Spontaneous Thrombosis of a Hepatic Pseudoaneurysm Following Blunt Liver Injury.

Hepatic pseudoaneurysm (HPA) is a rare complication of liver injury in children. Prophylactic embolization is preferable to prevent life-threatening hemorrhage due to pseudoaneurysm rupture. We present the case of a four-year-old boy who sustained a grade III liver injury from blunt abdominal trauma.

Estimated Gestational Age From Infant's Foot Length in Japanese.

Aim In developed countries including Japan, gestational age (GA) is predicted by the last menstrual period (LMP) and/or fetal ultrasound. In some developing countries, GA is predicted by infant's foot length (FL). Pregnant women who did not have pregnancy check-up is not infrequent in Japan, therefore there are sometimes opportunities to estimate the GA from infants after the delivery.

Elucidation of the statistical factors that influence anti-drug antibody cut point setting through a multi-laboratory study.

Appropriateness of anti-drug antibody (ADA) assay is critical for immunogenicity assessment of biopharmaceuticals. Although cut point setting in ADA assay has a large impact on the results, a standard statistical approach for its setting has not been well established. In this multi-laboratory study, to elucidate factors influencing the cut point setting, we compared the statistical approaches and calculated cut points for multiple datasets of ADA assays using the individual procedure employed at each laboratory.

Collaborative study using common samples to evaluate the performance of anti-drug antibody assays constructed by different companies.

This study was undertaken to evaluate the performance of anti-drug antibody (ADA) assays constructed by each participating company using common samples including ADA, drug and human serum. The ADA assays constructed by each company showed good sensitivity and precision for evaluation of ADA. Cut points for screening and confirmatory assays and assay selectivity were determined by various calculation methods.

[Practice of Regulatory Science (Development of Medical Devices)].

Prototypes of medical devices are made in accordance with the needs of clinical practice, and for systems required during the initial process of medical device development for new surgical practices. Verification of whether these prototypes produce the intended performance specifications is conducted using basic tests such as mechanical and animal tests. The prototypes are then improved and modified until satisfactory results are obtained.

In Vitro Endothelialization Test of Biomaterials Using Immortalized Endothelial Cells.

Functionalizing biomaterials with peptides or polymers that enhance recruitment of endothelial cells (ECs) can reduce blood coagulation and thrombosis. To assess endothelialization of materials in vitro, primary ECs are generally used, although the characteristics of these cells vary among the donors and change with time in culture. Recently, primary cell lines immortalized by transduction of simian vacuolating virus 40 large T antigen or human telomerase reverse transcriptase have been developed.

A biological study establishing the endotoxin limit of biomaterials for bone regeneration in cranial and femoral implantation of rats.

The purpose of this study was to accurately quantify the risk of endotoxin contamination in biomaterials for bone regeneration in order to establish the acceptable endotoxin limit. Collagen sheets containing varying amounts of purified endotoxin from Escherichia coli and dried, heat-killed E. coli or Staphylococcus aureus cells were implanted into cranial or femoral defects in rats.

[Polyploidy induction by spherical size standard polystyrene particles in a Chinese hamster cell line CHL].

To investigate relationships between particle (as a model of aggregates) size in a nanomaterial test suspension and its cytotoxicity, a series of eleven sizes of polystyrene (PS) particles were tested in the cytotoxicity test and the chromosome aberration test by using a Chinese hamster cell line CHL. The PS particles were spheres with defined diameters ranging from 0.1 to 9.

[Development of guidance for the approval process of brand-new medical products and regenerative medicine products].

Ministry of Health, Labour and Weltare has been conducting development of guidance for the approval process of brand-new medical products/development of guidance for medical devices in collaboration with Ministry of Economy, Trade and Industry as part of measures to promote practical use of brand-new medical products since 2005. The objective of this project is to expedite the processes from developmental process of medical devices to approval review and to introduce the medical devices to medical front quickly..

Impact of lipid-induced degradation on the mechanical properties of ultra-high molecular weight polyethylene for joint replacements.

Gamma or electron beam irradiation of ultra-high molecular weight polyethylene (UHMWPE) used in artificial joints for sterilization and/or crosslinking purposes generates free radicals in the material, which causes long-term oxidative degradation of UHMWPE. Recently, another mechanism for the degradation of UHMWPE by the absorption of lipids during in vivo clinical use was proposed. However, knowledge on lipid-induced degradation is quite limited, compared with that on radical-induced degradation.

[Projects to accelerate the practical use of innovative medical devices to collaborate with TWIns, Center for Advanced Biomedical Sciences, Waseda University and School of Engineering, The University of Tokyo].

Division of Medical Devices has been conducting the projects to accelerate the practical use of innovative medical devices to collaborate with TWIns, Center for Advanced Biomedical Sciences, Waseda University and School of Engineering, The University of Tokyo. The TWIns has been studying to aim at establishment of preclinical evaluation methods by "Engineering Based Medicine", and established Regulatory Science Institute for Medical Devices. School of Engineering, The University of Tokyo has been studying to aim at establishment of assessment methodology for innovative minimally invasive therapeutic devices, materials, and nanobio diagnostic devices.

Characterization of the cell growth analysis for detection of immortal cellular impurities in human mesenchymal stem cells.

The analysis of in vitro cell senescence/growth after serial passaging can be one of ways to show the absence of immortalized cells, which are frequently tumorigenic, in human cell-processed therapeutic products (hCTPs). However, the performance of the cell growth analysis for detection of the immortalized cellular impurities has never been evaluated. In the present study, we examined the growth rates of human mesenchymal stem cells (hMSCs, passage 5 (P = 5)) contaminated with various doses of HeLa cells, and compared with that of hMSCs alone.

Development and performance evaluation of a positive reference material for hemolysis testing.

This study deals with the development and performance evaluation of a positive reference material for hemolysis testing, which is used for evaluating the biological safety of medical devices. Genapol X-080, a nonionic detergent, was selected as a candidate hemolytic substance in a survey of 23 chemical compounds; it showed significant hemolytic activity against rabbit defibrinated blood at concentrations more than 20 µg/mL. A polyvinyl chloride (PVC) sheet spiked with 0.

Role of p16(INK4a) in the inhibition of DNA synthesis stimulated by HGF or EGF in primary cultured rat hepatocytes.

In the present study, we investigated the role of p16(INK4a) in the inhibition of DNA synthesis stimulated by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) using RNA interference in primary cultured rat hepatocytes. The transfection of small interfering RNAs targeting p16(INK4a) reduced the corresponding mRNA and protein expression by more than approximately 90% and 50%, respectively, at 24 h after transfection. In the cells transfected with p16(INK4a) small interfering RNA, control, HGF, and EGF-stimulated DNA synthesis as assessed by (3)H-thymidine incorporation increased by approximately 1.

Screening study on hemolysis suppression effect of an alternative plasticizer for the development of a novel blood container made of polyvinyl chloride.

The aim of this study is to identify a plasticizer that is effective in the suppression of the autohemolysis of the stored blood and can be used to replace di(2-ethylhexyl) phthalate (DEHP) in blood containers. The results of hemolysis test using mannitol-adenine-phosphate/red cell concentrates (MAP/RCC) spiked with plasticizers included phthalate, phthalate-like, trimeliate, citrate, and adipate derivatives revealed that di-isononyl-cyclohexane-1,2-dicarboxylate (Hexamoll(®) DINCH), di(2-ethylhexyl)-1,2,3,6-tetrahydro-phthalate (DOTP), and diisodecyl phthalate (DIDP) exhibited a hemolysis suppression effect almost equal to that of DEHP, but not other plasticizers. This finding suggested that the presence of 2 carboxy-ester groups at the ortho position on a 6-membered ring of carbon atoms may be required to exhibit such an effect.

Involvement of reactive oxygen species in osteoblastic differentiation of MC3T3-E1 cells accompanied by mitochondrial morphological dynamics.

Bone remodeling is regulated by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Recent studies have shown that reactive oxygen species (ROS) act as an intracellular signal mediator for osteoclast differentiation. However the role of ROS on osteoblast differentiation is poorly understood.

[Determination of the relative light scattering intensity of aggregates induced by stirring of humanized monoclonal antibody product using dynamic light scattering].

To evaluate the usefulness of dynamic light scattering for estimation of the relative level of aggregates in the manufacturing process of monoclonal antibody substance and its final product, the particle sizes and relative light scattering intensities of monomer and aggregates induced by stirring of humanized monoclonal antibody product were determined by dynamic light scattering. The particle sizes of monomer and aggregates were approximately 5 and 500 nm, respectively. When aggregates and monomer were mixed at the ratio of 1 to 6, the relative light scattering intensity of aggregates was approximately 50%.

Annexin A3 as a negative regulator of adipocyte differentiation.

Annexin A3 is a protein belonging to the annexin family, and it is mainly present in cellular membranes as a phospholipid-binding protein that binds via the calcium ion. However, its physiological function remains to be clarified. We examined the expression of annexin A3 in mouse tissues and found for the first time that annexin A3 mRNA and its protein were expressed more strongly in adipose tissues than in other tissues.

[Determination of the particle size and relative light scattering intensity of aggregates of human IgG and humanized monoclonal antibody product induced by various stress using dynamic light scattering].

To evaluate the usefulness of dynamic light scattering for the analysis of aggregates in the manufacturing process of monoclonal antibody and its final product, the particle size and relative light scattering intensity of aggregates of human IgG and humanized monoclonal antibody product induced by various stress such as stirring, increasing temperature, shaking and freeze-thaw were determined using dynamic light scattering. It was found that 1.3% of relative light scattering intensity as the minimum range and the range of particle size from 28.

Spheroid formation and expression of liver-specific functions of human hepatocellular carcinoma-derived FLC-4 cells cultured in lactose-silk fibroin conjugate sponges.

This study presents a hepatic tissue engineering application of three-dimensional (3D) porous sponges composed of lactose-silk fibroin (SF) conjugates (Lac-CY-SF) bearing β-galactose residues, hepatocyte-specific ligands. Lac-CY-SF sponges were prepared by freeze-drying, followed by immersion in a series of methanol aqueous solutions. Lac-CY-SF sponges showed heterogeneous pore structure with round pores about 100 μm in diameter and elongated pores 250-450 μm in length and 100-150 μm in breadth.

Possible role of mitochondrial remodelling on cellular triacylglycerol accumulation.

Mitochondrial fusion and fission processes play a role in a variety of cell functions, including energy metabolism, cell differentiation and programmed cell death. Still, it is not clear how these processes contribute to the cell functions. Here, we investigated the role of mitochondrial remodelling on lipid metabolism in adipocytes.

Triple combinations of lower and longer alkyl gallates and oxacillin improve antibiotic synergy against methicillin-resistant Staphylococcus aureus.

Using liposome systems, we found that gallates with short alkyl chains were located in the external medium and those with longer alkyl chains were located in the surface region of lipid bilayer. Combinations of these gallates remarkably reduced oxacillin MICs against methicillin-resistant Staphylococcus aureus to below the antibiotic breakpoint (< or = 2 microg/ml).