This paper describes an approach that provides Internet-based support for a genome center to map human chromosome 12, as a collaboration between laboratories at the Albert Einstein College of Medicine in Bronx, New York, and the Yale University School of Medicine in New Haven, Connecticut. Informatics is well established as an important enabling technology within the genome mapping community. The goal of this paper is to use the chromosome 12 project as a case study to introduce a medical informatics audience to certain issues involved in genome informatics and in the Internet-based support of collaborative bioscience research. Central to the approach described is a shared database (DB/12) with Macintosh clients in the participating laboratories running the 4th Dimension database program as a user-friendly front end, and a Sun SPARCstation-2 server running Sybase. The central component of the database stores information about yeast artificial chromosomes (YACs), each containing a segment of human DNA from chromosome 12 to which genome markers have been mapped, such that an overlapping set of YACs (called a "contig") can be identified, along with an ordering of the markers. The approach also includes 1) a map assembly tool developed to help biologists interpret their data, proposing a ranked set of candidate maps, 2) the integration of DB/12 with external databases and tools, and 3) the dissemination of the results. This paper discusses several of the lessons learned that apply to many other areas of bioscience, and the potential role for the field of medical informatics in helping to provide such support.

Chromosome Mapping↗

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[Urinary excretion of mineral arsenic, methylarsonic acid and dimethylarsinic acid in workers exposed to gallium arsenide].

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Arsenic↗

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Detection of K-ras mutations by denaturing gradient gel electrophoresis (DGGE): a study on pancreatic cancer.

In pancreatic neoplasias mutations in the first exon (codon 12) of K-ras gene occur at high frequency and seem to have a diagnostic significance. We set up the DGGE conditions to search for these mutations in pancreatic tumor sample DNAs. All samples were directly classified by simply comparing their DGGE patterns with those of control cell lines carrying known K-ras base substitutions. We found a mutation frequency of 73% in pancreatic adenocarcinoma, whereas no mutations were observed in benign lesions. The non-isotopic method we used turned out to be rapid and sensitive. DGGE could therefore be utilized for the detection of K-ras mutations in pancreatic lesions, to evaluate their actual or potential malignancy. In general, DGGE could be useful for K-ras gene screening on pathological tissue samples.

Adenocarcinoma↗

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[Possibilities and limits of the evoked potentials method and of its treatment by computers to approach the study of visual perception in man].

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Electronic Data Processing↗

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p53 gene mutations and protein nuclear accumulation are early events in intestinal type gastric cancer but late events in diffuse type.

We screened for p53 alterations in 71 early gastric cancers of differing histological types and growth patterns, 18 advanced cancers of diffuse type, 19 dysplastic lesions, and 12 extensive intestinal metaplasia cases. Tumors were investigated for gene mutations (exons 5-8) with PCR-based denaturing gradient gel electrophoresis and sequencing techniques, and for protein accumulation with immunohistochemical methods. Nontumor samples were studied with immunohistochemistry alone. Of the early cancers, intestinal tumors showed a much higher p53 mutation frequency (41%) than did diffuse cancers (4%). When comparing early and advanced tumors of the same type, we observed a similarity in mutation frequency (41 versus about 50%) for intestinal tumors, and a significant increase for diffuse tumors (from 4 to 33%). Immunopositive case distribution between tumor types and stages paralleled that of mutated cases. Immunohistochemical and genetic analysis gave concordant results for all samples with gene mutations. Eighteen of the 65 (28%) nonmutated tumors displayed significant immunoreactivity. Early tumors that massively penetrated the submucosa, i.e., the early tumors for which prognosis is worst, showed the highest frequency both of p53 gene mutation and of nonmutated protein accumulation. Twelve of 19 dysplastic lesions showed significant immunoreactivity, whereas intestinal metaplasias proved unreactive in all but a few cells. Our results yield two implications: that p53 alterations have a crucial and early role in gastric carcinogenesis of intestinal type, likely acting at the transition step between metaplasia and dysplasia; and that the alterations are mainly associated with tumor progression in cancer of diffuse type.

Adenocarcinoma↗

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[Automatic information processing, the frontal system and blunted affect. From clinical dimensions to cognitive processes toward a psychobiological explanation of temperament].

Several theorists have drawn a distinction between automatic and attentional or controlled processing. Hasher and Zacks (1979), were the very first to argue that effortful processes are reduced under conditions of stress including depression. They suggested that, in these conditions, no such deficit occurs in automatic processing. Then, Weingartner and co-workers provided some experiments which seemed to support such an interpretation of the cognitive dysfunction in depressed patients. However, some recent data do not fit with this well admitted theoretical framework. The purpose of our article is to try to clarify this issue both from a theoretical and from a methodological point of view. First, we make a critical review of the most recent results in three fields of experimentation related to the "automatic versus controlled" topic: 1) The classical neuropsychology of memory which manipulates the level of effort required to perform the tasks. Confusion arises when theories at the process level are tested with reference to data collected at the task level. The transparency assumption could be false: Impairment in an effort-demanding task could be due to a defect in automatic processes and it is possible to hypothesize that the more automatic processes are deficient, the more controlled processes are saturated and the effort demanding task impaired. The emergence of controlled processes could depend on the level of automaticity and the regulation of automatic processes could be determinant for the ability of the subject to make associations. 2) The recent studies on implicit memory in depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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Sites and types of p53 mutations in an unselected series of colorectal cancers in The Netherlands.

An unselected series of colorectal adenocarcinomas together with their corresponding normal mucosa, derived from 24 Dutch patients, was investigated for the loss of a marker mapping close to the region of p53 on chromosome 17p and for mutations in exons 5, 6, 7 and 8 of the p53 gene. The observed loss of heterozygosity of the marker on chromosome 17p was 36% of the informative cases, while 58% of the tumors contained a mutation in p53. This might be an indication that the mutation in p53 precedes the loss involving p53 on the homologous chromosome. Four tumors showed the presence of two different missense mutations in the p53 gene; in one of them the mutations involved the first two nucleotides of one and the same codon, while in a second case they were found within the same exon. In the remaining two cases the assessment of their situation, cis or trans, was not feasible. Six of the 18 mutations observed during this study were base transversions, including 3 G- > T substitutions. The hotspot codons 248, 273 and 282, were found to be involved in a third of the mutations.

Adult↗

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Attentional deficits in Parkinson's disease: partial reversibility with naphtoxazine (SDZ NVI-085), a selective noradrenergic alpha 1 agonist.

Several authors have suggested that catecholamine depletion may affect attentional processes in human subjects and could be implicated in the frontal lobe syndrome that has been described in Parkinson's disease (PD). The present study reports the effects of a placebo and naphtoxazine (SDZ-NVI-085), a selective noradrenergic alpha 1 agonist. These substances were administered to nine parkinsonian patients who were assessed on measures of attention, including neuropsychological tests and evoked potentials. The results indicate that naphtoxazine may improve performance on some tests of "frontal functions," including the Stroop and the Odd-Man-Out tests, which have been previously found to be affected in PD. However, the results of some other neuropsychological tests of frontal function were not affected by naphtoxazine. Specific evoked potentials such as the Nd1 and Nd2 curves--which are thought to reflect attentional processes and which have been found to be affected in PD--were improved by naphtoxazine. Finally, naphtoxazine reduced the percentage of errors and restored the lateralization of N100 during the Shifting Reaction Time Task, suggesting that this substance may act on the processes underlying the shifting deficit in these patients. The results are discussed in terms of the specific cognitive processes that may be affected by naphtoxazine and in terms of the role of the noradrenaline in attentional deficits found in PD.

Adrenergic alpha-Agonists↗