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Inhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation.

BACKGROUND: The endothelium protects the vascular wall through the nitric oxide (NO) release. Coronary endothelial dysfunction occurs early after heart transplantation and predicts the development of intimal thickening typical of graft coronary vasculopathy. OBJECTIVE: We designed this study to examine the effect of endothelial NO synthase (eNOS) inhibition on the endothelial dysfunction caused by rejection and on the development of accelerated atherosclerosis after heart transplantation. METHODS: To study the effect on these 2 end-points of inhibiting eNOS with intracoronary L-nitro arginine methyl ester (L-NAME; 1 mg/kg/day), infused with an osmotic pump for 30 days, we used a porcine model of heterotopic heart transplantation with pre-operative immunologic typing, to permit slow rejection without the need for immunosuppression. The endothelium-dependent relaxations of allografted coronary arteries, allografted arteries infused with L-NAME, allografted arteries mounted with the pump, and vehicle and native coronary arteries were compared 30 days after graft implantation using standard organ chamber experiments. We evaluated intimal thickening using a semi-quantitative scale (0-4+ grading). RESULTS: A significant decrease in relaxations to serotonin (5-HT) occurred in allografted arteries infused directly with L-NAME compared with allografted arteries from swine receiving 5-HT, and relaxations in the latter were decreased compared with those of swine receiving the vehicle and native coronary arteries (p < 0.05). We found no significant differences in endothelium-dependent relaxations to bradykinin among coronary rings from all groups. We observed a significant increase in the prevalence and severity of intimal thickening in allografted coronary arteries infused with L-NAME compared with allografts not infused (p < 0.05), which had significantly more intimal thickening compared with native coronary arteries (p < 0.05). CONCLUSION: These results demonstrate that inhibiting the NO pathway worsens the endothelial dysfunction caused by rejection after heart transplantation and accelerates the intimal thickening process, leading to graft coronary vasculopathy. Strategies designed to preserve endothelial integrity and function of the endothelial NO pathway should be used to prevent graft coronary vasculopathy.

Animals↗

Effects of gender on blood flow correlates of naming concrete entities.

A cross-cohort PET analysis was performed in 62 normal subjects (31 men and 31 women) to address the issue of whether men and women have different physiologic correlates of naming visually presented concrete entities. The subjects named nonunique concrete entities in one or more conceptual categories and also performed a face orientation decision task. A second analysis was performed in 24 additional subjects to assess whether there were gender effects related to the face orientation decision task and to constrain the interpretation of the first analysis. Male subjects engaged the left inferotemporal region and several other left hemisphere regions more than female subjects did during visual naming. Areas showing more activity in female subjects included the right inferior frontal gyrus and right precentral cortex, regions that were less active in visual naming than in the face orientation decision task. In other words, the male subjects engaged the latter regions less or deactivated them more than female subjects. The results can be interpreted as showing a greater modulation of activity in both hemispheres for men compared to women. Although the gender effects we found are smaller than the task effects, they are not negligible for the purposes of performing and interpreting functional imaging studies.

Adult↗

Administration of N(omega)-L-arginine methyl ester (L-NAME) impairs endothelium-dependent relaxation in gravid but not nongravid rats.

OBJECTIVE: To characterize the impairment of endothelium-dependent relaxation induced by administration of the nitric oxide synthase (NOS) inhibitor N(omega)-L-arginine methyl ester (L-NAME) to gravid rats and to determine whether L-NAME affects nongravid rats in a similar manner. METHODS: Acetylcholine (ACh; 0.01-10 microM) relaxation was studied in aortic segments (contracted with 10 nM norepinephrine) from Wistar rats that were hypertensive after receiving L-NAME (0.5 mg/mL in drinking water) before gravidity (hypertensive virgin rats [HVR]), during gravidity (hypertensive gravid rats [HGR]), or during the last 10 days of gravidity to 24 hours postpartum (hypertensive puerperal rats [HPR]). We also studied aortic segments from corresponding groups of untreated normotensive rats (normotensive gravid rats [NGR], normotensive puerperal rats [NPR], and normotensive virgin rats [NVR]). The approximate participations of NO and the hyperpolarizing mechanisms in ACh relaxation were calculated from the reduction of relaxation observed, respectively, after incubation with the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 0.1 mM) or after contraction with 50 mM of potassium chloride. Expression of endothelial NOS protein was studied by Western blot in segments of HGR and NGR. RESULTS: Acetylcholine relaxation was reduced in HGR compared with NGR, and this reduction correlated with the severity of hypertension. In contrast, ACh relaxation in HVR was similar to that in NVR, and that of HPR was similar to that in NPR. The NO component of relaxation was reduced in HGR but preserved in the other groups. Nevertheless, there were no differences in endothelial NOS protein expression between NGR and HGR. The hyperpolarizing component in relaxation was enhanced in HVR and HPR but not HGR. CONCLUSION: Administration of L-NAME induced an impairment of endothelium-dependent relaxation, involving both nitric oxide- and hyperpolarizing-dependent mechanisms in gravid but not virgin rats; this impairment resolved with delivery.

Acetylcholine↗

Naming skills of children born preterm in comparison with their term peers at the ages of 9 and 16 years.

The linguistic abilities of children born preterm at 32 weeks' gestation or earlier at Kuopio University Hospital during 1984 to 1986 were evaluated during successive phases of a prospective study. The study protocol included the Rapid Automatic Naming test and Wechsler Intelligence Scale for Children - Revised at 9 years of age and a modified Stroop Color-Word test and the Wechsler Intelligence Scale - Revised at the age of 16 years. Fifty-one children born preterm (26 males, 25 females) and 51 age-matched and sex-matched term controls (26 males, 25 females) were studied at the age of 9 years. At the age of 16 years, 40 children born preterm (19 males, 21 females) and 31 term controls (14 males, 17 females) participated in the study. The children born preterm scored significantly lower in two naming tasks than the controls at the age of 9 years. However, there was no difference between the study groups in naming skills at the age of 16 years or in verbal IQ in either study phase. Maternal education level was not associated with naming skills. Thus, the consequences of preterm birth seem to be minor in relation to linguistic skills during school age and diminish by adolescence.

Adolescent↗

Tachistoscopic tests of colour naming and matching in schizophrenia: evidence for posterior callosum dysfunction?

Neuropsychological studies have shown that the integrity of the posterior corpus callosum is necessary for accurate colour naming in the left visual field (LVF) and colour matching across hemifields. Using this model, 22 schizophrenics, 14 depressive and 16 healthy matched controls were given a battery of tachistoscopic tests of colour perception. The schizophrenics made significantly more errors, in naming colours in the LVF compared to depressives, and in matching colours across fields compared to depressives and normals. There were no differences between groups for right visual (RVF) colour naming or matching within right and left visual fields. These findings support the hypothesis that trans-callosal transmission may be impaired in schizophrenia and are unlikely to be due to a specific disorder of colour perception, neuroleptic drugs or generally impaired performance. Those schizophrenics whose LVF naming errors exceeded RVF errors were more likely to have first rank symptoms and showed less cerebral atrophy but did not differ on other variables. The techniques described may be useful for further research into interhemispheric function in schizophrenia.

Adult↗

Phonological priming in children's picture naming.

Two experiments examined phonological priming in children and adults, using a cross-modal picture-word interference task. Pictures of familiar objects were presented on a computer screen, while interfering words (IWs) were presented over headphones. In terms of their relation to target pictures, IWs were either phonologically related, unrelated, neutral (the word go), or identical. Ninety children (30 aged 4;11 to 5;11, 30 aged 6;11 to 7;11, and 30 aged 9;5 to 11;9) and 30 adults were instructed to name the pictures as quickly as possible while ignoring the IWs. In Experiment 1, related IWs shared onset consonants with the names of the pictures. Across ages, participants named pictures faster with related IWs than with unrelated IWs. In Experiment 2, related IWs rhymed with the targets. Here, only the youngest children (five to seven-year-olds) named pictures faster with related IWs than with unrelated IWs. The results indicate that priming effects reach a peak during a time when articulatory information is being consolidated in the output phonological buffer. The disappearance of the rhyme priming effect with age may reflect the gradual emergence of the onset as an organizing structure in speech production. This increased prominence of the onset can be viewed as one component of a just-in-time, incrementalist approach to speech production that allows adults to speak more fluently than children.

Child↗

An appearance-function shift in children's object naming.

The relative importance of appearance and potential function in children's object naming was examined. Potential function is an object capability that may not be currently realized (e.g. an empty mug has the potential to hold coffee). In Study 1, sixteen children from each of three age groups (3;8, 4;8, and 6;1) were taught novel names for unfamiliar objects; they then had to decide whether these applied to items that resembled the training objects in either appearance or potential function. The youngsters were also shown deceptive objects (e.g., an eraser that looked like a pencil) and had to choose between familiar appearance and function names for them (e.g., pencil or eraser). The frequency of function-based responding in both tasks increased with age. In Study 2, the name training procedure was revised so that equal emphasis was given to both apparent and functional features. The main results of the first study were replicated. Neither study obtained evidence of a strong relation between the appearance-function shift and increased understanding of the appearance-reality distinction.

Child Language↗

Color naming and categorization in inherited color vision deficiencies.

Dichromatic subjects can name colors accurately, even though they cannot discriminate among red-green hues (Jameson & Hurvich, 1978). This result is attributed to a normative language system that dichromatic observers developed by learning subtle visual cues to compensate for their impoverished color system. The present study used multidimensional scaling techniques to compare color categorization spaces of color-vision deficient (CVD) subjects to those of normal trichromat (NT) subjects, and consensus analysis estimated the normative effect of language on categorization. Subjects sorted 140 Munsell color samples in three different ways: a free sorting task (unlimited number of categories), a constrained sorting task (number of categories limited to eight), and a constrained naming task (limited to eight basic color terms). CVD color categories were comparable to those of NT subjects. For both CVD and NT subjects, a common color categorization space derived from the three tasks was well described by a three-dimensional model, with the first two dimensions corresponding to reddish-greenish and yellowish-bluish axes. However, the third axis, which was associated with an achromatic dimension in NTs, was not identified in the CVD model. Individual differences multidimensional scaling failed to reveal group differences in the sorting tasks. In contrast, the personal color naming spaces of CVD subjects exhibited a relative compression of the yellowish-bluish dimension that is inconsistent with the typical deutan-type color spaces derived from more direct measures of perceptual color judgments. As expected, the highest consensus among CVDs (77%) and NTs (82%) occurred in the naming task. The categorization behaviors studied in this experiment seemed to rely more on learning factors, and may reveal little about CVD perceptual representation of colors.

Adult↗

Towards a model to predict macular dichromats' naming errors: effects of CIE saturation and dichromatism type.

Thirty macular dichromat children (12 protanopes + 18 deuteranopes) and 29 controls, between 5 and 9 years old, participated in a monolexemic denomination task. Their clinical status was determined after a repeated application of a chromatic test set (Ishihara, CUCVT, and TIDA). The stimuli to be named were 12 tiles from the Color-Aid set belonging to the green, blue, and purple basic categories. Results showed that: (a) Dichromats made more naming errors when low saturation stimuli were used; (b) protanopes made more errors that deuteranopes; and (c) pseudoisochromatic lines predicted accurately the type of most frequent naming errors but they underestimated macular dichromats' functional capacity to name colors. Results are consistent with a model of macular dichromats' vision that hypothesizes a residual third type of cone in the periphery of the retina. Implications of this fact for everyday use of colors by macular dichromats' and for the validity of standard clinical diagnoses are discussed.

Child↗

Confrontation naming in Chinese patients with left, right or bilateral brain damage.

Confrontation naming of 52 unilateral or bilateral brain-damaged Chinese patients were examined with a modified version of the Boston Naming Test (BNT). Chinese patients with left or right hemisphere lesions, contrary to studies on English speakers, demonstrated similar levels of naming impairments, supporting the notion that English and Chinese are mediated by different neuroprocessing systems. In addition, the psychometric properties of the BNT on Chinese population were examined. While the test demonstrated satisfactory internal consistency and discriminant validity, level of education was found to be a significant factor affecting participants' performance. A cut-off score of 24 in spontaneous naming yielded a sensitivity of 73.1% and specificity of 75.3% in differentiating normal from brain-damaged participants, suggesting that the modified BNT is applicable to the Chinese population.

Adolescent↗

Nitric oxide synthase inhibition by L-NAME prevents the decrease of Na+,K+-ATPase activity in midbrain of rats subjected to arginine administration.

In the present study we investigated the effect of acute administration of L-arginine on Na(+),K(+)-ATPase and Mg(2+)-ATPase activities and on some parameters of oxidative stress (chemiluminescence and total radical-trapping antioxidant parameter-TRAP) in midbrain of adult rats. We also tested the effect of L-NAME on the effects produced by arginine. Sixty-day-old rats were treated with an acute intraperitoneal injection of saline (group I, control), arginine (0.8 g/kg) (group II), L-NAME (2 mg/kg) (group III) or arginine (0.8 g/kg) plus L-NAME (2 mg/kg) (group IV). Na(+),K(+)-ATPase activity was significantly reduced in the arginine-treated rats, but was not affected by other treatments. In contrast, Mg(2+)-ATPase activity was not altered by any treatment. Furthermore, chemiluminescence was significantly increased and TRAP was significantly decreased in arginine-treated rats, whereas the simultaneous injection of L-NAME prevented these effects. These results demonstrate that in vivo arginine administration reduces Na(+),K(+)-ATPase activity possibly through free radical generation induced by NO formation.

Animals↗

Drugs modifying nitric oxide metabolism affect plasma cholesterol levels, coagulation parameters, blood pressure values and the appearance of plasma myocardial necrosis markers in rabbits: opposite effects of L-NAME and nitroglycerine.

UNLABELLED: Various experiments have shown that decreased nitric oxide values alter plasma lipid levels or coagulation parameters or blood pressure values or cause myocardial necrosis phenomena, but it is not clear whether these alterations are reciprocally connected, or whether nitric oxide changes are involved in the appearance of some coronary disease risk factors (lipid, coagulation, blood pressure alterations) and myocardial necrosis. AIMS: We modified nitric oxide levels in rabbits using L-NAME (a NO synthase blocker) or nitroglycerine (a NO donor), and simultaneously evaluated variations in total and HDL cholesterol levels, some coagulation parameters, mean blood pressure values and myocardial necrosis patterns. RESULTS: L-NAME lowered plasma nitric oxide values, increased plasma total cholesterol and decreased HDL cholesterol levels, enhanced the amount of plasma fibrinogen, shortened prothrombin times, elevated the mean blood pressure values and caused the appearance of cardiac necrosis markers (c-troponin I, creatine kinase) in plasma and coagulative necrosis lesions in the myocardium. The administration of nitroglycerine to rabbits treated with L-NAME increased plasma nitric oxide levels and reversed the biochemical lesions caused by L-NAME. CONCLUSIONS: Our data show that the studied alterations in cholesterol values, coagulation parameters, increased mean blood pressure values and myocardial necrosis markers are strictly related to modified plasma nitric oxide levels, and that the regulation of nitric oxide metabolism affects the presence or absence of some coronary disease risk factors (lipid, coagulation and blood pressure alterations) and plasma indicators of myocardial necrosis.

Animals↗

Object names and object functions serve as cues to categories for infants.

Can object names and functions act as cues to categories for infants? In Study 1, 14- and 18-month-old infants were shown novel category exemplars along with a function, a name, or no cues. Infants were then asked to "find another one," choosing between 2 novel objects (1 from the familiar category and the other not). Infants at both ages were more likely to select the category match in the function than in the no-cue condition. However, only at 18 months did naming the objects enhance categorization. Study 2 shows that names can facilitate categorization for 14-month-olds as well when a hint regarding the core meaning of the objects (the function of a single familiarization object) is provided.

Association Learning↗

Investigating single-word syntactic primes in naming tasks: a recurrent network approach.

Three experiments compared the qualitative pattern of participants' word-naming performance in a syntactic priming task with the qualitative pattern of performance generated by a recurrent network model. Experiments 1 and 2 demonstrated that when participants had a 600-ms response deadline, the appropriateness of a syntactic prime affected their naming times for high-frequency words but not low-frequency words. However, Experiment 2 also demonstrated that participants made the most pronunciation errors when naming inconsistent low-frequency words (e.g., pint) that were preceded by an inappropriate prime. The results of Experiment 3 suggest that participants' naming times to both high- and low-frequency words are affected by syntactic primes when there is no response deadline. The implication of these findings for the study of syntactic priming in English and other languages is discussed.

Attention↗

Effects of word frequency and spelling-to-sound regularity in naming with and without preceding lexical decision.

The effects of word frequency and spelling-to-sound regularity were examined using standard naming, standard lexical-decision, go/no-go naming, and go/no-go lexical-decision tasks. In both the standard and go/no-go naming tasks, tasks requiring phonological coding, a significant Frequency x Regularity interaction was observed. That is, the regularity effect was limited to low-frequency words. In the standard and go/no-go lexical-decision tasks, tasks not requiring phonological coding, no Frequency x Regularity interaction was observed. These results indicate not only that the Frequency x Regularity interaction is a product of phonological coding processes but also that these processes are similar in the standard and go/no-go naming tasks. Results are discussed in terms of the dual-route and the parallel distributed processing frameworks.

Adult↗

Why do non-color words interfere with color naming?

In the non-color-word Stroop task, university students' response latencies were longer for low-frequency than for higher frequency target words. Visual identity primes facilitated color naming in groups reading the prime silently or processing it semantically (Experiment 1) but did not when participants generated a rhyme of the prime (Experiment 3). With auditory identity primes, generating an associate or a rhyme of the prime produced interference (Experiments 2 and 3). Color-naming latencies were longer for nonwords than for words (Experiment 4). There was a small long-term repetition benefit in color naming for low-frequency words that had been presented in the lexical decision task (Experiment 5). Facilitation of word recognition speeds color naming except when phonological activation of the base word increases response competition.

Analysis of Variance↗

Naming, rehearsal, and interstimulus interval effects in memory processing.

Recognition memory was tested for lists of 6 briefly (0.08 s) presented pictures at different interstimulus intervals (ISI) of 0.08, 1, and 4 s. Experiment 1 showed a 16% performance increase (ISI effect) for increasing ISI for travel slide but not kaleidoscope pictures. Experiment 2 showed that learning names for the kaleidoscope pictures then resulted in a substantial (20%) ISI effect, not attributable solely to the added exposure to the pictures. Experiment 3 required names, color evaluations, or blank stares during list-memory presentations. Interviews established that the most effective memory strategy was chaining the names together, followed by repeating the most current name, and in turn followed by reliance upon only the sensory experience. All groups in Experiments 2 and 3, independent of ISI effects, showed U-shaped serial position functions. Rehearsal is shown to be nonessential and cannot be the general cause of the primary effect of the serial position function.

Adolescent↗

Factors influencing word naming in younger and older adults.

The present study examined age differences in the influence of 3 factors that previous research has shown to influence word-naming performance. The influence of word frequency, orthographic length, and orthographic neighborhood measures was examined using large-scale regression analyses on the naming latencies for 2,820 words. Thirty-one younger adults and 29 older adults named all of these words, and age differences in the influence of these factors were examined. The results revealed that all 3 factors predicted reliable amounts of variance in word-naming latencies for both groups. However, older adults showed a larger influence of word frequency and reduced influences of orthographic length and orthographic neighborhood density compared with younger adults. Overall, these results suggest that lexical level factors increase in influence in older adults whereas sublexical factors decrease in influence.

Adolescent↗