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Biomedical subjects

M L Müller

Publications and source records attributed to M L Müller.

12 recordsLinked to original sources

Regulation of the lemon-fruit V-ATPase by variable stoichiometry and organic acids.

The lemon-fruit V-ATPase can exist in two forms: nitrate-sensitive and nitrate-insensitive. Here we report the results of measurements of H+ /ATP stoichiometries using two kinetic methods: one based on steady-state DpH and one based on initial rates of H+-pumping. Our findings indicate that the nitrate-insensitive fruit V-ATPase has an H+ /ATP stoichiometry of ~1, while both the nitrate-sensitive fruit V-ATPase and the epicotyl V-ATPase have stoichiometries of 2, under zero-load conditions. As DpH increases, the stoichiometry of the nitrate-sensitive fruit V-ATPase decreases to 1. Under similar conditions, the stoichiometry of the epicotyl enzyme remains 2. Thus, the pH-dependent variable stoichiometry of the lemon-fruit V-ATPase may represent a key factor in juice sac vacuolar hyperacidification. On the other hand, the H+ /ATP stoichiometry of the epicotyl V-ATPase can decrease from 2 to 1 in the presence of a membrane potential. The low pH of the fruit vacuole is not due solely to the lower H+/ATP stoichiometry of its pump. We show that lumenal citrate and malate improve the coupling of both the epicotyl and fruit V-ATPases and enhance their ability to generate a pH gradient. Since citrate accumulation is restricted to fruit vacuoles, it may be another important determinant of vacuolar pH.

Adenosine Triphosphate↗

Optimizing coding quality: the role of the electronic medical record in the context of diagnosis related groups.

In 2003, a new prospective payment system will be introduced in Germany, which is based on the Australian Refined Diagnosis related Groups (AR-DRGs). Physicians must code diagnoses and procedures themselves. Inaccurately or incompletely coded patient records can result in considerable underpayment, so enhancing physicians' coding compliance and competence seems crucial. Coding shall be well integrated in the electronic patient record, providing a simple interface with background information, which is invoked out of the clinical documentation. This paper describes an existing implementation and possible further development.

Diagnosis-Related Groups↗

Towards integration of clinical decision support in commercial hospital information systems using distributed, reusable software and knowledge components.

PROBLEM: Clinicians' acceptance of clinical decision support depends on its workflow-oriented, context-sensitive accessibility and availability at the point of care, integrated into the Electronic Patient Record (EPR). Commercially available Hospital Information Systems (HIS) often focus on administrative tasks and mostly do not provide additional knowledge based functionality. Their traditionally monolithic and closed software architecture encumbers integration of and interaction with external software modules. Our aim was to develop methods and interfaces to integrate knowledge sources into two different commercial hospital information systems to provide the best decision support possible within the context of available patient data. METHODS: An existing, proven standalone scoring system for acute abdominal pain was supplemented by a communication interface. In both HIS we defined data entry forms and developed individual and reusable mechanisms for data exchange with external software modules. We designed an additional knowledge support frontend which controls data exchange between HIS and the knowledge modules. Finally, we added guidelines and algorithms to the knowledge library. RESULTS: Despite some major drawbacks which resulted mainly from the HIS' closed software architectures we showed exemplary, how external knowledge support can be integrated almost seamlessly into different commercial HIS. This paper describes the prototypical design and current implementation and discusses our experiences.

Abdominal Pain↗

[Electronic documentation in medicine; flexible concepts versus isolated solutions].

Computer-based medical documentation so far proved advantageous especially through standardization of data entry and increased access speed. Additional benefits can be achieved through the implementation of integrated, cross-project documentation tools and their integration into the clinical work-flow, which allow data to be used for a wide variety of applications (e.g. quality management, clinical research, clinic management). The presence of incompatible documentation software often complicates the realization of these goals. Implementation of new documentation tools therefore should consider flexibility and multiple-use of data as primary design goals. In the presented paper requirements for flexible documentation tools are introduced. The Entity-Attribute-Value-Model is described as a possible means of implementation. Practical experiences made with a prototype application are reported.

Germany↗

Telepathology network: conceptual groundwork and evaluation.

Telepathology uses telecommunication technology to transmit microscopic images for diagnostic or teaching purposes. Basic requirements for a telepathology system are described. Usage scenarios for a telepathology network are presented including applications in intraoperative frozen section diagnosis, scientific collaboration and computer based training. Results of an evaluation of 4 currently available telepathology systems are presented.

Computer Communication Networks↗

Integrating knowledge based functionality in commercial hospital information systems.

Successful integration of knowledge-based functions in the electronic patient record depends on direct and context-sensitive accessibility and availability to clinicians and must suit their workflow. In this paper we describe an exemplary integration of an existing standalone scoring system for acute abdominal pain into two different commercial hospital information systems using Java/Corba technolgy.

Abdomen, Acute↗

The vacuolar H+-ATPase of lemon fruits is regulated by variable H+/ATP coupling and slip.

Lemon fruit tonoplasts, unlike those of seedling epicotyls, contain nitrate-insensitive H+-ATPase activity (Müller, M. L., Irkens-Kiesecker, U., Rubinstein, B., and Taiz, L. (1996) J. Biol. Chem. 271, 1916-1924). However, the degree of nitrate-insensitivity fluctuates during the course of the year with a seasonal frequency. Nitrate uncouples H+ pumping from ATP hydrolysis both in epicotyls and in nitrate-sensitive fruit V-ATPases. Neither bafilomycin nor oxidation cause uncoupling. The initial rate H+/ATP coupling ratios of epicotyl and the nitrate-sensitive fruit proton pumping activities are the same. However, the H+/ATP coupling ratio of the nitrate-insensitive fruit H+ pumping activity is lower than that of nitrate-sensitive and epicotyl V-ATPases. Several properties of the nitrate-insensitive H+-ATPase of the fruit indicate that it is a modified V-ATPase rather than a P-ATPase: 1) insensitivity to low concentrations of vanadate; 2) it is initially strongly uncoupled by nitrate, but regains coupling as catalysis proceeds; 3) both the nitrate-sensitive and nitrate-insensitive fruit H+-pumps have identical Km values for MgATP, and show similar pH-dependent slip and proton leakage rates. We conclude that the ability of the juice sac V-ATPase to build up steep pH gradients involves three factors: variable coupling, i.e. the ability to regain coupling under conditions that initially induce uncoupling; a low pH-dependent slip rate; the low proton permeability of the membrane.

Adenosine Triphosphate↗

Purification and reconstitution of the vacuolar H+-ATPases from lemon fruits and epicotyls.

The vacuolar H+-ATPases (V-ATPases) of lemon fruits and epicotyls were detergent-solubilized, purified by column chromatography, and reconstituted into artificial proteoliposomes. During purification, a vanadate- and nitrate-sensitive ATPase activity, consisting of partially disassembled V-ATPase complexes, was resolved from the V-ATPase peak. ATPase and H+-transport activities of the purified, reconstituted V-ATPases of both fruit and epicotyl exhibited similar inhibitor profiles, except that the fruit V-ATPase retained partial vanadate sensitivity. Since the V-ATPase activity of native fruit tonoplast vesicles is insensitive to inhibitors (Müller, M. L., Irkens-Kiesecker, U., Rubinstein, B., and Taiz, L. (1996) J. Biol. Chem. 271, 1916-1924), membrane lipids or other factors may protect the fruit V-ATPase from inactivation in vivo. A kinetic analysis of H+-pumping and H+-leakage indicated that the reconstituted epicotyl V-ATPase exhibited twice as much intrinsic uncoupling or slip as the reconstituted fruit V-ATPase. Comparison of their subunit compositions by SDS-polyacrylamide gel electrophoresis indicated that the reconstituted fruit V-ATPase is enriched in two polypeptides of 33/34 and 16 kDa. Moreover, the stalks of negatively stained juice sac V-ATPases appeared thicker than those of epicotyl V-ATPases in electron micrographs.

Chromatography, Gel↗

Differential immunological cross-reactions with antisera against the V-ATPase of Kalanchoë daigremontiana reveal structural differences of V-ATPase subunits of different plant species.

Two antisera (ATP88 and ATP95) raised against the V-ATPase holoenzyme of Kalanchoë daigremontiana were tested for their cross-reactivity with subunits of V-ATPases from other plant species. V-ATPases from Kalanchoë blossfeldiana, Mesembryanthemum crystallinum, Nicotiana tabacum, Lycopersicon esculentum, Citrus limon, Lemna gibba, Hordeum vulgare and Zea mays were immunoprecipitated with an antiserum against the catalytic V-ATPase subunit A of M. crystallinum. As shown by silver staining and Western blot analysis with ATP88, subunits A, B, C, D and c were present in all immunoprecipitated V-ATPases. In contrast, ATP95 recognized the whole set of subunits only in K. blossfeldiana, M. crystallinum, H. vulgare and Z. mays. This differential cross reactivity of ATP95 indicates the presence of structural differences of certain V-ATPase subunits. Based on the Bafilomycin A1-sensitive ATPase activity of tonoplast enriched vesicles, and on the amount of V-ATPase solubilized and immunoprecipitated, the specific ATP-hydrolysis activity of the V-ATPases under test was determined. The structural differences correlate with the ability of V-ATPases from different species to hydrolyze ATP at one given assay condition for ATP-hydrolysis measurements. Interestingly V-ATPases showing cross-reactivity of subunits A, B, C, D and c with ATP95 showed higher rates of specific ATP hydrolysis compared to V-ATPases containing subunits which were not labeled by ATP95. Thus, V-ATPases with high turnover rates in our assay conditions may show common structural characteristics which separate them from ATPases with low turnover rates.

Adenosine Triphosphate↗

The ultrastructure of campaniform sensilla on the eye of the cricket, Gryllus campestris.

The structure of the campaniform sensilla of the cricket eye was investigated by light and electron microscopy. Each sensillum is innervated by a single bipolar neuron. Its axon extends through the retina into a side-branch of the nervus tegumentarius. The dendrite extends through a cuticular channel to the surface of the cornea. The distal part of the dendrite, the sensory process, contains a tubular body and is attached to a cuticular cap which is obliquely inserted into the exocuticle between the corneal lenslets. Some particular structural features as well as the function of the campaniform sensillum of the cricket eye are discussed.

Animals↗