Yamaguchi-shi, Japan
Yamaguchi-shi, Japan

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Mukai T.,Tokyo Medical University | Nagamura-Inoue T.,Tokyo Medical University | Shimazu T.,Tokyo Medical University | Mori Y.,Tokyo Medical University | And 4 more authors.
Cytotherapy | Year: 2016

BACKGROUND AIMS: The human umbilical cord (UC) is a rich source of mesenchymal stromal cells (MSCs), which have been reported to have multi-lineage potential. The objectives of this study were to investigate the characteristics and capacity of UC-MSC neurosphere formation and whether this event enhances the propensity of UC-MSCs to undergo neural differentiation.METHODS: UC-MSCs were collected by the improved explant method. UC-MSCs and neurosphere-forming UC-MSCs (UC-MSC-neurospheres) were induced to undergo neurogenic differentiation, the latter of which were induced by suspension culturing in the presence of epidermal growth factor and basic fibroblast growth factor. The differentiation and migratory capacities of the individual cultures were then compared on the basis of the expression of neural markers, as measured by immunocytochemistry, immunoblotting and quantitative real-time polymerase chain reaction and transwell assays, respectively.RESULTS: Both UC-MSCs and UC-MSC-neurospheres were capable of differentiating into neurogenic cells when cultured in neurogenic differentiation medium. However, pre-conditioned UC-MSC-neurospheres exhibited significantly higher expression of neural markers--including microtubule-associated protein (MAP2), MUSASHI1, glial fibrillary acidic protein (GFAP), and NESTIN--compared with those derived from UC-MSCs directly. Moreover, UC-MSC-neurospheres expressed significantly higher levels of the stemness markers NANOG, KLF4 and OCT4 than did UC-MSCs. Migration assays also revealed that both UC-MSCs and UC-MSC-neurospheres actively migrate toward glucose-depleted cells.CONCLUSIONS: Neurogenic differentiation potential probably is greater in UC-MSC-neurospheres than in UC-MSCs. Thus, UC-MSC-neurospheres may serve as a better source of cells for neurogenic regenerative medicine. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.


PubMed | Yamaguchi Hospital, Tokyo Medical University and Nippon Telegraph and Telephone
Type: Journal Article | Journal: Cytotherapy | Year: 2016

The human umbilical cord (UC) is a rich source of mesenchymal stromal cells (MSCs), which have been reported to have multi-lineage potential. The objectives of this study were to investigate the characteristics and capacity of UC-MSC neurosphere formation and whether this event enhances the propensity of UC-MSCs to undergo neural differentiation.UC-MSCs were collected by the improved explant method. UC-MSCs and neurosphere-forming UC-MSCs (UC-MSC-neurospheres) were induced to undergo neurogenic differentiation, the latter of which were induced by suspension culturing in the presence of epidermal growth factor and basic fibroblast growth factor. The differentiation and migratory capacities of the individual cultures were then compared on the basis of the expression of neural markers, as measured by immunocytochemistry, immunoblotting and quantitative real-time polymerase chain reaction and transwell assays, respectively.Both UC-MSCs and UC-MSC-neurospheres were capable of differentiating into neurogenic cells when cultured in neurogenic differentiation medium. However, pre-conditioned UC-MSC-neurospheres exhibited significantly higher expression of neural markers--including microtubule-associated protein (MAP2), MUSASHI1, glial fibrillary acidic protein (GFAP), and NESTIN--compared with those derived from UC-MSCs directly. Moreover, UC-MSC-neurospheres expressed significantly higher levels of the stemness markers NANOG, KLF4 and OCT4 than did UC-MSCs. Migration assays also revealed that both UC-MSCs and UC-MSC-neurospheres actively migrate toward glucose-depleted cells.Neurogenic differentiation potential probably is greater in UC-MSC-neurospheres than in UC-MSCs. Thus, UC-MSC-neurospheres may serve as a better source of cells for neurogenic regenerative medicine.


Sakurai K.,Kumamoto University | Nagahara A.,Juntendo University | Inoue K.,Red Cross | Inoue K.,Kawasaki Medical School | And 21 more authors.
BMC Gastroenterology | Year: 2012

Background: In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms.Methods: This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily). The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2). UMIN clinical trial registration number: UMIN000005399.Results: Of 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverse events.Conclusions: The favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss) should receive further investigation, including prompt referral for endoscopy.Trial registration: UMIN000005399. © 2012 Sakurai et al; licensee BioMed Central Ltd.


Omori A.,Hirosaki University | Hirai M.,New York Blood Center | Hirai M.,Tokyo Medical University | Chiba T.,Hirosaki University | And 5 more authors.
Transfusion and Apheresis Science | Year: 2012

Umbilical cord blood (CB) has been widely used for unrelated allogeneic stem cell transplantation. It is important to determine the quality of CB units to avoid frequent problem of limited cell yields. However, no practical and/or optimum obstetric factors to predict them are yet available. This study analyzed the relationship between maternal/neonatal obstetric factors and the laboratory parameters of CB units to identify the optimum factors associated with a high yield of total nucleated cells (TNC). Primiparae in their early 30s may be one of the first selection criteria for CB donors to obtain higher yield of TNC. © 2011 Elsevier Ltd.


Fuse Y.,National Health Research Institute | Ohashi T.,Hitachi Ltd. | Yamaguchi S.,Yamaguchi Hospital | Yamaguchi M.,Yamaguchi Hospital | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: Iodine deficiency in pregnant and lactating women results in serious damage to their fetuses, newborns, and weaning infants. The effect of dietary iodine intake on maternal and infantile thyroid function has not been well studied in iodine-sufficient areas, and there are few data on appropriate gestational age-specific reference ranges for urinary iodine excretion during pregnancy and lactation. Objectives: The aim of the study was to characterize the gestational change of urinary iodine excretion in Japanese women and to assess the effects of iodine status on thyroid function in mother and infant. Methods: A total of 934 Japanese women and their 722 newborn infants were enrolled in the study. Iodine and creatinine concentrations were determined in spot urine samples in the three trimesters of pregnancy and the postpartum period at 34.0 d after delivery. Serum thyroperoxidase antibody and thyroglobulin antibody, TSH, and free T 4 were measured in each trimester, and neonatal TSH was measured on postnatal d 4. Results: The overall median urinary iodine concentration (UIC) during pregnancy was 219.0 μg/liter, higher than that in postpartum women (135.0 μg/liter). The prevalence of pregnant women with low UIC less than 100 μg/liter or high UIC greater than 500 μg/liter was 16.1 and 22.2%, respectively. Urinary iodine excretion increased from 220.0 μg/liter in the first trimester to 258.0 μg/liter in the second trimester, decreased to 195.0 μg/liter in the third trimester, and then remained at 137.0 μg/liter postpartum. The maternal UIC correlated positively with serum TSH during pregnancy. There was no significant difference in UIC between subjects with positive thyroid autoantibodies and those with negative antibodies. Conclusions: Iodine intake assessed by UIC in Japanese pregnant women is regarded as sufficient and not excessive according to World Health Organization criteria. Although the data are local, our results provide additional information on the reference range for UIC throughout gestation in iodine-sufficient areas. Copyright © 2011 by The Endocrine Society.


Yamasaki K.,University of Occupational and Environmental Health Japan | Yatera K.,University of Occupational and Environmental Health Japan | Noguchi S.,University of Occupational and Environmental Health Japan | Oda K.,University of Occupational and Environmental Health Japan | And 8 more authors.
Respiratory Medicine | Year: 2013

Background The incidence of bepridil-induced pulmonary toxicity, such as interstitial pneumonia, is still unknown. The aim of the present study was to evaluate the incidence of bepridil-induced pulmonary toxicity. Methods and results A total of 253 patients treated with bepridil between January 2009 and January 2011 were retrospectively evaluated. Eight out of the 222 evaluable patients (male/female: 5/3, age range: 64-97 years, average age: 80.5 years, median age: 81.0 years) showed bepridil-induced pulmonary toxicity. Conclusions The incidence of bepridil-induced pulmonary toxicity was 3.60% in our study population. © 2013 Elsevier Ltd. All rights reserved.


Sugawara M.,MARUSAN AI Co. | Tsuzuki K.,MARUSAN AI Co. | Honda Y.,MARUSAN AI Co. | Yamaguchi A.,Yamaguchi Hospital | And 2 more authors.
Japanese Pharmacology and Therapeutics | Year: 2013

In this study, soymilk fermented with Lactobacillus delbrueckii subsp. delbrueckii TUA4408L (TUA4408L) was used in an experimental diet to examine whether its intake affects i) stool frequency, ii) the number of days with bowel movement, iii) stool quantity, and iv) stool consistency. This single-blind study involving 21 female test subjects (mean age, 32.7±5.3 years) with a tendency for constipation was conducted in four 2-week-long phases, including i) an observational phase, ii) a control diet phase (intake of 90 g of a diet without soymilk and TUA4408L twice per day), iii) a resting phase, and iv) an experimental diet phase (intake of 90 g of the experimental diet containing soymilk and TUA4408L twice per day). According to the results, the number of days with bowel movement, stool frequency and stool quantity during the experimental diet phase increased significantly compared to those during the control diet phase (P<0.01 or P<0.05). As for stool consistency, compared to the control diet phase, banana-like or toothpaste-like stool increased and hard, nut-like stool decreased during the experimental diet phase. In other words, there was an improvement in stool consistency. These results indicate that the intake of soymilk fermented with TUA4408L shows promise in improving bowel movement.


PubMed | Yamaguchi Hospital
Type: Journal Article | Journal: Orthopedic reviews | Year: 2011

The meniscus plays important roles in proper knee function. It was recently reported that meniscus degeneration was associated with progression of osteoarthritis (OA). However, little is known about the effects of degradative enzymes on the meniscus matrix, primarily collagen type I and aggrecan, during OA. This study examined the effects of metalloproteinase (MMP) and aggrecanase on the destruction of aggrecan in the human meniscus. Eighteen trimmed meniscus portions were collected during partial menisectomy. Specimens were categorized into 3 groups according to the modified Copenhaver classification based on the degrees of damage to collagen bundles. Histological and immunohistochemical studies were conducted. Sections were stained with antibodies against MMP-3, aggrecanase 1 and 2, and their specific cleavage sites of aggrecan. Their localizations and staining ratios in the inner superficial and outer deep zones of the meniscus were determined separately. The population of chondrocyte-like cells increased with degeneration of the meniscus. MMP-3 and aggrecanase 1 and 2 are primarily expressed and activated in chondrocyte-like cells. MMP-3 expression and activation increased with degeneration and the population of chondrocyte-like cells. Changes in aggrecanase 1 expression with the degeneration were not clearly detected, whereas the expression of aggrecanase 2 was associated with progression of degeneration. MMP-3 and aggrecanases, particularly aggrecanase 2, expressed in chondrocyte-like cells could play important roles in aggrecan degradation in the human meniscus.

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