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Structural diversity of cancer-related and non-cancer-related prostate-specific antigen.

BACKGROUND: Heterogeneity among the various molecular forms of prostate-specific antigen (PSA) has not been well characterized, despite the critical importance of PSA in the detection of prostate cancer. The purpose of this study was to examine PSA heterogeneity in cancerous and noncancerous materials by extensive and systematic protein analysis. METHODS: A catalog of molecular forms of PSA was established with the PSA purified from seminal fluid. This catalog was used to analyze PSA heterogeneity in cancerous and noncancerous materials by immunoblotting with polyclonal antibodies. RESULTS: PSA from noncancerous materials showed a wider range of molecular mass, from 6000 to 28 000 Da. PSA from cancerous materials did not contain lower molecular mass forms. CONCLUSIONS: The PSA protein catalog may be useful for the analysis of differences among PSA forms in men with and without prostate cancer and for analysis of antibodies used to detect PSA.

Electrophoresis, Polyacrylamide Gel↗

[Drug utilization and recommended conditions for use in children].

BACKGROUND: Studies carried out in other countries show that drugs are used in children outside the approved conditions, in a context in which investigation, information and authorization of medications in the pediatric population are scarce. OBJECTIVES: To evaluate the conditions of drug use recommended in children and variability in sources of drug information. METHODS: We performed a descriptive, retrospective study. Data on medication consumption in 1997 were obtained from a pediatric university hospital. Information on conditions of drug use in children was analyzed using a Spanish catalog of medications. This information was compared with that of a North American catalog for international reference. RESULTS: Most of the drugs used were of unrestricted (43; 47 %) or restricted (26; 28 %) pediatric use, but drugs that are not recommended (8; 9 %) or those with unspecified conditions of use in children were also used (15; 16 %). Approximately 12 % of the drugs were not identified in the North American catalog; of the remaining drugs, 60 % were of unrestricted pediatric use, 35 % of restricted use and 5 % were not recommended. CONCLUSIONS: A substantial proportion of drugs administered to hospitalized children are not recommended or their possible use in this population is not specified. It is worth encouraging research, having sources of information that help to make decisions, especially in conditions that have not been approved, and adapting regulatory attitudes, as far as possible, to the evidence and therapeutic needs.

Adolescent↗

Gene expression profiling by DNA microarray analysis in mouse embryonic fibroblasts transformed by rasV12 mutated protein and the E1A oncogene.

BACKGROUND: Ras is an area of intensive biochemical and genetic studies and characterizing downstream components that relay ras-induced signals is clearly important. We used a systematic approach, based on DNA microarray technology to establish a first catalog of genes whose expression is altered by ras and, as such, potentially involved in the regulation of cell growth and transformation. RESULTS: We used DNA microarrays to analyze gene expression profiles of rasV12/E1A-transformed mouse embryonic fibroblasts. Among the approximately 12,000 genes and ESTs analyzed, 815 showed altered expression in rasV12/E1A-transformed fibroblasts, compared to control fibroblasts, of which 203 corresponded to ESTs. Among known genes, 202 were up-regulated and 410 were down-regulated. About one half of genes encoding transcription factors, signaling proteins, membrane proteins, channels or apoptosis-related proteins was up-regulated whereas the other half was down-regulated. Interestingly, most of the genes encoding structural proteins, secretory proteins, receptors, extracellular matrix components, and cytosolic proteins were down-regulated whereas genes encoding DNA-associated proteins (involved in DNA replication and reparation) and cell growth-related proteins were up-regulated. These data may explain, at least in part, the behavior of transformed cells in that down-regulation of structural proteins, extracellular matrix components, secretory proteins and receptors is consistent with reversion of the phenotype of transformed cells towards a less differentiated phenotype, and up-regulation of cell growth-related proteins and DNA-associated proteins is consistent with their accelerated growth. Yet, we also found very unexpected results. For example, proteases and inhibitors of proteases as well as all 8 angiogenic factors present on the array were down-regulated in transformed fibroblasts although they are generally up-regulated in cancers. This observation suggests that, in human cancers, proteases, protease inhibitors and angiogenic factors could be regulated through a mechanism disconnected from ras activation. CONCLUSIONS: This study established a first catalog of genes whose expression is altered upon fibroblast transformation by rasV12/E1A. This catalog is representative of the genome but not exhaustive, because only one third of expressed genes was examined. In addition, contribution to ras signaling of post-transcriptional and post-translational modifications was not addressed. Yet, the information gathered should be quite useful to future investigations on the molecular mechanisms of oncogenic transformation.

Adenovirus E1A Proteins↗

MELVYL MEDLINE: a library services perspective.

The MELVYL MEDLINE project resulted in the addition of a full five-year subset of MEDLINE to the University of California's (UC) MELVYL online union catalog. As one of the nation's largest MEDLINE end-user searching systems, MELVYL MEDLINE provides online bibliographic access to the biomedical journal literature for all UC personnel at over seventy library sites or by remote access. This paper summarizes the project's accomplishments, reports MELVYL MEDLINE use and its impact on library services, and provides insights for other end-user search systems. The project serves as a model for adding databases to the MELVYL catalog and demonstrates the potential for use by other disciplines of a specialized database when readily accessible. Evaluation results report high user satisfaction and high usage. However, many advanced searching features of the interface are little used by searchers. Effects on library services include marked increases in reference transactions and interlibrary loans, with significant declines in mediated search services. Future MELVYL MEDLINE enhancements include matching search retrievals to journal locations, linkage to an online document delivery system, and consideration of building a superset of databases by combining MELVYL MEDLINE with citations from another database in the MELVYL catalog.

California↗

Retrieval variability: sources and consequences.

A memory model that differentiates between active traces (ongoing electrochemical neural transmission) and passive traces (chemical/structural modification of neurons) is briefly outlined. Evidence suggests that new information is initially encoded as a passive representation within a fraction of a second, leaving little opportunity for retroactive interference with storage processes. Instead, it appears that retroactive interference results from disruption of post-acquisition processing which is necessary for subsequent retrieval. Using this hybrid cognitive-physiological framework, we examine possible sources of associative performance deficits. A distinction is made between similarity interference (arising from the content similarity of the target and interfering traces) and processing interference (arising from the competition between the two traces for use of a limited capacity processor). Both types of interference can act proactively or retroactively, and the similarity-processing and proactive-retroactive dimensions are viewed as orthogonal to the question of whether information is permanently lost or merely subject to a reversible retrieval failure. When reminder techniques (pretest cuing) are used, numerous instances of memory failure commonly identified as "acquisition failures" are found to be reversible without the occurrence of relevant new learning. This literature review constitutes the greater part of the paper. It is concluded that many memory failures are due at least in part to retrieval failure. Consideration of potential retrieval processes in light of the studies that are reviewed argues for the expansion of the initial active-passive trace distinction to three types of traces. In addition to active traces, these include two distinct types of passive traces, i.e., a small content-addressable reference catalog with innately defined dimensions that is used to locate more detailed passive traces, and a large capacity store of detailed passive traces that is location-addressable. The latter type of passive trace presumably is laid down almost instantaneously as events occur, i.e., in real time, whereas the reference catalog type of passive trace, which is used to address the detailed traces, is established somewhat after the sequence of events is complete. Hence, the reference catalog trace is more vulnerable and results in retrieval failure when it is disrupted.(ABSTRACT TRUNCATED AT 400 WORDS)

Amnesia↗

Through the looking glass: finding Internet sites to mirror your collection.

Many libraries are grappling with the new freedom to link to the Internet directly from a Web-based catalog. A conservative approach that locates only Web sites replicating a library's print holdings is described. Methods for locating URLs include reviewing front matter in reference materials, scouring the Internet for material produced both in print and full text on the Web, electronic mailing lists, publishers' promotional materials, conferences, and journal articles. Readers are encouraged to make links from the catalog to any original material produced in Web-readable form by the university, including dissertations and conference proceedings.

Catalogs, Library↗

Low cost organization of a mental retardation facility staff library.

A mental retardation facility staff library of 700 volumes required complete organization. Two restraining factors were lack of personnel and limited funds. A plan was developed to classify titles according to Library of Congress, with the subject heading catalog predominantly based on Medical Subject Headings (MeSH). A cataloging service was located which produced custom card sets and book labels from CATLINE and MARC computer databases. Where necessary, MARC records were edited to alter LC subject headings to MeSH terminology. Organization was accomplished at an average cost per title of less than $1.50.

Cataloging↗

Evolution of a processing system in a large biomedical library.

The processing system used in the UCLA Biomedical Library is modest in size and still under development. Its origins date back to a batch mode serials control system begun in the mid-1960s. This was converted to an on-line system which currently has modules for check-in, updating and retrieval, claims, bindery preparation, and invoice information. Titles can be retrieved at the terminal by search of any word in the title, by subject heading, language, country of publication, and type of publication. The system is adaptable to network use and at present is shared with one other library. To the serials system has been added a computer-assisted cataloging and card production system. The latter utilizes serials nucleus software as well as design for data input and data storage. In-house listings and coding procedures overlap in a general way. Work is under way on further integration of the two processing subsystems and a feasibility study has been completed for addition of a subsystem for acquisitions which will combine and adapt features of the other two; for example, information retrieval characteristics from both, catalog coding and programs for acceptance of data, serials programs for claims, and other output programs. Cost benefits of the subsystems are described and discussed.

Cataloging↗

Automating Veterans Administration libraries: II. Implementation at the Kansas City Medical Center Library.

In 1985, the Kansas City Veterans Administration Medical Center began implementation of the Decentralized Hospital Computer Program (DHCP). An integrated library system, a subset of that program, was started by the medical library for acquisitions and an outline catalog. To test the system, staff of the Neurology Service were trained to use the outline catalog and electronic mail to request interlibrary loans and literature searches. In implementing the project with the Neurology Service, the library is paving the way for many types of electronic access and interaction with the library.

Catalogs, Library↗

Computer information project for monographs at the Medical Research Library of Brooklyn.

The article describes a resource library's computer-based project that provides cataloging and other bibliographic services and promotes greater use of the book collection. A few studies are cited to show the significance of monographic literature in medical libraries. The educational role of the Medical Research Library of Brooklyn is discussed, both with regard to the parent institution and to smaller medical libraries in the same geographic area. Types of aid given to smaller libraries are enumerated. Information is given on methods for providing machine-produced catalog cards, current awareness notes, and bibliographic lists. Actualities and potentialities of the computer project are discussed.

Bibliographies as Topic↗

A survey of organizational practices in North Carolina schools of nursing libraries.

Prompted by the apparent unavailability of published information regarding the cataloging practices in North Carolina schools of nursing libraries, this study was conducted using a questionnaire sent to the thirty-eight schools of nursing in the state. The "average" North Carolina school of nursing library is an autonomous facility administered by nonprofessional personnel or by a person with an undergraduate degree in a nonlibrary field. The materials are organized by the National Library of Medicine Classification and Medical Subject Headings in combination with the Library of Congress classification and subject headings, except for bound journals which are shelved alphabetically by exact title. It is recommended that separate school of nursing and hospital or medical school libraries be consolidated under a trained librarian in order to standardize and unify cataloging practices on the local level and to gain the advantages available through regional and national cooperation of health sciences libraries.

Cataloging↗

Polydactyly: how many disorders and how many genes?

Disorders that include polydactyly as a manifestation are diverse and numerous. Cataloging these disorders by phenotype and genotype demonstrates numerous overlapping phenotypes, genetic heterogeneity of phenotypes, and distinct phenotypes generated from mutations in single genes. To assess these issues, a list of disorders with polydactyly has been compiled from several sources. Among 119 disorders, 39 disorders are associated with mutations in genes, and among these, genotypic and phenotypic overlap is demonstrated. These issues highlight the need for a diagnostic system that catalogs both genotype and phenotype. Published 2002 Wiley-Liss, Inc.

Abnormalities, Multiple↗

Computerized, comprehensive databases of cellular and secreted proteins from normal human embryonic lung MRC-5 fibroblasts: identification of transformation and/or proliferation sensitive proteins.

Databases of protein information from human embryonal lung fibroblasts (MRC-5) have been established using computer analyzed two-dimensional gel electrophoresis. One thousand four hundred and eighty-two cellular proteins (1060 with isoelectric focusing and 422 with nonequilibrium pH gradient electrophoresis, in the first dimension) ranging in molecular mass between 8 and 234 kDa were separated and numbered. Information entered in the database (in most cases for major proteins) includes: protein name, HeLa protein catalog number, mouse protein catalog number, proteins matched in transformed human epithelial amnion cells (AMA) and peripheral blood mononuclear cells (PBMC), transformation and/or proliferation sensitive proteins, synthesis in quiescent cells, cell cycle regulated proteins, mitochondrial and heat shock proteins, cytoskeletal proteins and proteins whose synthesis is affected by interferons. Additional information entered for a few transformation-sensitive proteins that have been selected for future studies includes levels of synthesis and amounts in fetal human tissues. A total of four hundred and seventy-six [35S]methionine labeled polypeptides (258 isoelectric focusing; 218, nonequilibrium pH gradient electrophoresis) secreted by MRC-5 fibroblasts were separated and recorded (J. E. Celis et al., Leukemia 1987, 1, 707-717). Information entered in this database includes molecular weight and transformation sensitive proteins. These databases, as well as those of epithelial and lymphoid cell proteins (J. E. Celis et al., Leukemia 1988, 9, 561-601), represent the initial stages of a systematic effort to establish comprehensive databases of human protein information. In the long run, these databases are expected to offer a useful framework in which to focus the human genome sequencing effort.

Cell Line, Transformed↗

High resolution two-dimensional gel analysis of proteins in the central nervous system of larvae of Drosophila melanogaster.

An improved method of high resolution two-dimensional gel electrophoresis was used to study the patterns of protein synthesis in the central nervous system (CNS) of late instar larvae of Drosophila melanogaster. A small number of CNSs was radiolabeled with a mixture of 14C-labeled amino acids or with [35S]methionine, and the pattern of labeled proteins was analyzed. One thousand and forty-five polypeptides, 800 acidic (IEF) and 245 basic (NEPHGE), from the CNS of several wild-type strains have so far been separated and cataloged. All these polypeptides were numbered and compared with our catalog of polypeptides from wing imaginal discs, and quantitative or qualitative changes were detected in more than 23% of the polypeptides. When comparing patterns of label of CNSs we found small quantitative differences in the rate of synthesis between individuals of the same strain, not due to sexual differences, and a minute number of quantitative and qualitative differences between groups of individuals of different strains.

Animals↗

Application of two-dimensional gel analysis to identification and characterization of tyrosine phosphorylated substrates for growth factor receptors.

The technique of two-dimensional gel electrophoresis was used for analysis of tyrosine phosphorylated polypeptide substrates after epidermal growth factor (EGF)-induced stimulation of receptor tyrosine kinase activity in a brush border fraction of human placental syncytiotrofoblast cells. After incubation with [gamma 32P]ATP, followed by autoradiography of the gels, 35 phosphorylated components were detected, of which 8 were strongly tyrosine phosphorylated by EGF. Using a more sensitive assay with phosphotyrosine-specific antibody, an additional 12 polypeptide components were found to be strongly tyrosine phosphorylated by EGF. A number of the phosphorylated substrates could be aligned with components in a protein catalog of the human brush border membrane fraction that was characterized by glycoprotein staining, Triton X-114 fractionation, immunoreaction with specific antibodies, and comigration with 35S-labeled AMA (transformed human amnion) cells. Identified components, stimulated by EGF, in addition to well-recognized substrates (calpactin II, ezrin, EGF receptor) included beta-tubulin and serum albumin, while other cytoskeletal proteins and alkaline phosphatase were excluded as substrates. A notable feature of the catalog was that a number of glycoproteins were present in both the membrane and cytoskeletal fraction, suggesting involvement in membrane/cytoskeletal interactions. The data demonstrate the feasibility of using two-dimensional gel electrophoresis in a global way to identify target substrates for tyrosine kinase activity. In addition they suggest that many of these are located in the vicinity of tyrosine kinase at the membrane/cytoskeletal border at a location which is probably involved, at the molecular level, in morphological changes of the plasma membrane associated with cell proliferation.

Adenosine Triphosphate↗

Arab genetic disease database (AGDDB): a population-specific clinical and mutation database.

Here we present the Arab Genetic Disease Database (AGDDB), a curated catalog of genetic disorders found in Arab populations. The first release of the database is populated primarily with information from the textbook Genetic Disorders Among Arab Populations [Teebi and Farag, 1997]. AGDDB is composed of data elements revolving around disorder reports. Other reports cover clinical, genomic, reference, and population frequency elements and their important attributes. The Arab Genetic Disease Consortium (30 investigators, 18 countries) is responsible for editing and reviewing AGDDB data. After initial indexing, AGDDB contains over 1,000 unique disorder entries. Entries are linked to their counterparts in the Online Mendelian Inheritance in Man (OMIM) database; similar associations with relevant locus-specific and central mutation databases are planned. The database can be queried by keyword across all its fields, with more focused searches allowed. The database is freely available and may be accessed at www.agddb.org. The database serves as a robust prototype for cataloging variation and disorder information within a specific population.

Arabs↗

Molecular phenotype of the human oocyte by PCR-SAGE.

Consecutive application of PCR and serial analysis of gene expression (SAGE) was used to generate a catalog of approximately 50, 000 SAGEtags from nine human oocytes. Matches for known genes were identified using the National Institutes of Health SAGEtag database. This database links directly to the UniGene database, providing rapid discrimination between SAGEtags that match known genes and expressed sequence tags and those that currently have no match. Matches in the oocyte SAGE catalog were found for surface receptors, second-messenger systems, and cytoskeletal, apoptotic, and secreted proteins. Many of these proteins were not previously known to be expressed in mammalian oocytes. The relative abundances of transcripts for cytoskeletal proteins and proteins known to be in oocytes are consistent with their documented expression, suggesting an absence of representational distortion by the PCR step. The expression profile of the human oocyte may help identify factors that reprogram somatic cell nuclei to totipotency.

Databases, Factual↗