堀 秀生

Abstract Introduction Indoxyl sulfate (IS) is a protein‐bound uremic toxin that causes uremic sarcopenia. IS has poor dialysis clearance; however, the addition of a binding competitor improves its removal efficiency. Methods Dialysis experiments were performed using N‐acetyl‐l‐tryptophan (L‐NAT) instead of l‐tryptophan (Trp) using pooled sera obtained from dialysis patients. The molecular structures of L‐NAT and Trp were similar to that of IS. Therefore, we examined whether Trp and L‐NAT were involved in muscle atrophy in the same manner as IS by performing culture experiments using a human myotube cell line. Results The removal efficiency of L‐NAT was the same as that of Trp. However, L‐NAT concentrations in the pooled sera increased at the end of the experiment. Trp (1 mM) decreased the area of human myocytes, similar to IS, whereas L‐NAT did not. Conclusion L‐NAT is a binding competitor with the ability to remove protein‐bound IS while preventing sarcopenia.

It has been a strong tendency to use information communication technology (ICT) to construct various education/training systems to help students or other learners to 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. In this study, we propose a medical training system for the operation of heart-lung machine. Two training contents, i.e., one for the basic operations and another for troubleshooting, are considered in the system.

The efficacy of skin regeneration devices consisting of nonwoven filters and peripheral blood cells was investigated for wound healing. We previously found that human peripheral blood cells enhanced their production of growth factors, such as transforming growth factor beta 1 (TGF-beta 1) and vascular endothelial growth factor, when they were captured on nonwoven filters. Cells on biodegradable filters were expected to serve as a local supply of growth factors and cell sources when they were placed in wounded skin. Nonwoven filters made of biodegradable polylactic acid (PLA) were cut out as 13-mm disks and placed into cell-capturing devices. Mouse peripheral blood was filtered, resulting in PLA filters with mouse peripheral blood cells (m-PBCs) at capture rates of 65.8 +/- A 5.2 %. Then, the filters were attached to full-thickness surgical wounds in a diabetic db/db mouse skin for 14 days as a model of severe chronic wounds. The wound area treated with PLA nonwoven filters with m-PBCs (PLA/B+) was reduced to 8.5 +/- A 12.2 % when compared with day 0, although the non-treated control wounds showed reduction only to 60.6 +/- A 27.8 %. However, the PLA filters without m-PBCs increased the wound area to 162.9 +/- A 118.7 %. By histopathological study, the PLA/B+ groups more effectively accelerated formation of epithelium. The m-PBCs captured on the PLA filters enhanced keratinocyte growth factor (FGF-7) and TGF-beta 1 productions in vitro, which may be related to wound healing. This device is useful for regeneration of wounded skin and may be adaptable for another application.

Increased levels of hypo-galactosylated immunoglobulin (Ig)A1 (HG-IgA1) in IgA nephropathy (IgAN) have been detected using a Helix aspersa agglutinin lectin enzyme-linked immunosorbent assay (ELISA). In this study, we developed monoclonal antibodies to evaluate the HG-IgA1 in IgA nephropathy, aiming to gain a more consistent and reproducible assay. As an analogue to the HG-IgA1 hinge region, a 19 mer synthetic peptide with five GalNAc (sHGP) residues at positions 4, 7, 9, 11 and 15 [VPST(GalNAc)PPT(GalNAc)PS(GalNAc)PS(GalNAc)TPPT (GalNAc)PSPS-NH2] was synthesized. Two monoclonal antibodies against sHGP (35A12 and 44H8) that reacted with human IgA were developed. Also, their reactivities to serum IgA from IgAN patients (n = 49), patients with other forms of kidney diseases (OKD, n = 48), and healthy controls (HC, n = 41) were evaluated using ELISA assays. The binding levels of the two monoclonal antibodies against serum IgA were significantly higher (all comparisons, p < 0.0001, Steel-Dwass non-parametric test) in IgAN patients compared to HC and OKD patients. In each individual, there was a close correlation of IgA binding levels between 35A12 and 44H8 (R (2) = 0.737). These results indicate that the monoclonal antibodies recognize similar epitopes in HG IgA1, which is found predominantly in IgAN patients. The developed antibodies are proposed as a clinically useful tool for IgAN screening.

Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 mu m fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 mu m captured over 70 % of leukocytes or 90 % of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor beta 1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues.

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.

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. © Springer International Publishing Switzerland 2014.

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. © Springer Science+Business Media Dordrecht 2014.

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. Copyright (c) 2007 S. Karger AG, Basel.

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 plasma's competitive binding affinity for ERα was significantly higher than that of control plasma (P &lt 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. © The Japanese Society for Artificial Organs 2005.