Hideo Hori

Accumulation of bisphenol A in hemodialysis patients.

Bisphenol A [BPA, 2,2-bis(4-hydoxyphenyl)propane], an industrial chemical used in the production of polycarbonate, epoxide resin, and polyarylate, is considered to be an endocrine-disrupting chemical. BPA may be present in some hollow-fiber dialyzers used in hemodialysis. In this study, we tested the amounts of BPA eluted from various hollow fibers. Furthermore, we measured the BPA concentration in the sera of 22 renal disease predialysis patients, as well as 15 patients who were receiving hemodialysis, to see if there is BPA accumulation in these patients. The elution test of BPA showed that a much larger amount of BPA was eluted from polysulfone (PS), and polyester-polymeralloy hollow fibers. Among renal disease patients who had not undergone hemodialysis, the serum BPA concentration increased as the renal function deteriorated, showing a significant negative association. In a crossover test between PS and cellulose (Ce) dialyzers, the predialysis serum BPA concentration of PS dialyzer users decreased after changing to a Ce dialyzer, and the serum BPA increased again after switching back to PS dialyzers. In patients who were using PS dialyzers, the BPA level significantly increased after a dialysis session. However, in the Ce dialyzer users, the BPA level decreased. Since accumulation of BPA could affect the endocrine or metabolic system of the human body, it is important to perform further investigations on dialysis patients.

Evaluation of endocrine disrupting activity of plasticizers in polyvinyl chloride tubes by estrogen receptor alpha binding assay

Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate (DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERα). Our results revealed that, while DEHP has some binding affinity for ERα, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative to DEHP) has any affinity for ERα. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free (PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the PVC tube. This plasmas competitive binding affinity for ERα was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance liquid chromatography chromatograms and competitive binding capacity for ERα, suggesting that the PF tube is biocompatible and is useful for reducing the elution of substances capable of binding to ERα.

A Training System for Operating Medical Equipment

There are continuously increased new possibilities for the application of computer-added learning-education systems as the result of highly developed information communication technology (ICT). In this study, a computer-added training system was proposed for the education of clinical engineers. As the first step, problems in operating medical equipment are made clear, and research subjects are focused accordingly with their solutions clarified.

Computer-Supported Training System for Clinical Engineer

It is required for a clinic engineer to have highly professional knowledge as well as skills for the operation of medical machines. Such knowledge and skills are normally difficult to master only by teaching and practicing at universities with limited time. Therefore, it is expected to have new training system supported by advanced computer system using the information and communication technology (ICT). In this study, a training system with ICT for clinical engineer was constructed. With the system, several problems in operating medical machines were made clear, and solutions and proposals for such problems were given with examples.

Development of a Polyclonal Antibody Against Synthetic Human Immunoglobulin A1 Hinge Glycopeptide

Background: Undergalactosylated IgA1 has been found to be increased in IgA nephropathy (IgAN) by an ELISA assay using Helix aspersa agglutinin (HAA) that recognizes N-acetylgalactosamine (GalNAc). In this study, we developed a polyclonal antibody (anti-sHGP antibody) against a synthetic IgA1 hinge peptide with five GalNAc residues. Methods: The specificity of the anti-sHGP antibody was evaluated through the incremental treatment of IgA with corresponding glycosidases. Then, the susceptibility of the IgA to anti-sHGP antibody was compared among IgAN patients (n=39), patients with other forms of kidney diseases (OKD, n= 36) and healthy controls (n=37), using ELISA assay. The association of the binding abilities between anti-sHGP antibody and HAA were evaluated blindly using same 85 sera. Results: The binding ability of the anti-sHGP antibody was increased relative to the incremental treatments of neuraminidase (desialo-IgA), galactosidase (desialo/degalacto IgA). The binding levels of anti-sHGP antibody against serum IgA were significantly higher in IgAN patients compared to both healthy controls (P=0.008) and those with OKD (P=0.049). The binding levels of anti-sHGP antibody were closely related to those of HAA ELISA in the same patient sera (RR2=0.5964). Conclusions: It was certified that the anti-sHGP antibody recognized GalNAc residues in the hinge peptide of human IgA1 as well as HAA. The increased antigenicity of IgA against the antibody in IgAN suggested that a serum IgA1 exposing GalNAc residue was increased in IgAN. It would be necessary to identify the precise structure of O-glycans specific to IgAN for developing a more specific antibody.

A medical training system for the operation of Heart-lung machine

It has been a strong tendency to use Information Communication Technology (ICT) to construct various education/training systems to help students or other learners master necessary skills more easily, among which such systems with operational practice are particularly welcome in addition to the conventional E-learning ones mainly for obtaining textbook-like knowledge only. In this study, we proposed a medical training system for the operation of Heart-lung machine. Two training contents, i.e., for the basic operations and trouble shooting, respectively, are considered in the system, with more attention paid to how to deal with trouble shooting.

Toward therapeutic system for Alzheimer's Disease by removal of blood Aβ: Hemodialysis improved the impaired cognitive states of renal failure patients

Background: Active anti-amyloid immunotherapy is a strategy developed against Alzheimer’s disease.ApproacheswithAs1-42 orK6As1-30 immunogens in an adjuvant decrease amyloid-s burden and prevent cognitive decline in transgenic mice (Asuni et al, 2006). However, clinical trials of As1-42 immunotherapy have induced side effects like encephalitis and possibly microhemorrhages (Orgogozo et al, 2003; Ferrer et al, 2004). Mouse lemurs can develop As plaques with age (Mestre-Franc es et al, 2000). Such a primate model may bemore predictive than rodents of human side effects.We studied, by magnetic resonance imaging (MRI), immunotherapies in these primates. Methods: A first cohort was used to compare K6As1-30 (n 1⁄4 4; 5.8 6 0.2years) and As1-42 (n1⁄4 4; 5.96 0.2years) immunogens in alum adjuvant. A second cohort was used to evaluateK6As1-30 (n1⁄4 6; 4.66 0.2years) compared to adjuvant alone (n 1⁄4 6; 4.7 6 0.3years). All the animals were followed-up by MRI (7T PharmaScan-Bruker) to evaluate neuroinflammation, microhemorrhages and other forms of iron deposition, with T2-weighted and T2*-weighted sequences (resolution 1⁄4 (234x234x234)Âmm3). The hypointense regions from T2*-weighted images were quantified and evaluate by histology. A complementary study of age effect was performed with twenty other naive animals (1.5 to 4.9years). Results: TheT2-weighted images did not show any neuroinflammation during immunization, irrespective of the immunogen. Microhemorrhages were detected in the cerebral parenchyma at the histological analysis of the first cohort. The animals treated with K6As1-30 presented less microhemorrhages compared to those treated with As1-42 vaccine (Mann-Whitney, p< 0.05). These small microhemorrhages were not detected on the T2*-weighted images. However hypointense signal was detected on MRI and corresponded to iron deposits in the choroid plexus. Its volume increased with natural aging (r1⁄4 0.60; p< 0.001) and with As1-42 compared toK6As1-30 treatment (ANOVA, p< 0.05). No difference was detected between K6As1-30 and adjuvant alone. Conclusions: The immunotherapies studied in the mouse lemur primate did not lead to any MRI sign of neuroinflammation. The K6As1-30 strategy appears to be safer than the As1-42 strategy as it provokes less microhemorrhages in the cerebral parenchyma and less iron deposits in the choroid plexus.