Biomedical subjects

C D White

Publications and source records attributed to C D White.

At least 19 recordsLinked to original sources

PubMed2001

Preliminary evidence of widespread morphological variations of the brain in dyslexia.

The MR images of 16 men with dyslexia and 14 control subjects were compared using a voxel-based analysis. Evidence of decreases in gray matter in dyslexic subjects, most notably in the left temporal lobe and bilaterally in the temporoparietooccipital juncture, but also in the frontal lobe, caudate, thalamus, and cerebellum, was found. Widely distributed morphologic differences affecting several brain regions may contribute to the deficits associated with dyslexia.

Adolescent↗

PubMed2001

A quantitative MRI study of posterior fossa development in velocardiofacial syndrome.

BACKGROUND: Velocardiofacial syndrome (VCFS) has been identified as a risk factor for developing schizophrenia. Qualitative neuroimaging studies indicated that VCFS was frequently associated with abnormal development of structures in the posterior fossa of the brain. The objective of this investigation was to identify the specific structures affected in the posterior fossa and investigate the association of these neuroanatomic variations with behaviors potentially related to later-onset psychiatric disorders. METHODS: Twenty-four children and adolescents with VCFS individually matched for age and gender with 24 control subjects received magnetic resonance imaging scans. Analysis of covariance models were used to investigate regional brain differences. Association between brain areas and behaviors measured on the Child Behavior Checklist (CBCL) were assessed using simple regression models. RESULTS: Children with VCFS had significantly smaller size of vermal lobules VI--VII and the pons after adjusting for overall brain size. There were no significant associations between scores on the CBCL and measures of neuroanatomic variation within the VCFS group. CONCLUSIONS: Structural alterations of the posterior fossa in VCFS are specifically limited to cerebellar vermis lobules VI--VII and pons. Previous literature has suggested that the vermis is involved in social cognition, and alteration of lobules VI--VII could therefore partially explain the neurobehavioral profile associated with VCFS.

Abnormalities, Multiple↗

PubMed2001

Error-related brain activation during a Go/NoGo response inhibition task.

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.

Adolescent↗

PubMed2001

Functional neuroanatomy of visuo-spatial working memory in Turner syndrome.

Turner syndrome (TS), a genetic disorder characterized by the absence of an X chromosome in females, has been associated with cognitive and visuo-spatial processing impairments. We utilized functional MRI (fMRI) to investigate the neural substrates that underlie observed deficits in executive functioning and visuo-spatial processing. Eleven females with TS and 14 typically developing females (ages 7-20) underwent fMRI scanning while performing 1-back and 2-back versions of a standard visuo-spatial working memory (WM) task. On both tasks, TS subjects performed worse than control subjects. Compared with controls, TS subjects showed increased activation in the left and right supramarginal gyrus (SMG) during the 1-back task and decreased activation in these regions during the 2-back task. In addition, decreased activation in the left and right dorsolateral prefrontal cortex (DLPFC) and caudate nucleus was observed during the 2-back task in TS subjects. Activation differences localized to the SMG, in the inferior parietal lobe, may reflect deficits in visuo-spatial encoding and WM storage mechanisms in TS. In addition, deficits in the DLPFC and caudate may be related to deficits in executive function during WM performance. Together these findings point to deficits in frontal-striatal and frontal-parietal circuits subserving multiple WM functions in TS.

Adolescent↗

PubMed2001

Pseudomonas aeruginosa LasA protease and corneal infections.

PURPOSE: A mutant strain of Pseudomonas aeruginosa deficient in LasA protease (staphylolytic protease) has been described as having reduced ocular virulence, suggesting that LasA is a major virulence factor. This study was undertaken to provide further genetic analysis of the role of P. aeruginosa LasA protease in ocular infections. METHODS: LasA protease-deficient mutants of P. aeruginosa PAO1-V and ATCC 19660 were constructed by allelic replacement. Mutants and their respective wild type parent strains were evaluated for virulence and growth in the eye using mouse scarification and rabbit intrastromal injection models of keratitis. RESULTS: LasA protease-deficient mutants of both strains were as virulent as wild type strains, growing to 4 to 6 log10 CFU/cornea and causing significant ocular pathology in the mouse (P > 0.42) and rabbit (P > 0.53). CONCLUSIONS: These data show that LasA protease is not a major corneal virulence factor, suggesting that the main mechanism of corneal damage has yet to be definitively identified.

Animals↗

PubMed2001

Corneal virulence of LasA protease--deficient Pseudomonas aeruginosa PAO1.

PURPOSE: Pseudomonas aeruginosa PAO1 deficient in LasA protease was reported to be ocularly avirulent. However, the avirulence of this mutant could not attributed to the loss of LasA protease. The purpose of this study was to define the mechanism for such a mutant's inability to cause corneal disease. METHODS: A LasA protease--deficient mutant of P. aeruginosa PAO1 was constructed by allelic exchange. Virulence of this mutant in mouse and rabbit models of keratitis was assessed by scoring for ocular disease and quantitating viable bacteria from infected corneas. Adherence to scarified mouse corneal tissue was determined with an organ culture assay. RESULTS: In the mouse eye, the LasA protease--deficient mutant was not virulent, despite being as adherent as its parent strain. Virulence of the mutant was also significantly reduced in the rabbit eye. Complementation with lasA did not restore virulence in either model of infection. Neither the mutant nor the mutant complemented with lasA grew well in ocular tissue. An analysis of the mutant showed that it was auxotrophic for leucine. CONCLUSION: These data show that the mutant's avirulence in the eye is caused by poor growth in the ocular environment and not the loss of a functional lasA gene.

Animals↗

PubMed2001

Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia?

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.

Abnormalities, Multiple↗

PubMed2001

Functional neuroanatomy of visuospatial working memory in fragile X syndrome: relation to behavioral and molecular measures.

OBJECTIVE: Fragile X syndrome is a neurogenetic disorder that is the most common known heritable cause of neurodevelopmental disability. This study examined the neural substrates of working memory in female subjects with fragile X syndrome. Possible correlations among behavioral measures, brain activation, and the FMR1 gene product (FMRP expression), as well as between IQ and behavioral measures, were investigated. METHOD: Functional magnetic resonance imaging was used to examine visuospatial working memory in 10 female subjects with fragile X syndrome and 15 typically developing female subjects (ages 10-23 years). Subjects performed standard 1-back and 2-back visuospatial working memory tasks. Brain activation was examined in four regions of the cortex known to play a critical role in visuospatial working memory. Correlations between behavioral, neuroimaging, and molecular measures were examined. RESULTS: Relative to the comparison group, subjects with fragile X syndrome performed significantly worse on the 2-back task but not on the 1-back task. In a region-of-interest analysis focused on the inferior frontal gyrus, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, comparison subjects showed significantly increased brain activation between the 1-back and 2-back tasks, but subjects with fragile X syndrome showed no change in activation between the two tasks. Significant correlations were found in comparison subjects between activation in the frontal and parietal regions and the rate of correct responses on the 2-back task, but not on the 1-back task. In subjects with fragile X syndrome, significant correlations were found during the 2-back task between FMRP expression and activation in the right inferior and bilateral middle frontal gyri and the bilateral supramarginal gyri. CONCLUSIONS: Subjects with fragile X syndrome are unable to modulate activation in the prefrontal and parietal cortex in response to an increasing working memory load, and these deficits are related to a lower level of FMRP expression in fragile X syndrome subjects than in normal comparison subjects. The observed correlations between biological markers and brain activation provide new evidence for links between gene expression and cognition.

Adolescent↗

PubMed2000

Dissociating prefrontal and parietal cortex activation during arithmetic processing.

Lesion and brain-imaging studies have implicated the prefrontal and parietal cortices in arithmetic processing, but do not exclude the possibility that these brain areas are also involved in nonarithmetic operations. In the present study, we used functional magnetic resonance imaging to explore which brain areas contribute uniquely to numeric computation. Task difficulty was manipulated in a factorial design by varying the number of operands and the rate of stimulus presentation. Both manipulations increased the number of operations to be performed in unit time. Manipulating the number of operands allowed us to investigate the specific effect of calculation, while manipulating the rate of presentation allowed us to increase task difficulty independent of calculation. We found quantitative changes in activation patterns in the prefrontal and parietal cortices as well as the recruitment of additional brain regions, including the caudate and midcerebellar cortex, with increasing task difficulty. More importantly, the main effect of arithmetic complexity was observed in the left and right angular gyrus, while the main effect of rate of stimulus presentation was observed in the left insular/orbitofrontal cortex. Our findings indicate a dissociation in prefrontal and parietal cortex function during arithmetic processing and further provide the first evidence for a specific role for the angular gyrus in arithmetic computation independent of other processing demands.

Adolescent↗

PubMed2000

Functional optimization of arithmetic processing in perfect performers.

Lesion and imaging studies to date have not clarified which sub-regions of the parietal lobe are specialized for arithmetic processing, and which perform supporting functions. We used functional magnetic resonance imaging to investigate parietal lobe function during arithmetic processing. Functional optimization was examined by analyzing regional differences in brain activation between perfect (100% accuracy) and imperfect performers. Perfect performers had significantly less activation only in the left angular gyrus, a finding that may be associated with skill mastery and long-term practice effects. The present results provide the first direct evidence of localized functional optimization for arithmetic processing in the human brain.

Adolescent↗

PubMed2000

Children and adolescents with velocardiofacial syndrome: a volumetric MRI study.

OBJECTIVE: Velocardiofacial syndrome is a common genetic condition often accompanied by mild cognitive impairment. Children and adolescents with velocardiofacial syndrome also are at greater risk for developing serious neuropsychiatric disorders in adulthood, particularly schizophrenia-like disorders. The purpose of this preliminary study was to 1) elucidate through brain imaging the neurobiological basis of cognitive and neuropsychiatric problems in velocardiofacial syndrome, and 2) consider the association between variations in neuroanatomy in velocardiofacial syndrome subjects and the associated neurobehavioral phenotype. METHOD: Fifteen children and adolescents with velocardiofacial syndrome were matched by age and gender with 15 comparison subjects. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of specified brain tissues and regions. Rater-blind morphometric analyses were conducted to examine tissue volumes of the four lobes and the cerebellum. RESULTS: Total brain volume was approximately 11% smaller in the children with velocardiofacial syndrome. Gray matter volume was reduced to a lesser extent (7.5%) than white matter volume (16.3%). Multivariate analyses of variance indicated a distinct pattern of regional morphological variation among the children with velocardiofacial syndrome. Specifically, frontal lobe tissue tended to be enlarged relative to the overall reduction in brain volume. Normal symmetry of parietal lobe tissue observed in the comparison group was not evident in the velocardiofacial syndrome group. This loss of symmetry was attributable to a significant reduction of gray matter in the left parietal lobe. CONCLUSIONS: Aberrant brain morphology is associated with velocardiofacial syndrome. These changes are potentially related to the language and learning deficits associated with the syndrome and may provide clues about neurodevelopmental pathways associated with schizophrenia.

Abnormalities, Multiple↗

PubMed2000

Analysis of a distributed neural system involved in spatial information, novelty, and memory processing.

Perceiving a complex visual scene and encoding it into memory involves a hierarchical distributed network of brain regions, most notably the hippocampus (HIPP), parahippocampal gyrus (PHG), lingual gyrus (LNG), and inferior frontal gyrus (IFG). Lesion and imaging studies in humans have suggested that these regions are involved in spatial information processing as well as novelty and memory encoding; however, the relative contributions of these regions of interest (ROIs) are poorly understood. This study investigated regional dissociations in spatial information and novelty processing in the context of memory encoding using a 2 x 2 factorial design with factors Novelty (novel vs. repeated) and Stimulus (viewing scenes with rich vs. poor spatial information). Greater activation was observed in the right than left hemisphere; however, hemispheric effects did not differ across regions, novelty, or stimulus type. Significant novelty effects were observed in all four regions. A significant ROI x Stimulus interaction was observed - spatial information processing effects were largest effects in the LNG, significant in the PHG and HIPP and nonsignificant in the IFG. Novelty processing was stimulus dependent in the LNG and stimulus independent in the PHG, HIPP, and IFG. Analysis of the profile of Novelty x Stimulus interaction across ROIs provided evidence for a hierarchical independence in novelty processing characterized by increased dissociation from spatial information processing. Despite these differences in spatial information processing, memory performance for novel scenes with rich and poor spatial information was not significantly different. Memory performance was inversely correlated with right IFG activation, suggesting the involvement of this region in strategically flawed encoding effort. Stepwise regression analysis revealed that memory encoding accounted for only a small fraction of the variance (< 16%) in medial temporal lobe activation. The implications of these results for spatial information, novelty, and memory processing in each stage of the distributed network are discussed.

Adolescent↗

PubMed1999

Expression of p53 in epithelial carcinoma of the ovary after chemotherapy.

OBJECTIVE: To compare the expression of p53 protein before and after chemotherapy in epithelial carcinoma of the ovary. STUDY DESIGN: Thirty patients were identified during a 10-year period with both their primary surgery and laparotomy after chemotherapy at the same institution. Tissue was processed from paraffin blocks, exposed to an antihuman p53 monoclonal antibody, then stained. Patient records were reviewed for survival data. RESULTS: Twelve of 30 (40%) patients' tissue initially stained positive for p53. Seventeen of 30 (56.7%) were negative, and one (3.3%) was mixed. Eight of 12 (66.7%) initially positive remained so after chemotherapy, 2 converted to negative, and 2 converted to mixed expression. One patient with mixed expression converted to positive after chemotherapy. Seventeen tissues initially negative remained unchanged. CONCLUSION: Chemotherapy did not permanently alter the expression of p53 detected by immunohistochemical staining in the majority (83.3%) of patients with epithelial ovarian cancer; 16.7% (all initially over-expressing p53) did show some decrease. This may have been due to deactivation of the mutated p53 gene, spontaneous mutation, selective growth within a heterogeneous population or alteration of p53 protein.

Adult↗

PubMed1998

Alterations in myocardial signal transduction due to aging and chronic dynamic exercise.

Normal aging without disease leads to diminished chronotropic and inotropic responses to catecholamine stimulation, resulting in depressed cardiac function with stress. The purpose of this study was to determine molecular mechanisms for decrements in adrenergic responsiveness of the left ventricle (LV) due to aging and to study the effects of chronic dynamic exercise on signal transduction. We measured beta-adrenergic receptor (beta-AR) density, adenylyl cyclase (AC) activity, and G-protein content and distribution in LV from 66 male Fischer 344 rats from three age groups that were either sedentary or treadmill trained (60 min/days, 5 days/wk, 10 wk at 75% of the maximal capacity). Final ages were 7 mo (young), 15 mo (middle-age), and 25 mo (old). There was no significant difference in beta-AR density among groups as a function of age or training. AC production of adenosine 3',5'-cyclic monophosphate (cAMP) with the use of five pharmacological stimulations revealed that old sedentary myocardium had depressed basal, receptor-dependent, G-protein-dependent, and AC catalyst stimulation (30-43%) compared with hearts from young and middle-age sedentary rats. Training did not alter AC activity in either middle-age or old groups but did increase G-protein-dependent cAMP production in young myocardium (12-34%). Immunodetectable concentrations of stimulatory and inhibitory G proteins (Gs and Gi, respectively) showed 43% less total Gs with similar Gi content in hearts from old sedentary compared with middle-age sedentary rats. When compared with young sedentary animals, Gi content was 39 and 50% higher in middle-age sedentary and old sedentary myocardium, respectively. With age, there was a significant shift in the alpha-subunit of Gs distribution from cytosolic fractions of LV homogenates to membrane-bound fractions (8-12% redistribution in middle-age sedentary vs. old sedentary). The most significant training effect was a decrease in Gi content in hearts from old trained rats (23%), which resulted in values comparable with young sedentary rats and reduced the Gi/Gs ratio by 27% in old-rat LV. We report that age-associated reductions in cardiovascular beta-adrenergic responsiveness correspond with alterations in postreceptor adrenergic signaling rather than with a decrease in receptor number. Chronic dynamic exercise partially attenuates these reductions through alterations in postreceptor elements of cardiac signal transduction.

Aging↗

PubMed1997

Application of an automated parcellation method to the analysis of pediatric brain volumes.

New techniques in quantitative imaging are needed to accelerate understanding of brain development and function in children. In this study we evaluate the reliability and validity of an automated parcellation method for the measurement of large and small brain regions in normal and developmentally disabled children. We utilized an adaptation of the Talairach atlas to semi-automatically quantify brain volumes from 10 children with fragile X syndrome, 10 age- and gender-matched controls and 10 adult controls comparing them to 'gold standard' manually delineated regions. Excellent sensitivity, specificity, intra-class correlation and positive predictive value were achieved for large structures although results were less satisfactory for smaller structures, illustrating the limits of resolution of the method. Statistically significant differences in regional brain volumes were shown between males and females, children and adults, and individuals with fragile X and matched controls. This study demonstrates an automated method which rapidly and accurately quantifies large neuroanatomical structures, but not smaller structures. This method is sufficiently accurate to demonstrate some known anatomical differences in individuals with fragile X; the results suggest that this method could be applied to the assessment of brain volume in other neurodevelopmental disabilities.

Adult↗

PubMed1997

Osteopenia and stable isotope ratios in bone collagen of Nubian female mummies.

Stable carbon and nitrogen isotopes were analysed on bone collagen of 43 Sudanese Nubians from the X-Group period to test dietary hypotheses for the high frequency of osteopenia in this population. Stable carbon isotope ratios indicate that both normal and osteopenic individuals consumed the same mixed diet of C3 and C4 sources, which are assumed to have been constituted by the grain staples wheat/barley and sorghum/millet respectively. Females with osteopenia, however, have significantly elevated delta 15N values. The enrichment effect is greatest in the third and fifth decades of life, and is consistently patterned with microstructural and frequency differences previously reported by other researchers. It is suggested that delta 15N is reflecting differences in urea excretion and the renal processing and clearance of calcium and phosphorus. The study not only alerts us to the susceptibility of stable nitrogen isotopes to non-dietary (i.e. physiological) factors, but also identifies nitrogen isotope ratios as a possible new marker for osteopenia.

Adolescent↗

PubMed1996

Sutural effects of fronto-occipital cranial modification.

Maya adult crania from the site of Lamanai, Belize provide a retrospective means of examining growth processes in the cranial vault. The Lamanai population practiced fronto-occipital deformation which is found to be significantly associated with premature sagittal synostosis and wormian bones of the lambdoidal suture. The undeformed members of the population also exhibit an abnormally high frequency of sagittal synostosis, but a significantly lower frequency than the deformed sample. It is suggested that the deforming apparatus creates tensile forces on the sagittal suture during the peak period of growth of the parietals, and that these forces might induce an adaptive response important in producing premature sagittal synostosis. The undeformed sample may have an increased congenital risk of sagittal synostosis created by their natural brachycephalic morphology in utero. The frequency patterning of wormian bones suggests a mixture of genetic and environmental causes in which tensile forces may also play a role.

Adult↗

PubMed1996

Differences between syncope resulting from rapid onset acceleration and orthostatic stress.

BACKGROUND AND HYPOTHESIS: Orthostatically-induced syncope is accompanied by venous pooling and vasodilatation. Loss of consciousness during head-to-foot acceleration (G-LOC) in aviators may be caused by a different mechanism, as venous pooling should be prevented through the use of an anti-G suit. This research was conducted to test the hypothesis that in individuals wearing a well-fitted anti-G garment, no important changes occur in the volume of dependent regions during loss of consciousness resulting from rapid onset acceleration stress. Further, this work compares venous pooling patterns in G-LOC subjects to patterns seen during syncope in volunteers and patients subjected to orthostatic stress. We conducted the tilt/LBNP tests to establish what level of venous pooling was required to induce syncope in the absence of a hydrostatic component (other than 1 G) and to confirm that our equipment was sensitive enough to detect volume changes large enough to cause syncope. METHODS: Shifts in blood volume to the calf, thigh and abdominal segments were compared in subjects with G-LOC to those in subjects taken to presyncope with orthostatic stress created by upright tilt and lower body negative pressure (LBNP). Centrifuge subjects were exposed to a 15 s rapid onset (6 G.s-1) + 5 Gz exposure on the centrifuge while remaining relaxed and wearing a well-fitting anti-G suit, but with the anti-G suit pressure inactivated. RESULTS: Blood volume decreased an average of 14.9 +/- 22.1 ml in the calf segment; increased an average of 64.1 +/- 7.9 ml in the thigh segment, and decreased an average of 80.1 +/- 29.7 ml in the abdominal segment. The mean net change in volume of the three combined regions was not significantly different from zero. Presyncope was induced in subjects by a progressive exposure to upright tilt, and then addition of LBNP at -20 mm Hg and -40 mm Hg. In the tilt/LBNP group, there was a net increase of 1022 +/- 269.8 ml for the combined segments. Changes in all three segments were significantly different than the mean segmental volume changes seen in centrifuge subjects at G-LOC endpoints. Significant changes from baseline mean arterial pressure, but not heart rate were also seen within, but not between the 2 groups, with mean eye level blood pressures (ELBP) falling an average of 45.6 +/- 7.7 mm Hg in the tilt/LBNP group at syncope and 105.1 +/- 15.5 mm Hg in the centrifuge subjects at G-LOC. CONCLUSIONS: These differences suggest that G-LOC may be due entirely to hydrostatic effects, with venous pooling being prevented by the wearing of an ant-G garment, even when it remains uninflated.

Acceleration↗