Quehn Park

A molecular model of a point mutation (Val297Met) in the serine protease domain of protein C

A heterozygous GTG to ATG (Val297Met) mutation was detected in a patient with inherited protein C deficiency and deep vein thrombosis. Cosegregation of the mutation with protein C deficiency was observed through a family pedigree study. Molecular models of the serine protease domains of wild type and mutant protein C were constructed by standard comparative method. Val 297 was found to be located in the hydrophobic core of the protein. Although the substitution of Met for Val does not greatly alter the hydrophobicity of the protein, it introduces a bulkier side chain, which yields steric hindrance between this residue and adjacent residues, such as Met364, Tyr393, Ile321, Ile323, and Val378. It seems that the Met can not fit into the tight packing into which it is trapped, thereby probably inducing misfolding and/or greater instability of the protein. Such misfolding and/or instability thereby eventually disturbs the catalytic triad, in consistent with the observed type I deficiency state.

Development of medical decision support system for leukemia management

Abstract A prototype Medical Decision Support System (MDSS) for leukemia patients was developed with emphasis on total management approach from patient registration to diagnosis and treatment. Thus, the MDSS consists of four modules: registry, knowledge model, simulator, and Computer-Assisted Instruction (CAI). Integration of each module improves overall patient management capability and knowledge acquisition capability of the system. Four different knowledge models were developed to predict diagnosis: rule-based reasoning, case-based reasoning, neural network, and discriminant analysis. Among the four, rule-based reasoning produced the most accurate prediction in diagnosis. In the future, the method of leukemia registry can further be extended to the hospital-based cancer registry for other types of cancer. In order to be more effective, the registry should also be integrated with the hospital information system for an easier data entry.

Prevalence of anti-beta2 glycoprotein-I antibody in patients with primary or secondary immune thrombocytopenia

We determined the prevalence of antibodies to beta(2) glycoprotein-I (beta(2) GPI) in sera of 57 patients with primary or secondary immune thrombocytopenia positive for platelet antibody (PAIgG) and in 16 healthy control subjects. Both isotypes (IgG and IgM) of anti-beta(2) GPI were detected by means of semiquantitative ELISA and platelet antibodies were measured by means of flow cytometry using FITC-labeled anti-human IgG. Six (10.5%) of 57 patients with immune thrombocytopenia had anti-beta(2) GPI, whereas none of the 16 healthy subjects had anti-beta(2) GPI. Four were positive for IgM anti-beta(2) GPI, one for IgG anti-beta(2) GPI, and one was positive both for IgM and IgG anti-beta(2) GPI. There was no significant association between the presence of anti-beta(2) GPI and the severity of thrombocytopenia. Our findings suggest that some patients with immune thrombocytopenia have anti-beta(2) GPI in addition to the increased PAIgG; however, the results do not support a major role for anti-beta(2) GPI in the pathogenesis of immune thrombocytopenia.