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From selective thalamotomy with microrecording to gamma thalamotomy for movement disorders.

A theoretical and practical process from microrecording-guided thalamotomy to gamma knife thalamotomy was briefly reviewed. Based on our own experiences of selective thalamotomy with microrecording, we are trying to apply gamma knife to the treatment of movement disorders. An important technical problem is how to determine the exact thalamic target. At first we refer to the posterior commissure and coordinate of the standard atlas for approximately determining the lateral part of the ventral intermediate nucleus. Then the point is further corrected by anatomical landmark (45% of the thalamic length) to compensate the individual difference. A final lesion is made by gamma knife using a 4-mm collimator, 130 Gy in 1 shot. The average delay of clinical improvement is about 6 months after irradiation. Thus far the results are satisfactory, being 80-85% successful without any noticeable complications. Only 3 days of hospitalization with minimal invasion could be a big advantage for the patient. Further technical progress may improve the clinical results in the future.

Humans↗

Atlas - a data warehouse for integrative bioinformatics.

BACKGROUND: We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development. DESCRIPTION: The Atlas system is based on relational data models that we developed for each of the source data types. Data stored within these relational models are managed through Structured Query Language (SQL) calls that are implemented in a set of Application Programming Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The methods in these API libraries are used to construct a set of loader applications, which parse and load the source datasets into the Atlas database, and a set of toolbox applications which facilitate data retrieval. Atlas stores and integrates local instances of GenBank, RefSeq, UniProt, Human Protein Reference Database (HPRD), Biomolecular Interaction Network Database (BIND), Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT), IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox applications are critical components that offer end-users flexible, easy, integrated access to this data. We present use cases that use Atlas to integrate these sources for genome annotation, inference of molecular interactions across species, and gene-disease associations. CONCLUSION: The Atlas biological data warehouse serves as data infrastructure for bioinformatics research and development. It forms the backbone of the research activities in our laboratory and facilitates the integration of disparate, heterogeneous biological sources of data enabling new scientific inferences. Atlas achieves integration of diverse data sets at two levels. First, Atlas stores data of similar types using common data models, enforcing the relationships between data types. Second, integration is achieved through a combination of APIs, ontology, and tools. The Atlas software is freely available under the GNU General Public License at: http://bioinformatics.ubc.ca/atlas/

Computational Biology↗

Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk.

A case-control study of colorectal cancer, consisting of 157 cases and 380 controls matched by sex, ethnicity, decade of age and county of residence was performed to explore the associations between environmental exposure, metabolic polymorphisms and cancer risk. Participants were required to provide a blood sample, undergo caffeine phenotyping and complete an in-person interview that evaluated meat consumption, cooking methods and degree of doneness. A color atlas of foods cooked to different degrees of doneness was used to estimate food preparation techniques and food models were used to estimate serving portion sizes. Data was analyzed using a reference database of heterocyclic amine (HCA) exposure based on the food preferences chosen from the atlas. Data regarding individual food items cooked to different levels of doneness, as well as summary variables of foods and of food groups cooked to different degrees of doneness were also evaluated in a univariate analysis for association with colorectal cancer case status. Three measures of metabolic variation, hGSTA1 genotype, SULT1A1 genotype and the phenotype for CYP2A6 were also evaluated for possible association with colon cancer. While higher exposure to HCAs was strongly associated with colorectal cancer risk, increased consumption of five red meats cooked well done or very well done produced comparable odds ratios (OR) for colorectal cancer risk (OR=4.36, 95% CI 2.08-9.60) for the highest quartile of exposure. Similarly, individuals in the most rapid CYP2A6 phenotype quartile showed an odds ratio (OR = 4.18, 95% CI 2.03-8.90). The ORs for the low activity hGSTA1 and low activity SULT1A1 alleles were 2.0, 95% CI 1.0-3.7 and 0.6, 95% CI 0.3-1.1, respectively. Individual measures of specific HCAs provided little improvement in risk assessment over the measure of meat consumption, suggesting that exposure to other environmental or dietary carcinogens such as nitrosamines or undefined HCAs may contribute to colorectal cancer risk.

Adult↗

An atlas of gene expression from seed to seed through barley development.

Assaying relative and absolute levels of gene expression in a diverse series of tissues is a central step in the process of characterizing gene function and a necessary component of almost all publications describing individual genes or gene family members. However, throughout the literature, such studies lack consistency in genotype, tissues analyzed, and growth conditions applied, and, as a result, the body of information that is currently assembled is fragmented and difficult to compare between different studies. The development of a comprehensive platform for assaying gene expression that is available to the entire research community provides a major opportunity to assess whole biological systems in a single experiment. It also integrates detailed knowledge and information on individual genes into a unified framework that provides both context and resource to explore their contributions in a broader biological system. We have established a data set that describes the expression of 21,439 barley genes in 15 tissues sampled throughout the development of the barley cv. Morex grown under highly controlled conditions. Rather than attempting to address a specific biological question, our experiment was designed to provide a reference gene expression data set for barley researchers; a gene expression atlas and a comparative data set for those investigating genes or regulatory networks in other plant species. In this paper we describe the tissues sampled and their transcriptomes, and provide summary information on genes that are either specifically expressed in certain tissues or show correlated expression patterns across all 15 tissue samples. Using specific examples and an online tutorial, we describe how the data set can be interrogated for patterns and levels of barley gene expression and how the resulting information can be used to generate and/or test specific biological hypotheses.

Databases, Genetic↗

Hypertext atlas of dermatopathology with expert system for epithelial tumors of the skin.

BACKGROUND: Image resolution required for reference histological images is high. Obtaining high-resolution images requires a system, composing large image from individual smaller components. Such systems must thus be capable of automatically taking individual image parts, performing shading compensation and fusion of the image parts into one large image. Distribution of such images over the Internet requires developing a suitable user's interface with access to the image details. METHODS: The ways of creating high-resolution images (virtual slides) and the interface enabling access to image details using Internet browser are described. RESULTS: A collection of about 3200 dermatopathological, mostly histologic images is available at http://www.muni.cz/atlases: Hypertext atlas of dermatopathology. Methods of high-resolution image acquisition were used in digitizing the collection of skin lymphomas (Dermatology Institute, University Hospital, Zurich), which is a part of the atlas. The atlas is continuously maintained and upgraded; the number of contributors is growing.

Dermatology↗

Subtle cortical thinning in the temporal pole in middle-aged APOE-ε4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45 ± 3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+ P+ (APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans↗

Tutorials in clinical research, part VI: descriptive statistics.

OBJECTIVES: This is the sixth in a series of Tutorials in Clinical Research. The objectives of this tutorial are to produce a brief, step-by-step, user-friendly atlas with clinical scenarios and illustrative examples to serve as ready references and, it is hoped, to open an inviting door to understanding statistics. STUDY DESIGN: Tutorial. METHODS: The authors met weekly for 6 months discussing clinical research articles and the applied statistics. Liberal use of reference texts and discussion focused on constructing a tutorial that is factual as well as easy to read and understand. RESULTS: The tutorial is organized into five sections: Overview, Key to Descriptive Summaries, Steps in Summarizing Descriptive Data, Understanding the Summaries of Specific Data Types, and Understanding Scope or Dispersion of Data. CONCLUSIONS: Assessing the validity of medical studies requires a working knowledge of statistics; however, obtaining this knowledge need not be beyond the ability of the busy surgeon. Desire is the only limiting factor. We have tried to construct an accurate, basic, easy-to-read-and-apply introduction to the task of summarizing the characteristics of a single variable. This is known as descriptive statistics.

Data Interpretation, Statistical↗

Consequences of large interindividual variability for human brain atlases: converging macroscopical imaging and microscopical neuroanatomy.

In human brain imaging studies, it is common practice to use the Talairach stereotaxic reference system for signifying the convergence of brain function and structure. In nearly all neuroimaging reports, the studied cortical areas are specified further with a Brodmann Area (BA) number. This specification is based upon macroscopic extrapolation from Brodmann's projection maps into the Talairach atlas rather than upon a real microscopic cytoarchitectonic study. In this review we argue that such a specification of Brodmann area(s) via the Talairach atlas is not appropriate. Cytoarchitectonic studies reviewed in this paper show large interindividual differences in 3-D location of primary sensory cortical areas (visual cortex) as well as heteromodal associational areas (prefrontal cortical areas), even after correction for differences in brain size and shape. Thus, the simple use of Brodmann cortical areas derived from the Talairach atlas can lead to erroneous results in the specification of pertinent BA. This in turn can further lead to wrong hypotheses on brain system(s) involved in normal functions or in specific brain disorders. In addition, we will briefly discuss the different 'Brodmann' nomenclatures which are in use for the cerebral cortex.

Adult↗

A stereotaxic template atlas of the macaque brain for digital imaging and quantitative neuroanatomy.

A stereotaxic brain atlas of the longtailed macaque (Macaca fascicularis) is presented in a format suitable for use as a template atlas of the macaque brain. It includes most of the brain segmented to show the boundaries of landmark structures such that every point in the brain can be represented by a unique set of coordinates in three-dimensional space and ascribed unambiguously to one and only one primary structure. More than 400 structures are represented, including 360 volumetric structures, which constitute the substance of the brain, and 50 superficial features. To facilitate use with ventriculography, magnetic resonance imaging, and other noninvasive imaging techniques, the stereotaxic space is referenced to internal landmarks, viz., the anterior commissure and posterior commissure; the center of the anterior commissure at the midline is the origin of the stereotaxic axes. Reference of stereotaxis to this bicommissural space facilitates structural comparison with human brain atlases, which are commonly referenced to the biocommissural line. It also facilitates comparison of brains of different nonhuman primate species by providing a template brain against which to compare size and internal variability. Thirty-three coronal sections at 1-mm intervals from the spinomedullary junction to the rostral extreme of the caudate nucleus show most structures of the hindbrain, midbrain, and subcortical forebrain. Separately, four side views and 16 coronal sections show cortical structures. Structures are represented by outlines of their boundaries and labeled according to NeuroNames, a systematic English nomenclature of human and nonhuman primate neuroanatomy. Abbreviations are based on a protocol designed to facilitate cross-species comparisons. Instructions are provided for: (1) locating sites from the Template Atlas in the conventional stereotaxic space of an experimental animal, (2) locating sites identified by conventional stereotaxis in the Template Atlas, and (3) using the Template Atlas to collate, compare, and display image information (e.g., labeled cells, recording sites, stimulation sites, lesions) from multiple animals.

Animals↗

Histopathological atlas of renal diseases: light chain deposition disease.

Monoclonal diseases of B-cell lineage, often referred to as plasma cell dyscrasias, are characterized by abnormal and uncontrolled proliferation of a single clone of B cells at different maturation stages, with a more or less marked differentiation to immunoglobulin (Ig)-secreting plasma cells. Thus B-cell proliferation is usually associated with the production and secretion in blood of a monoclonal Ig or a fragment thereof. An ominous consequence of secretion of monoclonal Ig products is their deposition in tissue. These proteinaceous deposits can take the form of casts (in myeloma cast nephropathy), cristals (in myeloma-associated Fanconi's syndrome), fibrils (in light-chain [LC] amyloidosis), or granular precipitates (in monoclonal Ig deposition disease [LCDD]).

B-Lymphocytes↗

Parametric brain MR atlases: standardization for imaging informatics.

This paper is focused on the development of normal MR brain atlases of intrinsic MR parameters. These parameters permit quantitative comparisons across imaging studies (as opposed to raw image intensity values) and are important markers of neurological diseases. The development includes fast sequences to generate three parameters (T1: spin-lattice relaxation, T2: spin-spin relaxation, and Diffusion Tensor) covering the whole brain with isotropic and high-resolution images. The analysis of raw data to generate the parametric images is followed by registration algorithms to bring the image studies acquired on normal subjects aligned to a common frame of reference. The registration method includes both linear and non-linear algorithms. Two atlas schemes are discussed: an average atlas and a probabilistic atlas. Initial results on sequence development and registration are presented. The atlases are envisaged as an integral part of an imaging informatics infrastructure that enables image analysis across imaging studies to perform automated image data mining.

Algorithms↗

Topography of auditory evoked long-latency potentials in normal children, with particular reference to the N1 component.

Topographic maps of late auditory evoked potentials were obtained with the Brain Atlas III system in 34 healthy, normal hearing children aged 8-16 years. The stimulus was a 100 msec, 500 Hz tone burst, presented separately to the left and right ears, at 75 dB HL. The resulting auditory evoked potentials showed a prominent N1, after about 100 msec, and a topographic map with a corresponding fronto-lateral focus designated as the focus of N1 (FN1). Foci with varying positions and amplitudes were identified in 33 of 34 subjects after left ear stimulation and in 29 of 32 subjects after right ear stimulation. The topography showed a high degree of stability in most subjects, with the position of the negative "peak" of FN1 in front of the interaural line and with a dominance contralateral to the ear stimulated. There was a significant decrease in the latency of N1 with increasing age. FN1 tended to change position with age and some differences from adults were also observed. In conclusion, a distinct topographic pattern of the N1 component of the late auditory evoked potentials was seen in the majority of children. It remains to be established to what extent this method may be clinically useful for disclosing functional disturbances in the central auditory pathways.

Acoustic Stimulation↗

Influence of motor activity on striatal dopamine release: A study using iodobenzamide and SPECT.

Pharmacologically induced dopamine release can influence the postsynaptic receptor binding of dopaminergic radioligands. This effect has recently been described using in vivo imaging methods and has been attributed to competition of radiotracers with the endogenous ligand. The present study examines the effect of a motor activation task on dopamine release and the consequences of this release on the binding of the selective D(2) receptor ligand (123)I-iodobenzamide (IBZM) to striatal dopamine D(2) receptors. Eight subjects were asked to write a text beginning immediately before IBZM injection and continuing for 30 min thereafter. Eighteen other subjects remained in a supine resting state during this period and served as a control group. All subjects were right handed. We hypothesized that the writing task would lead to an increase of dopamine release. The increased competition of the endogenous ligand with IBZM should lead to a decreased postsynaptic IBZM binding in the experimental group. Images were acquired and reconstructed identically and anatomically normalized to a computerized brain atlas. Regions of interest were drawn covering the striatum and three different reference regions. Ratios of striatal-to-reference-tissue radioactivity accumulation were calculated as semi-quantitative estimates of D(2) receptor binding potential. This decreased bilaterally, although right-sided significantly more than left, regardless of the choice of reference region. These data show that writing with the right hand compared to a supine resting state leads to a decrease of striatal IBZM accumulation. According to our primary hypothesis this reflects dopamine release.

Adult↗

Activities and current research from the EC, standards, measurements and testing programme (SMT) in the area of food contact materials.

The EC, Standards, Measurements and Testing Programme (SMT) is the successor of the Measurements and Testing Programme (M&T) and the Community Bureau of Reference (BCR). Its objectives include the provision of research and technical support to standardization and health of the society when it is required to improve the competitive position of European industry, and for the development or implementation of Community policy. The SMT-Programme is currently supporting a number of different types of collaborative projects in the food packaging sphere. Their objectives range from method development via preparation and certification of reference materials, preparation of a handbook and the update of a spectral atlas to pre-normative research providing information on a number of sources and wide range of packed products being transported throughout Europe.

European Union↗

Three-dimensional motion analysis of the upper cervical spine during axial rotation.

Rotational motion of the normal upper cervical spine was analyzed in 20 men using biplanar roentgenograms, a system digitizer, and a personal computer. To detect the bony landmarks of the atlas, the subjects' heads were fixed and their trunks rotated in the reference frame while these biplanar studies were obtained. Coupling motions observed included 10 degrees extension at C0-C1, with 11 degrees of lateral bending between C1-C2. Almost all (80%) cervical axial rotation took place at C1-C2, whereas only 4 degrees of rotation occurred at C0-C1. Furthermore, as C1-C2 axial rotation increased, so did rotation in the opposite direction at C0-C1 while less rotation was noted below C2. The instantaneous axis of rotation was located anterior to the foramen magnum at the C0-C1 level, in the central portion of the dens at C1-C2.

Adult↗

An anatomic and morphometric study of C2 nerve root ganglion and its corresponding foramen.

STUDY DESIGN: Exposing and measuring the dorsal root ganglion of the second cervical spinal nerve (C2 ganglion) and the second intervertebral space, which is present between posterior arch of atlas (APA) and lamina of axis (LA). OBJECTIVES: This study aims to investigate the shape, size, and relation of the C2 ganglion with the adjacent structures that limits the corresponding intervertebral space and the alterations of relation between C2 ganglion and APA and between C2 ganglion and LA with the movements of the head bilaterally. SUMMARY OF BACKGROUND DATA: In previous studies, the position and the heights of the C2 ganglion have been described. But the shape of the C2 ganglion and its relation to APA and LA by the movement of the head had not been considered previously. METHODS: Upper cervical spines of 20 cadavers were dissected posteriorly. The muscles attaching to the atlas and axis were resected to ease the head movements. The heights of the C2 ganglion and space were measured in anatomic position and in hyperextension with opposite rotation position of the head. Originally in this study, plastic dough casts were used to obtain reliable outcomes. RESULTS: The shape of the ganglions was defined in three types: 70% were oval, 20% were spindle-like, and 10% were spherical. The height of the C2 ganglion was 4.97 +/- 0.92 mm on the right side and 4.6 +/- 0.84 mm on the left side. The height of the intervertebral space in anatomic position and in hyperextension with rotation to the opposite position of the head were, respectively, 9.74 +/- 1.77 mm and 7.48 +/- 1.44 mm on the right side and 9.64 +/- 1.47 mm and 7.12 +/- 0.96 mm on the left side. There was no bone contact or impact to the ganglion in each position of the head. CONCLUSION: The C2 ganglions are confident in their place between APA and LA. No bone contact to the C2 ganglion was detected in either normal limited or in forced head motions.

Adult↗

Further studies on the cyto-, fibro- and dendro-architectonic structures of chicken diencephalon and mesencephalon.

Cyto-, fibro- and dendro-architectonic analyses of the diencephalic and mesencephalic area in chickens were carried out by means of the Nissl staining, silver impregnation and Golgi-Cox techniques. Within this area, a number of nuclei and fiber bundles were described and summarized in the form of cyto- and fibro-architectonic atlases of the frontal planes at the same level. Furthermore, with special reference to the optic tectum, detailed cyto- and dendro-architectonic observations were performed. Cytoarchitectonically, this area was composed of 15 alternately arranged layers from the surface inward, 3 of which were fiber bundle zones demonstrated more clearly in silver-impregnated preparations. On the other hand, in dendro-architectonic preparations, only 4 zones were identified; external horizontal, external vertical, internal horizontal and internal vertical cell layers. Among them, small fusiform and large pyramidal cell types in the external vertical cell layer as well as large stellate cells in the internal horizontal zone were histologically characterized. Further means of performing more detailed architectonic analysis of all nuclei and fiber bundles in the diencephalic and mesencephalic area were discussed and this may be useful for the physiological and anatomical studies.

Animals↗

A digital atlas to characterize the mouse brain transcriptome.

Massive amounts of data are being generated in an effort to represent for the brain the expression of all genes at cellular resolution. Critical to exploiting this effort is the ability to place these data into a common frame of reference. Here we have developed a computational method for annotating gene expression patterns in the context of a digital atlas to facilitate custom user queries and comparisons of this type of data. This procedure has been applied to 200 genes in the postnatal mouse brain. As an illustration of utility, we identify candidate genes that may be related to Parkinson disease by using the expression of a dopamine transporter in the substantia nigra as a search query pattern. In addition, we discover that transcription factor Rorb is down-regulated in the barrelless mutant relative to control mice by quantitative comparison of expression patterns in layer IV somatosensory cortex. The semi-automated annotation method developed here is applicable to a broad spectrum of complex tissues and data modalities.

Anatomy, Artistic↗