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Biomedical subjects

S Tu

Publications and source records attributed to S Tu.

At least 37 records · Page 2Linked to original sources

Guideline classification to assist modeling, authoring, implementation and retrieval.

The National Guideline Clearinghouse (NGC) and its guideline classification system are significant contributions to the study of clinical practice guidelines (CPGs) and their incorporation into routine clinical care. The NGC classification system is primarily designed to support guideline retrieval. We believe that a guideline classification system should also support identification of features that relate to incorporation of executable CPGs into computer-based applications for sharing and delivering guideline-based advice. We have developed a proposed expansion of the NGC guideline classification for this purpose. The axes of the proposed scheme have implications for designing formal models and structures for representing and authoring CPGs. This scheme also has implications for future research.

Classification↗

Using scenarios in chronic disease management guidelines for primary care.

The Prodigy system is a guideline-based decision-support system designed to assist general practitioners in England choose the appropriate therapeutic action for their patients. As part of the system, we developed a novel model for encoding clinical guidelines for managing patients with chronic diseases such as asthma and hypertension. The model structures a guideline as a set of choices to be made by the clinician. It models patient scenarios which drive decision making and are used to synchronize the management of a patient with guideline recommendations. The model is robust with respect to available input data and leaves the control of decision-making to the clinician. We have built execution engines to verify the computability of the model. We intend to test the model integrated in up to 200 live systems from at least four system vendors in English General practice.

Angina Pectoris↗

GLIF3: the evolution of a guideline representation format.

The Guideline Interchange Format (GLIF) is a language for structured representation of guidelines. It was developed to facilitate sharing clinical guidelines. GLIF version 2 enabled modeling a guideline as a flowchart of structured steps, representing clinical actions and decisions. However, the attributes of structured constructs were defined as text strings that could not be parsed, and such guidelines could not be used for computer-based execution that requires automatic inference. GLIF3 is a new version of GLIF designed to support computer-based execution. GLIF3 builds upon the framework set by GLIF2 but augments it by introducing several new constructs and extending GLIF2 constructs to allow a more formal definition of decision criteria, action specifications and patient data. GLIF3 enables guideline encoding at three levels: a conceptual flowchart, a computable specification that can be verified for logical consistency and completeness, and an implementable specification that can be incorporated into particular institutional information systems.

Decision Support Techniques↗

Epidermal growth factor protects epithelial cells against Fas-induced apoptosis. Requirement for Akt activation.

Chemotherapeutic drugs that damage DNA kill tumor cells, in part, by inducing the expression of a death receptor such as Fas or its ligand, FasL. Here, we demonstrate that epidermal growth factor (EGF) stimulation of T47D breast adenocarcinoma and embryonic kidney epithelial (HEK293) cells protects these cells from Fas-induced apoptosis. EGF stimulation of epithelial cells also inhibited Fas-induced caspase activation and the proteolysis of signaling proteins downstream of the EGF receptor, Cbl and Akt/protein kinase B (Akt). EGF stimulation of Akt kinase activity blocked Fas-induced apoptosis. Expression of activated Akt in MCF-7 breast adenocarcinoma cells was sufficient to block Fas-mediated apoptosis. Inhibition of EGF-stimulated extracellular signal-regulated kinase (ERK) activity did not affect EGF protection from Fas-mediated apoptosis. The findings indicate that EGF receptor stimulation of epithelial cells has a significant survival function against death receptor-induced apoptosis mediated by Akt.

Androstadienes↗

Effect of Sinomenine on IL-8, IL-6, IL-2 produced by peripheral blood mononuclear cells.

The effect of Sinomenine on IL-8, IL-6, IL-2 and mIL-2R produced by peripheral blood mononuclear cells was investigated by using cell culture, radioimmunoassay and flow cytometry. It was showed that production of IL-8 and mIL-2R was inhibited, but the levels of IL-6 were enhanced by Sinomenine. Our results also demonstrated that Sinomenine did not have any effect on the production of IL-2. The study demonstrated that Sinomenine was able to regulate the production of cytokines. This may be one of the mechanisms by which Sinomenine works on rheumatoid arthritis.

Antirheumatic Agents↗

Integrating a modern knowledge-based system architecture with a legacy VA database: the ATHENA and EON projects at Stanford.

We present a methodology and database mediator tool for integrating modern knowledge-based systems, such as the Stanford EON architecture for automated guideline-based decision-support, with legacy databases, such as the Veterans Health Information Systems & Technology Architecture (VISTA) systems, which are used nation-wide. Specifically, we discuss designs for database integration in ATHENA, a system for hypertension care based on EON, at the VA Palo Alto Health Care System. We describe a new database mediator that affords the EON system both physical and logical data independence from the legacy VA database. We found that to achieve our design goals, the mediator requires two separate mapping levels and must itself involve a knowledge-based component.

Artificial Intelligence↗

In vivo nuclear magnetic resonance study of the osmoregulation of phosphocholine-substituted beta-1,3;1,6 cyclic glucan and its associated carbon metabolism in Bradyrhizobium japonicum USDA 110.

A phosphocholine-substituted beta-1,3;1,6 cyclic glucan (PCCG), an unusual cyclic oligosaccharide, has been isolated from Bradyrhizobium japonicum USDA 110 (D. B. Rolin, P. E. Pfeffer, S. F. Osman, B. S. Swergold, F. Kappler, and A. J. Benesi, Biochim. Biophys. Acta 1116:215-225, 1992). Data presented here suggest that PCCG synthesis is dependent on the carbon metabolism and that osmotic regulation of its biosynthesis parallels regulation of membrane-derived oligosaccharide biosynthesis observed in Escherichia coli (E. P. Kennedy, M. K. Rumley, H. Schulman, and L. M. G. van Golde, J. Biol. Chem. 251:4208-4213, 1976) and Agrobacterium tumefaciens (G. A. Cangelosi, G. Martinetti, and E. W. Nester, J. Bacteriol. 172:2172-2174, 1990). Growth of B. japonicum USDA 110 cells in the reference medium at relatively low osmotic pressures (LO) (65 mosmol/kg of H2O) caused a large accumulation of PCCG and unsubstituted beta-1,3;1,6 cyclic glucans (CG). Sucrose and polyethylene glycol, nonionic osmotica, reduce all growth rates and inhibit almost completely the production of PCCG at high osmotic pressures (HO) above 650 and 400 mosmol/kg of H2O), respectively. We used in vivo 13C nuclear magnetic resonance spectroscopy to identify the active osmolytes implicated in the osmoregulation process. The level of alpha,alpha-trehalose in B. japonicum cells grown in autoclaved or filter-sterilized solutions remained constant in HO (0.3 M sucrose or 250 g of polyethylene glycol 6000 per liter) medium. Significant amounts of glycogen and extracellular polysaccharides were produced only when glucose was present in the autoclaved HO 0.3 M sucrose media. The results of hypo- and hyperosmotic shocking of B. japonicum USDA 110 cells were monitored by using in vivo 31P and 13C nuclear magnetic resonance spectroscopy. The first observed osmoregulatory response of glycogen-containing cells undergoing hypoosmotic shock was release of P(i) into the medium. Within 7 h, reabsorption of P(i) was complete and production of PCCG was initiated. After 12 h, the PCCG content had increased by a factor of 7. Following the same treatment, cells containing little or no glycogen released trehalose and failed to produce PCCG. Thus the production of PCCG/CG in response to hypoosmotic shocking of stationary-phase cells was found to be directly linked to the interconversion of stored glycogen. Hyperosmotic shocking of LO-grown stationary-phase cells with sucrose had no effect on the content of previously synthesized CG/PCCG. The PCCG/CG content and its osmotically induced biosynthesis are discussed in terms of carbon metabolism and a possible role in hypoosmotic adaptation in B. japonicum USDA 110.

Carbon↗

TQuery: a context-sensitive temporal query language.

Users of electronic medical databases request pertinent information by recasting their clinical questions into a formal database query language. Because the query language is the user's only access to the data, the query language must be powerful enough to enable users to express their data requirements. However, a competing need is for the query language to be restrictive enough so that queries can have unambiguous semantics and the query processor can generate correct answers. We describe a query language, called TQuery , that was designed specifically to formulate database queries that are dependent on temporal and contextual relationships. TQuery specifications express contextual constraints without the need to explicitly reference calendar dates. TQuery is the database query language used to retrieve patient data from an object-oriented electronic patient medical-record system called the temporal network (TNET). TNET and TQuery were developed to support the real-time temporal reasoning and representation needs of a LISP workstation-based medical expert system.

Databases, Factual↗

Extensions to the time-oriented database model to support temporal reasoning in medical expert systems.

Physicians faced with diagnostic and therapeutic decisions must reason about clinical features that change over time. Database-management systems (DBMS) can increase access to patient data, but most systems are limited in their ability to store and retrieve complex temporal information. The Time-Oriented Databank (TOD) model, the most widely used data model for medical database systems, associates a single time stamp with each observation. The proper analysis of most clinical data requires accounting for multiple concurrent clinical events that may alter the interpretation of the raw data. Most medical DBMSs cannot retrieve patient data indexed by multiple clinical events. We describe two logical extensions to TOD-based databases that solve a set of temporal reasoning problems we encountered in constructing medical expert systems. A key feature of both extensions is that stored data are partitioned into groupings, such as sequential clinical visits, clinical exacerbations, or other abstract events that have clinical decision-making relevance. The temporal network (TNET) is an object-oriented database that extends the temporal reasoning capabilities of ONCOCIN, a medical expert system that provides chemotherapy advice. TNET uses persistent objects to associate observations with intervals of time during which "an event of clinical interest" occurred. A second object-oriented system called the extended temporal network (ETNET), is both an extension and a simplification of TNET. Like TNET, ETNET uses persistent objects to represent relevant intervals; unlike the first system, however, ETNET contains reasoning methods (rules) that can be executed when an event "begins", and that are withdrawn when that event "concludes". TNET and ETNET capture temporal relationships among recorded information that are not represented in TOD-based databases. Although they do not solve all temporal reasoning problems found in medical decision making, these new structures enable patient database systems to encode complex temporal relationships, to store and retrieve patient data based on multiple clinical contexts and, in ETNET, to modify the reasoning methods available to an expert system based on the onset or conclusion of specific clinical events.

Diagnosis, Computer-Assisted↗

A chromogranin A-derived peptide differentially regulates the secretion of calcitonin gene products.

We studied the regulation of the secretion of CT and CGRP by chromogranin A (CgA)-derived peptides in a human lung tumor cell line. The amino-terminal peptide of CgA, CgA1-40, stimulated the secretion of CGRP and inhibited the secretion of CT; both effects occurred in a dose-dependent manner. These studies demonstrate a differential effect of a CgA-derived peptide on two products of the CT gene, CT itself and CGRP. CgA may be processed at its multiple dibasic sites to peptides that specifically regulate the secretion of its coresident hormones, in this case two calcitonin gene products that are present in the same secretory vesicle. This novel mechanism represents a new pathway for the control of calcium regulating hormones.

Calcitonin↗

PTHrP secretion is stimulated by CT and inhibited by CgA peptides.

We studied the regulation of the secretion in vitro of the parathyroid hormone-related protein (PTHrP) associated with the hypercalcemia of malignancy by Chromogranin A (CgA)-derived peptides and by human calcitonin (CT) in the BEN human lung tumor cell line. The amino terminal peptide of CgA, CgA1-40, inhibited the secretion of PTHrP, whereas other peptides had no such effect. Human CT stimulated the secretion of PTHrP, whereas other hormones had no such effect. Both effects occurred in a dose-dependent manner. These studies reveal novel regulatory pathways among peptides and proteins that are commonly associated with each other and can have paracrine interactions. CgA may be processed at its multiple dibasic sites to peptides that regulate the secretion of its co-resident hormones, in this case PTHrP. In addition to a paracrine effect, CT may be clinically useful as a provocative agent for PTHrP secretion. Complex interactions are present among the calcium-regulating hormones and their associated proteins.

Calcitonin↗

Prognosis of nasopharyngeal carcinoma by Epstein-Barr virus antibody titer.

A total of 433 samples of serum were collected from 305 patients with histopathologically proved anaplastic nasopharyngeal carcinoma (NPC). Antibodies against viral capsid antigens (VCA) of Epstein-Barr (EB) virus were titrated by means of indirect fluorescent antibody technique, using P3HR-1 cells as the target. High anti-VCA antibody titer in patients with NPC was found beginning to decline at the end of radiotherapy. Most (66.7%) of the patients were found to have a detectable reduction in antibody titer within six months after radiotherapy. Persistent high antibody titer after treatment correlates to high risk of the recurrence of the disease. This prognostic importance of anti-VCA titer becomes apparent at the end of radiotherapy, significant (P less than .05) within one year after treatment, and highly significant (P less than .0005) over one year after treatment.

Antibodies, Viral↗