Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban).
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Abciximab↗
Biomedical subjects
S Hale
Publications and source records attributed to S Hale.
Adenovirus hexon protein enhances nuclear delivery and increases transgene expression of polyethylenimine/plasmid DNA vectors.
Inefficient nuclear delivery restricts transgene expression using polyelectrolyte DNA vectors. To increase transfer from the cytoplasm to the nucleus, we have covalently linked adenovirus hexon protein to polyethylenimine (PEI, 800 kDa). Activity of the conjugate was compared with PEI and PEI linked to albumin. Hexon-containing complexes gave 10-fold greater transgene expression in HepG2 cells than PEI/DNA or complexes containing albumin, without increasing cell uptake. Following cytoplasmic injection into Xenopus laevis oocytes, hexon-containing complexes showed reporter gene expression to be elevated by 10-fold compared with PEI/DNA. The ability of hexon to promote nuclear delivery of PEI/DNA nanoparticles was compared with that of classical nuclear localization sequences (NLS) by measuring transgene expression following intracytoplasmic microinjection of hexon-PEI/DNA complexes and NLS-albumin-PEI/DNA complexes in rat-1 fibroblasts. The resulting nuclear transfer efficiency was in the following order: hexon-PEI/DNA>NLS-albumin-PEI/DNA>PEI/DNA>DNA alone>albumin-PEI/DNA. The activities of both NLS-albumin-PEI and hexon-PEI were abolished by co-injection of wheat germ agglutinin, suggesting that both act by means of the nuclear pore complex (NPC); in contrast, excess free NLS-albumin abolished transgene expression with NLS-albumin-PEI/DNA, but only partially inhibited hexon-PEI/DNA. Nuclear transfer efficiency following cytoplasmic injection was dependent on DNA concentration for all materials, although hexon conjugates showed much better activity than NLS-albumin at low DNA doses (500-1000 plasmids/cell). Our data are consistent with hexon mediating nuclear delivery of plasmid complexes by means of the NPC, using mechanisms that are only partially dependent on the classical NLS import pathway. The hexon-mediated mechanism of nuclear import enables substantially better transgene expression, particularly when DNA concentrations in the cytoplasm are limiting.
Active Transport, Cell Nucleus↗
Subscapular mass in a 68-year-old woman.
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Aged↗
Percutaneous intervention in saphenous venous grafts: in-stent restenosis lesions are safer than de novo lesions.
BACKGROUND: The histological appearance of stenosis in de novo saphenous venous grafts (DNSVG) consists of diffuse atherosclerosis that contains blood elements, necrotic debris and limited fibrocollagenous tissue. The friable nature of these lesions complicates percutaneous intervention (PCI) procedures. On the other hand, in-stent restenosis (ISR) of SVG is due primarily to atherosclerotic plaque or fibromuscular hyperplasia, with thrombus formation playing a secondary role. The purpose of this study is to compare the results of PCI in these two types of SVG lesions. METHODS: We reviewed our institutional interventional database from March 1996 through February 2000 and identified all consecutive patients who underwent PCI of at least one SVG. One hundred and ten patients were identified: 89 undergoing DNSVG intervention and 21 patients with ISR lesions. RESULTS: Acute coronary syndromes, degenerated and thrombus-containing lesions were more common in the DNSVG group. "Slow-, no-reflow" complicated 20% of the DNSVG lesions compared to none of the ISR lesions (p = 0.02). Post-procedural myocardial infarction was higher in the DNSVG group (13.5% versus 0%; p = 0.1) and correlated significantly with the occurrence of "slow-, no-reflow" (r = 0.43; p = 0.0001). Utilizing statistical modeling to adjust for baseline differences between the groups, ISR lesions were associated with a low risk of procedural complications (r = 0.22; p = 0.03). CONCLUSION: This study demonstrates that in this relatively high-risk population, PCI is safer in ISR lesions than in de novo SVG lesions.
Aged↗
Behavioral evidence for brain-based ability factors in visuospatial information processing.
The present study examined possible parallels between the structure of human visuospatial abilities and the organization of the neural systems. Forty-eight participants were tested on seven speeded visuospatial tasks. Three of these tasks were constructed so as to rely primarily on known ventral stream functions and four were constructed so as to rely primarily on known dorsal stream functions. Both sets of tasks spanned approximately the same range of difficulty as indexed by both the speed and accuracy of decision making. Factor analysis of response times on the seven tasks revealed only two significant factors. The putative ventral stream tasks all loaded heavily on one factor (mean loading=0.843) but only weakly on the other factor (mean loading=0.222); the putative dorsal stream tasks showed the opposite pattern in that they all loaded heavily on the second factor (mean loading=0.828) but only weakly on the first factor (mean loading=0.229). These findings are consistent with the hypothesis that human visuospatial abilities can be classified using categories based on the specializations of underlying neural structures and systems.
Adult↗
Relationships among processing speed, working memory, and fluid intelligence in children.
The present review focuses on three issues, (a) the time course of developmental increases in cognitive abilities; (b) the impact of age on individual differences in these abilities, and (c) the mechanisms by which developmental increases in different aspects of cognition affect each other. We conclude from our review of the literature that the development of processing speed, working memory, and fluid intelligence, all follow a similar time course, suggesting that all three abilities develop in concert. Furthermore, the strength of the correlation between speed and intelligence does not appear to change with age, and most of the effect of the age-related increase in speed on intelligence appears to be mediated through the effect of speed on working memory. Finally, most of the effect of the age-related improvement in working memory on intelligence is itself attributable to the effect of the increase in speed on working memory, providing evidence of a cognitive developmental cascade.
Child↗
Converging evidence that visuospatial cognition is more age-sensitive than verbal cognition.
In 3 separate experiments, the same samples of young and older adults were tested on verbal and visuospatial processing speed tasks, verbal and visuospatial working memory tasks, and verbal and visuospatial paired-associates learning tasks. In Experiment 1, older adults were generally slower than young adults on all speeded tasks, but age-related slowing was much more pronounced on visuospatial tasks than on verbal tasks. In Experiment 2, older adults showed smaller memory spans than young adults in general, but memory for locations showed a greater age difference than memory for letters. In Experiment 3, older adults had greater difficulty learning novel information than young adults overall, but older adults showed greater deficits learning visuospatial than verbal information. Taken together, the differential deficits observed on both speeded and unspeeded tasks strongly suggest that visuospatial cognition is generally more affected by aging than verbal cognition.
Adolescent↗
Age and individual differences in visuospatial processing speed: testing the magnification hypothesis.
Forty young adults and 40 older adults performed seven visuospatial information processing tasks. Factor analyses of the response times (RTs) yielded a single principal component with a similar composition in both age samples. For both samples, regressing the mean RTs of fast and slow subgroups for the seven tasks (18 conditions) on the corresponding mean RTs for their age group accounted for 99% of the variance. Taken together, these findings suggest that individual differences in processing time were largely task independent. The magnification hypothesis, a simple mathematical model of the interaction between age and ability, is presented. This model correctly predicts the finding that in both the young and the older adult groups, individual differences increased systematically with task difficulty. The magnification hypothesis also explains the regression parameters describing individual differences among young adults and predicts correctly that equivalent parameters describe individual differences among older adults. According to the magnification hypothesis, the RTs of slower individuals are more affected by aging than those of faster individuals, and slower individuals may be more at risk with respect to other biological insults (e.g., changes in health status) as well.
Adult↗
Answers to century-sized questions.
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Humans↗
Selective interference with verbal and spatial working memory in young and older adults.
Young and older adults were administered digit and location memory span tasks with and without verbal and spatial secondary tasks. Age differences were greater in location span than in digit span; however, there were no age differences in either the magnitude or pattern of effects of secondary tasks. There were also no age differences in the effects of secondary tasks on a combined (digit and location) task. On the digit and location span tasks, both young and older adults showed only domain-specific interference: naming colors selectively interfered with memory for digits, leaving memory for locations unaffected; pointing to matching colors selectively interfered with memory for locations, leaving memory for digits unimpaired. The results of the present study suggest a greater age deficit in spatial working memory than in verbal working memory, but provide no evidence of an age deficit in susceptibility to interference by secondary tasks in either domain.
Adolescent↗
Individual and developmental differences in working memory across the life span.
The effects of secondary tasks on verbal and spatial working memory were examined in multiple child, young adult, and older adult samples. Although memory span increased with age in the child samples and decreased with age in the adult samples, there was little evidence of systematic change in the magnitude of interference effects. Surprisingly, individuals who had larger memory spans when there was no secondary task showed greater interference effects than their age-mates. These findings are inconsistent with the hypothesis that age and individual differences in working memory are due to differences in the ability to inhibit irrelevant information, at least as this hypothesis is currently formulated. Moreover, our results suggest that different mechanisms underlie developmental and individual differences in susceptibility to interference across the life span. A model is proposed in which memory span and processing speed both increase with development but are relatively independent abilities within age groups.
Adult↗
Cerebellar contribution to linguistic processing efficiency revealed by focal damage.
The cerebellum's role in cognitive skills was examined in a child (L.C.) with focal injury to the left cerebellum. Initial symptoms included aphasia and dysarthria. At 3 and 9 months post-injury, clinical neuropsychological tests revealed persistent psychomotor slowing as well as deficits in executive functions. Further cognitive testing at 13 and 16 months post-injury demonstrated that L.C. processed information from both the linguistic and nonlinguistic domains more slowly than age-, grade- and sex-matched controls. Notably, her linguistic processing was more than twice as slow as that of her peers, whereas her nonlinguistic processing was only approximately 20% slower. Within each domain the degree of cognitive slowing was approximately the same across diverse tasks. These results are consistent with the hypothesis of a cerebellar contribution to cognitive processing, particularly the processing of linguistic information.
Cerebellar Diseases↗
Short-term and long-term memory in early temporal lobe dysfunction.
Following medial temporal damage, mature humans are impaired in retaining new information over long delays but not short delays. The question of whether a similar dissociation occurs in children was addressed by testing children (ages 7-16) with unilateral temporal lobe epilepsy (TLE) and controls on short- and long-term memory tasks, including a spatial delayed response task (SDR). Early-onset TLE did not affect performance on short delays on SDR, but it did impair performance at the longest delay (60 s), similar to adults with unilateral medial temporal damage. In addition, early-onset TLE affected performance on pattern recall, spatial span, and verbal span with rehearsal interference. No differences were found on story recall or on a response inhibition task.
Age of Onset↗
General lexical slowing and the semantic priming effect: the roles of age and ability.
Older adults performed three lexical information-processing tasks approximately 1.3 times slower than young adults. Consistent with general lexical slowing, slopes of regressions based on individual subjects' RTs on two of the tasks (single lexical decision and category judgment) did not differ from slopes based on the third (double lexical decision) task. Moreover, slopes based on the single lexical decision and category judgment tasks accurately predicted the size of semantic priming effects on the third (double lexical decision) task. This was true for the older group as a whole, and also for subgroups of fast, medium and slow older adults, as well as for young adult subgroups. The size of the semantic priming effects for the fast old and slow young subgroups (who differed in age but not in processing speed) were approximately equal, consistent with the idea that the effect of age on priming is entirely attributable to slowing. Across all tasks, each old subgroup (fast, medium, or slow) showed the same degree of slowing relative to the corresponding young subgroup, so that the differences in RTs observed between subgroups in the young sample were magnified in the old sample. Taken together, the present findings suggest that ability-related differences in lexical processing speed may be functionally equivalent to age-related differences and that both factors interact to determine performance on speeded lexical tasks.
Adult↗
Verbal and spatial working memory in school-age children: developmental differences in susceptibility to interference.
The development of verbal and spatial working memory was investigated with an interference paradigm. Memory spans were obtained from 3 groups (8-, 10-, and 19-year-olds) under 6 different conditions: Two primary memory tasks (1 verbal, 1 spatial) were administered in isolation and in conjunction with 2 versions of a secondary task. The primary tasks required recalling a series of visually presented digits and recalling the locations of Xs in a series of visually presented grids. The secondary tasks required reporting the color of the stimuli as they were presented using either a verbal or a spatial response. Analyses revealed that all age groups showed domain-specific interference (i.e., interference by a secondary task from the same domain as the primary task), but only the 8-year-olds also showed nonspecific interference (i.e., interference by a secondary task from a domain different than the primary memory task), suggesting that at least some executive functions do not reach adult levels of efficiency until approximately age 10.
Adolescent↗
A novel biologic function of serum amyloid A. Induction of T lymphocyte migration and adhesion.
In the course of an inflammatory response, the concentration of serum amyloid A (SAA), a hepatocyte-derived acute phase protein, increases up to 1000-fold above the normal level. Although SAA was previously thought to be immunosuppressive, we recently reported that SAA is a potent chemoattractant for monocytes and neutrophils. The present study shows that recombinant human (rh) SAA also induces directional migration of T cells in vitro. Phenotypic analyses revealed that CD4+ and CD8+ T cell subsets were equally responsive to rhSAA, whereas CD45RA cells were also not selectively attracted by rhSAA. The T cell chemotaxis induced by rhSAA was inhibited by pretreatment of cells with pertussis toxin, suggesting the interaction of rhSAA with a G-protein-coupled receptor species. T cells pretreated with an optimal concentration of SAA exhibited enhanced adherence to human umbilical cord endothelial cell monolayers. Subcutaneous administration of rhSAA into huPBL-SCID mice caused the infiltration of human T lymphocytes at the injection sites by 4 h. These results suggest that SAA may play an important role in recruiting T lymphocytes, as well as neutrophils and monocytes into inflammatory lesions.
Animals↗
Preconditioning stimuli and inadvertent preconditioning.
There are several factors besides brief episodes of total coronary occlusion which can provide sufficient stress to result in a preconditioning-like effect on the size of a myocardial infarction. Partial coronary artery stenosis, hypoxia, stretch, catecholamines, rapid pacing, and certain pharmacologic therapies may provide preconditioning stimuli. These same factors as well as mechanical complications in which a coronary artery is briefly occluded or stenosed prior to a subsequent coronary occlusion may lead to inadvertent preconditioning and confound the results of experimental cardiology studies.
Coronary Disease↗
Working memory following improvements in articulation rate in children with cerebral palsy.
It has been postulated that rehearsal rate is the primary determinant of working memory capacity for verbal material (Baddeley et al., 1975). A previous study of normal control children and children with spastic diplegic cerebral palsy (SDCP) suggested that covert rather than overt rehearsal rate determines working memory capacity (White et al., 1994). In the current study, a subset of SDCP children who received a surgical treatment to relieve spasticity were retested on measures of articulation rate and memory span. A subset of control children from the original study were also retested. The SDCP group showed improvements in articulation rate at follow-up, though memory span did not change and was again equivalent to that of controls. These findings indicate that increases in articulation rate are not necessarily accompanied by improvements in memory span, and provide additional evidence that working memory capacity may be determined by covert rather than overt articulatory rehearsal.
Articulation Disorders↗