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Biomedical subjects

W W Chu

Publications and source records attributed to W W Chu.

10 recordsLinked to original sources

A medical digital library to support scenario and user-tailored information retrieval.

Current large-scale information sources are designed to support general queries and lack the ability to support scenario-specific information navigation, gathering, and presentation. As a result, users are often unable to obtain desired specific information within a well-defined subject area. Today's information systems do not provide efficient content navigation, incremental appropriate matching, or content correlation. We are developing the following innovative technologies to remedy these problems: 1) scenario-based proxies, enabling the gathering and filtering of information customized for users within a pre-defined domain; 2) context-sensitive navigation and matching, providing approximate matching and similarity links when an exact match to a user's request is unavailable; 3) content correlation of documents, creating semantic links between documents and information sources; and 4) user models for customizing retrieved information and result presentation. A digital medical library is currently being constructed using these technologies to provide customized information for the user. The technologies are general in nature and can provide custom and scenario-specific information in many other domains (e.g., crisis management).

Database Management Systems↗

A human prostatic stromal myofibroblast cell line WPMY-1: a model for stromal-epithelial interactions in prostatic neoplasia.

Here we report the characterization of an SV40 large-T antigen-immortalized stromal cell line, WPMY-1, derived from the same prostate as our previously described epithelial cell lines. The WPMY-1 cells were determined to be myofibroblasts on the basis of co-expression of smooth muscle alpha-actin and vimentin. They also show positive staining for androgen receptor, large-T antigen, and positive but heterogeneous staining for p53 and pRb. Their growth is stimulated by the synthetic androgen mibolerone to 145% of control (100%). Platelet-derived growth factor BB, epidermal growth factor and basic fibroblast growth factor, at 10 ng/ml, stimulated growth to 138, 143 and 146% of control, respectively. Transforming growth factor-beta, at 10 ng/ml, inhibited serum-induced growth to 65% of control in the presence of 1% serum, and bFGF-induced growth to 30% of control. A serum-free medium was developed for optimal growth of WPMY-1 cells. They show anchorage-independent growth in soft agar. Studies on paracrine interactions show that myofibroblast-conditioned medium causes a marked inhibition of growth in WPE1-10 cells, while conditioned medium from WPE1-10 prostatic epithelial cells caused only a small increase in the growth of WPMY-1 cells. WPMY-1 cells secrete very low levels of MMP-9 but high levels of MMP-2, markedly higher than the epithelial cells. These epithelial and myofibroblast cell lines, derived from the same prostate, provide novel and useful models for studies on paracrine stromal-epithelial interactions in carcinogenesis, tumor progression, prevention and treatment of prostate cancer and benign prostatic hyperplasia.

Actins↗

Term domain distribution analysis: a data mining tool for text databases.

In this paper, we give a case history illustrating the real-world application of a useful technique for data mining of text databases. The technique, which we call Term Domain Distribution Analysis (TDDA), consists of keeping track of term frequencies for specific finite domains and announcing significant differences from standard frequency distributions over these domains as a hypothesis. TDDA is part of a larger framework, the Digital Filter Model, for data mining of text documents. In the case study presented, the domain of terms was the pair {right, left}, over which we expected a uniform distribution. In analyzing term frequencies in a thoracic lung cancer database, the TDDA technique led to the surprising discovery that primary thoracic lung cancer tumors appear in the right lung more often than the left lung, with a ratio of 3:2. Treating the text discovery as a hypothesis, we verified this relationship against the medical literature in which primary lung tumor sites were reported, using a standard chi 2 statistic. We subsequently developed a working theoretical model of lung cancer that may explain the discovery. This discovery and our model may change how oncologists view the mechanisms of primary lung tumor location.

Humans↗

Creating and indexing teaching files from free-text patient reports.

Teaching files based on real patient data can enhance the education of students, staff and other colleagues. Although information retrieval system can index free-text documents using keywords, these systems do not work well where content bearing terms (e.g., anatomy descriptions) frequently appears. This paper describes a system that uses multi-word indexing terms to provide access to free-text patient reports. The utilization of multi-word indexing allows better modeling of the content of medical reports, thus improving retrieval performance. The method used to select indexing terms as well as early evaluation of retrieval performance is discussed.

Abstracting and Indexing↗

A composite regulatory element in the first intron of the estrogen-responsive very low density apolipoprotein II gene.

During periods of egg laying in the chicken, when circulating levels of estrogen are increased, the liver-specific estrogen-dependent very low density apolipoprotein II (apoVLDLII) gene is expressed. This expression takes place primarily at the level of transcription, driven by two estrogen response elements that reside in the promoter. In transient transfection assays, expression is increased fourfold when the first intron is added to the promoter construct, indicating that 75% of the regulation comes from intron A. Using in vitro DNase I footprinting, six protein-binding sites were revealed throughout the first intron. The functional significance of these binding sites was evaluated by mutation and transient transfection. Two of the protein-binding regions were shown to increase transcription. Site-specific mutations introduced at either the +66 to +86 or +112 to +129 sites disrupted trans-factor binding and reduced the estrogen-dependent expression by 45% and 34%, respectively. A plasmid containing both mutations resulted in a 43% decrease in expression, indicating that the contributions of these regions are not additive. Competition with known sequences in electrophoretic mobility shift assays suggested that the +66 to +86 site binds a chicken member of the nuclear receptor transcription factor family.

Animals↗

A multimedia database system for thermal ablation therapy of brain tumors.

A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the use to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.

Brain Neoplasms↗

Integrated multimedia timeline of medical images and data for thoracic oncology patients.

A prototype multimedia medical database has been developed to provide image and textual data for thoracic oncology patients undergoing treatment of advanced malignancies. The database integrates image data from the hospital picture archiving and communication system with textual reports from the radiology information system, alphanumeric data contained in the hospital information system, and other electronic medical data. The database presents information in a timeline format and also contains visualization programs that permit the user to view and annotate radiographic measurements in tabular or graphic form. The database provides an efficient and intuitive display of the changing status of oncology patients. The ability to integrate, manage, and access relevant multimedia information may substantially enhance communication among distributed multidisciplinary health care providers and may ensure greater consistency and completeness of patient-related data.

Databases, Factual↗

Insulin inhibits the estrogen-dependent expression of the chicken very low density apolipoprotein II gene in Leghorn male hepatoma cells.

Expression of the very low density apolipoprotein II (apoVLDLII) gene in the chicken is absolutely dependent on estrogen. ApoVLDLII mRNA is expressed in the Leghorn male hepatoma (LMH) cell line in response to estrogen in completely defined medium. Addition of serum to these cultures results in a decrease in apoVLDLII mRNA. Data in this report demonstrate that 1 nM insulin has the same inhibitory effect as 10% serum. Insulin inhibits apoVLDLII mRNA in a dose-dependent manner; 100 fM insulin inhibits the estrogen-dependent response by 76%. After transfection of LMH cells with apoVLDLII sequences from an 8.9-kilobase (kb) genomic clone (pApo107) that contains the entire 2.9-kb coding sequence along with approximately 3 kb each of 5'- and 3'-flanking DNA, the estrogen-dependent expression of apoVLDLII mRNA from both the endogenous gene and transfected DNA is reduced by insulin. Furthermore, insulin reduces by more than 90% the estrogen-dependent expression from a chimeric construct, pApoCAT, which contains apoVLDLII sequences -900/+1455 cloned 5' of the bacterial chloramphenicol acetyltransferase (CAT) reporter gene. To determine the specificity of the response, expression of the pApoCAT construct was tested with insulin-like growth factor-I and insulin. Three hundred picomolar insulin inhibits the estrogen-mediated CAT activity by 50%. Insulin-like growth factor-I at this concentration has no effect or slightly increases the estrogen-dependent expression of pApoCAT, suggesting that the observed inhibitory action is mediated by the insulin receptor. Consequently, the LMH cells provide an excellent model system in which to study the molecular mechanism of insulin and estrogen interaction in the regulation of gene expression.

Animals↗

A unified timeline model and user interface for multimedia medical databases.

A multimedia medical database model and prototype is described for supporting a timeline-based presentation of information. The database links image and text data in a way that permits users to look at medical information in a single unified view. Various visualization programs permit the user to view data in various ways, including full image views, graphs, and tables. Our technology is applied for proof-of-concept to two areas: thoracic oncology and thermal tumor ablation therapy of the brain. This effort is part of the multidisciplinary KMeD project in collaboration with medical research and clinical treatment projects at UCLA.

Data Display↗