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PubMed2006

Genome scanning by composite likelihood.

Ambitious programs have recently been advocated or launched to create genomewide databases for meta-analysis of association between DNA markers and phenotypes of medical and/or social concern. A necessary but not sufficient condition for success in association mapping is that the data give accurate estimates of both genomic location and its standard error, which are provided for multifactorial phenotypes by composite likelihood. That class includes the Malecot model, which we here apply with an illustrative example. This preliminary analysis leads to five inferences: permutation of cases and controls provides a test of association free of autocorrelation; two hypotheses give similar estimates, but one is consistently more accurate; estimation of the false-discovery rate is extended to causal genes in a small proportion of regions; the minimal data for successful meta-analysis are inferred; and power is robust for all genomic factors except minor-allele frequency. An extension to meta-analysis is proposed. Other approaches to genome scanning and meta-analysis should, if possible, be similarly extended so that their operating characteristics can be compared.

Chromosome Mapping↗
PubMed1998

Direct amplification of length polymorphisms (DALP), or how to get and characterize new genetic markers in many species.

Direct amplification of length polymorphisms (DALP) uses an arbitrarily primed PCR (AP-PCR) to produce genomic fingerprints and to enable sequencing of DNA polymorphisms in virtually any species. Oligonucleotide pairs were designed to each produce a specific multi-banded pattern and all the fragments thus generated can be directly sequenced with the same two universal M13 sequencing primers. This strategy combines the advantages of a high resolution fingerprint technique and the possibility of characterizing the polymorphisms. The use of family members as templates in the multi-locus detection step allows a direct test of allele transmission, as well as early mapping of the markers or selection of loci associated with some traits or diseases. We used this method to detect micro-deletions/insertions and microsatellite DNA loci useful in population genetics studies, but it could be applied in many other fields of biology, such as genome mapping for definition of polymorphic sequence tagged sites, directly localized on a genetic map.

Animals↗
PubMed1997

The cortical processing of perceived emotion: a DC-potential study on affective speech prosody.

Direct current (DC) components of the EEG signal were recorded in 16 right-handed subjects during presentation of pairs of declarative sentences with either happy, sad or neutral intonation. Each stimulus pair had identical wording, but differed at the acoustic level either in pitch (fundamental frequency = FO) range or in duration of stressed syllables. Subjects were asked, first, to identify the emotional category of each sentence pair and, second, to indicate the utterance displaying stronger emotional expressiveness. Stimuli with happy or sad intonation, as well as FO-manipulated neutral sentences, yielded a significantly lateralized negativity towards the right hemisphere (RH). Compared with FO-varied neutral utterances, the discrimination of time-manipulated neutral stimuli resulted in significantly reduced amplitudes, predominantly over RH areas. These results corroborate the suggestion of a dominant role of the RH for the evaluation of the emotional significance of sensory input.

Acoustic Stimulation↗
PubMed1998

Magnetic resonance imaging assessment of cerebral hemodynamics during spreading depression in rats.

High-speed magnetic resonance imaging was used to perform simultaneous measurements of relative cerebral blood volume (rCBV) and water diffusion changes during spreading depression (SD) induced by cortical potassium chloride application. Rats were fitted epidurally with a rubber chamber. Potassium chloride was perfused through the chamber until SD was indicated by a negative direct current (DC) potential shift. Magnetic resonance imaging scans used echo planar diffusion and T2-weighted images. Iron dextran was injected as a blood pool contrast agent to make subsequent changes in T2 (or T2*) directly proportional to changes in CBV. Multislice maps of apparent diffusion coefficient (ADC) and rCBV were generated with 6- to 16-second time resolution, which revealed transient ADC and rCBV changes propagating over the cortex after potassium chloride application. Transient ADC declines appeared simultaneously with the DC shift, whereas rCBV increase followed with a delay of 16.4+/-14.9 seconds. Prolonged rCBV decrease was observed after the initial increase during the SD in half of the animals. The delayed rCBV response after the ADC change supports the observation of increased energy demand because of repolarization. Simultaneous DC potential recording and ADC measurements in corresponding sites of the cortex indicate that transient ADC decreases during SD reflect water shifts associated with cell depolarization.

Animals↗
PubMedDate not supplied

The necessity for sphenoidal electrodes in the presurgical evaluation of temporal lobe epilepsy: con position.

This article reviews several lines of evidence that efface the requirement for sphenoidal leads in the EEG investigation of temporal lobe epilepsy. Mandibular notch or anterior temporal electrodes, each situated well within the anterior temporal spike field, detect interictal and ictal epileptiform phenomena virtually as well as do sphenoidal leads, provide consistent recording circumstances, do not require physician expertise for their placement, and create no discomfort. This article also cites many studies demonstrating the reliability of ictal semeiology and of MRI in lateralizing and localizing temporal epileptogenesis. Thus, EEG constitutes one element in a matrix of lateralizing data.

Brain Mapping↗
PubMed2006

Conceptual issues in psychiatric neuroimaging.

PURPOSE OF REVIEW: Psychiatric neuroimaging has made a dramatic impact on the understanding of the brain in mental illness in a relatively brief period of time and continues to be evolving in terms of methodology, analysis and utilization of the combination of techniques. Given the level of sophistication of the techniques and the importance of imaging in current academic psychiatry, it is timely to review its conceptual influence on psychopathology. RECENT FINDINGS: The study will review scientific advances in psychiatric neuromaging, around the themes of functional connectivity, diffusion tensor imaging, magnetoencephalography, modality integration, meta-analyses and mega-analyses of data and discuss recent influential findings in contemporary research. We then focus on more conceptual issues relating to biological psychiatry and its relationship with cognitive neuroscience. We discuss the dominant paradigm of scientific psychopathology, namely cognitive neuropsychiatry and how it relates more broadly to imaging and cognitive science and elaborate on the philosophical positions of the paradigm and how it views abnormal mental states. SUMMARY: We conclude that despite the advances in biological psychiatry and the power of the cognitive neuropsychiatry paradigm, its findings are logically contingent upon psychopathology and the normatively defined terms employed therein.

Biological Psychiatry↗
PubMed2002

An X-ray-based method for the determination of the contrast agent propagation in 3-D vessel structures.

A method for the determination of the contrast-agent propagation in vessel trees is presented. A standard three-dimensional (3-D) rotational angiography procedure is performed to reconstruct the morphology of the contrast-filled vessel tree in a 3-D volume. An additional fluoroscopy projection series acquired with a fixed projection angle delivers the temporal information of the bolus propagating. The mapping of the propagation information from the two-dimensional projections to the 3-D image data set is the topic of this paper. A symbolic tree structure is built up that represents the vessel tree including bifurcations. Neighborhood relations between vessel pieces are given in three dimensions. This facilitates filtering procedures and plausibility controls of the resulting time dependent 3-D data set. The presented method proved to be accurate with phantom data and gives novel insight in the feeding structure of arterio-venous malformations and aneurysms.

Algorithms↗
PubMed1997

Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin.

Retinoids exert their biologic effects through two families of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which belong to the superfamily of steroid/thyroid hormone nuclear receptors. By using a subtraction hybridization approach, we have identified a cDNA sequence TIG2 (Tazarotene-induced gene 2), whose expression is up-regulated by the treatment of skin raft cultures by an RAR beta/gamma-selective anti-psoriatic synthetic retinoid tazarotene [AGN 190168/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl] nicotinate]. The retinoid-mediated up-regulation in the expression of TIG2 was confirmed by Northern blot analysis. Upon sequencing, TIG2 was found to be a cDNA whose complete sequence was not in the GenBank and EMBL data bases. The TIG2 cDNA is 830 bp long and encodes a putative protein product of 164 amino acids. TIG2 is neither expressed nor induced by tazarotene in primary keratinocyte and fibroblast cultures. Thus, TIG2 is expressed and induced by tazarotene only when keratinocytes and fibroblasts form a tissue-like 3-dimensional structure. We further demonstrate that RAR-specific retinoids increase TIG2 mRNA levels. In contrast, neither RXR-specific retinoids nor 1,25-dihydroxyvitamin D3 increased TIG2 levels. Finally, we demonstrate that TIG2 is expressed at high levels in nonlesional psoriatic skin but at lower levels in the psoriatic lesion and that its expression is up-regulated in psoriatic lesions after topical application of tazarotene.

Administration, Topical↗
PubMed1994

Bootstrapping in human genetic linkage.

Linkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.

Chromosome Mapping↗
PubMed1992

Isolation and characterization of a species-specific DNA fragment for detection of Candida albicans by polymerase chain reaction.

A 2-kbp DNA fragment, EO3, that was present in multiple copies in the Candida albicans genome was isolated for use in developing a detection method for C. albicans by polymerase chain reaction (PCR). Dot blot hybridization revealed that EO3 was specific for the 40 isolates of C. albicans serotypes A and B used. Using a set of primers (20-mer each) derived from the nucleotide sequence of EO3, we performed specific amplification of a 1.8-kbp DNA fragment within EO3 by PCR. All 40 isolates belonging to C. albicans serotypes A and B contained amplifiable 1.8-bkp fragments, although the DNA of the amplified products exhibited small variations in size, yielding three different fragment groups. Southern blot hybridization probed with EO3 showed that these 1.8-kbp fragments were derived from the EO3 region. Conversely, the 1.8-kbp fragment was not amplified from 38 isolates belonging to seven other medically important Candida species or from isolates of Cryptococcus neoformans, Saccharomyces cerevisiae, various bacteria, and a human cell line. The detection limit of the PCR assay for C. albicans with the EO3 fragment was shown to be approximately 2 to 10 cells and 100 cells in saline and human urine, respectively, by ethidium bromide staining and 2 and 10 cells, respectively, by Southern blot analysis. In addition, EO3 was assumed to originate from mitochondrial DNA on the basis of the results of its characterizations. These results indicate that the PCR system using the 1.8-kbp fragment as a target is a reliable method for identifying C. albicans isolates, thereby suggesting its potentials for specific and sensitive detection of C. albicans in samples from patients with candidiasis.

Base Sequence↗
PubMed2006

Functional MR imaging of language processing: an overview of easy-to-implement paradigms for patient care and clinical research.

Functional magnetic resonance (MR) imaging is one of the most commonly used functional neuroimaging techniques for studying the cerebral representation of language processing and is increasingly being used for both patient care and clinical research. In patient care, functional MR imaging is primarily used in the preoperative evaluation of (a) the relationship of a lesion to critical language areas and (b) hemispheric dominance. In clinical research, this modality is used to study language disorders due to neurologic disease and is generally aimed at language function recovery. A variety of language paradigms (verbal fluency, passive listening, comprehension) have been developed for the study of language processing and its separate components. All of the tasks are easy to implement, analyze, and perform. Silent gap acquisition is preferable for the imaging of specific language processing components because auditory stimuli are not degraded by imager noise. On the other hand, continuous acquisition allows more data to be acquired in less time, thereby increasing statistical power and decreasing the effects of motion artifacts. Although functional MR imaging cannot yet replace intraoperative electrocortical stimulation in patients undergoing neurosurgery, it may be useful for guiding surgical planning and mapping, thereby reducing the extent and duration of craniotomy.

Biomedical Research↗
PubMed1998

Correlation of qEEG with PET in schizophrenia.

PET relative metabolism was correlated with quantitative EEG in 9 schizophrenic patients. The PET metabolic regions of interest were the frontal lobes, thalamus and basal ganglia, and right and left temporal lobes. Significant positive correlations were seen for the frontal lobes and delta EEG power, and alpha power with subcortical metabolism. The physiologic plausibility of those correlations is discussed with reference to the possible effect of neuroleptic medication.

Adult↗
PubMed1999

Electrical inhibition of basal ganglia nuclei in Parkinson's disease: long-term results.

Since 1995 a group of 57 patients with familial tremor and Parkinson's disease have been operated in two main sets: the first, with 11 cases, with predominant tremor, where the ventro-oralis posterior (Vop) thalamic nucleus was stimulated, and the second, with 44 cases, with mainly rigidity and akinesia, where the globus pallidus internus (GPi) was unilaterally (10 cases) or bilaterally (34 cases) stimulated. In 2 cases, a combined thalamic-pallidal stimulation was achieved. In the last cases, an image fusion software with 3D correlation of MR and CT images and volumetric image matching has been used to correct MRI distortion. In all cases, an Itrell II stimulation system (Medtronic) was implanted. Result analysis shows that Vop stimulation is mostly effective for tremor, and GPi stimulation is better for rigidity and akinesia. Transcortical magnetic stimulation tests suggest that GPi pallidal electrical inhibition increases cortical excitability, as opposed to Vop thalamic stimulation, which implies a different mechanism of action.

Adult↗