PubMed HealthSearch

Biomedical subjects

S Tu

Publications and source records attributed to S Tu.

11 recordsLinked to original sources

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

Cortisol modification of HeLa 65 alkaline phosphatase. Decreased phosphate content of the induced enzyme.

Alkaline phosphatase activity of HeLa cells is increased 5-20-fold during growth in medium with cortisol. The increase in enzyme activity is due to an enhanced catalytic efficiency rather than an increase in alkaline phosphatase protein in induced cells. In the present study the chemical composition of control and induced forms of alkaline phosphatase were investigated to determine the enzyme modification that may be responsible for the increased catalytic activity. HeLa alkaline phosphatase is a phosphoprotein and the induced form of the enzyme has approximately one-half of the phosphate residues associated with control enzyme. The decrease in phosphate residues of the enzyme apparently alters its catalytic activity. Other chemical components of purified alkaline phosphatase from control and induced cells are similar; these include sialic acid, hexosamine and sulfhydryl residues.

Alkaline Phosphatase

Differential effects of 8-anilino-1-naphthalenesulfonate upon binding of oxidized and reduced flavines by bacterial luciferase.

Upon binding to bacterial luciferase, both the absorption and the fluorescence excitatiom maxima of 8-anilino-1-naphthalensulfonate (ANS) shift from 353 to 370 nm while the fluorescence emission optimum shifts from 540 to 480 nm, and the fluorescence quantum yield increases from 0.003 to 0.39, indicating that the environment of the ANS binding site is hydrophobic. ANS binds to luciferase with dissociation constants of 1.9 X 10(-5) and 2.3 X 10(-5) M at 5 and 23 degrees, repsectively. As with both oxidized flavine mononucleotide (FMN) and reduced flavine mononucleotide (FMNH2), ANS also binds to luciferase with a stoichiometry of 1 site per dimeric luciferase molecule. ANS acts as a luciferase inhibitor, competitive with FMNH2, with an inhibitor constant of 2.3 X 10(-5) M at 23 degrees. However, the binding of ANS does not significantly displace FMN from binding to luciferase. Interactions of FMN and FMNH2 with luciferase are thus differentially regulated by the ANS binding.

Anilino Naphthalenesulfonates