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Biomedical subjects

S C Williams

Publications and source records attributed to S C Williams.

At least 145 records · Page 8Linked to original sources
PubMed1997

The impact of a picture archiving and communication system on nuclear medicine examination interpretation.

Radiographic correlation is essential for many of the examinations performed in nuclear medicine. The purpose of this study was to evaluate the impact of a picture archiving and communications system (PACS) on the function and efficiency of a nuclear medicine department at a tertiary care institution. We evaluated 250 consecutive noncardiac nuclear medicine imaging examinations and asked the interpreting physician the following questions: (1) Was PACS used in the interpretation of the study? (2) Did the use of PACS expedite examination completion or aid in study interpretation? And (3) Did the use of PACS permit a definitive diagnosis to be made? PACS was accessed for correlative radiographic images in 155 of the 250 (62%) nuclear medicine examinations. Images available on PACS for review aided in study interpretation in 74% (115 of 155) of cases. The use of PACS was thought to expedite examination completion in 55% (86 of 155) of cases. The system was accessed but not operational in only 1% of cases (2 of 155). PACS provides reliable, rapid access to multimodality correlative radiographic images that aid in the interpretation of nuclear medicine examinations. Such systems also increase the efficiency of a nuclear medicine service by allowing timely and conclusive interpretations to be made.

Evaluation Studies as Topic↗
PubMed1997

Functional magnetic resonance imaging of the acute effect of intravenous heroin administration on visual activation in long-term heroin addicts: results from a feasibility study.

This preliminary report is the first demonstration of the acute effects of diacetylmorphine (heroin) administration on functional activation in the human brain using functional magnetic resonance imaging (fMRI). Four opiate addicts who received regular prescriptions for heroin, underwent fMRI using a visual activation paradigm before and after a dose of 30 mg heroin. All four showed a decrease after the heroin dose in the extent of significant activation. This method shows promise for sequential scanning to determine brain activity in response to different drugs and routes of drug administration.

Acute Disease↗
PubMed1997

Dynamic multi-planar EPI of the urinary bladder during voiding with simultaneous detrusor pressure measurement.

Magnetic resonance imaging gives high quality images of the urinary bladder with excellent contrast. We report here the first application of dynamic, multi-slice, echo planar imaging to a study of urinary bladder emptying. Changes in urinary bladder volumes and rates of urine expulsion from the bladder have been measured simultaneously with bladder pressure. The method shows promise for clinical applications involving compromised bladder function, for reappraising bladder contraction strength-volume relationships, and for investigating the rate of change of length, three-dimensional shape, and wall tension in different parts of the bladder during micturition.

Echo-Planar Imaging↗
PubMed1997

Generic brain activation mapping in functional magnetic resonance imaging: a nonparametric approach.

We report a novel method to identify brain regions generically activated by periodic experimental design in functional magnetic resonance imaging data. This involves: 1) registering each of N individual functional magnetic resonance imaging datasets in a standard space; 2) computing the median standardised power of response to the experimental design; 3) testing median standardised power at each voxel against its nonparametrically ascertained distribution under the null hypothesis of no experimental effect; and 4) constructing a generic brain activation map. The method is validated by analysis of 6 null images, acquired under conditions when the null hypothesis was known to be true; 8 images acquired during periodic auditory-verbal stimulation; and 6 images acquired during periodic performance of a covert verbal fluency task.

Acoustic Stimulation↗
PubMed1997

The ability of C/EBP beta but not C/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain.

The rat CYP2D5 P-450 gene is activated in the liver during postnatal development. We previously showed that liver-specific transcription of the CYP2D5 gene is dictated by a proximal promoter element, termed 2D5, that is composed of a binding site for Sp1 or a related factor, and an adjacent cryptic C/EBP (CCAAT/enhancer-binding protein) site. Despite the fact that both C/EBP alpha and C/EBP beta are expressed abundantly in liver, only C/EBP beta is capable of stimulating the 2D5 promoter in HepG2 hepatocarcinoma cells. In addition, activation of the 2D5 promoter by C/EBP beta is completely dependent on the presence of the Sp1 site. Domain switch experiments reveal that C/EBP beta proteins containing either the leucine zipper or the activation domain of C/EBP alpha are unable to stimulate the 2D5 promoter yet are fully capable of transactivating an artificial promoter bearing a high-affinity C/EBP site. Thus, the leucine zipper and the activation domain of C/EBP beta are absolutely required to support transactivation of the 2D5 promoter. Using Drosophila cells that lack endogenous Sp1 activity, we show that the serine/threonine- and glutamine-rich activation domains A and B of Sp1 are required for efficient cooperatively with C/EBP beta. Furthermore, analysis of c/ebp beta-deficient mice shows that mutant animals are defective in expression of a murine CYP2D5 homolog in hepatic cells, confirming the selective ability of C/EBP beta to activate this liver-specific P-450 gene in vivo. Our findings illustrate that two members of a transcription factor family can achieve distinct target gene specificities through differential interactions with a cooperating Sp1 protein.

Animals↗
PubMed1997

Functional MR imaging during odor stimulation: preliminary data.

PURPOSE: To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cingulate, temporal, cerebellar, and occipital activation. Activation with combined trigeminal and olfactory system odors increased more than sixfold with repeated testing. CONCLUSION: Olfactory nerve-mediated and combined olfactory and trigeminal nerve-mediated odorants activate different regions of the brain. Orbitofrontal stimulation spreads to all parts of the brain when a trigeminal component is added. Habituation (deactivation) occurs with repeated testing of olfactory nerve-mediated odorants, while, paradoxically, activation increases with repeated exposure to odors that also stimulate the trigeminal nerve.

Adult↗
PubMed1997

Auditory hallucinations and the temporal cortical response to speech in schizophrenia: a functional magnetic resonance imaging study.

OBJECTIVE: The authors explored whether abnormal functional lateralization of temporal cortical language areas in schizophrenia was associated with a predisposition to auditory hallucinations and whether the auditory hallucinatory state would reduce the temporal cortical response to external speech. METHOD: Functional magnetic resonance imaging was used to measure the blood-oxygenation-level-dependent signal induced by auditory perception of speech in three groups of male subjects: eight schizophrenic patients with a history of auditory hallucinations (trait-positive), none of whom was currently hallucinating; seven schizophrenic patients without such a history (trait-negative); and eight healthy volunteers. Seven schizophrenic patients were also examined while they were actually experiencing severe auditory verbal hallucinations and again after their hallucinations had diminished. RESULTS: Voxel-by-voxel comparison of the median power of subjects' responses to periodic external speech revealed that this measure was reduced in the left superior temporal gyrus but increased in the right middle temporal gyrus in the combined schizophrenic groups relative to the healthy comparison group. Comparison of the trait-positive and trait-negative patients revealed no clear difference in the power of temporal cortical activation. Comparison of patients when experiencing severe hallucinations and when hallucinations were mild revealed reduced responsivity of the temporal cortex, especially the right middle temporal gyrus, to external speech during the former state. CONCLUSIONS: These results suggest that schizophrenia is associated with a reduced left and increased right temporal cortical response to auditory perception of speech, with little distinction between patients who differ in their vulnerability to hallucinations. The auditory hallucinatory state is associated with reduced activity in temporal cortical regions that overlap with those that normally process external speech, possibly because of competition for common neurophysiological resources.

Adult↗
PubMed1997

Changes in putamen N-acetylaspartate and choline ratios in untreated and levodopa-treated Parkinson's disease: a proton magnetic resonance spectroscopy study.

We have carried out single-voxel proton magnetic resonance spectroscopy centered on the putamen both ipsilateral and contralateral to the worst affected side in nine subjects with drug naive idiopathic Parkinson's disease (IPD); seven chronically levodopa-treated dyskinetic IPD subjects; and 11 age-matched healthy controls. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/(Creatine + Phosphocreatine) (Cr + PCr), and Cho/(Cr + PCr) were made. We found a significant reduction in NAA/Cho ratios from the putamen contralateral to the most affected side in the drugnaive group (p = 0.009), but not the levodopa-treated IPD groups compared with controls. There were no significant differences in NAA/(Cr + PCr) or Cho/(Cr + PCr) ratios. In untreated IPD, reduced putaminal NAA/Cho ratios may reflect loss of nigrostriatal dopamine terminals or alternatively indicate a functional abnormality of striatal putaminal neurons, such as membrane dysfunction due to striatal deafferentation. This study suggests that NAA/Cho ratios may be affected by L-dopa therapy and this may provide a reversible marker of neuronal dysfunction in the striatum.

Adult↗
PubMed1997

C/EBP proteins contain nuclear localization signals imbedded in their basic regions.

The C/EBP-related proteins (C/EBPalpha, CRP1, C/EBPbeta, and C/EBPdelta) form a subfamily of bZIP (basic region/leucine zipper) transcription factors that display sequence homology within the bZIP domain. The conserved basic region contains two motifs that exhibit significant homology to the bipartite nuclear localization signal (NLS) first described in nucleoplasmin. CRP1 and C/EBPbeta proteins bearing deletions of the basic region accumulate in the cytoplasm, in contrast to their normal nuclear location. Analysis of chimeric proteins consisting of CRP1 basic region sequences fused to beta-galactosidase revealed that the CRP1 basic region contains a single NLS that differs from conventional bipartite signals in two ways. First, mutation of a pair of arginine residues at the N-terminus of the proposed NLS does not disrupt its function. Second, the CRP1 NLS requires additional nonbasic residues at its C-terminus. A basic residue within the CRP1 NLS that is not conserved within the C/EBP family is occupied instead by an uncharged residue in C/EBPalpha and C/EBPbeta. When this nonconserved arginine residue was changed to alanine the CRP1 NLS behaved as a classical bipartite signal, suggesting that bipartite NLSs are present in all family members but that NLSs of the individual members differ slightly. Additionally, mutation of critical NLS residues in the intact CRP1 and C/EBPbeta proteins showed that these elements exhibit more bipartite-like characteristics when present in their normal sequence context. Finally, we observed that a C/EBPbeta protein lacking its NLS can be localized to the nucleus when coexpressed with C/EBPalpha, indicating that a single NLS is sufficient to promote nuclear transport of a bZIP dimer.

Amino Acid Sequence↗
PubMed1996

Sequence and evolution of the human germline V lambda repertoire.

We recently completed a map of the human immunoglobulin lambda (IGL) locus on chromosome 22q11.2 and showed that the V lambda genes are arranged in three distinct clusters, each containing members of different V lambda families. We have now sequenced each of these V lambda genes and determined which are functional by comparison with the expressed repertoire. Our analysis indicates that there are approximately 30 functional V lambda genes, depending on the haplotype, that belong to ten V lambda families (five V lambda 1, five V lambda 2, eight V lambda 3, three V lambda 4, three V lambda 5, one V lambda 6, two V lambda 7, one V lambda 8, one V lambda 9 and one V lambda 10). V lambda genes related to the major human V lambda families (V lambda 1, V lambda 2 and V lambda 3) predominate in species that express mainly lambda light chains.

Amino Acid Sequence↗
PubMed1996

Auditory hallucinations inhibit exogenous activation of auditory association cortex.

Percepts unaccompanied by a veridical stimulus, such as hallucinations, provide an opportunity for mapping the neural correlates of conscious perception. Functional magnetic resonance imaging (fMRI) can reveal localized changes in blood oxygenation in response to actual as well as imagined sensory stimulation. The safe repeatability of fMRI enabled us to study a patient with schizophrenia while he was experiencing auditory hallucinations and when hallucination-free (with supporting data from a second case). Cortical activation was measured in response to periodic exogenous auditory and visual stimulations using time series regression analysis. Functional brain images were obtained in each hallucination condition both while the patient was on and off antipsychotic drugs. The response of the temporal cortex to exogenous auditory stimulation (speech) was markedly reduced when the patient was experiencing hallucinating voices addressing him, regardless of medication. Visual cortical activation (to flashing lights) remained normal over four scans. From the results of this study and previous work on visual hallucinations we conclude that hallucinations coincide with maximal activation of the sensory and association cortex, specific to the modality of the experience.

Acoustic Stimulation↗
PubMed1996

Design of a C/EBP-specific, dominant-negative bZIP protein with both inhibitory and gain-of-function properties.

We have developed a bZIP protein, GBF-F, with both dominant-negative (DN) and gain-of-function properties. GBF-F is a chimera consisting of two components: the DNA binding (basic) region from the plant bZIP protein GBF-1 (GBF) and a leucine zipper (F) designed to preferentially heterodimerize with the C/EBP alpha leucine zipper. Biochemical studies show that GBF-F preferentially forms heterodimers with C/EBP alpha and thus binds a chimeric DNA sequence composed of the half-sites recognized by the C/EBP and GBF basic regions. Transient transfections in HepG2 hepatoma cells show that both components of GBF-F are necessary for inhibition of C/EBP alpha transactivation. When the C/EBP alpha leucine zipper is replaced with that of either GCN4 or VBP, the resulting protein can transactivate a C/EBP cis-element but is not inhibited by GBF-F, indicating that the specificity of dominant-negative action is determined by the leucine zipper. All known members of the C/EBP family contain similar leucine zipper regions and are inhibited by GBF-F. GBF-F also exhibits gain-of-function properties, since, with the essential cooperation of a C/EBP family member, it can transactivate a promoter containing the chimeric C/EBP/GBF site. This protein therefore has potential utility both as a dominant-negative inhibitor of C/EBP function and as an activator protein with novel DNA sequence specificity.

Base Sequence↗
PubMed1996

Metabolic changes associated with vacuolation in murine models of scrapie using in vitro 1H-NMR spectroscopy.

In this study, metabolic changes in the 79A/C3H, ME7/VM, ME7/C3H, 87V/VM and 22A/SV scrapie mouse models were investigated during the clinical phase of the disease, using in vitro proton nuclear magnetic resonance spectroscopy. N-acetyl-aspartate was found to be significantly reduced in infected mice of the ME7/ C3H (40% reduction), ME7/VM (26%) and 79A/C3H (17%) models when compared to control mice, but not in the 87V/VM and 22A/SV models. The concentration of choline containing compounds and creatine remain unchanged in all models when compared with control murine brains. The level of N-acetyl-aspartate reduction correlated with the extent of grey-matter brain vacuolation. The levels of myo-inositol were found to be significantly increased in the ME7/VM (143%) and 79A/C3H (132%) models only and no significant changes were observed in the ME7/C3H, 87V/VM and 22A/SV models. These changes did not correspond to the severity of gliosis.

Animals↗
PubMed1996

Statistical methods of estimation and inference for functional MR image analysis.

Two questions arising in the analysis of functional magnetic resonance imaging (fMRI) data acquired during periodic sensory stimulation are: i) how to measure the experimentally determined effect in fMRI time series; and ii) how to decide whether an apparent effect is significant. Our approach is first to fit a time series regression model, including sine and cosine terms at the (fundamental) frequency of experimental stimulation, by pseudogeneralized least squares (PGLS) at each pixel of an image. Sinusoidal modeling takes account of locally variable hemodynamic delay and dispersion, and PGLS fitting corrects for residual or endogenous autocorrelation in fMRI time series, to yield best unbiased estimates of the amplitudes of the sine and cosine terms at fundamental frequency; from these parameters the authors derive estimates of experimentally determined power and its standard error. Randomization testing is then used to create inferential brain activation maps (BAMs) of pixels significantly activated by the experimental stimulus. The methods are illustrated by application to data acquired from normal human subjects during periodic visual and auditory stimulation.

Acoustic Stimulation↗