Live sequence charts to model medical information

ABSTRACT: BACKGROUND: Medical records accumulate data concerning patient health and the natural history of disease progression. However, methods to mine information systematically in a form other than an electronic health record are not yet available. The purpose of this study was to develop an object modeling technique as a first step towards a formal database of medical records. METHOD: Live Sequence Charts (LSC) were used to formalize the narrative text obtained during a patient interview. LSCs utilize a visual scenario-based programming language to build object models. LSC extends the classical language of UML message sequence charts (MSC), predominantly through addition of modalities and providing executable semantics. Interobject scenarios were defined to specify natural history event interactions and different scenarios in the narrative text. Result A simulated medical record was specified into LSC formalism by translating the text into an object model that comprised a set of entities and events. The entities described the participating components (i.e., doctor, patient and record) and the events described the interactions between elements. A conceptual model is presented to illustrate the approach. An object model was generated from data extracted from an actual new patient interview, where the individual was eventually diagnosed as suffering from Chronic Fatigue Syndrome (CFS). This yielded a preliminary formal designated vocabulary for CFS development that provided a basis for future formalism of these records. CONCLUSIONS: Translation of medical records into object models created the basis for a formal database of the patient narrative that temporally depicts the events preceding disease, the diagnosis and treatment approach. The LSCs object model of the medical narrative provided an intuitive, visual representation of the natural history of the patient's disease.     

Heterogeneity in Composition along the Length of Cuscuta filaments

Considerable variations in the content of free amino acids, elhanol-soluble carbohydrates, starch, protein, chlorophyll, phylic acid, RNA and DNA exist in different regions of the long filaments of Cuscuta reflexa. The distinction is especially pronounced when comparison is made between the hanstoria-bearing curls of the parasite and the apical portions of the overhanging filament.     

ESCRT-I Function is Required for Tyrp1 Transport from Early Endosomes to the Melanosome Limiting Membrane

Melanosomes are lysosome-related organelles that coexist with lysosomes within melanocytes. The pathways by which melanosomal proteins are diverted from endocytic organelles toward melanosomes are incompletely defined. In melanocytes from mouse models of Hermansky-Pudlak syndrome that lack BLOC-1, melanosomal proteins such as tyrosinase-related protein 1 (Tyrp1) accumulate in early endosomes. Whether this accumulation represents an anomalous pathway or an arrested normal intermediate in melanosome protein trafficking is not clear. Here, we show that early endosomes are requisite intermediates in the trafficking of Tyrp1 from the Golgi to late stage melanosomes in normal melanocytic cells. Kinetic analyses show that very little newly synthesized Tyrp1 traverses the cell surface and that internalized Tyrp1 is inefficiently sorted to melanosomes. Nevertheless, nearly all Tyrp1 traverse early endosomes since it becomes trapped within enlarged, modified endosomes upon overexpression of Hrs. Although Tyrp1 localization is not affected by Hrs depletion, depletion of the ESCRT-I component, Tsg101, or inhibition of ESCRT function by dominant-negative approaches results in a dramatic redistribution of Tyrp1 to aberrant endosomal membranes that are largely distinct from those harboring traditional ESCRT-dependent, ubiquitylated cargoes such as MART-1. The lysosomal protein content of some of these membranes and the lack of Tyrp1 recycling to the plasma membrane in Tsg101-depleted cells suggests that ESCRT-I functions downstream of BLOC-1. Our data delineate a novel pathway for Tyrp1 trafficking and illustrate a requirement for ESCRT-I function in controlling protein sorting from vacuolar endosomes to the limiting membrane of a lysosome-related organelle.     

Direct measurement of the initial proton extrusion to oxygen uptake ratio accompanying succinate oxidation by rat liver mitochondria.

The problem of obtaining very early ratios for the H+/O stoichiometry accompanying succinate oxidation by rat liver mitochondria was attacked using new techniques for direct measurement rather than extrapolations based on data obtained after mixing and the recovery of the electrode from initial injection of O2. Respiration was quickly initiated in a thoroughly mixed O2-containing suspension of mitochondria under a CO atmosphere by photolysis of the CO-cytochrome c oxidase complex-. Fast responding O2 and pH electrodes were used to collect data every 10 ms. The response time for each electrode was experimentally measured in each experiment and suitable corrections for electrode relaxations were made. With uncorrected data obtained after 0.8 s, the extrapolation back to zero time on the basis of single-exponential curve fitting confirmed values close to 8.0 as previously reported (Costa et al., 1984). The data directly obtained, however, indicate an initial burst in H+/O ratio that peaked to values of approximately 20 to 30 prior to 50 ms and which was no longer evident after 0.3 s. Newer information and considerations that place all extrapolation methods in question are discussed.     

CDRI-85/287: studies on competition to estrogen binding sites in the immature rat uterus.

Ability of compound CDRI-85/287, a new nonsteroidal antiestrogen with negligible inherent estrogenicity, to inhibit uptake of 3H-estradiol (3H-E2) by the immature rat uterus in vivo was investigated. Different doses of 85/287 were administered either intraperitoneally 30 min before 3H-E2 or orally 1 and 6 hr before 3H-E2. A dose dependent inhibition in 3H-E2 uptake was observed after administration of the compound by either route and was 69% at 50 micrograms/rat ip dose and 80% at 2.5 mg/kg po dose. In in vitro competitive binding assay, however, the compound showed poor affinity (RBA 0.42% of estradiol-17 beta) for cytosolic estrogen receptors. Considering the potent anti-estrogenic as well as anti-implantation efficacy of the compound, its action in vivo appears to be mediated via its active metabolite(s).     

Abnormalities in vascular arachidonic acid metabolism in the infant of the diabetic mother.

The infant of the diabetic mother has an increased incidence of thromboses in utero and in the neonatal period. In the adult with diabetes a decrease in prostacyclin formation has been suggested as a cause for the atherothrombotic tendency. We therefore evaluated arachidonic acid metabolism in infants of diabetic mothers. Endogenous radioimmunoassayable 6-keto prostaglandin F1 alpha (PGF1 alpha) was normal in umbilical vessels obtained from the infants of diabetic mothers whose glucose homoeostasis was maintained when compared with control values. Nevertheless, a significant inhibition of vascular production of 6-keto PGF1 alpha was observed in infants born to mothers with raised HbA1C concentrations. A decrease in the concentration of plasma 6-keto PGF1 alpha was also seen in the infants of diabetic mothers when compared with control neonates. The correlation observed between plasma 6-keto PGF1 alpha concentrations and endogenous vascular prostacyclin formation in the infants of diabetic mothers indicates that the in vitro deficiency of prostacyclin formation reflects a concomitant in vivo abnormality.