Publications by authors named "Tetsuya Ogino"

49 Publications

The relationship among factors of organizational justice, organizational citizenship behavior, job satisfaction, and ease of work among Japanese nurses.

Appl Nurs Res 2021 Oct 8;61:151479. Epub 2021 Aug 8.

Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja 719-1197, Japan. Electronic address:

Aim: This work is aimed to create a strategy to improve the nurses' working environment.

Background: As the working-age population is expected to decline in Japan, the maintenance of the nurse workforce is important. In order to create a strategy to improve the nurses' working environment, we studied the relationship among factors of organizational justice (procedural, distributive, and interactional justices), organizational citizenship behavior, job satisfaction, and ease of work.

Methods: A cross-sectional, self-administered questionnaire was distributed to 969 nurses and 322 effective responses were analyzed (effective response rate 33.2%). The questionnaire contained demographic information, ease of work, and three scales for organizational justice, organizational citizenship behavior, and job satisfaction. The factor structure of the scales was studied using exploratory and confirmatory factor analysis. Structural equation modeling was used to investigate the relationship among measurements. The protocol was approved by the ethical committee of the author's university.

Results: The final model showed a fair fit to the data (χ = 1803.15, df = 1014, p < 0.001, comparative fit index = 0.907, root mean square error of approximation = 0.049). Interactional justice showed the most significant correlation to job satisfaction (r = 0.590). Job satisfaction and ease of work also showed a significant positive correlation (r = 0.696). Distributive justice had a slight negative indirect effect on job satisfaction, whereas procedural justice had no significant effect.

Conclusion: In order to enhance job satisfaction/ease of work among Japanese nurses, improvement of interactional justice may be the best strategy.
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http://dx.doi.org/10.1016/j.apnr.2021.151479DOI Listing
October 2021

The relationship among factors of organizational justice, organizational citizenship behavior, job satisfaction, and ease of work among Japanese nurses.

Appl Nurs Res 2021 Oct 8;61:151479. Epub 2021 Aug 8.

Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja 719-1197, Japan. Electronic address:

Aim: This work is aimed to create a strategy to improve the nurses' working environment.

Background: As the working-age population is expected to decline in Japan, the maintenance of the nurse workforce is important. In order to create a strategy to improve the nurses' working environment, we studied the relationship among factors of organizational justice (procedural, distributive, and interactional justices), organizational citizenship behavior, job satisfaction, and ease of work.

Methods: A cross-sectional, self-administered questionnaire was distributed to 969 nurses and 322 effective responses were analyzed (effective response rate 33.2%). The questionnaire contained demographic information, ease of work, and three scales for organizational justice, organizational citizenship behavior, and job satisfaction. The factor structure of the scales was studied using exploratory and confirmatory factor analysis. Structural equation modeling was used to investigate the relationship among measurements. The protocol was approved by the ethical committee of the author's university.

Results: The final model showed a fair fit to the data (χ = 1803.15, df = 1014, p < 0.001, comparative fit index = 0.907, root mean square error of approximation = 0.049). Interactional justice showed the most significant correlation to job satisfaction (r = 0.590). Job satisfaction and ease of work also showed a significant positive correlation (r = 0.696). Distributive justice had a slight negative indirect effect on job satisfaction, whereas procedural justice had no significant effect.

Conclusion: In order to enhance job satisfaction/ease of work among Japanese nurses, improvement of interactional justice may be the best strategy.
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http://dx.doi.org/10.1016/j.apnr.2021.151479DOI Listing
October 2021

The relationship among factors of organizational justice, organizational citizenship behavior, job satisfaction, and ease of work among Japanese nurses.

Appl Nurs Res 2021 Oct 8;61:151479. Epub 2021 Aug 8.

Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja 719-1197, Japan. Electronic address:

Aim: This work is aimed to create a strategy to improve the nurses' working environment.

Background: As the working-age population is expected to decline in Japan, the maintenance of the nurse workforce is important. In order to create a strategy to improve the nurses' working environment, we studied the relationship among factors of organizational justice (procedural, distributive, and interactional justices), organizational citizenship behavior, job satisfaction, and ease of work.

Methods: A cross-sectional, self-administered questionnaire was distributed to 969 nurses and 322 effective responses were analyzed (effective response rate 33.2%). The questionnaire contained demographic information, ease of work, and three scales for organizational justice, organizational citizenship behavior, and job satisfaction. The factor structure of the scales was studied using exploratory and confirmatory factor analysis. Structural equation modeling was used to investigate the relationship among measurements. The protocol was approved by the ethical committee of the author's university.

Results: The final model showed a fair fit to the data (χ = 1803.15, df = 1014, p < 0.001, comparative fit index = 0.907, root mean square error of approximation = 0.049). Interactional justice showed the most significant correlation to job satisfaction (r = 0.590). Job satisfaction and ease of work also showed a significant positive correlation (r = 0.696). Distributive justice had a slight negative indirect effect on job satisfaction, whereas procedural justice had no significant effect.

Conclusion: In order to enhance job satisfaction/ease of work among Japanese nurses, improvement of interactional justice may be the best strategy.
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http://dx.doi.org/10.1016/j.apnr.2021.151479DOI Listing
October 2021

Relationship among independence of daily living, human relationships, and preparation for bereavement among healthy elderly Japanese people.

Psychogeriatrics 2020 Jul 17;20(4):437-446. Epub 2020 Feb 17.

Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Japan.

Background: Given Japan's rapidly ageing society, an increasing number of elderly people live in their communities with mutual support after the death of their spouse. The purpose of this study is to clarify the relationship among independence of daily living, human relationships, and preparation for bereavement.

Methods: An anonymous, self-administered questionnaire was given to 864 community-dwelling elderly people aged 65 and older who attended an Elderly Citizens' Welfare Study Group. A total of 404 responses (effective response ratio: 46.8%) were analyzed. Their mean ± SD age was 75.6 ± 5.1 years. The purpose of the questionnaire was to obtain demographic information as well as information about three scales: independence of daily living, human relationships, and preparation for bereavement. The factor structure of the scales was studied by using exploratory and confirmatory factor analysis. Structural equation modelling was used to investigate the relationship among independence of daily living, human relationships, and preparation for bereavement. This study's protocol was approved by the Ethics Committee of Okayama Prefectural University.

Results: Factor analysis indicated a three-factor second-order factor model for independence of daily living and human relationships and a one-factor model for preparation for bereavement. Structural equation modelling showed that independence of daily living was significantly correlated with human relationships (r = 0.261, P < 0.001), and human relationships was significantly correlated with preparation for bereavement (r = 0.295, P < 0.001). There was no significant direct correlation between the independence of daily living and preparation for bereavement.

Conclusions: Encouraging elderly people to form good human relationships may help their preparation for bereavement. Further studies are required to determine whether this actually attenuates difficulties after bereavement.
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http://dx.doi.org/10.1111/psyg.12526DOI Listing
July 2020

Tapping enhances vasodilation for venipuncture even in individuals with veins that are relatively difficult to palpate.

Clin Anat 2020 Apr 12;33(3):440-445. Epub 2020 Jan 12.

Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama, Japan.

Introduction: This study evaluated whether tapping enhances vasodilation in individuals with veins that are relatively difficult to palpate.

Materials And Methods: Twenty participants (4 men and 16 women, aged 19-22 years) with cutaneous veins that were relatively difficult to palpate even after tourniquet application were recruited. A crossover trial with/without tapping (10 times in 5 s) was performed under tourniquet inflation on the upper arm. Vasodilation was evaluated by venous cross-sectional area, depth of the vein, and elevation of the overlying skin by ultrasonography. Venous palpation scores were also measured. The degree of improvement was estimated by simulation.

Results: In total, 60% of participants "sometimes" or "often" experienced unsuccessful venipuncture. After the tapping procedure, the venous cross-sectional area significantly increased (14.6 ± 9.12 mm for control and 15.2 ± 9.79 mm for tapping) and venous depth significantly decreased (4.57 ± 2.31 mm for control and 4.23 ± 2.41 mm for tapping). A simulation study using these values suggested that tapping increased the longitudinal and crosswise successful ranges of venipuncture by 5-6%.

Conclusions: Tapping in this study enhanced the vasodilation of cutaneous veins that are relatively difficult to palpate. The effectiveness of various vasodilation methods may be compared through the estimation of improvement.
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http://dx.doi.org/10.1002/ca.23559DOI Listing
April 2020

Identification of possible hypoxia sensor for behavioral responses in a marine annelid, .

Biol Open 2019 Mar 14;8(3). Epub 2019 Mar 14.

Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan.

Hypoxia often occurs in summer and causes deleterious effects on marine benthic animals. A marine annelid, , is tolerant to hypoxia, as shown by the fact that it inhabits organically polluted areas, where severe hypoxia is often observed. To understand how this species adapts to the environment, we focused on its hypoxia sensor, and we showed that TRPAbasal was a possible contributor to hypoxia detection in To examine the involvement of TRPA1 in the response of to hypoxia, we exposed to hypoxic water with or without a TRPA1-specific inhibitor, A-967079. Hypoxic stimulation induced escape behavior in from the sediment, and this behavior was suppressed by the inhibitor. The cloned TRPA gene from was phylogenetically categorized into , and contains an oxygen-dependent degradation domain, which is important for the detection of hypoxia. Whole-mount hybridization analysis showed that the gene was transcribed in the prostomium, where sensing functions are localized. These results suggested that the worm has a hypoxia-sensing system possibly utilizing CtTRPAbasal, and this system contributes to expanding the organism's niches in hypoxic environments by detecting whether hypoxia exceeds a level that would imperil its survival.
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http://dx.doi.org/10.1242/bio.037630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451338PMC
March 2019

Glutathione accelerates osteoclast differentiation and inflammatory bone destruction.

Free Radic Res 2019 Feb 1;53(2):226-236. Epub 2019 Mar 1.

a Department of Cytology and Histology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.

Chronic inflammation associated with bone tissues often destructs bones, which is essentially performed by osteoclasts in the presence of immunoregulatory molecules. Hence, regulating osteoclastogenesis is crucial to develop therapeutics for bone-destructive inflammatory diseases. It is believed that reactive oxygen species (ROS) are involved in receptor activator of NF-κB (RANK) ligand (RANKL)-induced osteoclast differentiation, and, therefore, glutathione (GSH), the most abundant endogenous antioxidant, suppresses osteoclast differentiation and bone resorption by RANKL. Interestingly, GSH also contributes to inflammatory responses, and the effects of GSH on osteoclast differentiation and bone destruction under inflammatory conditions have not yet been determined. Here, we investigated how GSH affects inflammatory cytokine-stimulated osteoclast differentiation in vitro and in a mouse model of inflammatory bone destruction. We found that GSH significantly promoted TNFα-stimulated osteoclast formation, while an inhibitor of GSH synthesis, buthionine sulfoximine, suppressed it. GSH facilitated the nuclear localisation of the nuclear factor of activated T cells c1 (NFATc1) protein, a master regulator of osteoclastogenesis, as well as the expression of osteoclast marker genes in a dose-dependent manner. N-acetylcysteine, a substrate of GSH synthesis, also stimulated osteoclast formation and NFATc1 nuclear localisation. GSH did not suppress cell death after osteoclast differentiation. In mouse calvaria injected with lipopolysaccharide, GSH treatment resulted in a fivefold increase in the osteolytic lesion area. These results indicate that GSH accelerates osteoclast differentiation and inflammatory bone destruction, suggesting GSH appears to be an important molecule in the mechanisms responsible for inflammatory bone destruction by osteoclasts.
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http://dx.doi.org/10.1080/10715762.2018.1563782DOI Listing
February 2019

Highly sensitive avoidance plays a key role in sensory adaptation to deep-sea hydrothermal vent environments.

PLoS One 2018 3;13(1):e0189902. Epub 2018 Jan 3.

Divison of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Kyoto, Japan.

The environments around deep-sea hydrothermal vents are very harsh conditions for organisms due to the possibility of exposure to highly toxic compounds and extremely hot venting there. Despite such extreme environments, some indigenous species have thrived there. Alvinellid worms (Annelida) are among the organisms best adapted to high-temperature and oxidatively stressful venting regions. Although intensive studies of the adaptation of these worms to the environments of hydrothermal vents have been made, little is known about the worms' sensory adaptation to the severe chemical conditions there. To examine the sensitivity of the vent-endemic worm Paralvinella hessleri to low pH and oxidative stress, we determined the concentration of acetic acid and hydrogen peroxide that induced avoidance behavior of this worm, and compared these concentrations to those obtained for related species inhabiting intertidal zones, Thelepus sp. The concentrations of the chemicals that induced avoidance behavior of P. hessleri were 10-100 times lower than those for Thelepus sp. To identify the receptors for these chemicals, chemical avoidance tests were performed with the addition of ruthenium red, a blocker of transient receptor potential (TRP) channels. This treatment suppressed the chemical avoidance behavior of P. hessleri, which suggests that TRP channels are involved in the chemical avoidance behavior of this species. Our results revealed for the first time hypersensitive detection systems for acid and for oxidative stress in the vent-endemic worm P. hessleri, possibly mediated by TRP channels, suggesting that such sensory systems may have facilitated the adaptation of this organism to harsh vent environments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189902PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752015PMC
January 2018

Effects of Postprandial Body Position on Gastrointestinal Motility, the Autonomic Nervous System and Subjective Comfort.

Acta Med Okayama 2017 Dec;71(6):485-491

Department of Nursing Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama 719-1197, Japan.

We examined postprandial body positions' effects on gastrointestinal motility, the autonomic nervous system and subjective comfort, i.e., whether lowering the head after a meal is beneficial for gastrointestinal motility and the prevention of pressure ulcer. We examined 10 healthy subjects and compared 3 body positions: (1) Seated upright. (2) Lying on a bed with the head at 60° and knees up by 20° (60° position). (3) Identical to (2) until post-meal; the head was then lowered to 30° (60°-30° position). Gastrointestinal motility was assessed as gastrointestinal sounds measured by sound-editing software. Digital plethysmography assessed autonomic nerve function as heart rate variability. The pressure ulcer risk was estimated as subjective comfort/discomfort using a visual analog scale. Gastrointestinal sounds increased post-meal. The 60°-30° position showed the highest number of sounds and longest cumulative sound duration. Post-meal, sympathetic activation was suggested in the 60° position, whereas vagal activity was relatively preserved in the 60°-30° position. The 60°-30° position was the most comfortable, and the 60° position was least comfortable. Lowering the head after a meal is beneficial to augment gastrointestinal motility and decrease the pressure ulcer risk. The 60° head-up position increases the pressure ulcer risk.
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http://dx.doi.org/10.18926/AMO/55585DOI Listing
December 2017

Successful management of unresectable small bowel lymphoma with laparoscopy-assisted surgical exclusion of the affected intestine.

Asian J Endosc Surg 2017 Nov 13;10(4):454-458. Epub 2017 Jun 13.

Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

The incidence of small bowel lymphoma (SBL) is increasing worldwide. In contrast to resectable SBL, the treatment of unresectable SBL is still contentious. Here, we report a case of unresectable SBL that was treated by laparoscopic exclusion of the affected intestine before systemic chemotherapy was administered. An 84-year-old man was diagnosed with primary SBL involving extranodal dissemination. The patient received prophylactic surgery, namely exclusion of the affected intestine. This therapy diminishes well-known and life-threatening complications, such as perforation, bleeding, and obstruction, which may still occur after chemotherapy, and it makes the administration of chemotherapy safer. In addition, the surgery provides easy access for direct endoscopic observation and biopsy, which are otherwise difficult to perform. Follow-up after two courses of chemotherapy showed that the patient had achieved complete remission. In conclusion, the procedure described here may be an effective strategy for unresectable SBL.
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http://dx.doi.org/10.1111/ases.12393DOI Listing
November 2017

Phytoestrogen Suppresses Efflux of the Diagnostic Marker Protoporphyrin IX in Lung Carcinoma.

Cancer Res 2016 04 2;76(7):1837-46. Epub 2016 Feb 2.

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

One promising method to visualize cancer cells is based on the detection of the fluorescent photosensitizer protoporphyrin IX (PpIX) synthesized from 5-aminolevulinic acid (ALA), but this method cannot be used in cancers that exhibit poor PpIX accumulation. PpIX appears to be pumped out of cancer cells by the ABC transporter G2 (ABCG2), which is associated with multidrug resistance. Genistein is a phytoestrogen that appears to competitively inhibit ABCG2 activity. Therefore, we investigated whether genistein can promote PpIX accumulation in human lung carcinoma cells. Here we report that treatment of A549 lung carcinoma cells with genistein or a specific ABCG2 inhibitor promoted ALA-mediated accumulation of PpIX by approximately 2-fold. ABCG2 depletion and overexpression studies further revealed that genistein promoted PpIX accumulation via functional repression of ABCG2. After an extended period of genistein treatment, a significant increase in PpIX accumulation was observed in A549 cells (3.7-fold) and in other cell lines. Systemic preconditioning with genistein in a mouse xenograft model of lung carcinoma resulted in a 1.8-fold increase in accumulated PpIX. Long-term genistein treatment stimulated the expression of genes encoding enzymes involved in PpIX synthesis, such as porphobilinogen deaminase, uroporphyrinogen decarboxylase, and protoporphyrinogen oxidase. Accordingly, the rate of PpIX synthesis was also accelerated by genistein pretreatment. Thus, our results suggest that genistein treatment effectively enhances ALA-induced PpIX accumulation by preventing the ABCG2-mediated efflux of PpIX from lung cancer cells and may represent a promising strategy to improve ALA-based diagnostic approaches in a broader set of malignancies. Cancer Res; 76(7); 1837-46. ©2016 AACR.
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http://dx.doi.org/10.1158/0008-5472.CAN-15-1484DOI Listing
April 2016

Tapping but not massage enhances vasodilation and improves venous palpation of cutaneous veins.

Acta Med Okayama 2015 ;69(2):79-85

Graduate School of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama 719-1197,

This paper investigated whether tapping on the median cubital vein or massaging the forearm was more effective in obtaining better venous palpation for venipuncture. Forty healthy volunteers in their twenties were subjected to tapping (10 times in 5 sec) or massage (10 strokes in 20 sec from the wrist to the cubital fossa) under tourniquet inflation on the upper arm. Venous palpation was assessed using the venous palpation score (0-6, with 0 being impalpable). Three venous factors-venous depth, cross-sectional area, and elevation-were also measured using ultrasonography. The venous palpation score increased significantly by tapping but not by massage. Moreover, all 3 venous measurements changed significantly by tapping, while only the depth decreased significantly by massage. The three venous measurements correlated significantly with the venous palpation score, indicating that they are useful objective indicators for evaluating vasodilation. We suggest that tapping is an effective vasodilation technique.
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http://dx.doi.org/10.18926/AMO/53336DOI Listing
February 2016

The characteristics of healthy adults with hardly palpable vein--Relations between easy venous palpation and physical factors.

Int J Nurs Pract 2015 Dec 14;21(6):805-12. Epub 2014 Apr 14.

Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama, Japan.

This study aimed to investigate relations between ease of venous palpation and various venous factors, and to elucidate characteristics of hardly palpable veins. Healthy adult volunteers (n = 110) were enrolled. The ease of venous palpation was scored from 0: impalpable to 3: well palpable. Venous factors, namely venous depth, elevation, area and minimal pressure that starts to collapse vein, were measured using an ultrasonography before and after tourniquet inflation at 60 mmHg for 60 s. Tourniquet inflation significantly increased the venous area and venous palpation score. The four venous factors correlated significantly with venous palpation score with the following correlation coefficient: Depth (r = -0.542), Elevation (0.486), area (0.258) and start-to-collapse pressure (-0.220). The characteristics of hardly palpable veins were small size, deep location and little elevation. Although vasodilatation facilitated venous palpation, venous depth and elevation were also important and should be included in future studies in which vasodilatation methods are evaluated.
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http://dx.doi.org/10.1111/ijn.12313DOI Listing
December 2015

Necrotic and apoptotic cells serve as nuclei for calcification on osteoblastic differentiation of human mesenchymal stem cells in vitro.

Cell Biochem Funct 2014 Jan 8;32(1):77-86. Epub 2013 May 8.

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

A close relationship between cell death and pathological calcification has recently been reported, such as vascular calcification in atherosclerosis. However, the roles of cell death in calcification by osteoblast lineage have not been elucidated in detail. In this study, we investigated whether cell death is involved in the calcification on osteoblastic differentiation of human bone marrow mesenchymal stem cells (hMSC) under osteogenic culture in vitro. Apoptosis and necrosis occurred in an osteogenic culture of hMSC, and cell death preceded calcification. The generation of intracellular reactive oxygen species, chromatin condensation and fragmentation, and caspase-3 activation increased in this culture. A pan-caspase inhibitor (Z-VAD-FMK) and anti-oxidants (Tiron and n-acetylcysteine) inhibited osteogenic culture-induced cell death and calcification. Furthermore, calcification was significantly promoted by the addition of necrotic dead cells or its membrane fraction. Spontaneously dead cells by osteogenic culture and exogenously added necrotic cells were surrounded by calcium deposits. Induction of localized cell death by photodynamic treatment in the osteogenic culture resulted in co-localized calcification. These findings show that necrotic and apoptotic cell deaths were induced in an osteogenic culture of hMSC and indicated that both necrotic and apoptotic cells of osteoblast lineage served as nuclei for calcification on osteoblastic differentiation of hMSC in vitro.
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http://dx.doi.org/10.1002/cbf.2974DOI Listing
January 2014

Mitochondrial localization of ABC transporter ABCG2 and its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation.

PLoS One 2012 26;7(11):e50082. Epub 2012 Nov 26.

Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Accumulation of protoporphyrin IX (PpIX) in malignant cells is the basis of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy. We studied the expression of proteins that possibly affect ALA-mediated PpIX accumulation, namely oligopeptide transporter-1 and -2, ferrochelatase and ATP-binding cassette transporter G2 (ABCG2), in several tumor cell lines. Among these proteins, only ABCG2 correlated negatively with ALA-mediated PpIX accumulation. Both a subcellular fractionation study and confocal laser microscopic analysis revealed that ABCG2 was distributed not only in the plasma membrane but also intracellular organelles, including mitochondria. In addition, mitochondrial ABCG2 regulated the content of ALA-mediated PpIX in mitochondria, and Ko143, a specific inhibitor of ABCG2, enhanced mitochondrial PpIX accumulation. To clarify the possible roles of mitochondrial ABCG2, we characterized stably transfected-HEK (ST-HEK) cells overexpressing ABCG2. In these ST-HEK cells, functionally active ABCG2 was detected in mitochondria, and treatment with Ko143 increased ALA-mediated mitochondrial PpIX accumulation. Moreover, the mitochondria isolated from ST-HEK cells exported doxorubicin probably through ABCG2, because the export of doxorubicin was inhibited by Ko143. The susceptibility of ABCG2 distributed in mitochondria to proteinase K, endoglycosidase H and peptide-N-glycosidase F suggested that ABCG2 in mitochondrial fraction is modified by N-glycans and trafficked through the endoplasmic reticulum and Golgi apparatus and finally localizes within the mitochondria. Thus, it was found that ABCG2 distributed in mitochondria is a functional transporter and that the mitochondrial ABCG2 regulates ALA-mediated PpIX level through PpIX export from mitochondria to the cytosol.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0050082PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506543PMC
May 2013

Favorable response of heavily treated Wilms' tumor to paclitaxel and carboplatin.

Onkologie 2012 24;35(5):283-6. Epub 2012 Apr 24.

Department of Hematology, Oncology and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.

Background: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported.

Case Report: A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days.

Conclusion: In a refractory case after intensive treatments, we succeeded to control the disease for a while.
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http://dx.doi.org/10.1159/000338532DOI Listing
January 2013

Spred-2 deficiency exacerbates acetaminophen-induced hepatotoxicity in mice.

Clin Immunol 2012 Sep 14;144(3):272-82. Epub 2012 Jul 14.

Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.

MAPKs are involved in acetaminophen (APAP)-hepatotoxicity, but the regulatory mechanism remains unknown. Here, we explored the role of Spred-2 that negatively regulates Ras/ERK pathway in APAP-hepatotoxicity. Spred-2 knockout (KO) mice demonstrated exacerbated liver injury, an event that was associated with increased numbers of CD4(+) T, CD8(+) T and NK cells in the liver compared to the control. Levels of CXCL9/CXCL10 that attract and activate these cells were increased in Spred-2 KO-liver. Kupffer cells isolated from Spred-2 KO mice after APAP challenge expressed higher levels of CXCL9/CXCL10 than those from the control. Upon stimulation with APAP or IFNγ, naïve Kupffer cells from Spred-2 KO mice expressed higher levels of CXCL9/CXCL10. NK cell-depletion attenuated APAP-hepatotoxicity with lowered hepatic IFNγ and decreased numbers of not only NK cells but also CD4(+) T and CD8(+) T cells in the liver. These results suggest that Spred-2 negatively regulates APAP-hepatotoxicity under the control of Kupffer cells and NK cells.
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http://dx.doi.org/10.1016/j.clim.2012.07.002DOI Listing
September 2012

[A case of advanced gastric cancer showing a complete histological response after S-1/CDDP neoadjuvant chemotherapy].

Gan To Kagaku Ryoho 2011 Aug;38(8):1329-32

Dept. of Surgery, Mihara Red Cross Hospital.

We experienced a case of advanced gastric cancer treated by curative operation after neoadjuvant chemotherapy with S-1/ CDDP. Gastric endoscopy was carried out on a 76-year-old man with epigastric discomfort and revealed a type 1 lesion in his stomach. Papillary adenocarcinoma was pathologically shown by endoscopic biopsy. The patient was initially treated by two courses of neoadjuvant chemotherapy with S-1/CDDP due to the large lymph node metastases around the lesser curvature of the stomach and celiac axis. Completion of chemotherapy resulted in a marked shrinkage of the primary lesion and a reduction of lymph node metastases. Later, total gastrectomy, splenectomy and D2 lymph node dissection were performed. Histopathological examination revealed no cancer cells in either the primary lesion of the stomach or dissected lymph nodes, confirming a pathologically complete response.
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August 2011

Serum-dependent export of protoporphyrin IX by ATP-binding cassette transporter G2 in T24 cells.

Mol Cell Biochem 2011 Dec 12;358(1-2):297-307. Epub 2011 Jul 12.

Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama 700-8558, Japan.

Accumulation of protoporphyrin IX (PpIX) in cancer cells is a basis of 5-aminolevulinic acid (ALA)-induced photodymanic therapy. We studied factors that affect PpIX accumulation in human urothelial carcinoma cell line T24, with particular emphasis on ATP-binding cassette transporter G2 (ABCG2) and serum in the medium. When the medium had no fetal bovine serum (FBS), ALA induced PpIX accumulation in a time- and ALA concentration-dependent manner. Inhibition of heme-synthesizing enzyme, ferrochelatase, by nitric oxide donor (Noc18) or deferoxamine resulted in a substantial increase in the cellular PpIX accumulation, whereas ABCG2 inhibition by fumitremorgin C or verapamil induced a slight PpIX increase. When the medium was added with FBS, cellular accumulation of PpIX stopped at a lower level with an increase of PpIX in the medium, which suggested PpIX efflux. ABCG2 inhibitors restored the cellular PpIX level to that of FBS(-) samples, whereas ferrochelatase inhibitors had little effects. Bovine serum albumin showed similar effects to FBS. Fluorescence microscopic observation revealed that inhibitors of ABC transporter affected the intracellular distribution of PpIX. These results indicated that ABCG2-mediated PpIX efflux was a major factor that prevented PpIX accumulation in cancer cells in the presence of serum. Inhibition of ABCG2 transporter system could be a new target for the improvement of photodynamic therapy.
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http://dx.doi.org/10.1007/s11010-011-0980-5DOI Listing
December 2011

Effect of risedronate on osteoblast differentiation, expression of receptor activator of NF-κB ligand and apoptosis in mesenchymal stem cells.

Basic Clin Pharmacol Toxicol 2011 Aug 16;109(2):78-84. Epub 2011 Mar 16.

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.

Nitrogen-containing bisphosphonates (BPs) are antiresorptive drugs used for the treatment of metabolic bone diseases. Bone marrow stromal cells such as mesenchymal stem cells (MSCs) and MSC-derived osteoblasts that originate from MSCs are known to regulate osteoclast differentiation and activation via the expression of receptor activator of NF-κB ligand (RANKL). Although the effects of nitrogen-containing BPs on osteoclasts and osteoblasts have been well investigated, their effects in MSCs have not been clarified. In this study, we investigated the effects of risedronate (RIS), a nitrogen-containing BP, on osteoblast differentiation, RANKL expression and apoptosis in human and rat MSCs. RIS suppressed the formation of mineralized nodules and mRNA expression of differentiation marker genes such as bone sialoprotein and osteocalcin in MSC-derived osteoblasts. The RANKL expression induced by 1,25-(OH)(2) vitamin D(3) was not affected by RIS in human MSC-derived osteoblasts. In addition, treatment with high-concentration RIS induced chromatin condensation, an apoptosis feature, in MSCs. RIS-induced chromatin condensation was suppressed by a pan-caspase inhibitor zVAD-FMK and a cell-permeable isoprenoid analogue geranylgeraniol. These results indicate that RIS suppressed osteoblast differentiation and induced caspase- and isoprenoid depletion-dependent apoptosis and suggest that the antiresorptive effect of RIS is not mediated by a decrease in the RANKL expression in MSC-derived osteoblasts.
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http://dx.doi.org/10.1111/j.1742-7843.2011.00685.xDOI Listing
August 2011

Oxidative stress enhances granulocytic differentiation in HL 60 cells, an acute promyelocytic leukemia cell line.

Free Radic Res 2010 Nov;44(11):1328-37

Pathology & Experimental Medicine, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama 700-8558, Japan.

This paper studied the effects of physiologically available oxidants on HL 60 differentiation induced by all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Hydrogen peroxide (15 μM) and taurine chloramine (200 μM) induced HL 60 differentiation, which was detected by CD11b expression and superoxide production. Cd11b and p67phox mRNA expression was also augmented by these oxidants. In contrast, reducing chemicals, such as dithiothreitol, 2,3-dimercapto-1-propanol and N-acetylcysteine inhibited CD11b expression. Notably, DMSO inhibited methionine sulfoxide reductase activity, induced heme oxygenase-1 (ho-1) mRNA and enhanced oxidant-induced cell death, which indicated that DMSO intensified oxidative stress. After the addition of oxidants, ho-1 expression preceded the cd11b expression. Vicinal dithiol-reactive phenylarsine oxide (50 nM) also increased CD11b expression induced by DMSO or ATRA. These observations suggested that oxidative stress enhanced granulocytic differentiation of HL 60 cells and that leukaemic cell differentiation was affected by cellular redox status.
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http://dx.doi.org/10.3109/10715762.2010.503757DOI Listing
November 2010

p66(Shc) has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism.

Lab Invest 2010 Dec 21;90(12):1718-26. Epub 2010 Jun 21.

Department of Molecular Surgery, Hokkaido University School of Medicine, Sapporo, Japan.

Liver regeneration involves complicated processes and is affected by various patho-physiological conditions. This study was designed to examine the molecular mechanisms underlying the aging-associated impairment of liver regeneration. Male C57BL/6J mice were used as young and aged mice (<10 weeks and >20 months old, respectively). These mice were subjected to 70% partial hepatectomy (PH). Liver regeneration and liver injury/stresses were evaluated chronologically after PH. Post-hepatectomy liver regeneration was markedly impaired in aged mice. Though the extent of hepatocyte proliferation in the regenerating liver was similar in aged and young mice, cell growth was absent in aged mice. Oxidative stress (OS) was observed immediately after hepatectomy, followed by marked apoptosis in aged mice. Signaling molecules regarding cell proliferation (mitogen-activated protein kinase, STAT3, p46/52(Shc)) and anti-oxidation (catalase, superoxide dismutase, Ref-1, glutathione peroxidase) were expressed/activated after hepatectomy in livers of both aged and young mice. Akt was not activated in aged-mouse liver, but its expression was similar to that in young mice. p66(Shc), known as an age-/oxidant-associated protein, was strongly phosphorylated. By knocking down p66(Shc), the impairment of liver regeneration was normalized. OS immediately after hepatectomy induced subsequent liver injury (apoptosis), and deletion of p66(Shc) suppressed both OS and hepatocyte apoptosis in the regenerating liver of aged mice. Though we need additional data in other animal models to fully understand the mechanism, p66(Shc) may have a pivotal function in the impairment of liver regeneration in aged mice by triggering OS and subsequent apoptosis. This data may provide a clue to understanding the mechanism underlying the association between aging and the impairment of liver regeneration.
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http://dx.doi.org/10.1038/labinvest.2010.119DOI Listing
December 2010

Forced expression of suppressor of cytokine signaling 3 in T cells protects the development of concanavalin A-induced hepatitis in mice.

Clin Immunol 2009 Dec 18;133(3):437-46. Epub 2009 Sep 18.

Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata, Okayama 700-8558, Japan.

T cells play central roles in liver diseases, but the regulatory mechanism by cytokine signaling is not well understood. In the present study, we explored the role of SOCS3 in T cells in concanavalin A (ConA)-induced hepatitis. Mice with T-cell-specific overexpression of SOCS3 (SOCS3-cTg) showed reduced hepatic damage and improved mice survival relative to the control, an event that was associated with decreased apoptotic signals Fas and pStat1. Expression of Th1-cytokines/chemokines was decreased in SOCS3-cTg liver with reduced expression of T-bet, a Th1-transcription factor. Flow cytometric analysis of the liver lymphocytes demonstrated that activated CD4(+) T cells, cytotoxic T cells and natural killer T cells were significantly decreased in SOCS3-cTg liver with decreased expression of perforin and granzyme B, injurious molecules for hepatocyte damage. These results suggest that forced expression of SOCS3 in T cells prevents ConA-induced liver injury by inhibiting several phases of Th1 responses.
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http://dx.doi.org/10.1016/j.clim.2009.08.015DOI Listing
December 2009

Mechanism of cell death by 5-aminolevulinic acid-based photodynamic action and its enhancement by ferrochelatase inhibitors in human histiocytic lymphoma cell line U937.

Cell Biochem Funct 2009 Dec;27(8):503-15

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Photodynamic therapy (PDT) for tumors is based on the tumor-selective accumulation of a photosensitizer, protoporphyrin IX (PpIX), followed by irradiation with visible light. However, the molecular mechanism of cell death caused by PDT has not been fully elucidated. The 5-aminolevulinic acid (ALA)-based photodynamic action (PDA) was dependent on the accumulation of PpIX, the level of which decreased rapidly by eliminating ALA from the incubation medium in human histiocytic lymphoma U937 cells. PDA induced apoptosis characterized by lipid peroxidation, increase in Bak and Bax/Bcl-xL, decrease in Bid, membrane depolarization, cytochrome c release, caspase-3 activation, phosphatidylserine (PS) externalization. PDT-induced cell death seemed to occur predominantly via apoptosis through distribution of PpIX in mitochondria. These cell death events were enhanced by ferrochelatase inhibitors. These results indicated that ALA-based-PDA induced apoptotic cell death through a mitochondrial pathway and that ferrochelatase inhibitors might enhanced the effect of PDT for tumors even at low concentrations of ALA.
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http://dx.doi.org/10.1002/cbf.1603DOI Listing
December 2009

Alpha-tocopheryl succinate induces rapid and reversible phosphatidylserine externalization in histiocytic lymphoma through the caspase-independent pathway.

Mol Cell Biochem 2010 Jan 26;333(1-2):137-49. Epub 2009 Jul 26.

Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama, 700-8558, Japan.

Phosphatidylserine (PS) externalization is a key feature of apoptotic cell death and plays an important role in clearance of apoptotic cells by phagocytes. PS externalization during apoptosis is generally an irreversible event mediated by caspase activation and is accompanied by other apoptotic events. We report here that an apoptosis inducer alpha-tocopheryl succinate (TOS) can induce PS externalization that is independent of apoptosis and reversible in the absence of fetal bovine serum (FBS) in histiocytic lymphoma U937 cells. In the presence of FBS, TOS induced PS externalization via a caspase-dependent mechanism accompanied by mitochondrial depolarization, cell shrinkage, increase of caspase-3 activity, and chromatin condensation. In contrast, in the absence of FBS, TOS induced the rapid PS externalization which was not accompanied by other apoptotic events. The PS externalization was reversible by removing TOS and was not involved in Ca(2+)-dependent scramblase activation and thiol oxidation of aminophospholipid translocase. A similar PS externalization was also induced by cholesteryl hemisuccinate (CS), the other succinate ester. These results suggested that the mechanism of TOS- and CS-induced PS externalization in the absence of FBS was different from it occurring during typical apoptosis.
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http://dx.doi.org/10.1007/s11010-009-0214-2DOI Listing
January 2010

Beneficial Effects of Fermented Green Tea Extract in a Rat Model of Non-alcoholic Steatohepatitis.

J Clin Biochem Nutr 2009 May 25;44(3):239-46. Epub 2009 Apr 25.

Anti-Aging Food Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Okayama 700-8558, Japan.

Oxidative stress is frequently considered as a central mechanism of hepatocellular injury in non-alcoholic steatohepatitis (NASH). The aim of this study was to investigate the effects of fermented green tea extracts (FGTE) on NASH. Rats were fed a choline-deficient high-fat diet for 4 weeks to nutritionally generate fatty livers. NASH was induced chemically by oxidative stress using repeated intraperitoneal injections of nitrite. Rats with NASH developed steatohepatitis and liver fibrosis after 6-week of such treatment. At 10 weeks, blood and liver samples were collected from anesthetized animals and assessed for extent of OS injury and effects of FGTE, by biochemical, histological and histochemical analyses. FGTE reduced serum levels of liver enzymes, lipid peroxidation and production of mitochondrial reactive oxygen species. In addition, FGTE showed inhibition of progressions of cirrhosis. Our findings suggest that our FGTE have strong radical scavenging activity and may be beneficial in the prevention of NASH progression.
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http://dx.doi.org/10.3164/jcbn.08-256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675021PMC
May 2009

Immunohistochemical staining of liver grafts with a monoclonal antibody against HCV-Envelope 2 for recurrent hepatitis C after living donor liver transplantation.

J Gastroenterol Hepatol 2009 Apr;24(4):574-80

Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata, Okayama 700-8558, Japan.

Aim: We evaluated the expression of hepatitis C virus (HCV) antigen on liver grafts by immunohistochemical staining (IHS) using IG222 monoclonal antibody (mAb) against HCV-envelope 2 (E2).

Methods: The study material was 84 liver biopsy specimens obtained from 28 patients who underwent living donor liver transplantation (LDLT) for HCV infection. The biopsy samples were examined histopathologically, and by IHS using IG222 mAb against HCV-E2. Serum HCV-RNA level was measured in all patients. The IHS grades were compared among the three groups classified according to the time elapsed from LDLT (at 1-30, 31-179 and > or =180 days post-LDLT) and among four post-transplant conditions, including acute cellular rejection (ACR).

Results: Immunoreactivity to IG222 was detected in 78.6% of the specimens obtained during the first month after LDLT, and there were no significant differences on the IHS grades between the three groups classified according to the time elapsed from LDLT. The IHS grades were significantly stronger in definite recurrent HCV (n = 12) and probable recurrent HCV (n = 7) than in definite ACR (n = 7) and other complications (n = 8). There were no significant differences in serum HCV-RNA levels among the four post-transplant conditions. There was no significant correlation between the IHS grades using IG222 mAb and serum HCV-RNA levels when data of 84 liver biopsy specimens were analyzed.

Conclusions: Constant HCV-E2 expression was observed in liver biopsy specimens obtained 1 month or longer. The strong HCV-E2 expression on liver grafts were associated with recurrent hepatitis C after LDLT, but the serum HCV-RNA levels were not.
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http://dx.doi.org/10.1111/j.1440-1746.2008.05638.xDOI Listing
April 2009

Taurine chloramine: a possible oxidant reservoir.

Adv Exp Med Biol 2009 ;643:451-61

Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Taurine is abundant in polymorphonuclear leukocytes (PMNs) where it reacts with PMN-derived hypochlorous acid to form taurine chloramine (Tau-NHCl), a substance that does not readily cross the cell membrane. When PMNs were stimulated in PBS lacking taurine, extracellular oxidant concentration was low, but the concentration increased 3-4 fold when 15 mM taurine was added, indicating that taurine lowers oxidant levels inside the cell. When Tau-NHCl was added to Jurkat cells in suspension, its half life was about 75 min. In contrast, membrane-permeable ammonia mono-chloramine (NH2Cl) has a half life of only 6 min. Accordingly, NH2Cl oxidizes cytosolic proteins, such as IkappaB, and inhibits NF-kappaB activation, whereas Tau-NHCl exhibits no comparable effect. However, when NH4+ was added to the medium, Tau-NHCl oxidizes IkappaB and inhibits NF-kappaB activation, probably through oxidant transfer to NH4+ leading to NH2Cl formation. These results indicate that Tau-NHCl can serve as an oxidant reservoir, exhibiting either delayed oxidant effects or acting as an oxidant at a distant site.
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http://dx.doi.org/10.1007/978-0-387-75681-3_47DOI Listing
March 2009

Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine.

Leuk Res 2009 Jan 20;33(1):151-8. Epub 2008 Aug 20.

Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama 700-8558, Japan.

Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondria. Within 10min of NH(2)Cl treatment, c-Jun N-terminal kinase (JNK) activation and elevation of cytosolic Ca(2+) were observed. JNK inhibitors (SP600125 or JNK inhibitor VIII) significantly suppressed the apoptosis as well as caspase cleavage and cytochrome c release. In contrast, Ca(2+) chelation by EGTA+acetoxymethyl-EGTA had no effects on apoptosis. Our results indicated that JNK activation contributed most importantly to the NH(2)Cl-induced apoptosis.
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http://dx.doi.org/10.1016/j.leukres.2008.07.009DOI Listing
January 2009
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