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Biomedical subjects

N Sakamoto

Publications and source records attributed to N Sakamoto.

At least 55 records · Page 3Linked to original sources
PubMed2001

The construction of a public key infrastructure for healthcare information networks in Japan.

The digital signature is a key technology in the forthcoming Internet society for electronic healthcare as well as for electronic commerce. Efficient exchanges of authorized information with a digital signature in healthcare information networks require a construction of a public key infrastructure (PKI). In order to introduce a PKI to healthcare information networks in Japan, we proposed a development of a user authentication system based on a PKI for user management, user authentication and privilege management of healthcare information systems. In this paper, we describe the design of the user authentication system and its implementation. The user authentication system provides a certification authority service and a privilege management service while it is comprised of a user authentication client and user authentication serves. It is designed on a basis of an X.509 PKI and is implemented with using OpenSSL and OpenLDAP. It was incorporated into the financial information management system for the national university hospitals and has been successfully working for about one year. The hospitals plan to use it as a user authentication method for their whole healthcare information systems. One implementation of the system is free to the national university hospitals with permission of the Japanese Ministry of Education, Culture, Sports, Science and Technology. Another implementation is open to the other healthcare institutes by support of the Medical Information System Development Center (MEDIS-DC). We are moving forward to a nation-wide construction of a PKI for healthcare information networks based on it.

Computer Communication Networks↗
PubMed2001

Identification of missense mutation (G365R) of the butyrylcholinesterase (BCHE) gene in a Japanese patient with familial cholinesterasemia.

A point mutation which caused a silent phenotype of human serum butyrylcholinesterase (BChE) was identified in the genomic DNA of a 57-year-old Japanese woman who visited our hospital because of pneumonia. The propositus exhibited an unusually low level of BChE activity, whereas her son and daughter had an intermediate level. Immunologically, there was an absence of BChE protein in the propositus's serum. DNA sequence analysis of the propositus demonstrated a point mutation at codon 365 (GGA-CGA), resulting in a Gly-Arg substitution. A family study showed her son and daughter to have the same mutation.

Butyrylcholinesterase↗
PubMed2000

Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae.

The precise subcellular localization of ion channels is often necessary to ensure rapid and efficient integration of both intracellular and extracellular signaling events. Recently, we have identified lipid raft association as a novel mechanism for the subcellular sorting of specific voltage-gated K(+) channels to regions of the membrane rich in signaling complexes. Here, we demonstrate isoform-specific targeting of voltage-gated K(+) (Kv) channels to distinct lipid raft populations with the finding that Kv1.5 specifically targets to caveolae. Multiple lines of evidence indicate that Kv1.5 and Kv2.1 exist in distinct raft domains: 1) channel/raft association shows differential sensitivity to increasing concentrations of Triton X-100; 2) unlike Kv2.1, Kv1.5 colocalizes with caveolin on the cell surface and redistributes with caveolin following microtubule disruption; and 3) immunoisolation of caveolae copurifies Kv1.5 channel. Both depletion of cellular cholesterol and inhibition of sphingolipid synthesis alter Kv1.5 channel function by inducing a hyperpolarizing shift in the voltage dependence of activation and inactivation. The differential targeting of Kv channel subtypes to caveolar and noncaveolar rafts within a single membrane represents a unique mechanism of compartmentalization, which may permit isoform-specific modulation of K(+) channel function.

Animals↗
PubMed2000

Role for cGATA-5 in transcriptional regulation of the embryonic chicken pepsinogen gene by epithelial-mesenchymal interactions in the developing chicken stomach.

A gene encoding embryonic chicken pepsinogen (ECPg), a zymogen of the digestive enzyme pepsin, is expressed specifically in epithelial cells of glands of embryonic stage proventriculus (glandular stomach) under the influence of mesenchyme. We found four GATA and one Sox binding motifs in 1.1 kb of the 5' flanking region of the ECPg gene which are essential to the organ-specific expression of the gene. The expression of cGATA-5 and cSox2 in the proventriculus from day 6 to day 12 of incubation was therefore analyzed. cGATA-5 was more strongly expressed in glandular epithelial cells than in luminal epithelial cells, while cSox2 gene expression was weaker in glandular epithelial cells. Using heterologous recombination explants we also discovered that the expression of cGATA-5 and cSox2 in epithelial cells was affected by mesenchyme when the latter induced ECPg gene expression in epithelial cells. Introduction of expression constructs into epithelial cells by electroporation demonstrated that cGATA-5 upregulated transcription of a reporter luciferase gene via a cis element in the 5' flanking region of the ECPg gene. The gel mobility shift assay revealed that the cGATA-5 protein specifically binds to the GATA binding sites. cSox2 downregulated the activity of luciferase but it was not through the Sox binding motif. These results suggest that cGATA-5 positively regulates transcription of the ECPg gene and is involved in spatial regulation of the pepsinogen gene during development.

Animals↗
PubMed2000

Precise measurement of dp elastic scattering at 270 MeV and three-nucleon force effects

The cross section, the deuteron vector A(d)(y) and tensor analyzing powers A(ij), the polarization transfer coefficients K(y('))(ij), and the induced polarization P(y(')) were measured for the dp elastic scattering at 270 MeV. The cross section and A(d)(y) are well reproduced by Faddeev calculations with modern data-equivalent nucleon-nucleon forces plus the Tucson-Melbourne three-nucleon force. In contrast, A(ij), K(y('))(ij), or P(y(')) are not described by such calculations. These facts indicate the deficiencies in the spin dependence of the Tucson-Melbourne force and call for extended three-nucleon force models.

Journal Article↗
PubMed2000

Production of macromolecular activators of phagocytosis by lysed platelets.

Macromolecular activators of phagocytosis from platelets (MAPP: 1-MAPP and s-MAPP) are released from activated fresh platelets and enhance leukocyte phagocytosis via the Fcgamma receptors. In this study, production of MAPP was investigated in lysate of freeze-thawed stored platelets (PL). Incubation of PL and thrombin with precursors of MAPP (pre-MAPP: pre-1-MAPP and pre-s-MAPP) produced 1-MAPP and s-MAPP, whereas products released from stored platelets by stimulation with thrombin or collagen did not produce MAPP after incubation with pre-MAPP. The action of thrombin in MAPP formation with PL and pre-MAPP was inhibited by antithrombin III and heparin, and sequential incubation studies indicated that the key site of action of thrombin was on a component of PL. Other serine proteases such as trypsin could be substituted for thrombin in this reaction, whereas the action of thrombin was specific when whole platelets were used instead of PL. Gel filtration of PL before and after treatment with thrombin suggested that a macromolecule in PL (PMA-I) is digested by thrombin and liberates a 700 to 800 Da substance (PMA-II) which converts pre-MAPP to MAPP.

Antithrombin III↗
PubMed2000

Three-nucleon force and the A(y) puzzle in intermediate energy p--> + d and d--> + p elastic scattering

New vector analyzing-power data on p-->+d elastic scattering at E(p) = 150 and 190 MeV have been measured. These are presented together with existing data and with recent d-->+p vector and tensor analyzing power data at E(d) = 270 MeV. The strong negative extremum of both vector analyzing powers A(p)(y) and A(d)(y) at straight theta(c.m.) approximately 80 degrees -120 degrees is underestimated by Faddeev calculations using modern NN forces. Inclusion of the Tucson-Melbourne 3N force shifts the minima upwards, but with conflicting results for A(p)(y), and leading to a good description for A(d)(y). An A(p)(y) puzzle, previously thought to exist at energies E(N)</=30 MeV only, appears to exist also at intermediate energies.

Journal Article↗
PubMed2000

Study on complex formation between recombinant human thrombomodulin fragment and thrombin using surface plasmon resonance.

Human thrombomodulin (hTM) is a newly described endothelial cell associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. The affinity constant of recombinant human soluble TM (rhs-TM) and a peptide containing active site of hTM fragment (f-hTM) with thrombin were determined using the surface plasmon resonance. The interaction of f-hTM with thrombin could be analyzed by a simple model, whereas the association and the dissociation steps of rhs-TM with thrombin consisted of at least two kinds of interaction phases. The dissociation constant for complex (K(D)) of f-hTM and thrombin was determined to be 205 nM, which was more than twice as high as that of rhs-TM (6.7 and 75 nM). The lower affinity of f-hTM was not due to the slow association rate but to the rapid dissociation rate. It comes clear that f-hTM interacts with thrombin rapidly.

Humans↗
PubMed2000

Molecular analysis of mechanisms regulating drug sensitivity and the development of new chemotherapy strategies for genitourinary carcinomas.

The emergence of drug-resistant tumors during treatment remains one of the major obstacles in cancer chemotherapy. Overexpression of P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene or multidrug resistance-associated protein (MRP) (or both) and decreased expression of DNA topoisomerase II are responsible for expression of the multidrug resistance (MDR) phenotype. The expression of P-glycoprotein is also often observed in untreated cancers showing spontaneous MDR, such as renal cell carcinoma. Regarding cisplatin resistance, decreased cisplatin accumulation, an increase in cisplatin detoxification by glutathione-related enzymes or metallothionein (or both), and increased repair of DNA damage are all considered to play an important role. The combination of reversal agents targeting such drug resistance markers may be a way to improve the outcome of chemotherapy. Regarding the presently available reversal agents, however, clinically relevant chemosensitizing doses cannot be given to humans without inducing significant toxicity. The development of new agents that reverse drug resistance without causing significant toxicity and their clinical application based on the mechanisms regulating drug sensitivity may therefore be a potentially effective new treatment strategy for genitourinary carcinomas.

Drug Resistance, Multiple↗
PubMed2000

A case of giant keratoacanthoma of the auricle.

Although keratoacanthomas are not rare in the head and neck area, patients with this type of tumor rarely consult an otolaryngologists for treatment. Keratoacanthoma should be considered in the differential diagnosis of squamous cell carcinoma. This tumor grows rapidly, usually attaining a size of about 10-20 mm in approximately 6 weeks. This is followed by slow involution over a period of 2-6 months. A keratoacanthoma larger than 20-30 mm is called as 'giant keratoacanthoma' and it is scarce. We encountered a case of giant keratoacanthoma (50 mm in diameter) on the right auricle of 84-year-old Japanese woman with a 3-year history of gradual tumor growth. Several clinical and histopathological factors made the diagnosis difficult. The tumor was completely removed by surgery and diagnosed as a keratoacanthoma by histopathological examination.

Aged↗
PubMed2000

Effects of eicosapentaenoic acid intake on plasma fibrinolytic and coagulation activity by using physical load in the young.

To assess the effect of eicosapentaenoic acid (EPA) intake on fibrinolysis and coagulation, 30 male subjects, approximately 19-23 y old, were examined for plasma fibrinolytic and coagulation activity by using a bicycle ergometer load (90 W, 20 min) before and after EPA intake of 1.125 g/d for 2 wk. Because of the EPA intake, the fibrinolytic activity was promoted, the plasmin-alpha 2 plasmininhibitor complex (PIC) level was decreased by 16.7%, and the thrombin-antithrombin III complex (TAT) level was increased by 75.4%; conversely, the D-dimer of the fibrin degradation peptide (D-dimer) level did not change from that before EPA intake. By the physical load, 1 h after ingesting the load, the PIC level was significantly decreased by 26.7%, the TAT level was significantly increased by 51.1%, and the D-dimer level was significantly decreased by 24% in comparison with levels before EPA intake. Thus, as determined by the load, a small amount of daily EPA intake clearly decreased fibrinolytic activity and increased coagulation activity. One hour after a physical load, the rate of change of the gamma-glutamyl transpeptidase (gamma-GTP) level correlated significantly and negatively to the rate of change in the PIC and TAT levels. Thus, EPA intake may affect liver and kidney function. EPA intake decreased systolic blood pressure by 5 mmHg and diastolic blood pressure by 10 mmHg.

Adult↗
PubMed2000

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.

Computer Communication Networks↗
PubMed2000

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.

Clinical Laboratory Techniques↗
PubMed2000

Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes.

IgM is the first antibody to be produced in a humoral immune response and plays an important role in the primary stages of immunity. Here we describe a mouse Fc receptor, designated Fc alpha/microR, and its human homolog, that bind both IgM and IgA with intermediate or high affinity. Fc alpha/microR is constitutively expressed on the majority of B lymphocytes and macrophages. Cross-linking Fc alpha/microR expressed on a pro-B cell line Ba/F3 transfectant with soluble IgM or IgM-coated microparticles induced internalization of the receptor. Fc alpha/microR also mediated primary B lymphocyte endocytosis of IgM-coated Staphylococcus aureus. Thus, Fc alpha/microR is involved in the primary stages of the immune response to microbes.

Amino Acid Sequence↗
PubMed2000

Application of efficient and specific gene transfer systems and organ culture techniques for the elucidation of mechanisms of epithelial-mesenchymal interaction in the developing gut.

Epithelial-mesenchymal interactions are very important in the development of the vertebrate gut. In the avian embryonic stomach (proventriculus), expression of embryonic chick pepsinogen (ECPg) gene, which is specific to developing glandular cells in stomach epithelium, is regulated by mesenchymal influence. Molecular mechanisms of tissue-specific transcriptional regulation of the ECPg gene and the molecular nature of the mesenchymal signals were analyzed using a combination of the classic organ culture system and gene transfer strategies. In the present review, three methods for the introduction of DNA into tissues are described: lipofection, electroporation and retroviral infection, and characteristics of each system are discussed.

Animals↗
PubMed2000

Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis: implications for molecular mimicry and cross-recognition among mitochondrial autoantigens.

The anti-mitochondrial antibody response in primary biliary cirrhosis (PBC) is primarily directed at E2 components of PDC, OGDC, and BCOADC, and E3BP. Previous work has shown that the immunodominant autoreactive T- cell epitope is the PDC-E2 163-176 peptide, restricted by HLA DR53. To address molecular mimicry and cross-recognition among mitochondrial autoantigens, we analyzed reactivity, including agonism and antagonism assays, to a series of single amino acid-substituted peptides using cloned T-cell lines in PBC and controls. Interestingly, fine specificities were unique for every single T-cell clone, but the clones could be categorized into two distinct groups based on recognition motifs of the T-cell receptor (TCR) ligand: group A (170)ExDK(173) and group B (168)EIExD(172). (170)E is the most critical TCR contact residue for both groups of cloned T-cell lines, whereas (173)K and (168)E are the critical TCR contact residues for group A and group B cloned T-cell lines, respectively. More importantly, some group A-cloned T-cell lines cross-reacted to human E3BP 34-47, human OGDC-E2 100-113, and several peptides derived from various microbial proteins carrying an ExDK motif, whereas group B-cloned T-cell lines reacted only to E3BP 34-47 carrying an EIExD motif. Furthermore, an RGxG motif was exclusively found in the complementarity-determining region (CDR3) of the TCR Vbeta in the group B-cloned T-cell lines, while G, S, and/or R were frequently found in the CDR3 of the TCR Vbeta in the group A-cloned T-cell lines. These data provide a framework for understanding molecular mimicry among mitochondrial antigens.

Amino Acid Sequence↗
PubMed2000

Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin levels.

To clarify the roles of vitamin K (VK) in the pancreas, twice oral, glucose tolerance tests were examined in 12 healthy young male volunteers before and after 1 week of VK tablet intake. Blood were collected by venipucture at 0, 30 and 120 min after 75 g oral glucose loading. They then took VK tablets (90 mg/d of menaquinone-4) for 1 week, and the second glucose tolerance test was examined. The subjects were divided into three groups by serum descarboxy prothrombin (DP) levels; four of lowest DP (L-DP), middle of DP (M-DP) and highest DP (H-DP) levels. They were compared by one-factor analysis of variance and Scheffè's F (group differences) and paired t -test (the effects of 1 week of VK intake). Age, body mass index and glucose status [plasma glucose (PG) and immunoreactive insulin (IRI), hemoglobin-Alc, fructosamine] of all groups were almost the same, but the IRI of the H-DP group was higher than that of the other groups at 120 min after the glucose loading (mean+/-SEM; L; 10.6+/-0.9, M-; 17.5+/-4.2, H-; 40.4+/-6.0 microU/ml). One week of VK intake tended to decrease the plasma DP levels of all groups and significantly reduced IRI of the H-DP at 120 min by half (before; 40.4+/-6.0 vs after: 18.4+/-4.6 microU/ml). The IRI/pG ratio in areas under the curve (AUC) of H-DP from 0 to 120 min after the loading was significantly decreased by 1 week of VK tablet intake (before: 31.0+/-7.4 vs after: 20/1+/-3.8 microU/g). These results suggested that there may be some relationship between pharmacological dose of vitamin K and insulin response.

Adult↗