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Biomedical subjects

T B Patrick

Publications and source records attributed to T B Patrick.

29 records · Page 2Linked to original sources

A service-oriented information sources database for the biological sciences.

Researchers in the biological sciences require access to a variety of information sources located in various places on different computer networks. In order to satisfy the information needs of a researcher, appropriate information sources must be selected and access to these information sources and the computing services supporting them must be provided in a way that does not distract the researcher from problems of real interest. At the University of Missouri-Columbia a service-oriented information sources database is being developed as a key component of a layered-model design of an intelligent system which will provide a research environment appropriate to the needs of researchers in the biological sciences.

Artificial Intelligence↗

An open system network for the biological sciences.

A description of an open system, distributed computing environment for the Biological Sciences is presented. This system utilizes a transparent interface in a computer network using NCS to implement an application system for molecular biologists to perform various processing activities from their local workstation. This system accepts requests for the services of a remote database server, located across the network, to perform all of the database searches needed to support the activities of the user. This database access is totally transparent to the user of the system and it appears, to the user, that all activities are being carried out on the local workstation. This system is a prototype for a much more extensive system being built to support the research efforts in the Biological Sciences at UMC.

Biological Science Disciplines↗

Radiolabeled hypoxic cell sensitizers: tracers for assessment of ischemia.

Hypoxic, non-functional, but viable, tissue may exist in heart and brain following an arterial occlusion. Identification of such tissue in vivo is crucial to the development of effective treatment strategies. It has been suggested that certain compounds capable of sensitizing hypoxic tumor cells to killing by x-rays (i.e., misonidazole) might serve as in vivo markers of hypoxic tissue in ischemic myocardium or brain if properly radiolabeled. To this end we have radiolabeled two fluorinated analogs of nitroimidazole based hypoxic cell sensitizers with the 110 minute half-lived positron-emitting fluorine-18. The ability of these tracers to quantitate the presence of hypoxic tissue has been studied in a gerbil stroke model. The in vivo uptake of one of these tracers [F-18]-fluoronormethyoxymisonidazole is dependent on the extent of tissue hypoxia, and thus, appears to have potential as a diagnostic indicator of non-functional but viable tissue when the tracer is used in conjunction with positron emission tomography.

Animals↗

Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: potential in vivo markers of hypoxic tissue.

Three 18F labeled fluoronitroimidazoles have been prepared as potential in vivo markers of hypoxic cells in tumors, and ischemic areas of the heart and brain. 1-(2-Nitroimidazolyl)-3-[18F]fluoro-2-hydroxypropanol (18F]fluoro-normethoxymisonidazole) 4, 1-(2-[18F]fluoroethyl)-2-nitroimidazole 7, and 1-(2-[18F]-fluoroethyl)-2-methyl-5-nitroimidazole ([18F]fluoro-norhydroxymetronidazole) 10 were prepared in average radiochemical yields of less than 1%, 23% and 15-43% (8% at the no carrier-added level) respectively at end-of-synthesis. The in vivo biodistribution in rats was determined for each of the 18F labeled fluoronitroimidazoles. At 1 and 3 h after administration, the tissue distribution of each of the 18F labeled nitroimidzaoles was quite uniform and consistent with that of nitroimidazoles previously studied. These results suggest the need for a suitable animal model to evaluate their potential as in vivo markers of hypoxic tissue in the brain.

Animals↗

2-[18F]fluoroputrescine: preparation, biodistribution, and mechanism of defluorination.

A new radiolabeled analog of putrescine, 18F labeled 2-fluoroputrescine, has been prepared as a potential in vivo imaging agent for prostate and prostate derived tumors. The radiosynthesis yielded 1.5-4.5 mCi amounts of the 18F labeled putrescine analog (1-3% yields at end-of-synthesis), with specific activities ranging from 0.85-4.3 Ci/mmol, in a synthesis time of 2 h. The in vivo biodistribution in mature male rats showed considerable uptake by the bone, indicating defluorination of the compound. In animals pretreated with aminoguanidine, an inhibitor of diamine oxidase, the enzyme important in the metabolism of putrescine, defluorination was markedly reduced, but uptake by the prostate did not improve. These results suggest the need for development of a 18F labeled analog of putrescine which does not defluorinate in vivo, and which has biological properties similar to putrescine.

Animals↗

Preparation and 13C NMR characterization of [[epsilon-13C] methionine-192]-alpha-chymotrypsin. The demethylation of [S-[13C] methylmethionine-192]-alpha-chymotrypsin by an active site-directed thiol.

Met-192 forms part of the binding crevice of alpha-chymotrypsin. The aim of this investigation was to find a nucleophile that would displace a methyl group from the sulfonium cation of [S-[13C]methylmethionine-192]-alpha-chymotrypsin without disrupting the five disulfide bridges of the protein, thereby producing [[epsilon-13C]methionine-192]-alpha-chymotrypsin, an isotopically enriched version of the native enzyme desirable for 13C NMR studies. Treatment of [S-methylmethionine-192]-alpha-chymotrypsin with mercaptoethanol and dithiothreitol failed to produce the latter protein, as deduced from elution profiles of reaction mixtures chromatographed on affinity columns of immobilized lima bean trypsin inhibitor. In contrast, when [S-methylmethionine-192]-alpha-chymotrypsin was incubated in a 3.0 mM solution of the active site-directed reagent 2-mercaptoacetyl-4'-methoxyanilide at pH 8.6 and 5 degrees C for 48 h, affinity chromatograms indicated the presence of a protein corresponding to native alpha-chymotrypsin. Upon repeating the experiment with [S-[13C]methylmethionine-192]-alpha chymotrypsin, we isolated in 40% yield a protein which was identified as [[epsilon-13C]methionine-192]-alpha-chymotrypsin by a combination of 13C NMR and chemical criteria. This work represents the first active site-directed demethylation of an S-[13C]methylmethionine residue at the binding site of an enzyme.

Carbon Isotopes↗

Enthalpies of hydrogen bonding in psychotropic drugs.

The enthalpy of hydrogen bonding of some antipsychotic, antidepressant, anticonvulsant, and antianxiety agents with phenol, as determined from IR and NMR spectroscopic measurements, was shown not to be responsible for differences in activity within the drug classes. These results support a theoretical prediction advanced for anticonvulsant activity.

Antidepressive Agents↗

Virtual shelves in a digital library: a framework for access to networked information sources.

OBJECTIVE: Develop a framework for collections-based access to networked information sources that addresses the problem of location-dependent access to information sources. DESIGN: This framework uses a metaphor of a virtual shelf. A virtual shelf is a general-purpose server that is dedicated to a particular information subject class. The identifier of one of these servers identifies its subject class. Location-independent call numbers are assigned to information sources. Call numbers are based on standard vocabulary codes. The call numbers are first mapped to the location-independent identifiers of virtual shelves. When access to an information resource is required, a location directory provides a second mapping of these location-independent server identifiers to actual network locations. RESULTS: The framework has been implemented in two different systems. One system is based on the Open System Foundation/Distributed Computing Environment and the other is based on the World Wide Web. CONCLUSIONS: This framework applies in new ways traditional methods of library classification and cataloging. It is compatible with two traditional styles of selecting information searching and browsing. Traditional methods may be combined with new paradigms of information searching that will be able to take advantage of the special properties of digital information. Cooperation between the library-informational science community and the informatics community can provide a means for a continuing application of the knowledge and techniques of library science to the new problems of networked information sources.

Catalogs, Library↗

Evaluation of controlled vocabulary resources for development of a consumer entry vocabulary for diabetes.

BACKGROUND: Digital information technology can facilitate informed decision making by individuals regarding their personal health care. The digital divide separates those who do and those who do not have access to or otherwise make use of digital information. To close the digital divide, health care communications research must address a fundamental issue, the consumer vocabulary problem: consumers of health care, at least those who are laypersons, are not always familiar with the professional vocabulary and concepts used by providers of health care and by providers of health care information, and, conversely, health care and health care information providers are not always familiar with the vocabulary and concepts used by consumers. One way to address this problem is to develop a consumer entry vocabulary for health care communications. OBJECTIVES: To evaluate the potential of controlled vocabulary resources for supporting the development of consumer entry vocabulary for diabetes. METHODS: We used folk medical terms from the Dictionary of American Regional English project to create extended versions of 3 controlled vocabulary resources: the Unified Medical Language System Metathesaurus, the Eurodicautom of the European Commission's Translation Service, and the European Commission Glossary of popular and technical medical terms. We extracted consumer terms from consumer-authored materials, and physician terms from physician-authored materials. We used our extended versions of the vocabulary resources to link diabetes-related terms used by health care consumers to synonymous, nearly-synonymous, or closely-related terms used by family physicians. We also examined whether retrieval of diabetes-related World Wide Web information sites maintained by nonprofit health care professional organizations, academic organizations, or governmental organizations can be improved by substituting a physician term for its related consumer term in the query. RESULTS: The Dictionary of American Regional English extension of the Metathesaurus provided coverage, either direct or indirect, of approximately 23% of the natural language consumer-term-physician-term pairs. The Dictionary of American Regional English extension of the Eurodicautom provided coverage for 16% of the term pairs. Both the Metathesaurus and the Eurodicautom indirectly related more terms than they directly related. A high percentage of covered term pairs, with more indirectly covered pairs than directly covered pairs, might be one way to make the most out of expensive controlled vocabulary resources. We compared retrieval of diabetes-related Web information sites using the physician terms to retrieval using related consumer terms We based the comparison on retrieval of sites maintained by non-profit healthcare professional organizations, academic organizations, or governmental organizations. The number of such sites in the first 20 Results from a search was increased by substituting a physician term for its related consumer term in the query. This suggests that the Dictionary of American Regional English extensions of the Metathesaurus and Eurodicautom may be used to provide useful links from natural language consumer terms to natural language physician terms. CONCLUSIONS: The Dictionary of American Regional English extensions of the Metathesaurus and Eurodicautom should be investigated further for support of consumer entry vocabulary for diabetes.

Community Participation↗