the hemispheric specialization and reading habit hypotheses, the average initial fixation curves for Arabic are asymmetric neither to the left nor to the right but depend on the morphological structure of the stimuli, thus lending support to the lexical constraint hypothesis.

Adult↗
PubMed1996

Orthographic processing in visual word recognition: a multiple read-out model.

A model of orthographic processing is described that postulates read-out from different information dimensions, determined by variable response criteria set on these dimensions. Performance in a perceptual identification task is simulated as the percentage of trials on which a noisy criterion set on the dimension of single word detector activity is reached. Two additional criteria set on the dimensions of total lexical activity and time from stimulus onset are hypothesized to be operational in the lexical decision task. These additional criteria flexibly adjust to changes in stimulus material and task demands, thus accounting for strategic influences on performance in this task. The model unifies results obtained in response-limited and data-limited paradigms and helps resolve a number of inconsistencies in the experimental literature that cannot be accommodated by other current models of visual word recognition.

Adult↗
PubMed1995

Letter-position coding in random constant arrays.

The processing of letter-position information in randomly arranged consonant strings was investigated using a masked prime variant of the alphabetic decision (letter/nonletter classification) task. In Experiment 1, primes were uppercase consonant trigrams (e.g., FMH) and targets were two uppercase Xs accompanied by the target letter or a nonletter (e.g., XMX X%X). Response times were systematically faster when target letters were present in the prime string than when target letters were not present in the primer string. These constituent letter-priming effects were significantly stronger when the target letter appeared in the same position in the prime and target stimuli. This contrast between position-specific and position-independent priming was accentuated when subjects responded only when all the characters in the target string were letters (multiple alphabetic decision) in Experiment 2 and 3. In Experiment 4, when prime exposure duration was varied, it was found that position-specific priming develops earlier than position-independent priming. Finally, Experiment 5 ruled out a perceptual-matching interpretation of these result. An interpretation is offered in terms of position-specific and position-independent letter-detector units in an interactive-activation framework.

Humans↗