A heparin-modified thermoresponsive surface with heparin-binding epidermal growth factor-like growth factor for maintaining hepatic functions and harvesting hepatocyte sheets.

A heparin-modified thermoresponsive surface bound with heparin-binding epidermal growth factor-like growth factor (HB-EGF) was designed to allow creation of transferrable and functional hepatocyte sheets. A heparin-modified thermoresponsive surface was prepared by covalently tethering heparin onto poly(-isopropylacrylamide--2-carboxyisopropylacrylamide)-grafted tissue culture polystyrene surfaces (Heparin-IC). HB-EGFs were able to stably bind to heparin-IC via affinity interaction.

The Superiority of AN69ST Membrane in the Adsorption of Fibroblast Growth Factor-23.

Background: The most frequent cause of acute kidney injury (AKI) needing renal replacement therapy is sepsis, with the prognosis of patients with septic AKI worse than for other causes of this disease. Recent studies have shown that fibroblast growth factor-23 (FGF-23) levels, one of the phosphaturic and prognostic factors in chronic kidney disease, are also elevated in patients with AKI and correlate with an increased risk of death or a need for dialysis. In addition, FGF-23 was found to inhibit the extra-renal synthesis of 1,25-dihydroxyvitamin D by human monocytes.

Abnormal Diurnal Patterns of Parathyroid Hormone are Associated with Sustained Mild Hypercalcemia in Non-Dialyzed Chronic Kidney Disease.

Background: Plasma PTH levels are normally high during the night and early morning and lowest at approximately 10 am (the PTH circadian rhythm). Our objective was to examine the relationship between the PTH circadian rhythm and calcium-phosphorus metabolism in non-dialyzed, chronic kidney disease (CKD) patients.

Methods: The characteristics of twenty-eight subjects comprised: male, 23; diabetic patients, 16; mean age, 71.

Brush biopsy of human oral mucosal epithelial cells as a quality control of the cell source for fabrication of transplantable epithelial cell sheets for regenerative medicine.

Autologous oral mucosal epithelial cell sheets have been used for treating epithelial defects such as cornea and esophagus. The cell source of patients' oral mucosal epithelial cell sheet should be examined in normality because it has individual difference. In this study, oral mucosal epithelial cells were less invasively collected by brush biopsy from the buccal, gingival, labial, and palate mucosa of four healthy volunteer donors without anesthesia, and analyzed the keratin expressions by western blotting and the obtained results were compared with those by immunohistochemistry of each of the native tissues.

Preparation of Thermoresponsive Nanostructured Surfaces for Tissue Engineering.

Thermoresponsive poly(N-isopropylacrylamide) (PIPAAm)-immobilized surfaces for controlling cell adhesion and detachment were fabricated by the Langmuir-Schaefer method. Amphiphilic block copolymers composed of polystyrene and PIPAAm (St-IPAAms) were synthesized by reversible addition-fragmentation chain transfer (RAFT) radical polymerization. A chloroform solution of St-IPAAm molecules was gently dropped into a Langmuir-trough apparatus, and both barriers of the apparatus were moved horizontally to compress the film to regulate its density.

TEMPOL increases NAD(+) and improves redox imbalance in obese mice.

Continuous energy conversion is controlled by reduction-oxidation (redox) processes. NAD(+) and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS) and is reduced to hydroxylamine by NADH.

Development of DS-5573a: A novel afucosylated mAb directed at B7-H3 with potent antitumor activity.

B7-H3 is highly overexpressed in a variety of human clinical tumors, and its expression is significantly associated with poor outcomes. In our study, we aimed to develop new antitumor mAbs by employing cancer cell immunization, and succeeded in generating a mouse anti-human B7-H3 antibody (M30) that shows antitumor activity. M30 was humanized (Hu-M30), and an afucosylated Hu-M30 (DS-5573a) was also generated.

Compassionate use of drugs and medical devices in the United States, the European Union and Japan.

Compassionate use, also called expanded access, provides an important pathway for patients with life-threatening conditions to gain access to unapproved investigational drugs, biologics and medical devices. Although the United States (US) and the countries of the Europe Union (EU) have mechanisms that are associated with the use of unapproved products, as of May 2015 there was no such mechanism in Japan. Instead, unapproved products are used under a physician's discretion in conjunction with the Japan Medical Practitioners' Act or Advanced Medical Care B.

Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model.

Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy.

Clinical utility of endoscopic ultrasound-guided fine-needle aspiration in mixed adenoneuroendocrine carcinoma with signet-ring cells of the pancreas: a case report and review of the literature.

A man in his 60s visited our hospital because of a pancreatic head tumor. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed that the tumor consisted of a neuroendocrine carcinoma (NEC) and adenocarcinoma, including signet-ring cell carcinoma, and that the ratio of these components was approximately 50:50. Therefore, he was diagnosed with mixed adenoneuroendocrine carcinoma (MANEC).

Distribution of Petrosavia sakuraii (Petrosaviaceae), a rare mycoheterotrophic plant, may be determined by the abundance of its mycobionts.

Petrosavia sakuraii (Petrosaviaceae) is a rare, mycoheterotrophic plant species that has a specific symbiotic interaction with a narrow clade of arbuscular mycorrhizal (AM) fungi. In the present study, we tested the hypothesis that the distribution and abundance of mycobionts in two P. sakuraii habitats, Nagiso and Sengenyama (central Honshu, Japan), determine the distribution pattern of this rare plant.

Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction.

Rationale: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure.

Objective: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction.

Fluorescence probe for the convenient and sensitive detection of ascorbic acid.

Ascorbic acid is an important antioxidant that plays an essential role in the biosynthesis of numerous bioactive substances. The detection of ascorbic acid has traditionally been achieved using high-performance liquid chromatography and absorption spectrophotometry assays. However, the development of fluorescence probes for this purpose is highly desired because they provide a much more convenient and highly sensitive technique for the detection of this material.

Massively-multicellular alignment with the self-aggregate of air bubbles.

This study proposes a cell manipulation method with aggregated air bubbles on cell culture medium. This method requires no additional regents nor devices, except for normal cell-culture materials such as cell culture dishes and pipettes. Bubbles generated by pipetting were spontaneously aggregated with regularity on the whole surface and used as a mask for avoiding cell adhesion after cell-seeding.

A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of human embryonic stem cells.

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from the processing of human embryonic stem cells (hESCs), taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-6, "Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Human Embryonic Stem Cells," issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012.

A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of allogeneic human induced pluripotent stem(-Like) cells.

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts and basic technical elements to ensure the quality and safety of therapeutic products derived from allogeneic human induced pluripotent stem cells (iPS cells) or iPS cell-like cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-5, "Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Allogeneic Human Induced Pluripotent Stem(-Like) Cells," issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012.

A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of allogeneic human somatic stem cells.

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from allogeneic human somatic stem cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-3, "Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Allogeneic Human Somatic Stem Cells," issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012.

A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from the processing of autologous human somatic stem cells.

To make sure that novel human cell-based products contribute to human health care, it is essential that, based on sound science at present, suitable measures be taken by the manufacturers and regulatory authorities on applying these products to the treatment of patients by taking into account specificity of starting cell lines, the manufacturing process, products, administration procedures, diseases in question, and patient population. As part of such an endeavor, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from autologous human somatic stem cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No.

A Biomimicking Tumor Tissue Model Using Hepatocellular Carcinoma Cell Sheet in a Collagen Sandwich System.

Cytotoxic efficacy of anticancer drugs has been widely studied with monolayer-cultured cancer cells. However, the drug efficacy under two-dimensional (2D) culture conditions usually differs from that of three-dimensional (3D) culture conditions. In the present study, an in vitro tumor tissue model was constructed by sandwiching a cancer cell monolayer (cancer cell sheet) between two collagen layers as a biomimicking tumor tissue model, and the in vitro cytotoxic efficacy of doxorubicin was investigated.

Great Ears: Low-Frequency Sensitivity Correlates in Land and Marine Leviathans.

Like elephants, baleen whales produce low-frequency (LF) and even infrasonic (IF) signals, suggesting they may be particularly susceptible to underwater anthropogenic sound impacts. Analyses of computerized tomography scans and histologies of the ears in five baleen whale and two elephant species revealed that LF thresholds correlate with basilar membrane thickness/width and cochlear radii ratios. These factors are consistent with high-mass, low-stiffness membranes and broad spiral curvatures, suggesting that Mysticeti and Proboscidea evolved common inner ear adaptations over similar time scales for processing IF/LF sounds despite operating in different media.

A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of autologous human induced pluripotent stem(-like) cells.

As a series of endeavors to establish suitable measures for the sound development of regenerative medicine using human stem cell-based products, we studied scientific principles, concepts, and basic technical elements to ensure the quality and safety of therapeutic products derived from autologous human iPS cells or iPS cell-like cells, taking into consideration scientific and technological advances, ethics, regulatory rationale, and international trends in human stem cell-derived products. This led to the development of the Japanese official Notification No. 0907-4, "Guideline on Ensuring the Quality and Safety of Pharmaceuticals and Medical Devices Derived from the Processing of Autologous Human Induced Pluripotent Stem(-Like) Cells," issued by Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare of Japan, on September 7, 2012.

Assessment of the Safety of Chondrocyte Sheet Implantation for Cartilage Regeneration.

We have previously studied the effects of chondrocyte sheets on the repair and regeneration of articular cartilage by using temperature-responsive culture inserts. On the basis of this work, we succeeded in rapid fabrication of chondrocyte sheets with the use of a coculture method in which inserts were placed between synoviocytes and chondrocytes. Treatment of cartilage defects using layered chondrocyte sheets promotes repair and regeneration; this method is compatible with in vivo osteoarthritis models that reproduce partial-thickness defects.