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    Osteoclasts are multinucleated cells of hematopoietic origin which are unique in their ability to resorb bone. Osteoclasts are generated from myeloid progenitors through a progression that involves the fusion of mononuclear precursor cells. The identification of RANK-RANKL signaling as the main signal regulating osteoclast differentiation was a major breakthrough in the bone biology field. In addition remarkable discoveries have been made to broaden the knowledge of the molecular mechanisms of osteoclast formation and differentiation. Despite the vital requirement of osteoclasts in bone modeling and remodeling‚ bone-related conditions like osteoporosis, Paget's disease and rheumatoid arthritis where accelerated bone resorption takes place pose a major socioeconomic burden to the society. Hence, a better understanding of the pathways leading to osteoclast differentiation is vital in successfully managing such diseases. This is an attempt to give a birds-eye-view of the players in osteoclast formation and differentiation in a brief and concise manner.departmental bulletin pape

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    Calcium alginate gel has some unique properties, such as the capability to keep the drugs, bioadhesiveness, safety, and low cost. The purpose of this study is to determine whether calcium alginate gel can be used as a matrix of electrodes for iontophoresis (IOP). We measured the concentration of lidocaine transported from calcium alginate gels with various concentrations of alginic acid using an in vitro experimental cell with square-wave alternating current (AC) application. Temperature and pH changes were also determined during AC-IOP. The results revealed that lidocaine was released from calcium alginate gels at concentrations nearly 1.71-fold larger at 5 V, 60 min after AC application than in the case of passive diffusion. Lidocaine transport depended on the alginic acid concentration in the gels. Although there were slight increases in temperature and pH, chemical and thermal burns were not severe enough to be a concern. In conclusion, the calcium alginate gel can be used as a possible matrix for IOP electrodes.departmental bulletin pape

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    In order to rapidly judge the response to intravenous tissue plasminogen activator (IV tPA) treatment, we retrospectively analyzed clinical data, such as MRI diffusion-weighted images (DWI), and treatment outcomes in 73 patients who developed anterior circulation disorders. The patients with favorable outcomes (modified Rankin Scale [mRS]: 2 or less) at discharge accounted for 32.9%. In these patients, the National Institutes of Health Stroke Scale (NIHSS) value, DWI Alberta Stroke Programme Early CT Score (ASPECTS), and the incidence of large artery (internal carotid artery [ICA]/sphenoidal segment of the middle cerebral artery [M1]) occlusion at their hospital visit were lower, higher, and lower, respectively (all P < 0.05 in univariate analysis). Multivariate analysis showed significant differences in DWI ASPECTS and the incidence of large artery occlusion. A DWI ASPECTS of at least 8 was found to be predictive of favorable outcomes. However, subclass analysis in the group with a DWI ASPECTS of 8 or higher predicting favorable outcome revealed 13 patients (41.9%) with unfavorable (mRS, 3-6) outcome. The factor associated with unfavorable outcomes is ICA occlusion. The combination of DWI ASPECTS and MRA appeared to be useful for predicting outcomes of IV tPA.departmental bulletin pape

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    We introduce a new method of external chest compression (ECC), an essential part of cardiopulmonary resuscitation, using a thumb and index finger method (TIFM) on infants, and compares, this with two standard methods of the two finger method (TFM) and the two-thumb encircling hands method (TTEM). Sixty trained PALS (Pediatric Advanced Life Support) providers were randomly assigned into three groups and provided one-rescuer ECC for a period of five continuous minutes. Results without coaching or feedback were recorded on a recording CPR simulator (Laerdal, Inc). ECC was performed according to the BLS recommendations of the International Liaison Committee on Resuscitation (ILCOR). The quality of ECC in the TFM group deviated considerably from guideline recommendations. The same parameters in the TTEM and new TIFM groups during this study were in accordance with the parameters recommended by the guidelines. Thus, our new TIFM technique of chest compression, in infants was shown to be better than the currently TFM, especially for achieving adequate compression depth and avoiding fatigue, and is equally as effective as the TTEM. We propose this new method (TIFM) should be considered as the method of choice in single rescuer situations.departmental bulletin pape

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    The aim of this study was to investigate the clinical outcome of removable partial dentures (RPDs) designed to minimize denture mobility during function. Using archived files of the undergraduate program between 2003 and 2005 at Tokyo Medical and Dental University, a list of 169 patients treated with 184 RPDs was created. The RPDs had either an acrylic resin-base or a cobalt-chrome framework-base. Two examiners telephoned all the listed patients and interviewed 118 patients (70%) regarding the use of their RPDs. Of 118 patients, 42 (36%) had stopped using, mainly due to problems with abutment teeth in resin-based dentures, and replacement in cobaltchrome- based dentures. There was no significant difference in mean age, gender distribution, mean number of remaining/abutment teeth, distribution of denture arch, and Kennedy classification between denture use and nonuse groups (p>0.05). The nonuse group showed a significantly higher percentage of resin-base compared to the use group (p = 0.006). Logistic regression analysis indicated that resin-base was a significant risk factor for nonuse (p = 0.008). The present findings suggest that abutment teeth should be selected carefully, especially in this type of resin-based RPDs, and that the denture base material may be a critical factor which determines denture use.departmental bulletin pape

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    Radiation therapy, inducing DNA damage, is one of the most effective tools for treatments of human cancers, but the effectiveness of the therapy is largely depending on the host specific conditions. Recently genetic constitution has proven to be important for apoptosis-induction responding to DNA damage. Regarding the host-specific manner of responses against DNA-damage in animal model, we have reported that infection with Friend leukemia virus (FLV) enhances the DNA damage-induced apoptosis in hematopoietic cells derived from C3H but DBA/2 mice. Furthermore, p53 or ATM knockout mice of C3H background and DNA-PK-deficient C3H SCID mice did not show the enhanced apoptosis by FLV. Recently, we could show that this host-specific apoptosis was mediated by the kinase activity of DNA-PK in association with FLV env-coding protein, gp70. Interestingly, two host proteins, acinus and MCM2, were also associated with DNA-PK and gp70 and were host-specifically overexpressed in C3H-derived cells. Our data suggest that gp70 enhances cellular DNA damage-induced signaling in association with host-specific cellular proteins, including acinus and MCM2, resulting in the activation of DNA-PK to phosphorylate P53. By introducing gp70/acinus/MCM2-associated pathways into tumor cells, cancer therapy with DNA damage-inducing agents might become much more effective. Our aim is to develop a novel form of targeted therapy that can be combined with other treatment modalities, such as radiotherapy and chemotherapy, using the host-specific regulatory mechanisms of apoptotic enhancement.departmental bulletin pape

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    Nuclear receptors mediate allosteric communications where ligand binding initiates a cascade of signal transduction. The interaction of vitamin D with vitamin D receptor (VDR) was investigated by 19F NMR spectroscopy of the complexes of three fluorinated vitamin D derivatives with the full-length rat VDR-LBD. In the 19F NMR spectra of the VDR-ligand complexes, the A-ring of 4,4-difluoro-1,25(OH)2D3 was revealed to adopt β-conformation in the VDR in solution, and the spectra were shown to be dependent on the dissociation constant. While the complex of 4,4-difluoro-1,25(OH)2D3 with VDR exhibited a clear distinguishable 19F NMR spectrum, those of 19F-1,25(OH)2D3 stereoisomers, which have 10-fold higher VDR affinity than 4,4-difluoro-1,25(OH)2D3, did not. The solid-phase NMR technique was useful for 19F-1,25(OH)2D3 stereoisomers. The fluorinated vitamin D derivatives showed marked changes in the chemical shift (Δ4−19.7 ppm) upon VDR-complex formation, and the ab initio MO method suggested that van der Waals interactions play a major role in the complex formationdepartmental bulletin pape

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    The aims of this study were to clarify which steps in approximal restorative procedure were difficult for the final-year undergraduate students at Tokyo Medical and Dental University, and to examine the relationship between perception of difficulty and clinical experience. At mid-term of the clinical education experience, a self-questionnaire was performed by final-year undergraduate students to clarify the difficulty of restorative procedures at the time. There were statistically significant differences in the number of clinical cases experienced at the time between students who designated the matrix application, shade selection and finishing as the easy steps and those who considered them as the difficult ones (Fisher exact test with Bonferroni correction, p<0.05). There was a significant difference in the total number of procedures designated as difficult between students who had treated above 15 cases and those who had fewer than 15 cases (Wilcoxon rank-sum test, p<0.05). In the final-year clinical education for operative dentistry, students might need to treat over 15 cases to gain confidence in performing approximal composite restorations independently.departmental bulletin pape

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    To contribute to the innovation of the medical education system in Japan, we visited 35 medical schools and 5 institutes in 12 countries of North America, Europe, Australia and Asia in 2008- 2010 and observed the education system. We met the deans, medical education committee and administration affairs and discussed about the desirable education system. We also observed the facilities of medical schools. Medical education system shows marked diversity in the world. There are three types of education course; non-graduate-entry program(non-GEP), graduate-entry program(GEP) and mixed program of non-GEP and GEP. Even in the same country, several types of medical schools coexist. Although the education methods are also various among medical schools, most of the medical schools have introduced tutorial system based on PBL or TBL and simulation-based learning to create excellent medical physicians. The medical education system is variable among countries depending on the social environment. Although the change in education program may not be necessary in Japan, we have to innovate education methods; clinical training by clinical clerkship must be made more developed to foster the training of the excellent clinical physicians, and tutorial education by PBL or TBL and simulation-based learning should be introduced more actively.departmental bulletin pape

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    Objectives: To measure platelet aggregation promoted by Porphyromonas gingivalis ( P. gingivalis ) in whole blood, and to investigate the relation between P. gingivalis and peripheral arterial disease (PAD). Methods and Results: Subjects were 30 patients who were diagnosed as having PAD (PAD Group), and 26 healthy adults without subjective symptoms or arteriosclerosis as a control (Control Group). PAD patients were classified depending on severity levels by Fontaine classification or toe pressure (TP). Twelve-minute changes of electrical impedance after adding P. gingivalis to whole blood was 10.2 ± 4.8 (range, 5.1-14.3) ohm in PAD Group, and 6.1 ± 5.6 (range, 0.2-10.8) ohm in Control Group. PAD Group showed significantly stronger whole-blood platelet aggregation by P. gingivalis . The patients with more severe PAD showed stronger whole-blood platelet aggregation by P. gingivalis . PAD Group had significantly higher serum IgG against P. gingivalis titers than Control Group. In PAD patients with teeth, there was a strong positive correlation between wholeblood platelet aggregation and IgG against P. gingivalis titers. Conclusions: Platelet aggregation promoted by P. gingivalis was significantly high in PAD patients, and was related to the deterioration of their symptoms even in whole blood, which was the environment closer to physiological conditions.departmental bulletin pape

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