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N Raz

Publications and source records attributed to N Raz.

At least 19 recordsLinked to original sources
PubMed1998

The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 are released from the cell surface upon antibody binding.

The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane form and a glycosylphosphatidylinositol (GPI)-anchored form. Here we report that CD58 is released from JY cells following cross-linking by immobilized anti-CD58 monoclonal antibodies. Antibodies to other cell surface proteins, as well as PMA and LPS, did not trigger CD58 release. The release resulted from membrane cleavage, since biotin-labeled CD58 was released from biotinylated cells, and down-modulation of CD58 surface expression accompanied accumulation of soluble CD58 IN culture media. We have previously reported the isolation of JY variant cells, which lack expression of GPI anchored proteins and thus express only the transmembrane form of CD58. Here we show that these variant cells release CD58 upon crosslinking, indicating that the transmembrane isoform is released, probably by proteolysis. Antibodies directed to the cytoplasmic domain of CD58, in contrast to antibodies against an extracellular epitope of CD58, did not react with released CD58, supporting a membrane cleavage mechanism. It is also shown that CD58, released from [3H]ethanolamine-labeled JY cells, contained ethanolamine. This result demonstrated that the GPI-anchored CD58 can be released in parallel to the transmembrane isoform and that this release does not result from proteolytic cleavage, since cleavage by a protease would have removed the ethanolamine. The present data suggest that the two isoforms of CD58 are released upon antibody binding and that their release is mediated by distinct mechanisms.

Antigen-Antibody Reactions↗
PubMed1998

The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 associate with protein kinases.

The significance of the glycosylphosphatidylinositol (GPI) anchor is unknown. Since GPI-anchored proteins mediate signaling, it has been suggested that the GPI structure serves as a signal-transducing element. However, the division of signaling functions between transmembrane and GPI-anchored proteins is unclear. Studies of distinct membrane-anchored forms of the same protein may resolve this issue. The adhesion molecule CD58 is expressed on the cell surface in both a transmembrane and a GPI-anchored form and hence provides a useful model. We studied CD58 in the human B lymphoblastoid cell line JY. In addition to mediating adhesion, CD58 is involved in signal transduction. Incubation of JY cells with immobilized anti-CD58 Abs results in extensive tyrosine phosphorylation and in secretion of TNF-alpha. We demonstrate that CD58 is associated with protein kinase(s) and with several kinase substrates. We further demonstrate that both CD58 isoforms are involved. CD58 in JY variant cells, which express only the transmembrane form, as well as CD58 in JY variant cells, which express only the GPI-anchored form, are associated with kinase activity. This association results in a phosphorylation pattern that is common to the variant and to wild-type JY cells. Thus, these findings suggest that the capacity of GPI-anchored proteins to interact with kinases is not always dependent on the GPI anchor itself.

B-Lymphocytes↗
PubMed1998

Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging.

To examine putative brain substrates of cognitive functions differentially affected by age the authors measured the volume of cortical regions and performance on tests of executive functions, working memory, explicit memory, and priming in healthy adults (18-77 years old). The results indicate that shrinkage of the prefrontal cortex mediates age-related increases in perseveration. The volume of visual processing areas predicted performance on nonverbal working memory tasks. Contrary to the hypotheses, in the examined age range, the volume of limbic structures was unrelated to any of the cognitive functions; verbal working memory, verbal explicit memory, and verbal priming were independent of cortical volumes. Nevertheless, among the participants aged above 60, reduction in the volume of limbic structures predicted declines in explicit memory. Chronological age adversely influenced all cognitive indices, although its effects on priming were only indirect, mediated by declines in verbal working memory.

Adolescent↗
PubMed1998

Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study.

PURPOSE: The purpose of this study was to determine the effects of age and sex on the size of the cerebellar hemispheres, the cerebellar vermis, and the pons in healthy adults. METHODS: We estimated the volumes of the cerebellar hemispheres (excluding the vermis and the peduncles), the cross-sectional area of the vermis, and the cross-sectional area of the ventral pons from MR images obtained in 146 healthy volunteers, 18 to 77 years old. RESULTS: We found a mild but significant age-related reduction in the volume of the cerebellar hemispheres and in the total area of the cerebellar vermis; however, the analysis of age trends in the vermian lobules revealed differential age-related declines. The areas of lobules VI and VII and of the posterior vermian lobules (VIII-X) declined significantly with age, whereas the anterior vermis (I-V) showed no significant age-related shrinkage. The volume of the cerebellar hemispheres (especially the right) and the area of the anterior vermis were greater in men, even after adjustment for height. Neither age nor sex affected the area of the ventral pons. CONCLUSIONS: Normal aging of the cerebellum is associated with selective regional shrinkage. The cerebellar hemispheres and the area of the anterior vermis may be larger in men than in women regardless of differences in body size.

Adolescent↗
PubMed1998

Differential aging of the human striatum: a prospective MR imaging study.

BACKGROUND AND PURPOSE: Advancing age is associated with declines in motor function; understanding age-related changes in the basal ganglia, therefore, is imperative for comprehension of such functional changes. The purpose of this study was to examine the age, sex, and hemispheric differences in volume of the caudate nucleus, the putamen, and the globus pallidus. METHODS: In a sample of 148 healthy right-handed adults (18-77 years old) with no evidence of age-related motor disorders, we estimated the volume of the head of the caudate nucleus, the putamen, and the globus pallidus from MR images. RESULTS: The analyses revealed bilateral age-related shrinkage of the head of the caudate nucleus and the putamen in both sexes. In men, the age-related shrinkage of the caudate was stronger on the left, whereas, in women, the opposite trend was evident. In both sexes, age-related shrinkage of the right putamen was greater than of its left counterpart. The mild bilateral age-related shrinkage of the globus pallidus was observed only in men. In both sexes, we observed significant rightward asymmetry in the putamen, significant leftward asymmetry in the caudate, and no asymmetry in the globus pallidus. CONCLUSIONS: Bilateral age-related shrinkage of the neostriatum is found in healthy adults. The shrinkage of the globus pallidus is less pronounced and may be restricted to men only.

Adolescent↗
PubMed1997

Memory impairment in multiple sclerosis: a quantitative review.

To assess the nature and magnitude of memory impairment in multiple sclerosis (MS), the authors analyzed quantitatively 36 studies comparing the memory performance of MS participants to healthy controls. The authors studied (a) the pattern of impairment across short-term memory (STM), working memory (WM), and long-term memory (LTM); (b) the moderating influence of retrieval support on LTM impairment; (c) the covariation of WM and LTM impairment; and (d) the moderating influence of clinical characteristics of the MS sample on memory impairment. The analyses revealed significant impairment across all memory domains and failed to support a retrieval-based account of LTM dysfunction in MS patients. In addition, robust associations were found between clinical features of MS and memory impairment. The findings suggest a more global pattern of memory deficits in MS than has been previously believed, with deficits clearly associated with neurological disability and disease course.

Cognition Disorders↗
PubMed1997

Aging and olfactory recognition memory: effect of encoding strategies and cognitive abilities.

The effects of two encoding manipulations on recognition memory for odors were examined in 20 young and 20 elderly males. Subjects were instructed to use two different encoding strategies: (1) labeling-plus-definition (i.e., naming the odor and giving a short description) and, (2) life-episode association (i.e., associating a memory of a life-episode with each odor). Results revealed that elderly subjects performed significantly worse than young subjects in the labeling-plus-definition condition, but not in the life-episode task in which they achieved a level of performance not significantly different from the young. Encoding specificity or precision did not significantly impact recognition memory for the odors in either group. Analysis of response bias revealed that, in the label-plus-definition condition, young subjects were more conservative in responding style, while more liberal in their responding in the life-episode condition. In contrast, elderly subjects exhibited nearly identical response bias across both encoding conditions. The results suggest that age-related deficits in olfactory memory may be strategy dependent.

Adult↗
PubMed1995

Age, gender, and hemispheric differences in human striatum: a quantitative review and new data from in vivo MRI morphometry.

We reviewed postmortem and neuroimaging studies of striatal neuroanatomy in humans. The quantitative review revealed evidence of moderate age-related shrinkage of the caudate nucleus and the putamen and consistent leftward asymmetry of the globus pallidus. The data on sex differences were very sparse. We examined neostriatal structures in two samples (healthy volunteers and patients with negative radiological findings) using in vivo magnetic resonance imaging. In both samples, bilateral age-related shrinkage of the caudate nucleus was found, although among the patients the effect was significant only for males. The putamen was measured only in the second sample, and age-related reduction in its volume was found also only among males. A trend for rightward asymmetry in the volume of caudate nucleus was observed in both samples, although it reached statistical significance only among the patients. Putative pathological and physiological mechanisms underlying the observed differences in teh neostriatum are discussed.

Adolescent↗
PubMed1995

Differential effects of aging on memory for content and context: a meta-analysis.

The authors reviewed the evidence of age differences in episodic memory for content of a message and the context associated with it. Specifically, the authors tested a hypothesis that memory for context is more vulnerable to aging than memory for content. In addition, the authors inquired whether effort at encoding and retrieval and type of stimulus material moderate the magnitude of age differences in both memory domains. The results of the meta-analysis of 46 studies confirmed the main hypothesis: Age differences in context memory are reliably greater than those in memory for content. Tasks that required greater effort during retrieval yielded larger age differences in content but not in context memory. The greatest magnitude of age differences in context memory was observed for those contextual features that were more likely to have been encoded independently from content. Possible mechanisms that may underlie age differences in context memory-attentional deficit, reduced working memory capacity, and failure of inhibitory processing are discussed.

Adult↗
PubMed1995

Selective neuroanatomic abnormalities in Down's syndrome and their cognitive correlates: evidence from MRI morphometry.

We examined the pattern of neuroanatomic abnormalities in adults with Down's syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer's disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hippocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefrontal white matter, the orbitofrontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer's disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlation analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.

Adult↗
PubMed1994

Procedural and declarative memory: a developmental study.

Measures of procedural and declarative memory were administered to 88 children forming two groups, aged 8 and 12. Two measures of priming, Gollin Figures and Degraded Words, were compared to declarative measures of recall. Strong support for a developmental dissociation between priming tasks and declarative memory was found. Both age groups showed a similar amount of priming facilitation, yet a significant age effect was observed for the declarative recall tasks. Current findings demonstrate that the level of procedural memory performance stabilizes during a period of development when declarative memory continues to improve.

Association Learning↗
PubMed1994

Toward the neural basis of verbal priming: a cognitive-neuropsychological synthesis.

Repetition priming is a mnemonic phenomenon that has attracted considerable attention from neuropsychologists and cognitive scientists. In an attempt at elucidating the putative mechanisms of priming, the present review draws on evidence from both domains. The review is restricted to verbal priming of visually presented stimuli--an area that accounts for the majority of empirical studies of priming. A number of theoretical accounts are presented. The interim conclusion is that neither multiple systems nor unitary system-multiple process theories can adequately explain the data on priming, although both contain many valid components. An integrative model is proposed to improve the explanation of the empirical evidence. The central assertion of the proposed model is that repetition priming depends on perceptual processes that can be mapped on specific neural systems. It is postulated that individual differences in perceptual processing ability predict variability in memory performance. It is proposed that data-driven priming of verbal stimuli critically depends on the activity of primary and secondary visual cortices in the right hemisphere, whereas conceptually-driven priming is hypothesized to rely on the activities of higher order tertiary association cortices in language areas and more anterior neocortical areas.

Alzheimer Disease↗
PubMed1994

Memory for facts, source, and context: can frontal lobe dysfunction explain age-related differences?

Age-related differences in memory for facts, source, and contextual details were examined in healthy young (18-35 years old) and old (65-80 years old) volunteers. In all tested memory functions, decline over time was greater in the elderly than in the young. A time-dependent increase in the prevalence of source amnesia errors was clearly associated with old age. Contrary to several recent reports, measures of frontal lobe functions did not predict source memory. Nevertheless, some of these putative frontal function measures were related to memory for contextual details. The number of perseverative responses on the Wisconsin Card Sorting Test was inversely related to performance on both factual and contextual memory tests, but the association with contextual memory was stronger. Difficulties with response selection on a Stroop task predicted poor contextual memory in young but not in old adults.

Adolescent↗
PubMed1992

Age-related regional differences in cerebellar vermis observed in vivo.

We investigated age-related differences in the cerebellar vermis. The areas of five vermal regions of interest were estimated from digitized midsagittal magnetic resonance imaging scans of 29 healthy volunteers and 30 neurologically intact patients (aged 18 to 78 years) who were free of vestibular symptoms, seizures, psychosis, or alcoholism. The five regions of interest included the following: (1) lingula and centralis, (2) culmen, (3) declive, folium, and tuber, (4) pyramis, and (5) uvula and nodulus. The ventral pons was used as a control region. After covarying skull size, we found a significant age-related reduction in the total area of the cerebellar vermis. The area of the dorsal regions declined with age, whereas the ventral segments of the vermis--lingula-centralis and uvula-nodulus--showed no significant age-related shrinkage. Notably, the area of the most dorsomedial portion, the declive-folium-tuber, tended to be more strongly associated with age than other segments. The pontine area was unaffected by age. No sex differences were found in the area of the vermis or its subdivisions, but the ventral pontine area was larger in male subjects than in female subjects, even after adjustment for skull size. The mechanisms underlying the observed differences are unclear. It appears, however, that phylogenetically more recent vermal regions, which are late to mature and are endowed with more extensive cortical connections, are the most vulnerable to the effects of aging.

Adolescent↗
PubMed1992

Age-related shrinkage of the mamillary bodies: in vivo MRI evidence.

Mamillary body (MB) is a diencephalic structure hypothesized to be involved in memory, a cognitive function that declines with age. In this study, age-related differences in the size of MB were examined in vivo using magnetic resonance (MR) imaging. The cross-sectional area of the MB was estimated from MR images of the brain in healthy volunteers and neurologically intact patients (age 18-78). The cross-sectional area of the tectum was used as a control region of interest. We found a significant age-related reduction in the area of the MB, but not of the tectum. No sex differences were observed in the size of either structure.

Adolescent↗
PubMed1990

Mechanism of age-related differences in frequency discrimination with backward masking: speed of processing or stimulus persistence?

In Experiment 1, frequency-discrimination thresholds were estimated in a 2-interval, forced-choice, backward masking procedure with a masker acoustically dissimilar to the targets. Young subjects were more efficient in escaping the effects of masking than were their elderly counterparts. In Experiment 2, young and elderly subjects performed the same task, with a masker acoustically similar to the targets and with a target-dissimilar masker. Under target-similar masking and at short target-masker intervals, the elderly demonstrated significant improvement, reaching the level of performance of the young, whereas under the target-dissimilar masker, the age-related differences were restored. Both age-related slowing of information processing and increase in stimulus persistence can account for the results of Experiment 1, but only increased stimulus persistence explains the results of Experiment 2.

Adolescent↗
PubMed1990

Structural brain abnormalities in the major psychoses: a quantitative review of the evidence from computerized imaging.

The neuroimaging literature on structural brain abnormalities in the major psychoses is quantitatively reviewed. The mean effect size for studies of lateral ventriculomegaly in schizophrenia (d = .70) corresponded to 43% nonoverlap between the distributions of schizophrenics and control Ss. Planimetry yielded larger effects than linear methods of ventricular size estimation. Although enlargement of the third ventricle was comparable to that of lateral ventriculomegaly (d = .66), it was found to be significantly greater after differences in measurement method were taken into account. The average cumulative length of hospitalization, adjusted for patients' age and duration of illness, predicted ventriculomegaly in schizophrenia. Studies on schizophrenia and affective disorder differed neither in the extent of reported ventriculomegaly nor in the amount of "cortical atrophy."

Brain↗