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PubMed1991

The epidemiology of headache among children with brain tumor. Headache in children with brain tumors. The Childhood Brain Tumor Consortium.

In this report we present aspects of the epidemiology of headache (i.e., pain in the head, face, ear, or neck) among children with brain tumors. The data are derived from the 3,291 subjects in the Childhood Brain Tumor Consortium databank. Overall, 62% of the children with brain tumors experienced chronic or frequent headaches prior to their first hospitalization: 58% of children with supratentorial tumors and 70% of children with infratentorial tumors. The relative frequency of headache increased through age 7 and then leveled off regardless of tumor location. For children under age 5, headache rarely had a duration of more than 1 year prior to hospitalization. Among children over age 4, headache duration of at least one year was significantly greater for supratentorial than for infratentorial tumors. Children with a brain tumor and headache had a different distribution of symptoms and neurologic signs than those without headache. Tumor location and headache status were interactively associated with the presence of other symptoms and neurologic signs. Children with headache had a greater number of other symptoms and neurologic signs. Regardless of tumor location among children with headache, nausea or vomiting, papilledema, and hypoactive tendon reflexes were more frequent, while upper extremity weakness, optic atrophy, and irritability were less frequent. Diplopia, coma, stiff neck, anesthesia or hypesthesia, pupillary abnormalities, and abnormalities of personality, academic performance, or speech were associated with headache in children with supratentorial tumors. No specific symptoms or neurologic signs were associated with headache in children with infratentorial tumors. Supratentorial craniopharyngioma, ependymoma, and protoplasmic astrocytoma were associated with significantly high rates of headache as was infratentorial pilocytic astrocytoma.

Adolescent↗
PubMed1991

Identification of 5-hydroxytryptamine1A receptor agents using a composite pharmacophore analysis and chemical database screening.

A composite pharmacophore analysis and computer-assisted chemical database screening were used to identify a previously unrecognized class of 5-hydroxy-tryptamine1A (5-HT1A) receptor active agents. An analysis of published data led to the identification of 20 different chemical structures which share nanomolar affinity for the 5-HT1A receptor. From a composite pharmacophore analysis of all 20 potent agents, we hypothesized that compounds containing a novel (in terms of 5-HT1A receptor analysis) 3 ring structure might be active at the 5-HT1A receptor. To test this hypothesis, the Chemical Abstracts database, which contains over 10 million compounds, was screened electronically for compounds that contain this core structure. A series of 319 agents was identified which contain this core structure. A total of 6 compounds was then obtained commercially and evaluated in radioligand binding studies. A single agent (Compound 69/183) conformed most closely to the composite 5-HT1A pharmacophore and displayed an affinity of 20 nmol/l for the 5-HT1A receptor binding site. Two other agents displayed affinities of 170 and 500 nmol/l, respectively, for the 5-HT1A receptor site. The 3 agents which differed most significantly from the composite 5-HT1A pharmacophore displayed affinities of 1,200- greater than 10,000 nmol/l for the 5-HT1A receptor binding site. These data suggest that a composite pharmacophore analysis and computer-assisted chemical database screening can be an effective technique for the identification of previously unrecognized receptor active agents.

Computer Simulation↗
PubMed1993

A method for constructing data-based models of spiking neurons using a dynamic linear-static nonlinear cascade.

This paper describes a general nonlinear dynamical model for neural system identification. It describes an algorithm for fitting a simple form of the model to spike train data, and reports on this algorithm's performance in identifying the structure and parameters of simulated neurons. The central element of the model is a Wiener-Bose dynamic nonlinearity that ensures that the model is able to approximate the behaviour of an arbitrary nonlinear dynamical system. Nonlinearities associated with spike generation and transmission are treated by placing the Wiener-Bose system in cascade with pulse frequency modulators and demodulators, and the static nonlinearity at the output of the Wiener-Bose system is decomposed into a rectifier and a multinomial. This simplifies the model without reducing its generality for neuronal system identification. Model elements can be characterised using standard methods of dynamical systems analysis, and the model has a simple form that can be implemented and simulated efficiently. This model bears a structural resemblance to real neurons; it may be regarded as a connectionist "neuron" that has been generalized in a realistic way to enable it to mimic the behaviour of an arbitrary nonlinear system, or conversely as a general nonlinear model that has been constrained to make it easy to fit to spike train data. Tests with simulated data show that the identification algorithm can accurately estimate the structure and parameters of neuron-like nonlinear dynamical systems using data sets containing only a few hundred spikes.

Animals↗
PubMed1991

Evolutionary relationship between human and mouse immunoglobulin kappa light chain variable region genes.

Similar to the Igh-V multigene family, the human or mouse Igk-V repertoire is a distorted continuum of homologous genes that may be grouped into families displaying greater than 80% nucleic acid sequence similarity among their members. Systematic interspecies sequence comparisons reveal that most human Igk-V gene families exhibit clear homology to mouse Igk-V families (sequence similarity generally greater than 74%). A hypothetical phylogenetic tree of Igk-V genes predicts that a minimum of seven Igk-V genes/families predate mammalian radiation. In two cases, several interrelated mouse Igk-V families exhibit phylogenetic equidistance with just one human Igk-V family, implying a more pronounced divergence for the elevated number of Igk-V gene families in the mouse. Mouse-human Igk-V comparisons, moreover, illustrate how expansion, contraction, and perhaps deletion of Igk-V gene families shape the Igk-V repertoire during mammalian evolution.

Animals↗
PubMed1993

NMR structure-based drug design.

NMR is a useful tool for rapidly determining the conformations of receptor-bound ligands and identifying those portions of the ligand in contact with the receptor. In addition, the complete 3D structures of receptors and ligand/receptor complexes can be obtained using recently developed heteronuclear multi-dimensional NMR techniques. This NMR-derived structural information is potentially useful for aiding in The design of improved pharmaceutical agents. Approaches for utilizing the NMR-derived structural information along with the computational tools that facilitate this process are discussed.

Carrier Proteins↗
PubMed1993

Database for serial magnetic resonance imaging in multiple sclerosis.

The unique sensitivity of magnetic resonance imaging (MRI) in detecting disease activity in multiple sclerosis (MS) and the objective nature of the information obtained suggest that MRI will be a useful and reliable way of monitoring treatment trials. There is a need to develop an appropriate database which would provide a standardised means of assessment, not only of MRI, but also of essential clinical information. As part of the program of Concerted Action in Multiple Sclerosis, funded by the Commission of the European Community (CEC), we have developed a database for recording serial brain MRI results. The database consists of core, entry and follow-up sections. Both entry and follow-up parts are subdivided into clinical, MR system and MRI data. We expect that the use of this database will maximise efficiency of MRI monitoring in MS treatment trials, particularly in multicentre studies.

Brain↗
PubMed1992

The effect of a multiple literature database search--a numerical evaluation in the domain of Japanese life science.

In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases.

Biological Science Disciplines↗
PubMed1991

Axonal cytoskeleton at the nodes of Ranvier.

The relationship between the degree of nodal narrowing and the changes in the structure of the axonal cytoskeleton was studied in 53 fibres of mouse sciatic nerve. Nodal narrowing increased with increasing fibre calibre to reach about 20% of the internodal area in the thicker fibres. The narrowing corresponded quantitatively to a decreased number of nodal neurofilaments. Nodal microtubule numbers varied greatly, and a majority of fibres had considerably (approximately 55%) more microtubules in their nodal profile than in the internode. Nodal profiles of different calibre showed an increase in the number of filaments and of microtubules with nodal calibre, although at rates different from those in the internode. The degree of observed axon non-circularities had no discernible effect on the restructuring of the axonal cytoskeleton at the node. A transnodal transport of the axonal cytoskeleton can occur with: (1) accelerated transnodal transport of filaments, (2) stationary internodal fraction of filaments, (3) depolymerization of filaments proximal to the node and repolymerization distally, or (4) different nodal and internodal polymerization equilibria.

Animals↗
PubMed1991

A relational database for sequence-specific protein NMR data.

A protein NMR database has been designed and is being implemented. The database is intended to contain solution NMR results from proteins and peptides (larger than 12 residues). A relational database format has been chosen that indexes data by: primary journal citation, molecular species, sequence-related and atom-specific assignments, and experimental conditions. At present, all data are entered from the primary refereed literature. Examples are given of sample queries to the database. Possible distribution formats are discussed.

Animals↗
PubMed2000

How to perform a comprehensive search for FDG-PET literature.

In this study, a comprehensive, unbiassed search strategy for identifying literature on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in Medline, Embase and Current Contents was developed, with specific search strategies for each database, using MeSH terms as well as free text words for PET and FDG. To examine which text words apply to FDG, we evaluated the ways of spelling FDG in a random sample of FDG-PET articles (n = 100). These words were used as free text words in the two databases and overlap was determined. PET publications were identified using the text words "positron emission tomography" and "pet$" combined with the respective MeSH terms for each database. To compare the yield of the combined FDG-PET strategy in each database, the retrieved citations were downloaded to Pro-Cite 4.0. Finally, we added search terms for lung cancer, breast cancer, melanoma, head and neck cancer and lymphoma to our strategy and to a short strategy (consisting of the text words "positron emission tomography" and "fdg"). In order to measure the yield and precision (positive predictive value, PPV) of our search strategy and compare it with the short one, we screened the title and abstract of the retrieved citations. Reviewing a random sample of the FDG-PET literature yielded 56 different ways of spelling FDG. We confined the list to 11 text words, without missing articles. Of the publications retrieved by these text words, only 4% were indexed by the MeSH term "Fludeoxyglucose F18" in Medline and 29% by the MeSH-term "Fluorodeoxyglucose F18" in Embase. Only 51% of PET articles were indexed by the MeSH term "Tomography, emission-computed" in Medline and 40% by the MeSH term "Positron emission tomography" in Embase. The combined search strategy for identifying studies on FDG and PET resulted in 2865 publications in Medline and 2646 in Embase. Medline identified 1662 publications not found by Embase; Embase identified 1422 publications not found by Medline. Compared with the short strategy, our search strategy yielded on average 52% more publications (94%, 41% and 20% more in Medline, Embase and Current Contents, respectively). The PPV of our strategy (percent of publications that were really on PET, FDG and the specified subject) was 70%, compared with 76% using the short strategy. Regardless of the strategy used, Embase yielded more publications and was also slightly more specific than Medline. With the recommended strategy, FDG-PET publications can be identified more efficiently. We have shown the importance of searching more than one database and emphasize the use of both MeSH terms and text words in a search strategy. Standardization of the spelling of FDG and indexing of articles on FDG would substantially simplify searching.

Abstracting and Indexing↗