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Biomedical subjects

C A Nelson

Publications and source records attributed to C A Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain.

Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochrome c oxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron deficient group (p < 0.001). Areas with significantly reduced CytOx activity (p < 0.001) included all measured subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic nucleus (28%), and the cingulate cortex (41%). In contrast, the anterior thalamic nucleus, the lateral amygdaloid nucleus, and the medial habenula, areas not involved in higher cognitive functions, did not have significantly reduced CytOx activity (0%, 10%, and 16%, respectively). We conclude that perinatal iron deficiency differentially reduces neuronal metabolic activity, specifically targeting areas of the brain involved in memory processing.

Aging↗
PubMed2000

Neurocognitive sequelae of infants of diabetic mothers.

On the basis of animal models, it was hypothesized that infants of diabetic mothers (IDMs) would be at risk for suffering damage to the hippocampus primarily because of fetal iron deficiency, chronic hypoxia, and hypoglycemia. This, in turn, may result in impairments in recognition memory at a young age. To test this model, the memory of 6-month-old IDMs and control infants was evaluated with electrophysiological (event-related potential [ERP]) and behavioral (looking time) measures. At 12 months, the Bayley Scales of Infant Development was administered. Our ERP measures showed robust evidence consistent with memory deficits in the IDMs. In contrast, the looking time measures and the Bayley exam failed to distinguish between the groups. From these results it was concluded that the ERP, but not the behavioral, measures are able to detect, in an at-risk population, deficits in recognition memory that are thought to be mediated by damage to the hippocampus.

Cognition Disorders↗
PubMed1999

Post-trial administration of H1 histamine receptor blocker improves appetitive reversal learning and memory in goldfish, Carassius auratus.

Based on the hypothesis that neuronal histamine exerts an inhibitory influence on learning and reinforcement, goldfish were tested for post-trial effects of the H1 receptor blocker chlorpheniramine (CPA) on learning the location of a food source in one of two compartments, one black the other white, with a feeder located in each compartment. Testing was carried out over 6 days. On the training day a food pellet was placed into the feeder of one of the compartments. After consumption of the food the fish were injected i.p. with either vehicle or CPA either immediately after training or 3 h later. Twenty-four-hours later, food was placed in the same compartment and the time to begin feeding was recorded. On the next day the location of the food pellet was reversed, and testing was continued for 4 days. On the first test day the time to begin feeding was significantly longer for the vehicle injected fish as compared with those injected with CPA. The vehicle group also took longer to begin feeding than the CPA group on the first reversal test day. The results of the 3-h delay groups indicated no significant differences between vehicle and drug for any experimental session. These results suggest that post-trial blockade of the H1 histamine receptor can affect appetitive learning in goldfish either by improving long-term memory consolidation and/or by the additive reinforcing effects of CPA (known from previous studies) on behavior.

Animals↗
PubMed1999

Neurobehavioral evidence for working-memory deficits in school-aged children with histories of prematurity.

Cognitive performance in 7- to 9-year-old preterm neonatal intensive-care survivors was compared with that in age-matched control children. Non-verbal memory span, spatial working-memory abilities, planning, set-shifting, and recognition memory for both spatial and patterned stimuli were assessed using the Cambridge Neuropsychological Testing Automated Battery. Relative to children in the control group, neonatal intensive-care unit (NICU) survivors demonstrated 25% more memory errors on the spatial working-memory task. Their use of strategy on this task was similar to a control group of 5-year-olds. Planning times on 'Tower of London' problems were long relative to those of term controls. NICU survivors demonstrated poorer pattern recognition as well as a shorter spatial memory span. The groups did not differ in visual-discrimination learning or in spatial-recognition memory. No specific neonatal risk factor accounted for the observed differences, although scores on the Neurobiological Risk Score (NBRS), a composite measure of neonatal risk, did predict several aspects of later task performance. Whether these data reflect a developmental delay in brain maturation in NICU survivors or the presence of a permanent information-processing deficit due to adverse neonatal events must be assessed through continued follow-up.

Child↗
PubMed1999

Brain activity differentiates face and object processing in 6-month-old infants.

Event-related potentials were used to determine whether infants, like adults, show differences in spatial and temporal characteristics of brain activation during face and object recognition. Three aspects of visual processing were identified: (a) differentiation of face vs. object (P400 at occipital electrode was shorter latency for faces), (b) recognition of familiar identity (Nc, or negative component, at fronto-temporal electrodes [FTEs] was of larger amplitude for familiar stimuli), and (c) encoding novelty (slow wave at FTEs was larger for unfamiliar stimuli). The topography of the Nc was influenced by category type: Effects of familiarity were limited to the midline and right anterior temporal electrodes for faces but extended to all temporal electrodes for objects. Results show that infants' experience with specific examples within categories and their general category knowledge influence the neural correlates of visual processing.

Adult↗
PubMed1999

Perinatal brain iron deficiency increases the vulnerability of rat hippocampus to hypoxic ischemic insult.

Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes mellitus or intrauterine growth retardation. Because neurocognitive deficits are more common in the offspring of these pregnancies, we tested the hypothesis that perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure important for memory processing, to injury. Brain iron concentration was reduced by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation. Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic-ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase activity (n = 30), and on d 14 by Nissl staining (n = 15). Acute right-sided cytochrome c oxidase activity loss occurred in CA1 (P = 0.02), CA3c (P < 0.001) and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P = 0. 003) was affected in the iron-sufficient group. Long-term right-sided Nissl substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus (P = 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron-sufficient group. No increase in right-sided free-iron staining was present in either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a greater acute loss of neuronal metabolic activity after an hypoxic-ischemic event, suggesting compromised cellular energetics. The subsequently greater loss of hippocampal neuronal integrity suggests poorer recoverability after injury in the perinatal iron-deficient brain.

Animals↗
PubMed1999

Structural principles of MHC class II antigen presentation.

Normal immune surveillance depends on the ability of MHC class II molecules to bind peptide antigens and carry them to the cell surface for display to T cells. To do this efficiently, class II molecules must be able to bind peptides from a broad array of antigen sequences and retain them at the cell surface long enough for T-cell recognition to occur. Class II molecules accomplish this task through a combination of clever structural biochemistry and the help of at least two different molecular chaperones: the class II-associated invariant chain (Ii); and a non-peptide binding class II molecule termed H2-DM in mouse and HLA-DM in man (DM). Here, we compare the existing 3-dimensional structures of class II-peptide complexes in order to review the general principles of peptide binding and presentation. We extend this analysis to include the structures of proteins known to interact with MHC class II, focusing primarily on the Ii chain and DM.

Alleles↗
PubMed1998

Isolation and quantitation of a minor determinant of hen egg white lysozyme bound to I-Ak by using peptide-specific immunoaffinity.

We report here the identification and quantitation of a minor epitope from hen egg white lysozyme (HEL) isolated from the class II MHC molecule I-Ak of APCs. We isolated and concentrated the peptides from the I-Ak extracts by a peptide-specific mAba, followed by their examination by electrospray mass spectrometry. This initial step improved the isolation, recovery, and quantitation and allowed us to identify 13 different minor peptides using the Ab specific for the HEL tryptic fragment 34-45. The HEL peptides varied on both the amino and carboxy termini. The shortest peptide was a 13-mer (residues 33-45), and the longest peptide was a 19-mer (residues 31-49). The two most abundant were 31-47 (1.3 pmol) and 31-46 (1 pmol), while the least abundant were 31-45 (40 fmol) and 32-45 (4 fmol). Only 0.3% of the total class II molecules were occupied by this family of HEL peptides. The amount of the 31-47 peptide, the predominant member of this series, was 22 times lower than that of 48-62, the major epitope of HEL. The 31-47 peptide bound about 20-fold weaker to I-Ak compared with the dominant 48-62 peptide. Thus, the lower abundance of the minor epitope correlated with its weaker binding strength.

Amino Acid Sequence↗
PubMed1998

Reproducibility of fMRI results across four institutions using a spatial working memory task.

Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites.

Adult↗
PubMed1998

The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children.

The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks.

Adolescent↗
PubMed1998

Delayed recognition memory in infants and adults as revealed by event-related potentials.

The present study sought to compare adult and infant ERP responses in analogous tests of visual recognition memory. Adults were tested under two test conditions, in which they were given either explicit instructions to respond to a previously-seen stimulus, or no instructions. Testing in both conditions took place after either a 1- or 5-min delay between familiarization and test. Eight-month-old infants were tested under the same 'passive' (no instruction) conditions as adults. ERP morphology differed across age groups. Adults evinced a P300 that was larger under 'active' as compared to 'passive' test conditions, and a late positive slow wave response that was greater to novel than familiar stimuli. There was no evidence in infants of a P300, although infants did demonstrate a late positive slow wave that was greater to familiar than to novel stimuli. Parallels between the infant and adult findings are discussed and in particular, whether the infant slow wave response is the precursor to the adult P300.

Adolescent↗
PubMed1998

Conditioned place-preference analysis in the goldfish with the H1 histamine antagonist chlorpheniramine.

The aim of this study was to investigate whether the histamine H1-receptor blocker, chlorpheniramine (CPA), has a reinforcing effect in goldfish. We used a place-preference procedure in an aquarium with two chambers colored black and white. On day 1, the animals were placed in the test chamber for 10 min for habituation. On day 2, they were placed in the start compartment for 30 s, the sliding doors were opened, and the time spent in each compartment was recorded over the 10 min to determine the natural compartment preference for each animal. On day 3, they were injected either with 0.1, 0.4, 1.0, or 4.0 mg/kg of CPA or only with vehicle and placed in the less preferred compartment for 25 min. On day 4, the animals were placed in the start compartment and the time spent in each compartment during the 10-min test period was recorded again. The groups treated with 1.0 and 4.0 mg/kg of CPA, spent significantly more time in the compartment in which they experienced the drug effect than the group treated with vehicle. On the other hand, the group treated with 0.4 mg/kg spent significantly less time in the drug-paired compartment. The results indicate a biphasic effect of CPA. Considering that there is evidence that low doses of CPA can also block H3-receptors, we suggest that in goldfish the histaminergic neural system has an inhibitory role in the reinforcing process.

Analysis of Variance↗
PubMed1998

Crystal structure of I-Ak in complex with a dominant epitope of lysozyme.

We have determined the structure of murine MHC class II I-Ak in complex with a naturally processed peptide from hen egg lysozyme (HEL residues 50-62) at 1.9 A resolution. These results provide a structural basis for the I-Ak peptide-binding motif. Binding is established by the deep burial of five anchor side chains into specific pockets of the I-Ak binding groove, with a zen-like fit of an aspartic acid in the P1 pocket. We also show that in the I-Ak alpha chain, a bulge occurs in the first strand of the peptide-binding platform, an insertion probably common to all I-A and HLA-DQ alleles. The I-Ak beta chain has a deletion in the helical region adjacent to the P7 pocket and an insertion in the helical region neighboring the P1 pocket. As a result of these structural features, the extended HEL peptide dips low into the center of the I-Ak groove and reaches toward solvent at its C-terminal end.

Amino Acid Sequence↗
PubMed1998

Social context in developmental psychopathology: recommendations for future research from the MacArthur Network on Psychopathology and Development. The MacArthur Foundation Research Network on Psychopathology and Development.

Accumulating evidence suggests that social contexts in early life have important and complex effects on childhood psychopathology. Spurred by the lack of an explicit operational definition that could guide the study of such effects, we define a social context operationally as "a set of interpersonal conditions, relevant to a particular behavior or disorder and external to, but shaped and interpreted by, the individual child." Building on this definition, we offer a series of recommendations for future research, based on five theoretically derived propositions: (a) Contexts are nested and multidimensional; (b) contexts broaden, differentiate, and deepen with age, becoming more specific in their effects; (c) contexts and children are mutually determining; (d) a context's meaning to the child determines its effects on the child and arises from the context's ability to provide for fundamental needs; and (e) contexts should be selected for assessment in light of specific questions or outcomes. As reflected in an increasingly rich legacy of literature on child development and psychopathology, social contexts appear to influence emerging mental disorders through dynamic, bidirectional interactions with individual children. Future research will benefit from examining not only statistical interactions between child- and context-specific factors, but also the actual transactions between children and contexts and the transduction of contextual influences into pathways of biological mediation. Because adverse contexts exert powerful effects on the mental health of children, it is important for the field to generate new, more theoretically grounded research addressing the contextual determinants of psychological well-being and disorder.

Child↗
PubMed1998

The effects of stress and trauma on brain and memory: a view from developmental cognitive neuroscience.

Many aspects of brain development depend on experience. Because the major macro-morphological events of brain development occur over the first 2-3 years of postnatal life, this time period can be considered both a period of opportunity as well as a period of vulnerability. In this paper we describe how experience with stress early in life can have a negative impact on certain aspects of brain development, and specifically, those neural circuits that underlie memory. We also describe the effects of traumatic events on the development of the neural basis of memory. In support of our argument, we review the literature on brain, stress, and memory in the context of development. Based on this review, we suggest that the developing brain is particularly vulnerable to the harmful physiological effects of stress, which in turn has the potential to lead to impairments in memory. Unfortunately, there are few empirical data that directly address this hypothesis. In this context we offer a number of suggestions for future research.

Aging↗
PubMed1998

Long-term recognition memory for faces assessed by visual paired comparison in 3- and 6-month-old infants.

It has been argued that operant conditioning is the only type of long-term memory present in infants prior to 6 months of age. In this study, memory for faces was investigated in 3- and 6-month-old infants with a visual paired-comparison task. In Experiment 1, infants were habituated to a face presented in different poses; recognition was assessed after a 2-min or a 24-hr retention interval. The 6-month-old infants and the male but not the female 3-month-old infants exhibited novelty preferences. A 2nd experiment showed that 3-month-old female infants were delayed relative to male infants in their face-processing ability rather than in their memory capacity. The results of Experiment 3 demonstrated in 3-month-olds an electrophysiological correlate of delayed recognition memory. These findings are discussed in the context of the neural systems thought to be involved in visual recognition memory (but not in procedural memory), namely the limbic system.

Child Development↗
PubMed1998

A prospective study of the efficacy of the physician order form for life-sustaining treatment.

OBJECTIVES: The Physician Orders for Life-Sustaining Treatment (POLST), a comprehensive, one-page order form, was developed to convey preferences for life-sustaining treatments during transfer from one care site to another. This study examined the extent to which the POLST form ensured that nursing home residents' wishes were honored for Do Not Resuscitate (DNR) and requests for transfer only if comfort measures fail. DESIGN: The study used chart record data to follow prospectively a sample of nursing home residents with the POLST. SETTING: Eight geographically diverse, long-term, adult-care facilities in Oregon in which the POLST was in use. PARTICIPANTS: Nursing home residents (n = 180), who had a POLST recording DNR designation and who indicated a desire for transfer only if comfort measures failed, were followed for 1 year. MEASUREMENTS: For all subjects: treatment and disposition after significant health status changes; orders for narcotics and for provision or limitation of aggressive interventions. For hospitalized subjects: diagnosis, medical interventions, and DNR orders. For those who died: cause and location of death, life-sustaining treatments attempted, and comfort measures provided. RESULTS: No study subject received CPR, ICU care, or ventilator support, and only 2% were hospitalized to extend life. Of the 38 subjects who died during the study year, 63% had an order for narcotics, and only two (5%) died in an acute care hospital. A total of 24 subjects (13%) were hospitalized during the year. Hospitalized subjects' mean length of stay was 4.9 days, and the mean rate of hospitalizations for all subjects was 174 per 1000 resident years. In 85% of all hospitalizations, patients were transferred because the nursing home could not control suffering. In 15% of hospitalizations (n = 4), the transfer was to extend life, overriding POLST orders. CONCLUSIONS: POLST orders regarding CPR in nursing home residents in this study were universally respected. Study subjects received remarkably high levels of comfort care and low rates of transfer for aggressive life-extending treatments.

Advance Care Planning↗