Biomedical subjects

G E Morgan

Publications and source records attributed to G E Morgan.

9 recordsLinked to original sources

PubMed1997

Further evidence for the importance of an androgen response element in the factor IX promoter.

Previous work involving the characterizing of a factor IX promoter mutation (-26 G-->C) of a 21-year-old patient with severe haemophilia B suggested that an androgen response element (ARE) was present in the wild-type factor IX promoter but was disrupted in this patient. However, other theories not involving this ARE have been suggested for the mechanism of recovery in the more typical (Leyden) promoter patients, so that the ARE hypothesis requires further evidence if it is to be accepted. We now present a case history and functional data on another 48-year-old severe haemophilia B patient (UK232) with a different (G-->A) mutation at the same position, -26. This mutation impairs transactivation of the minimal factor IX promoter region (-220-->+43) by HNF4 in transient transfection experiments in HepG2 and HeLa cells. It disrupts binding of both androgen receptor (AR) and HNF4 to oligonucleotides spanning this region (-40-->-9) in competition gel mobility shift assays. It impairs AR/testosterone transactivation of these oligonucleotides (-40-->-9) when tetramerized upstream of a CAT reporter gene in cotransfection assays in HeLa cells. And, finally, no clinical recovery has occurred since puberty. These results strengthen the evidence for the importance of nucleotide -26, both for the normal transcription of the gene in response to HNF4 and for the proposed Leyden recovery mechanism in response to AR and testosterone acting directly through the factor IX ARE.

Adult↗

PubMed1996

Qualitative analysis of temporal information in Iliad: implications for linking Iliad to an electronic medical record as a knowledge server.

In linking Iliad to an electronic medical record (EMR) as a knowledge server, our objective is to convert the date and time stamped data from the EMR to the temporal representations existing in the Iliad knowledge base. First, an empirical analysis of Iliad's temporal information content is described: categorizing, estimating the amount (22%), and offering a temporal template to canonically represent it. Second, we analyze the effect of history and physical examination temporal information on the diagnostic performance of the system using data from 241 real cases. Third, we discuss knowledge engineering mapping techniques to convert time information found in EMRs. We conclude that the Iliad system includes a large amount of explicit and implicit time information and this information improves the system's diagnostic accuracy, both in terms of diagnosis ranking and confidence.

Artificial Intelligence↗

PubMed1995

The high frequency of the -6G-->A factor IX promoter mutation is the result both of a founder effect and recurrent mutation at a CpG dinucleotide.

We report a new Liverpool family with a mild haemophilia B Leyden phenotype caused by a -6G-->A mutation in a CpG dinucleotide in the promoter of the clotting factor IX gene. This mutation had previously been identified in three other U.K. pedigrees and six others worldwide. To investigate whether these mutations were of independent origin, the haplotype was determined for eight polymorphic loci, within or immediately adjacent to the factor IX gene, for nine of the 10 existing patients. Six probands had identical haplotypes, including all four U.K. probands, suggesting that they arose from a common founder. The other three probands differed in haplotype from the common haplotype, and from each other, suggesting that they were independent mutations at this CpG dinucleotide.

Child↗

PubMed1995

Iliad and Medical HouseCall: evaluating the impact of common sense knowledge on the diagnostic accuracy of a medical expert system.

Diagnostic expert systems are gaining acceptance among physicians. Recently, a comparative study of the performance of four major commercial diagnostic programs demonstrated that the information they produce contains a certain amount of irrelevancy that the trained physician ignores. Medical HouseCall is a consumer health information expert system based on a medical expert system for physicians, Iliad. To enhance the usefulness of Medical HouseCall to health care consumers, we are interested in significantly reducing the amount of irrelevancy contained in the diagnostic differential list. Testing with over 470 'textbook' cases revealed that a large part of the irrelevancy can be eliminated by adding universal and medical 'common sense' knowledge. Using four performance measures, we compared, on a subset of cases, the differential lists from two versions of the program: the refined knowledge base (1995) and an older version (1994) 'pre-common sense'. The results suggest that the performance of a diagnostic expert system can be significantly improved with the addition of common sense knowledge.

Artificial Intelligence↗

PubMed1990