Norihiro Sakamoto

Gly145 to Arg substitution in HBs antigen of immune escape mutant of hepatitis B virus.

A Japanese child born to an HBeAg-positive carrier mother received anti-HBs immunoglobulins and a plasma-derived HBs vaccine with a poor anti-HBs-antibody response. The child, who is now 3 years old, is presently suffering from chronic hepatitis with unusual serological findings that are positive for HBsAg, anti-HBs and HBeAg, since being infected with a measles virus at 12 months of age. The nucleotide sequences of the S region of HBV DNA obtained from the patient, the mother and an HBeAg-positive brother were completely identical except for one nucleotide at position 587 (mother and brother: guanosine, patient: adenosine), giving an amino acid change: Gly - greater than Arg at position 145 of the major HBs protein.

Cytochrome b558, a component of the phagocyte NADPH oxidase, is a flavoprotein

Cytochrome b558 is the only membrane component of the phagocyte O2(-)-producing NADPH oxidase. The O2- production by the oxidase reconstituted in vitro with the crude membrane fraction is enhanced several-fold by addition of FAD, whereas that with the partially purified cytochrome is completely dependent on exogenous FAD, suggesting that FAD acts through the membrane component, cytochrome b558. The alignments of the amino acid sequence of the large subunit of the cytochrome (gp91-phox) with those of previously characterized flavoproteins reveal that the middle and C-terminal portions of gp91-phox are likely to be FAD- and NADPH-binding domains, respectively. Cytochrome b558, thus, appears to be a flavoprotein with an NADPH-binding site, of the NADPH oxidase.

Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis

BACKGROUND & AIMS The mechanism for development of primary biliary cirrhosis (PBC) remains enigmatic, but molecular mimicry has been implicated because of well-known cross-reactivity of human mitochondrial autoantigens and equivalent bacterial antigens. Virtually all patients with PBC have antimitochondrial autoantibodies (AMA), but, interestingly, approximately 50% also manifest antinuclear antibodies (ANA). METHODS To determine whether generation of ANA are due to molecular mimicry of mitochondrial peptides, we established 6 T-cell clones selected by a peptide corresponding to the E2 subunit of mitochondrial pyruvate dehydrogenase complex and analyzed for reactivity to mimicry peptides derived from mitochondrial and nuclear autoantigens, including control sequences. RESULTS For mitochondrial autoantigens, 1 peptide from the E2 subunit of the pyruvate dehydrogenase complex, 1 peptide from the E2 subunit of the oxo-glutarate dehydrogenase complex, 1 peptide from the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex, and 1 peptide from the E3-binding protein cross-reacted with these T-cell clones. For the nuclear autoantigens, 5 peptides from gp210 and 1 from Sp100 cross-reacted with these clones. Furthermore, 1 of 3 T-cell clones selected by recombinant gp210 protein reacted with a mimicry peptide corresponding to amino acids 188-201 of gp210, indicating that this part of the protein is a naturally processed immunodominant T-cell epitope. CONCLUSIONS These results demonstrate molecular mimicry between mitochondrial and nuclear autoantigens in PBC and that a mimicry peptide may become an immunodominant T-cell epitope. These data have significance not only for PBC but also for the production of ANA in other disease processes.

Architecture for networked electronic patient record systems.

There have been two major approaches to the development of networked electronic patient record (EPR) architecture. One uses object-oriented methodologies for constructing the model, which include the GEHR project, Synapses, HL7 RIM and so on. The second approach uses document-oriented methodologies, as applied in examples of HL7 PRA. It is practically beneficial to take the advantages of both approaches and to add solution technologies for network security such as PKI. In recognition of the similarity with electronic commerce, a certificate authority as a trusted third party will be organised for establishing networked EPR system. This paper describes a Japanese functional model that has been developed, and proposes a document-object-oriented architecture, which is-compared with other existing models.

Medical Markup Language (MML) for XML-based Hospital Information Interchange

Medical Markup Language (MML) has been developed over the last 6 years in order to create a set of standards by which medical data, within Japan and hopefully worldwide, can be stored, accessed and exchanged in any number of physical locates. The MML version 2.21 is characterized by XML as meta-language, module structure for each document and enhancement of linking function among documents. Data exchange specification has been also added for query and reply. MML instances are composed of MML header and MML body. The MML header includes information for data transmission, while MML body includes several module items. One module item contains two elements: document information and module content. Nine MML module contents are defined at the present time: patient information, health insurance information, diagnosis information, lifestyle information, basic clinic information, particular information at the time of first visit, progress course information, surgery record information and clinical summary information.

Redesigning of an existing software using design patterns

We describe a case study on redesigning of existing software using design patterns. Although design patterns have spread widely in object-oriented software design, the disordered application of them often makes the design more complicated or worsens performance. In the case study, we introduce a hot-spot based approach to apply design patterns effectively. Then we quantitatively evaluate the effectiveness of applying design patterns to the redesigning. The C&K metrics suite is used for the evaluation. We collect C&K metrics values for two versions of the decision tree learning system. One is a prototype version designed without using design patterns while the other is redesigned using design patterns. We conduct the Mann-Whitny U-test, one of the nonparametric statistics for testing hypotheses about whether two sample values differ. As a result, we find significant differences between the C&K metrics values of the two versions. Finally we discuss the applicability of the C&K metrics to criterion for evaluation of the flexibility and extensibility of software.

Applying design patterns to decision tree learning system

In this paper we describe an application of design patterns to the development of a decision tree learning system. A decision tree learning system constructs a classifier as a form of tree from a given data set. It is required to be as flexible as possible when used in real application domains. Design patterns help us construct reusable software components and construct flexible and extensible systems. The approach employed in this study is as follows. First we examine several decision tree learning systems and identify hot-spots in the systems at points we anticipate future demand for modification and extension of the system. Second we determine which design pattern to apply to each hot-spot. We evaluate the extensibility of the system experimentally. Our experience shows that using design patterns in object-oriented software design allows the easy construction of flexible systems.

Genomic organization of the α chain of the human C4b-binding protein gene

Abstract C4b-binding protein (C4bp) is a serum glycoprotein that is one of the regulators of the complement activation (RCA) family. This protein is composed of structurally related 70-kDa (α chain) and 45-kDa (β chain) polypeptides. The α chain of C4bp (C4bpα) consists of eight short consensus repeats (SCR), which constitute the amino-terminal 491 residues. Human C4bp is also one of the acute-phase reactants. In order to clarify the genetic basis of the SCR and to understand the regulatory mechanisms of C4bp synthesis, we isolated 6 genomic DNA clones covering all of the human C4bpα gene. This gene consists of 12 exons and spans about 40 kb. Each of the SCRs is encoded by a single exon, except for the second SCR (SCR II), which is encoded by two separate exons, demonstrating that human C4bpα has a split SCR at the genomic level. The 5′ flanking region was sequenced up to 380 bases upstream from the putative transcription initiation site. Several possible binding sites for transcription factors were identified.

Object-oriented development of a concept learning system for time-centered clinical data

A concept learning system is expected to be a powerful tool for filtering and analyzing a large amount of data in a variety of scientific fields. A simple application of it to clinical data, however, fails to mine medical information and knowledge. One of the major obstacles in mining a clinical database is time, which is a very important concept in clinical medicine. To be successful in data mining in clinical medicine, an efficient model of clinical data with time and a flexible concept learning system augmented to handle the model are both necessary. Herein we modeled clinical data to easily express and manipulate time and extended a concept learning system to utilize a time-centered clinical data model. The modified concept learning system is based on themessage-value method rather than the traditionalattribute-value method. The object-oriented technology was of great help in modeling time-centered clinical data and in developing a modified concept learning system.

A secure model for communication of health care information by sub-division of information and multiplication of communication paths.

Hospital information systems (HIS) for office tasks such as order entry of laboratory examination, prescription, medical treatment, and patients accounting are common. Furthermore, an electronic patient record (EPR) which records all the clinical procedures is now being developed. The electronic patient record is expected to gather, store and manage all the health care information regarding an individual patient during his whole life. In general, every piece of information in order entry systems is generated, transmitted, analysed, processed and stored in one hospital or clinic. Few pieces of information except prescriptions for outpatients and referrals to doctors of other hospitals and clinics should be transferred to other medical institutes. Therefore, the information security of order entry systems in a given hospital is regarded to be the same as that of its whole hospital information system. In most hospitals, security of HIS is at a sufficiently high level including physical protection of the system since security control for limited and registered users of a system such as medical staff is relatively straightforward. The security control of an EPR is completely different from that of an existing HIS. The EPR should deal with all the medical information regarding an individual patient. Since a patient usually visits more than one hospital in his life and takes medical advice, medical examinations, medicines and medical treatments here and there, an EPR system must gather pieces of information on a patient which are distributed in many medical institutes and integrate them to show them to a user effectively. * Corresponding author.