Research priorities in critical care nursing.
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Critical Care↗
Biomedical subjects
M Funk
Publications and source records attributed to M Funk.
Automatic classification of two-dimensional gel electrophoresis pictures by heuristic clustering analysis: a step toward machine learning.
The interpretation of two-dimensional gel electrophoresis (2-DGE) profiles can be facilitated by artificial intelligence and machine learning programs. We have incorporated into our 2-DGE computer analysis system (termed MELANIE-Medical Electrophoresis Analysis Interactive Expert system) a program which automatically classifies 2-DGE patterns using heuristic clustering analysis. This program is a step toward machine learning. In this publication, we describe the classification method and the preliminary results obtained with liver biopsy electrophoretograms. Heuristic clustering is also compared to other classification techniques.
Algorithms↗
Protein heterogeneity of lipoprotein particles containing apolipoprotein A-I without apolipoprotein A-II and apolipoprotein A-I with apolipoprotein A-II isolated from human plasma.
The protein heterogeneity of fractions isolated by immunoaffinity chromatography on anti-apolipoprotein A-I and anti-apolipoprotein A-II affinity columns was analyzed by high resolution two-dimensional gel electrophoresis. The two-dimensional gel electrophoresis profiles of the fractions were analyzed and automatically compared by the computer system MELANIE. Fractions containing apolipoproteins A-I + A-II and only A-I as the major protein components have been isolated from plasma and from high density lipoproteins prepared by ultracentrifugation. Similarities between the profiles of the fractions, as indicated by two-dimensional gel electrophoresis, suggested that those derived from plasma were equivalent to those from high density lipoproteins (HDL), which are particulate in nature. The established apolipoproteins (A-I, A-II, A-IV, C, D, and E) were visible and enriched in fractions from both plasma and HDL. However, plasma-derived fractions showed a much greater degree of protein heterogeneity due largely to enrichment in bands corresponding to six additional proteins. They were present in trace amounts in fractions isolated from HDL and certain of the proteins were visible in two-dimensional gel electrophoresis profiles of the plasma. These proteins are considered to be specifically associated with the immunoaffinity-isolated particles. They have been characterized in terms of Mr and pI. Computer-assisted measurements of protein spot-staining intensities suggest an asymmetric distribution of the proteins (as well as the established apolipoproteins), with four showing greater prominence in particles containing apolipoprotein A-I but no apolipoprotein A-II.
Apolipoprotein A-I↗
Computerized classification of two-dimensional gel electrophoretograms by correspondence analysis and ascendant hierarchical clustering.
A powerful data processing methodology for analysis and classification of two-dimensional gels is introduced. The approach is based on correspondence analysis (CA) and ascendant hierarchical classification (AHC), and significantly differs from the more classical principal-component decomposition. Starting with a series of gels, each having a large number of spots, CA allows their representation in a factorial space of reduced dimension; classification into meaningful groups is then performed using AHC. Simultaneous representation of both spots and gels in the same space can be done. This precisely indicates the key spots pertinent for the classification, and therefore the characteristic proteins representative of a particular class of gels (i.e. of a particular disease or biological status). In addition, knowledge of these characteristic spots greatly simplifies the screening of future gels. After a brief overview of the Mélanie system for analyzing 2D gels, the theory of correspondence analysis and ascendant hierarchical classification is summarized. Equations are given that are easily ammenable to computation. How classification of two-dimensional gel electrophoretograms is accomplished is then detailed. Experimental results support the power of this approach.
Cluster Analysis↗
[Medial tarsal tunnel syndrome. A not infrequent, but often mistaken, nerve compression syndrome].
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Diagnosis, Differential↗
[Leber's optic atrophy - an interdisciplinary study (author's transl)].
Clinical-neurological, electrocephalographic, ophthalmological and genetic observations of a family with related persons with Leber's optic atrophy is described. 6 male subjects of the altogether ca. 100 members of the family tree stretching over 4 generations were manifestly affected relatives - that is possible carriers, an unusually large number of EEG's were abnormal, and, less often, colour vision disturbances were seen. The results suggest that Leber's optic atrophy is a hereditary neuro-ophthalmological systemic condition, whose most striking symptom is the optic atrophy. The genetic factors of the condition are also discussed.
Adolescent↗
Valproate therapy induces von Willebrand disease type I.
To investigate the increased tendency of hemorrhage in patients receiving valproate (VPA) therapy, we studied coagulation parameters in 30 randomized children of a group of 83 children receiving antiepileptic drug (AED) therapy. Besides a reduction in fibrinogen concentration and platelet count, we observed a significant decrease in factor VIII-complex. A decrease in factor VIII:C was noted in 33%, a decrease in von Willebrand factor (vWF:Ag) was noted in 83% and a decrease in ristocetin-cofactor activity (vWF:Rcof) was noted in 66% of the children. We classified a von Willebrand syndrome type I in 67% of our patients receiving VPA therapy. Sixty-three percent of patients had a history of bleeding, and 23% had a prolonged bleeding time. We compared our results with those of a control group and of a group of patients with congenital von Willebrand disease (vWD), from which patients with multimer types II and III were excluded. Because coagulation parameters in patients with congenital vWD are similar to those receiving AED therapy, we designated the increased tendency to hemorrhage as VPA-induced vWD. The decrease in coagulation parameters were not dependent on either VPA dose or period of administration. In patients receiving VPA therapy, this result must be considered, especially during surgical intervention and after traumatic events.
Epilepsy↗
A clinical molecular scanner: the Melanie project.
We developed an expert system to analyze and interpret protein maps. This system, Melanie (medical electrophoresis analysis interactive expert), can distinguish between normal and cirrhotic liver and identify various types of cancer on the basis of protein patterns in biopsy specimens. Our findings suggest that some diseases associated with toxic compounds or modifications of the human genome can be diagnosed by expert systems that analyze protein maps. The combination of protein mapping and computer analysis could result in a clinically useful "molecular scanner". The massive amount of information analyzed and stored in such studies requires new strategies, including centralized databases and image transmission over networks. Increased understanding of protein expression and regulation will enhance the importance of the human genome project in medicine and biology.
Computer Systems↗