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PubMed1999

An experimental pain model based on electric stimulations of the colon mucosa.

BACKGROUND: Pain intensity and distribution related to diseases of the gut are important diagnostic indicators in gastroenterology. Experimental pain models provide a unique possibility for standardized activation of the nociceptive system, but only few human models exist. METHODS: An experimental pain model based on electric stimuli in the human colon was developed and applied. Eleven patients who were referred for surveillance colonoscopy due to earlier polyps in the colon were included. None had any abdominal pain complaints. The following areas were stimulated with 'single', 'repeated', or 'continuous' electric current: the cecum, the hepatic and splenic flexures, and the rectosigmoid junction. RESULTS: All subjects felt deep, diffuse pain during the stimulation, with referral to localized somatic structures. The pain detection thresholds after repeated stimuli were similar in the four areas. The threshold for single stimulation was higher than the threshold for repeated stimulation. Most reported pain in the lower and left site of the abdominal wall during stimuli at the splenic flexure and rectosigmoid junction. Stimuli at the right colon, however, resulted mostly in pain at the contralateral site of the abdomen. CONCLUSIONS: The presented model was robust and suitable for eliciting pain in different regions of the large intestine. The importance of temporal summation in visceral pain was shown. Mapping of the referred pain areas mimics clinical observations and has ontogenetic and anatomic consistency. The model may therefore improve the evaluation of pain in patients with diseases of the colon.

Abdominal Pain↗

PubMed1997

Genome structure and phylogeny in the genus Brucella.

PacI and SpeI restriction maps were obtained for the two chromosomes of each of the six species of the genus Brucella: B. melitensis, B. abortus, B. suis, B. canis, B. ovis, and B. neotomae. Three complementary techniques were used: hybridization with the two replicons as probes, cross-hybridization of restriction fragments, and a new mapping method. For each type strain, a unique I-SceI site was introduced in each of the two replicons, and the location of SpeI sites was determined by linearization at the unique site, partial digestion, and end labeling of the fragments. The restriction and genetic maps of the six species were highly conserved. However, numerous small insertions or deletions, ranging from 1 to 34 kb, were observed by comparison with the map of the reference strain of the genus, B. melitensis 16M. A 21-kb Spel fragment specific to B. ovis was found in the small chromosome of this species. A 640-kb inversion was demonstrated in the B. abortus small chromosome. All of these data allowed the construction of a phylogenetic tree, which reflects the traditional phenetic classification of the genus.

Brucella↗

PubMedDate not supplied

Inter- and intra-individual probability maps in EEG cartography by use of nonparametric Fisher tests.

The three types of non-parametric permutation Fisher tests have been applied to inter-individual group studies and further to intra-individual multiple EEG recording sequences, providing computations of EEG probability maps testing two ordinal hypotheses. Two examples of previous group studies with "EEG local cerebral activation" are given: mental computation in a group of 20 controls and caffeine effects versus placebo in a group of 10 controls. For the intra-individual study, two successive recordings of 2.3 min eyes closed (EC1 and EC2), obtained at 50 min intervals, were compared by paired exact permutation Fisher tests (over 15 or 42 synchronous EEG sequences). These tests were applied to descriptive spectral parameters: RMS and % amplitudes, mean frequencies, resonance coefficient, for raw unfiltered EEG and delta, theta, alpha, alpha 1, alpha 2, beta 1, beta 2 frequency bands. Two hypotheses were tested for each of the computed 31 parameters, providing two probability maps indicating if the parameter was greater or lower in the first EEG recording or in the second. The second EEG sequence, EC2, was "EEG activated" compared to the first sequence EC1 if the following were present: decreased amplitudes mainly in raw EEG, low activity and alpha bands; increased frequencies mainly, in raw EEG, delta and beta 1 fast activities; increased fast activity percentages; decreased coefficient of resonance. The effect of choice of reference was also evaluated: probability maps for a frontal reference were different than other probability maps obtained after computation of average reference or source derivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Mapping↗

PubMed1999

Automatic 3-D segmentation of internal structures of the head in MR images using a combination of similarity and free-form transformations: Part I, Methodology and validation on normal subjects.

The study presented in this paper tests the hypothesis that the combination of a global similarity transformation and local free-form deformations can be used for the accurate segmentation of internal structures in MR images of the brain. To quantitatively evaluate our approach, the entire brain, the cerebellum, and the head of the caudate have been segmented manually by two raters on one of the volumes (the reference volume) and mapped back onto all the other volumes, using the computed transformations. The contours so obtained have been compared to contours drawn manually around the structures of interest in each individual brain. Manual delineation was performed twice by the same two raters to test inter- and intrarater variability. For the brain and the cerebellum, results indicate that for each rater, contours obtained manually and contours obtained automatically by deforming his own atlas are virtually indistinguishable. Furthermore, contours obtained manually by one rater and contours obtained automatically by deforming this rater's own atlas are more similar than contours obtained manually by two raters. For the caudate, manual intra- and interrater similarity indexes remain slightly better than manual versus automatic indexes, mainly because of the spatial resolution of the images used in this study. Qualitative results also suggest that this method can be used for the segmentation of more complex structures, such as the hippocampus.

Algorithms↗

PubMed1991

Predictive testing for Wilson's disease using tightly linked and flanking DNA markers.

We studied DNA polymorphisms for five new chromosome 13 markers in 52 Wilson's disease (WD) families from Europe, North America, and the Middle East. There was significant evidence for linkage between the Wilson's disease locus (WND) and all the marker loci. Multilocus linkage analysis, using a genetic linkage map established from reference pedigrees, suggested that WND is most likely between D13S31 and D13S59, at distances of 0.4 and 1.2 centimorgans, respectively. Our results suggest that the chromosomal location of the Wilson's disease gene is the same in all families from the populations studied. This evidence and the availability of many close, flanking, and polymorphic DNA markers make possible accurate and informative testing of potential carriers and WD homozygotes in families with at least one previously affected child. An advantage of a genetic linkage test over other laboratory methods for prediction of genotype in WD is that a reliable diagnosis can be made at a much earlier stage in life, including prenatally. In addition, DNA testing can be used in place of an invasive liver biopsy procedure to confirm a diagnosis in patients with borderline serum ceruloplasmin levels. Presymptomatic identification will also allow therapeutic intervention to prevent symptoms before irreparable liver or neurologic damage occurs. We describe the implementation of prenatal and preclinical diagnosis for two families with WD.

Chromosome Mapping↗

PubMed1990

Afferent and efferent connections of the oculomotor region of the fastigial nucleus in the macaque monkey.

Afferent and efferent connections of the fastigial oculomotor region (FOR) were studied in macaque monkeys by using axonal transport of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). When injected HRP is confined to the FOR, retrogradely labeled cells appear in lobules VIc and VII of the ipsilateral vermis and in group b of the contralateral medial accessory olive (MAO). In reference to the maps of topographical organization, the extent of the effective site in the fastigial nucleus (FN) could be assessed from the distributions of labeled Purkinje cells (P cells) in the vermis and labeled olivary neurons in the MAO. In contrast to the unilateral nature of the P-cell and climbing-fiber projections, those from the other brainstem regions to the FOR were bilateral. Following the injection of HRP into the FOR, the largest number of retrogradely labeled cells appeared in the pontine nuclei. Although the number of labeled cells was greater on the contralateral side in both the peduncular and dorsomedial pontine nuclei (DMPN), the number of each side was virtually identical in the dorsolateral pontine nucleus (DLPN). In the nucleus reticularis tegmenti pontis (NRTP), labeled cells were located only in its medial and dorsolateral portions bilaterally. In the vestibular complex, labeled cells appeared in the superior (SVN), medial (MVN), and inferior vestibular nuclei (IVN) bilaterally. The lateral vestibular nucleus (LVN), including y group and the ventrolateral vestibular nucleus, were free of labeled cells. Labeled cells appeared also in the perihypoglossal nucleus (PHN) bilaterally. In the pontine raphe (PR) and paramedian pontine reticular formation (PPRF), labeled cells appeared bilaterally in the caudal third of the area between the oculomotor and abducens nuclei. Labeled cells appeared also in the mesencephalic and medullary reticular formation. Tracing of anterogradely labeled axons demonstrated that most fibers from the FOR decussated within the cerebellum and entered the brainstem via the contralateral uncinate fasciculus. Some crossed fibers ascended with the contralateral brachium conjunctivum and terminated in the midbrain tegmentum. A small contingent of fibers advanced further to the thalamus. In the mesodiencephalic junction, labeled terminals were found contralaterally in the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF) and a medial portion of FOrel's H Field. They appeared also in the central mesencephalic reticular formation (cMRF), the periaqueductal gray (PAG), the posterior commissure nucleus, and the superior colliculus. The oculomotor and trochlear nuclei, the red nucleus, and the interstitial nucleus of Cajal were free of labeled terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed2001

Fully automatic anatomical, pathological, and functional segmentation from CT scans for hepatic surgery.

OBJECTIVE: To improve the planning of hepatic surgery, we have developed a fully automatic anatomical, pathological, and functional segmentation of the liver derived from a spiral CT scan. MATERIALS AND METHODS: From a 2 mm-thick enhanced spiral CT scan, the first stage automatically delineates skin, bones, lungs, kidneys, and spleen by combining the use of thresholding, mathematical morphology, and distance maps. Next, a reference 3D model is immersed in the image and automatically deformed to the liver contours. Then an automatic Gaussian fitting on the imaging histogram estimates the intensities of parenchyma, vessels, and lesions. This first result is next improved through an original topological and geometrical analysis, providing an automatic delineation of lesions and veins. Finally, a topological and geometrical analysis based on medical knowledge provides hepatic functional information that is invisible in medical imaging: portal vein labeling and hepatic anatomical segmentation according to the Couinaud classification. RESULTS: Clinical validation performed on more than 30 patients shows that delineation of anatomical structures by this method is often more sensitive and more specific than manual delineation by a radiologist. CONCLUSION: This study describes the methodology used to create the automatic segmentation of the liver with delineation of important anatomical, pathological, and functional structures from a routine CT scan. Using the methods proposed in this study, we have confirmed the accuracy and utility of the creation of a 3D liver model compared with the conventional reading of the CT scan by a radiologist. This work may allow improved preoperative planning of hepatic surgery by more precisely delineating liver pathology and its relationship to normal hepatic structures. In the future, this data may be integrated with computer-assisted surgery and thus represents a first step towards the development of an augmented-reality surgical system.

Humans↗

PubMed1990

The decomposition of the middle latency auditory evoked potential (MLAEP) Pa component into superficial and deep source contributions.

The results of recent investigations have suggested that the Middle Latency Auditory Evoked Potential (MLAEP) Pa component derives its physiological origins from both cortical and subcortical sources. The purpose of the present investigation was to determine if support for this hypothesis could be obtained from the off-line manipulation of the topographically recorded Pa component. The multichannel MLAEP from 15 normal hearing, neurologically intact subjects was collected following monaural left and right ear click stimulation. Data was originally collected using the linked ear reference and was subsequently re-referenced using the common average reference (CAR). These mapped data were converted off-line to source current density using the source derivation (SD) technique described by Hjorth (1975, 1980). This technique is sensitive to current activity that is generated in the superficial cerebral cortex. These SD maps of the MLAEP were subsequently subtracted from the CAR maps of the MLAEP. The derived CAR-SD maps are believed to represent that activity that is generated deep to the cerebral cortex (Hjorth and Rodin 1988). Interpretation of the mapped data have demonstrated support for the hypothesis that Pa is generated by a minimum of two systems including: 1) bilateral sources located in the posterior temporal lobes, and 2) a deeper midline generator system.

Acoustic Stimulation↗

PubMed1985

Variation among hepatitis A virus strains. I. Genomic variation detected by T1 oligonucleotide mapping.

The genomes of eight hepatitis A virus (HAV) strains originating from far distant geographic regions such as Europe, North Africa, Middle and North America, Australia and The People's Republic of China were compared by RNase T1 oligonucleotide mapping. For this purpose, the viruses were propagated in cell cultures and viral RNA was isolated from highly purified mature virions. It could be shown that variation in nucleotide sequence is common among HAV isolates, but is in the order of magnitude reported for other picornaviruses. For viruses isolated in cell culture directly from stool samples of diseased individuals, changes usually amounted to 1-4% of RNA genome sites. Genomic differences between two virus strains derived from one fecal sample but replicating at either 32 or 37 degrees C were in the same order of magnitude. Thereby, the number of consecutive in vitro passages proved to have only limited influence on the development of genetic variation. For two HAV strains, however, adaptation to and passage in marmosets evidently had imposed highly selective conditions which had favored the appearance of viral genomes differing in up to 75% of their large oligonucleotides (about 10% in sequence) from the oligonucleotide map of a reference HAV strain.

Animals↗

PubMed2026

A genome-wide coverage-based pipeline for the identification of host-derived candidate DNA biomarkers from cell-free blood.

We have created a new data-analysis pipeline for the discovery of host-specific candidate DNA biomarkers derived from sequencing data of cell-free blood. Unlike approaches that rely on specific molecular or genetic signatures, our method leverages the coverage distribution of cell-free DNA sequences mapped to a reference genome, applying statistical analyses to identify informative short genomic regions for biomarker discovery. The pipeline is applicable to diverse diseases and can be used to analyze cell-free DNA sequences from plasma or serum to identify candidate biomarkers that are characteristic of disease states in mammals. Core functionalities were developed in Java and integrated with open-source software tools for the preprocessing of raw sequencing data, complemented by Python scripts for the machine-learning analysis and statistical validation. The pipeline is designed for HPC use and users can access the pipeline through a Galaxy workflow, which offers a user-friendly web interface for input selection prior to execution and analysis progress monitoring. Performance tests, carried out using duplicate sets of COVID-19 samples and controls, showed linear scalability of execution time with an increasing dataset size, as well as a substantial reduction in execution time through parallelized computation, whereby each HPC node is used to process the data of one chromosome. Further statistical tests confirmed the quality of the pipeline's results by showing that the set of identified candidate biomarkers remained stable across varying dataset sizes.

Biomarkers↗

PubMed1997

Human genetic diseases: a cross-talk between man and yeast.

A sequence similarity search has been carried out against the complete Saccharomyces cerevisiae genome to identify the yeast homologues of human disease-associated genes. Using the BLAST algorithm (Basic Local Alignment Search Tool), it was found that 52 out of the 170 disease genes identified without reference to chromosomal map position and 22 of the 80 (27.5%) positionally cloned genes match yeast genes with a P-value of <e(-40). The percentage of the disease genes identified by positional cloning which bear homology to yeast is similar to that of a random collection of human cDNAs. The biochemical and physiological functions of the large majority of these human genes remain poorly understood and, even though a strict conservation of function cannot safely be assessed from structural homology analysis without the support of experimental and three-dimensional data, functional analogies can often be established between the human and yeast genes.

Chromosome Mapping↗

PubMed1998

The effect of gaze eccentricity on perceived sound direction and its relation to visual localization.

This study investigates the influence of eye position on the localization of a free-field sound source by employing a pointing method. While fixating visual targets in various directions, the subjects indicated the perceived direction of a sound source by adjusting the azimuthal angle of a swivel pointer. The perceived sound azimuth shifted consistently opposite to the direction of eccentric gaze. i.e. to the left when gaze was to the right and vice versa. This shift resembled an approximately linear function of horizontal gaze direction. The mean magnitude of the shift was 3.1 degrees when the gaze was 45 degrees to the side (mean slope 0.069 degrees per degree eccentricity in gaze direction). An additional experiment investigated the relation of this effect to visual localization. Using the same method, the shift of perceived visual azimuth was measured as a function of gaze direction. The results indicate a shift in the same direction as the auditory shift (opposite to the direction of eccentric gaze), but with a significantly greater magnitude, which was 5.7 degrees for 45 degrees eccentricity in gaze direction. The perceived shifts of sound direction depending on gaze eccentricity may result from incomplete transformations of the auditory spatial coordinates from a craniocentric to an oculocentric frame of reference within neural maps of space, as has been suggested by previous neurophysiological investigations.

Acoustic Stimulation↗

PubMed1986

Correspondence analysis applied to steroid receptor binding.

The relative binding affinities of 48 steroids for four classes of hormone receptor (progestin, PR; androgen, AR; glucocorticoid, GR; mineralocorticoid, MR) have been analyzed by correspondence analysis. The steroids were, for the most part, derivatives of nortestosterone, differing by their degree of unsaturation, by the presence or absence of a 17 alpha-ethynyl group, and by the length of the C-13 alkyl substituent. Derivatives of norprogesterone were included as reference compounds. Distribution maps visualizing the results of the mathematical analysis revealed that the majority of the test steroids were within the zone of influence of AR and PR and had limited affinity for GR and MR. Overall lack of specificity and enhanced affinity for GR and MR were induced by increasing unsaturation and by the presence of a C-13 ethyl group. The general and specific conclusions of the analysis confirm and extend previous intuitive and partial interpretations of the data. Correspondence analysis, however, has the advantage of taking into account the sum total of the available information, without any preconceived notion of the relative importance of a specific structural feature or biological parameter and, furthermore, enables simultaneous representation on a single graph of the receptor and steroid fields. The present example demonstrates the use of this type of methodology in processing routine screening data involving multiple parameters.

Chemical Phenomena↗

PubMed1994

Acquisition of procedural skills from examples.

Three experiments were run in which Ss first memorized examples of input-output pairs and then generated the outputs for a series of new inputs by analogy to the original examples. Ss first performed these mappings by explicit analogy to an example, but with practice they learned to make these input-output mappings directly without reference to the examples. Ss sped up as a power function of practice over a day (Experiment 1) or days (Experiments 2 and 3). Ss developed a directional asymmetry such that they were slower to calculate the input from the output than the output from the input (whereas initially they had not been). Ss showed similar speed up in their ability to recall the original examples but did not show the same directional asymmetry. Initially, there was some transfer from practicing the procedure to recalling the examples, but this diminished over days.

Cognition↗

PubMed2001

Intron distribution difference for 276 ancient and 131 modern genes suggests the existence of ancient introns.

o introns delineate elements of protein tertiary structure? This issue is crucial to the debate about the role and origin of introns. We present an analysis of the full set of proteins with known three-dimensional structures that have homologs with intron positions recorded in GenBank. A computer program was generated that maps on a reference sequence the positions of all introns in homologous genes. We have applied this program to a set of 665 nonredundant protein sequences with defined three-dimensional structures in the Protein Data Bank (PDB), which yielded 8,217 introns in 407 proteins. For the subset of proteins corresponding to ancient conserved regions (ACR), we find that there is a correlation of phase-zero introns with the boundary regions of modules and no correlation for the phase-one and phase-two positions. However, for a subset of proteins without prokaryotic counterparts (131 non-ACR proteins), a set of presumably modern proteins (or proteins that have diverged extremely far from any ancestral form), we do not find any correlation of phase-zero intron positions with three-dimensional structure. Furthermore, we find an anticorrelation of phase-one intron positions with module boundaries: they actually have a preference for the interior of modules. This finding is explicable as a preference for phase-one introns to lie in glycines, between G/G sequences, the preference for glycines being anticorrelated with the three-dimensional modules. We interpret this anticorrelation as a sign that a number of phase-one introns, and hence many modern introns, have been inserted into G/G "protosplice" sequences.

Evolution, Molecular↗

PubMed1985

Chromosomal location of the gene encoding the neural cell adhesion molecule (N-CAM) in the mouse.

The gene encoding the neural cell adhesion molecule, N-CAM, has been localized on mouse chromosome 9. A BALB/cJ mouse genomic library prepared in lambda bacteriophage EMBL4 was screened by using a cDNA probe, pEC204, that corresponds to the coding region of the chicken N-CAM gene. Four weakly reactive and one strongly reactive recombinant phage were isolated. A region of the latter that was strongly homologous to pEC204 was subcloned to yield a new probe, pEC501. RNA transfer blots and nucleotide sequencing indicated that pEC501 encoded part of the mouse N-CAM gene. This probe defined a unique genetic locus, Ncam, associated with a restriction fragment length polymorphism that allowed the definition of two alleles. The locus could be provisionally assigned either to chromosome 9 or to chromosome 10 by correlating the presence or absence of mouse-specific DNA fragments reactive with the probe in a panel of somatic hybrid cell lines with the presence or absence of the various mouse chromosomes. Analysis of the inheritance of the Ncam-associated DNA polymorphism in recombinant inbred strains of mice revealed close linkage between Ncam and the Lap-1, Sep-1, and Thy-1 loci on chromosome 9. This result suggests an additional linkage between Ncam and the locus for the cerebellar mutation staggerer (sg). The Ncam locus provides an important reference point for mapping the genes for additional cell adhesion molecules as well as genes for other molecules involved in neural development and function.

Animals↗

PubMed1986

Words created by children versus aphasic adults: an analysis of their form and communicative effectiveness.

The creation of words through the novel combination of English morphemes (e.g., "map ball" to refer to a globe) was studied in 40 preschool children, 40 grade school children, and 40 adults. These lexical innovations were collected while subjects named pictured objects, and were evaluated in terms of incidence, communicative effectiveness, novelty, semantic accuracy, and certain linguistic characteristics. Preschool children's innovations were as communicatively effective as those of grade school children and adults and contained the highest proportion of innovations with redundant elements. Grade school children produced the highest proportion with semantic inaccuracies. This suggests that preschoolers invent words from a limited set of highly familiar terms, whereas grade schoolers rely more on partially known terms. In addition, the children's innovations differed significantly from those previously collected from aphasic adults. This demonstrates that aphasia does not cause a regression to an early level of linguistic sophistication.

Anomia↗

PubMed1984

The nucleotide recognized by the Escherichia coli A restriction and modification enzyme.

The nucleotide recognition sequence for the restriction-modification enzyme of Escherichia coli A (EcoA) has been determined to be GAG-7N-GTCA. This sequence is fairly similar, but distinctly different from the two other type I restriction enzyme recognition sites known for E. coli B and E. coli K12, respectively. N6-adenosine methylation has been observed at nucleotide positions 2 and 12 within that sequence after modification by EcoA. As a reference point for mapping the single EcoA site in lambda, the position of lambda point mutation Oam29 has been determined also.

Base Sequence↗