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1.
BMJ Open ; 13(9): e073559, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37669839

ABSTRACT

OBJECTIVES: The aim of this study was to clarify and compare the socioeconomic backgrounds of medical students with those of other health professions and non-health faculty students in an era of increasing inequity in Japanese society. DESIGN: This was a quantitative nationwide study. Data were collected by a cross-sectional web-based anonymous questionnaire. SETTING: Data from years 3 and 4 medical, health professions and non-health faculty students across Japan were collected in 2021. PARTICIPANTS: Participants were 1991 students from medical schools, 224 from dental, 419 from pharmacy, 326 from nursing, 144 from other health professions and 207 from non-health faculties. RESULTS: The proportion of high-income families (>18 million yen: ca. US$140 000) among medical students was 25.6%, higher than that of pharmacy (8.7%) and nursing students (4.1%) (p<0.01). One-third of medical students had a physician parent, more common than in non-medical students (p<0.01). Students who only applied to public medical schools and a regional quota 'Chiiki-waku' students with scholarship had lower family income and physician parents compared with those who applied to private medical schools (p<0.01), but they still had higher physician parents compared with non-medical students (p<0.01). Logistic regression revealed that having a physician parent (p<0.01), aspiring to the present profession during elementary school (p<0.01) and private upper secondary school graduation (p<0.01) predicted the likelihood of studying medicine. There were regional differences of backgrounds among medical students, and 80% of medical students with urban backgrounds intended to work in urban localities after graduation. CONCLUSIONS: This study provides evidence that medical students in Japan hail from urban and higher income classes and physicians' families. This finding has implications for the health workforce maldistribution in Japan. Widening the diversity of medical students is essential for solving physician workforce issues and meeting broad healthcare needs.


Subject(s)
Schools, Medical , Students, Medical , Humans , Cross-Sectional Studies , Japan , Income , Internet
2.
Surg Today ; 52(8): 1212-1217, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35091847

ABSTRACT

PURPOSE: To analyze the effectiveness of incorporating virtual reality (VR) in lectures on esophageal and mediastinal anatomy and surgical procedures for medical students at Gifu University during clinical training. METHODS: We divided medical students participating in clinical training, randomly, into two groups of 30 students each: those who received a lecture using 3D images (3D group) and those who received a lecture using VR images (VR group). Four days after the lecture, the students completed a written test to allow us to evaluate their comprehension, and a questionnaire on their opinion of the lectures. RESULTS: Based on the results of the written test, the VR group achieved better understanding of computed tomography (CT) images (p = 0.0001) and better interpretation of surgical images (p = 0.0163). However, there was no difference in the scores for spatial recognition and general problems. The questionnaire revealed that the VR group became more interested in mediastinal anatomy (p = 0.0165) and surgery (p = 0.0135). CONCLUSIONS: Our findings suggest that VR enhances the learning process. The lecture incorporating the VR experience was more effective than the traditional lecture for promoting an understanding of CT images and interpretation of surgical images; thus, it enhances the learning experience for medical students studying surgery.


Subject(s)
Education, Medical, Undergraduate , Students, Medical , Virtual Reality , Education, Medical, Undergraduate/methods , Humans , Imaging, Three-Dimensional , Learning
4.
BMC Med Educ ; 20(1): 419, 2020 Nov 10.
Article in English | MEDLINE | ID: mdl-33167945

ABSTRACT

BACKGROUND: Students who fail to pass the National Medical Licensure Examination (NMLE) pose a huge problem from the educational standpoint of healthcare professionals. In the present study, we developed a formula of predictive pass rate (PPR)" which reliably predicts medical students who will fail the NMLE in Japan, and provides an adequate academic support for them. METHODS: Six consecutive cohorts of 531 medical students between 2012 and 2017, Gifu University Graduate School of Medicine, were investigated. Using 7 variables before the admission to medical school and 10 variables after admission, we developed a prediction formula to obtain the PPR for the NMLE using logistic regression analysis. In a new cohort of 106 medical students in 2018, we applied the formula for PPR to them to confirm the capability of the PPR and predicted students who will have a strong likelihood of failing the NMLE. RESULTS: Medical students who passed the NMLE had the following characteristics: younger age at admission, graduates of high schools located in the surrounding area, high scores in the graduation examination and in the comprehensive computer-based test provided by the Common Achievement Test Organization in Japan. However, total score of examination in pre-clinical medical sciences and Pre-CC OSCE score in the 4th year were not correlated with the PPR. Ninety-one out of 531 students had a strong likelihood of failing the NMLE between 2012 and 2017 and 33 of these 91 students failed NMLE. Using the PPR, we predicted 12 out of 106 students will have a strong likelihood of failing the NMLE. Actually, five of these 12 students failed NMLE. CONCLUSIONS: The PPR can be used to predict medical students who have a higher probability of failing the NMLE. This prediction would enable focused support and guidance by faculty members. Prospective and longitudinal studies for larger and different cohorts would be necessary.


Subject(s)
Licensure, Medical , Students, Medical , Educational Measurement , Humans , Japan , Prospective Studies , School Admission Criteria , Schools, Medical
5.
BMC Med Educ ; 20(1): 67, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32143611

ABSTRACT

BACKGROUND: Clinical decision-making skills are essential for providing high-quality patient care. To enhance these skills, many institutions worldwide use case-based learning (CBL) as an educational strategy of pre-clinical training. However, to date, the influence of different learning modalities on students' clinical decision-making processes has not been fully explored. This study aims to explore the influence of video and paper case modalities on the clinical decision-making process of midwifery students during CBL. METHODS: CBL involving a normal pregnant woman was provided for 45 midwifery students. They were divided into 12 groups; six groups received the video modality, and six groups received the paper modality. Group discussions were video-recorded, and focus groups were conducted after the CBL. Transcripts of the group discussions were analysed in terms of their interaction patterns, and focus groups were thematically analysed based on the three-stage model of clinical decision-making, which includes cue acquisition, interpretation, and evaluation/decision-making. RESULTS: The students in the video groups paid more attention to psychosocial than biomedical aspects and discussed tailored care for the woman and her family members. They refrained from vaginal examinations and electric fetal heart monitoring. Conversely, the students in the paper groups paid more attention to biomedical than psychosocial aspects and discussed when to perform vaginal examinations and electric fetal heart monitoring. CONCLUSION: This study clarified that video and paper case modalities have different influences on learners' clinical decision-making processes. Video case learning encourages midwifery students to have a woman- and family-centred holistic perspective of labour and birth care, which leads to careful consideration of the psychosocial aspects. Paper case learning encourages midwifery students to have a healthcare provider-centred biomedical perspective of labour and childbirth care, which leads to thorough biomedical assessment.


Subject(s)
Clinical Decision-Making , Learning , Midwifery/education , Video Recording , Adult , Female , Focus Groups , Humans , Pregnancy , Qualitative Research , Young Adult
6.
Pediatr Int ; 62(5): 549-555, 2020 May.
Article in English | MEDLINE | ID: mdl-31883414

ABSTRACT

BACKGROUND: The purpose of this study was to identify the attributes of good clinical teachers in pediatrics (CTPs) in Japan, and to elucidate pediatricians and pediatric trainees' perceptions of these attributes. METHODS: The attributes of good CTPs were identified qualitatively by conducting a thematic analysis of questionnaires answered by board-certified pediatricians and pediatric trainees. The attributes identified were rated quantitatively by a large number of participants in both groups. RESULTS: Forty-eight individual attributes of good CTPs were identified, which were classified into three domains: personal, pediatrician, and teacher. The three domains and most of the attributes were consistent with previous studies. However, a few additional attributes, including "is kind/thoughtful toward others" and "defends trainees", which may be unique to pediatricians in Japan, were identified. Significant differences in the pediatricians' and trainees' perceptions of these attributes were elucidated: The differences were most noticeable for teacher attributes and least for personal attributes. CONCLUSION: Although most of the identified attributes of good CTPs in our study appear to be universal, there were significant differences in the pediatricians' and trainees' perceptions of good CTPs, especially in relation to teacher attributes. Our study provides additional bases for good CTPs and future faculty development, for enhanced pediatric clinical education.


Subject(s)
Education, Medical/methods , Pediatricians/education , Pediatrics/education , Female , Humans , Japan , Male , Middle Aged , Pediatricians/psychology , Personality , Students, Medical/psychology , Surveys and Questionnaires , Teaching
7.
Pediatr Int ; 62(5): 542-548, 2020 May.
Article in English | MEDLINE | ID: mdl-31834972

ABSTRACT

BACKGROUND: While it is well known that the cognitive apprenticeship is an effective workplace-based teaching approach for clinical teachers, the effects of faculty development (FD) have not been analyzed from that perspective. The purpose of this study was to investigate self-assessment by clinical teachers of their educational perceptions and behaviors after a FD program using the cognitive apprenticeship model. METHODS: Board-certified pediatricians who participated in a 3-day FD program on practical clinical teaching were asked to complete questionnaires. Fifty participants completed two questionnaires prior to and 3 and 6 months after the FD program: the first was on the participants' general perceptions and behaviors in relation to their own clinical education and the second was a self-assessment using the Maastricht Clinical Teaching Questionnaire (MCTQ) that was developed based on the cognitive apprenticeship model. RESULTS: The general survey demonstrated that 78% of the participants experienced positive changes in their educational perceptions 6 months after FD. Self-assessment using the MCTQ showed that the scores in the categories of "articulation," "exploration," and "safe learning environment" remained significantly improved 6 months after the FD program. CONCLUSIONS: The participants' self-perceived improvement in behaviors was sustainable for 6 months after participation the FD program. The results of the MCTQ show that through their experiences in the FD program, the participants seemingly transformed their clinical teaching to become interactive facilitators, encouraging self-directed learning. Our results also suggest that the MCTQ can be used for self-assessment of clinical teachers and to enhance the effectiveness of the FD program.


Subject(s)
Education, Medical/methods , Faculty, Medical/education , Pediatrics/education , Program Development , Adult , Cognition , Female , Humans , Learning , Male , Middle Aged , Models, Educational , Program Evaluation , Self-Assessment , Surveys and Questionnaires , Teaching
8.
BMC Med Educ ; 13: 158, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24289490

ABSTRACT

BACKGROUND: Problem-based learning (PBL) involves discussions among students who resolve loosely-structured problems to facilitate learning. In the PBL curriculum, faculty tutors are employed as facilitators for small groups of students. Because of lack of time and staff shortage, the effectiveness of tutorless PBL has been discussed as an alternate option. METHODS: Sessions in which tutored and tutorless PBL groups are mixed were presented by 1st-year medical students, who experienced both tutored and tutorless groups alternately in the two sessions of a year. To examine the effectiveness of tutored and tutorless PBL, written examination scores (WES) and self-contentment scores (SCS) were statistically analysed. RESULTS: WES averages did not significantly differ between the tutored and tutorless groups; however, a significantly greater variation was observed in WES in the tutorless group. SCS averages tended to be higher in the tutored PBL than in tutorless PBL groups. CONCLUSIONS: Students in these tutorless PBL groups performed well in their written examinations, whereas those in the tutored PBL groups, achieved this and reported better self-contentment with their learning experience. Tutorless PBL sessions were considered to be comparable to tutored PBL sessions at least in the early stages.


Subject(s)
Education, Medical/methods , Problem-Based Learning/methods , Teaching/methods , Educational Measurement , Faculty, Medical , Group Processes , Humans
9.
Sci Rep ; 3: 1829, 2013.
Article in English | MEDLINE | ID: mdl-23670402

ABSTRACT

Domain walls, nanoscale transition regions separating oppositely oriented ferromagnetic domains, have significant promise for use in spintronic devices for data storage and memristive applications. The state of these devices is related to the wall position and thus rapid operation will require a controllable onset of domain wall motion and high speed wall displacement. These processes are traditionally driven by spin transfer torque due to lateral injection of spin polarized current through a ferromagnetic nanostrip. However, this geometry is often hampered by low maximum wall velocities and/or a need for prohibitively high current densities. Here, using time-resolved magnetotransport measurements, we show that vertical injection of spin currents through a magnetic tunnel junction can drive domain walls over hundreds of nanometers at ~500 m/s using current densities on the order of 6 MA/cm(2). Moreover, these measurements provide information about the stochastic and deterministic aspects of current driven domain wall mediated switching.


Subject(s)
Magnetics , Magnets/chemistry , Nanotechnology , Torque , Computer Simulation , Information Storage and Retrieval , Spin Labels
10.
BMC Neurosci ; 14: 4, 2013 Jan 07.
Article in English | MEDLINE | ID: mdl-23289926

ABSTRACT

BACKGROUND: Domoic acid (DA) is an excitatory amino acid analogue of kainic acid (KA) that acts via activation of glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in vitro. We have reported that WDR35, a WD-repeat protein, may mediate apoptosis in several animal models. In the present study, we administered DA to rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS) to identify and quantify DA in the brains of the rats and performed histological examinations of the hippocampus. We further investigated the potential involvement of glutamate receptors, ROS, p38 MAPK, and WDR35 in DA-induced toxicity in vivo. RESULTS: Our results showed that intraperitoneally administered DA was present in the brain and induced neurodegenerative changes including apoptosis in the CA1 region of the hippocampus. DA also increased the expression of WDR35 mRNA and protein in a dose- and time-dependent manner in the hippocampus. In experiments using glutamate receptor antagonists, the AMPA/KA receptor antagonist NBQX significantly attenuated the DA-induced increase in WDR35 protein expression, but the NMDA receptor antagonist MK-801 did not. In addition, the radical scavenger edaravone significantly attenuated the DA-induced increase in WDR35 protein expression. Furthermore, NBQX and edaravone significantly attenuated the DA-induced increase in p38 MAPK phosphorylation. CONCLUSION: In summary, our results indicated that DA activated AMPA/KA receptors and induced ROS production and p38 MAPK phosphorylation, resulting in an increase in the expression of WDR35 in vivo.


Subject(s)
Gene Expression Regulation/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Kainic Acid/analogs & derivatives , MAP Kinase Signaling System/drug effects , Neuromuscular Depolarizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Repetitive Sequences, Amino Acid/genetics , Animals , Apoptosis/drug effects , Excitatory Amino Acid Antagonists/pharmacology , In Situ Nick-End Labeling , Kainic Acid/pharmacology , Male , Proteins/genetics , Proteins/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry
11.
BMC Neurosci ; 13: 149, 2012 Dec 10.
Article in English | MEDLINE | ID: mdl-23227925

ABSTRACT

BACKGROUND: Bupivacaine-induced neurotoxicity has been shown to occur through apoptosis. Recently, bupivacaine was shown to elicit reactive oxygen species (ROS) production and induce apoptosis accompanied by activation of p38 mitogen-activated protein kinase (MAPK) in a human neuroblastoma cell line. We have reported that WDR35, a WD40-repeat protein, may mediate apoptosis through caspase-3 activation. The present study was undertaken to test whether bupivacaine induces apoptosis in mouse neuroblastoma Neuro2a cells and to determine whether ROS, p38 MAPK, and WDR35 are involved. RESULTS: Our results showed that bupivacaine induced ROS generation and p38 MAPK activation in Neuro2a cells, resulting in apoptosis. Bupivacaine also increased WDR35 expression in a dose- and time-dependent manner. Hydrogen peroxide (H(2)O(2)) also increased WDR35 expression in Neuro2a cells. Antioxidant (EUK-8) and p38 MAPK inhibitor (SB202190) treatment attenuated the increase in caspase-3 activity, cell death and WDR35 expression induced by bupivacaine or H(2)O(2). Although transfection of Neuro2a cells with WDR35 siRNA attenuated the bupivacaine- or H(2)O(2)-induced increase in expression of WDR35 mRNA and protein, in contrast to our previous studies, it did not inhibit the increase in caspase-3 activity in bupivacaine- or H(2)O(2)-treated cells. CONCLUSIONS: In summary, our results indicated that bupivacaine induced apoptosis in Neuro2a cells. Bupivacaine induced ROS generation and p38 MAPK activation, resulting in an increase in WDR35 expression, in these cells. However, the increase in WDR35 expression may not be essential for the bupivacaine-induced apoptosis in Neuro2a cells. These results may suggest the existence of another mechanism of bupivacaine-induced apoptosis independent from WDR35 expression in Neuro2a cells.


Subject(s)
Anesthetics, Local/pharmacology , Apoptosis/drug effects , Bupivacaine/pharmacology , Proteins/metabolism , Anesthetics, Local/antagonists & inhibitors , Animals , Antioxidants/pharmacology , Bupivacaine/antagonists & inhibitors , Caspase 3/metabolism , Cell Death/drug effects , Cell Line, Tumor , Cytoskeletal Proteins , Dose-Response Relationship, Drug , Drug Interactions , Enzyme Inhibitors/pharmacology , Ethylenediamines/pharmacology , Gene Expression/drug effects , Hydrogen Peroxide/antagonists & inhibitors , Hydrogen Peroxide/pharmacology , Imidazoles/pharmacology , Intracellular Signaling Peptides and Proteins , Mice , Organometallic Compounds/pharmacology , Oxidants/antagonists & inhibitors , Oxidants/pharmacology , Pyridines/pharmacology , RNA, Small Interfering/pharmacology , Reactive Oxygen Species/metabolism , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/biosynthesis
12.
World J Surg Oncol ; 10: 99, 2012 May 31.
Article in English | MEDLINE | ID: mdl-22651848

ABSTRACT

BACKGROUND: Nitric oxide (NO) has been reported to be a key mediator in hepatocyte proliferation during liver regeneration. NO is the oxidative metabolite of L-arginine, and is produced by a family of enzymes, collective termed nitric oxide synthase (NOS). Thus, administration of L-arginine might enhance liver regeneration after a hepatectomy. Another amino acid, L-glutamine, which plays an important role in catabolic states and is a crucial factor in various cellular and organ functions, is widely known to enhance liver regeneration experimentally. Thus, the present study was undertaken to evaluate the effects of an L-arginine supplement on liver regeneration, and to compared this with supplementation with L-glutamine and L-alanine (the latter as a negative control), using a rat partial hepatectomy model. METHODS: Before and after a 70% hepatectomy, rats received one of three amino acid solutions (L-arginine, L-glutamine, or L-alanine). The effects on liver regeneration of the administered solutions were examined by assessment of restituted liver mass, staining for proliferating cell nuclear antigen (PCNA), and total RNA and DNA content 24 and 72 hours after the operation. RESULTS: At 72 hours after the hepatectomy, the restituted liver mass, the PCNA labeling index and the DNA quantity were all significantly higher in the L-arginine and L-glutamine groups than in the control. There were no significant differences in those parameters between the L-arginine and L-glutamine groups, nor were any significant differences found between the L-alanine group and the control. CONCLUSION: Oral supplements of L-arginine and L-glutamine enhanced liver regeneration after hepatectomy in rats, suggesting that an oral arginine supplement can clinically improve recovery after a major liver resection.


Subject(s)
Arginine/administration & dosage , Hepatectomy , Liver Diseases/surgery , Liver Regeneration/drug effects , Administration, Oral , Alanine/administration & dosage , Animals , DNA/genetics , Glutamine/administration & dosage , Immunoenzyme Techniques , Male , Polymerase Chain Reaction , Proliferating Cell Nuclear Antigen/metabolism , RNA/genetics , Rats , Rats, Wistar
13.
Hepatol Res ; 42(7): 696-705, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22409254

ABSTRACT

AIM: Lipopolysaccharide (LPS) causes apoptosis of hepatocytes, which is probably mediated by inflammatory substances released from Kupffer cells (KCs). Recently, we have reported that naofen, a newly found intracellular WD40-repeat protein, has a role in inducing the apoptosis in HEK293 cells. Hence, the present study was undertaken to investigate a role of naofen in the LPS-induced apoptosis of rat hepatocytes. METHODS: Rats were treated with i.v. injections of LPS, and livers were extirpated to evaluate expression of naofen and apoptosis. In in vitro experiments, hepatocytes and KCs were separately isolated from rat livers. The incubation medium for KCs treated with LPS (KC-CM) was used for hepatocyte culture. RESULTS: Intravenous injections of LPS enhanced the expression of naofen in the livers. Livers showed terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive staining, and elevated caspase-3 activity. In isolated KCs or hepatocytes, LPS hardly affected naofen expression and caspase-3 activity, whereas incubation of hepatocytes with KC-CM enhanced both naofen expression and caspase-3 activation. Transfection of hepatocyte with naofen siRNA prevented such effects of KC-CM, and clearly eliminated KC-CM-induced reduction of Bcl-2 and Bcl-xL. In contrast, overexpression of naofen in hepatocytes downregulated Bcl-2 and Bcl-xL, released cytochrome c from mitochondria, and activated caspase-3. CONCLUSION: These results indicate that LPS may induce the hepatic apoptosis in association with enhanced naofen expression, and that naofen may mediate the activation of caspase-3 through downregulating the Bcl-2 and Bcl-xL expression, and releasing cytochrome c from mitochondria to cytoplasm.

14.
Hepatol Res ; 40(6): 613-21, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20412328

ABSTRACT

AIM: The present study was undertaken to evaluate the effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, on carbon tetrachloride (CCl(4))-induced cirrhosis. METHODS: Rats were treated with hypodermic injections of CCl(4) twice a week to induce the hepatic cirrhosis, and given drinking water containing HTHQ or solvent. Primary cultures of rat hepatocytes were performed to evaluate the effects of HTHQ on the expression of inducible nitric oxide synthase (iNOS). RESULTS: Masson's staining of rat livers showed fibrosis around pseudo-lobules in the CCl(4) group, the lesions being reduced in the CCl(4) HTHQ group. Increases in liver tissue hydroxyproline and alpha(1)(I) collagen, alpha-smooth muscle actin and iNOS induced by CCl(4), were also markedly diminished by HTHQ. Furthermore, both HTHQ and vitamin E attenuated interleukin-1beta-induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10-times higher than that of vitamin E. CONCLUSION: HTHQ may inhibit development of hepatic cirrhosis in rats, more potently than vitamin E, by inhibiting the iNOS expression in hepatocytes. Because vitamin E has a radical scavenging action, roles of NO and peroxynitrite will be discussed in the effects of HTHQ on the fibrosis.

15.
Clin Exp Nephrol ; 14(3): 205-12, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20224876

ABSTRACT

BACKGROUND: Hyperglycemia/high glucose may induce apoptosis in diabetic kidney, but the mechanism is not fully understood. Naofen was found as a Shiga toxin (Stx)-2-related protein. Based on renal dysfunction in infection with Stx-producing Escherichia coli and on participation of naofen in apoptosis of human embryonic kidney cells, the present study was undertaken to investigate the mechanism of renal dysfunction in diabetes mellitus with particular reference to naofen. METHODS: In in vivo studies utilizing streptozotocin (STZ)-induced diabetic rats, and also in in vitro cultured rat kidney epithelial (NRK52E) cells, naofen messenger RNA (mRNA) and protein expressions were analyzed. Naofen mRNA location in diabetic kidney was studied by in situ hybridization. Apoptosis was assessed by caspase-3 activity assay. RESULTS: Rat diabetic kidney showed significant increases in caspase-3 activities and naofen mRNA. Naofen was mainly observed at both proximal and distal urinary tubules. Incubation of NRK52E cells in high glucose medium resulted in elevated naofen mRNA expression, whereas neither interleukin-1, interleukin-6, nor tumor necrosis factor-alpha elicited such action. Moreover, treatment of NRK52E cells with naofen small interfering RNA (siRNA) inhibited naofen mRNA expression induced by high glucose and blocked the increase in caspase-3 activity. CONCLUSIONS: These data suggest that naofen expression may be upregulated by hyperglycemia, with possible correlation to apoptosis of tubular epithelial cells and thereby to diabetic nephropathy.


Subject(s)
Proteins/genetics , Animals , Apoptosis/physiology , Caspase 3/genetics , Cell Line , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/physiopathology , Epithelial Cells/metabolism , Hyperglycemia/metabolism , Kidney/physiopathology , Kidney Tubules/pathology , Male , RNA, Messenger/metabolism , Rats , Rats, Wistar
16.
Biochem Biophys Res Commun ; 394(1): 153-7, 2010 Mar 26.
Article in English | MEDLINE | ID: mdl-20193664

ABSTRACT

Naofen has recently been identified from the rat brain/spinal cord cDNA library as a substance reactive against an anti-shigatoxin (Stx)-2 antibody. Naofen mRNA is composed of 4620 nucleotides and encodes 1170 amino acids. Naofen contains four WD-repeat domains in its N-terminus and is ubiquitously distributed in many tissues of the rat. Tumor necrosis factor (TNF)-alpha enhanced the expression of naofen mRNA in HEK293 cells in a dose-dependent manner. Furthermore, naofen siRNA, which predominantly knocked down the expression of naofen mRNA, significantly reduced both TNF-alpha-induced caspase-3 activation and apoptosis in HEK293 cells. Overexpression of naofen in HEK293 cells (FLAG-NF) spontaneously induced caspase -3 activation and apoptosis, and showed extremely high susceptibility to TNF-alpha-induced apoptosis. These results indicated that naofen may function as a novel modulator activating caspase-3, and promoting TNF-alpha-stimulated apoptosis.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis , Proteins/metabolism , Animals , Apoptosis Regulatory Proteins/genetics , Caspase 3/biosynthesis , Cell Line , Enzyme Activation , Humans , Proteins/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Tissue Distribution , Tumor Necrosis Factor-alpha/pharmacology , Tumor Necrosis Factor-alpha/physiology
17.
Eur J Pharmacol ; 587(1-3): 285-90, 2008 Jun 10.
Article in English | MEDLINE | ID: mdl-18472094

ABSTRACT

Naofen (GenBank accession no. EF613262), a newly found intracellular protein in the WD-repeat-2 protein family, has been cloned as an anti-verotoxin II antibody immunoreactive substance, and the nucleotide- and amino acid-sequences have been clarified. The present study was undertaken to evaluate the roles of naofen especially in carbon tetrachloride (CCl4-induced cirrhosis model of rats, also in partial hepatectomy. Naofen mRNA expressions were observed from the early phases of cirrhosis development and during regenerative phases after partial hepatectomy, more remarkable in the former. Naofen immunoreactive fragments located in the vascular endothelial cells and peri-vascular spaces in normal livers especially in Glisson's areas, being strongly stained in the connective tissues 8 weeks after starting CCl4-injections, besides in the cytoplasm of hepatocytes in pseudo-lobules. In contrast, partial hepatectomy caused a small increase of naofen expressions in the whole hepatocytes, and significantly in the endothelial cells of portal veins and hepatic arterioles. Furthermore, in parallel to the degree of naofen mRNA and protein expressions, the rates of double-nuclei cells to total hepatocytes in the Glisson's areas increased in both cirrhosis and partial hepatectomy, suggesting a relationship between naofen expression and mitosis. In in-vitro studies with cell lines, vascular endothelial growth factor, a cell proliferation stimulant, increased the naofen mRNA expressions in HepG(2) cell lines, whereas paclitaxel, a cytotoxic anti-cancer drug, diminished them in NRK52E, both concentration-dependently. These results indicated that naofen immunoreactive fragments play an important role in the cell proliferation, relevant for analyzing the regenerative phases during cirrhosis developments and after partial hepatectomy.


Subject(s)
Carbon Tetrachloride Poisoning/pathology , Cell Proliferation , Liver Cirrhosis, Experimental/pathology , Proteins/physiology , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Cell Count , Cell Line , Cells, Cultured , Hepatectomy , Hepatocytes/metabolism , Humans , Immunohistochemistry , In Situ Hybridization , Kinetics , Liver/metabolism , Liver Cirrhosis, Experimental/chemically induced , Male , Mitosis/physiology , Paclitaxel/pharmacology , Proteins/genetics , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Vascular Endothelial Growth Factor A/biosynthesis
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