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Although artificial vessels are available for large diameter arteries, there are no artificial vessels for small diameter arteries of < 4 mm. We created a decellularized vascular scaffold (length, 10 mm; outer diameter, 1.5 mm; inner diameter, 1.3 mm) from rat abdominal arteries. We measured the biomechanical characteristics of the scaffolds, implanted them to defects made in rat carotid arteries, and evaluated their patency and the endothelial cell linings. Silastic grafts were implanted as controls. The decellularized scaffolds demonstrated similar mechanical characteristics to normal arteries. All of the control grafts were occluded. Fibroblast-like cells were discovered in the thrombus, and fibrous organization was apparent. In contrast, patency of the grafts in 10 of 12 animals was observed 4 weeks after implantation. The internal cavity of the patent scaffold was completely lined by endotheliallike cells. Thus, the possibility of small artery reconstruction using decellularized scaffolds was demonstrated.departmental bulletin pape
Connective tissue attachment to a mesh structure incorporated on the surface of oral implants and extra-oral endosseous craniofacial implants (EOECI) was investigated. Two types of implants were prepared: TI and TI-Mesh. TI was composed of an upper and a lower component, both comprised of a titanium cylinder, which could be connected using a titanium screw. The composition of the TIMesh was similar, but the lower cylinder had a lateral groove that was covered with a titanium mesh. In animal experiments performed using rat calvaria, the lower component was first implanted and was left submerged for 3 weeks, then the upper component was mounted percutaneously. After an additional 2 weeks, each implant and the surrounding tissues were harvested and evaluated. Histological observations revealed collagen fibers originating from surrounding hypodermal tissues anchored to the mesh structures of the TI-Mesh whereas no such collagen fibers were observed around TI. Significantly greater values of the attachment strength, the thickness of the dermal tissue, the thickness of hypodermal tissue, and the attachment lengths were observed in TI-Mesh than those of TI. Thus connective tissue attachment with collagen fibers anchored to the mesh was achieved by incorporating mesh structures into the percutaneously placed implants.departmental bulletin pape
In the present study, we developed a novel color scale for visual assessment, conforming to theoretical color changes of a gum, to evaluate masticatory performance; moreover, we investigated the reliability and validity of this evaluation method using the color scale. Ten participants (aged 26–30 years) with natural dentition chewed the gum at several chewing strokes. Changes in color were measured using a colorimeter, and then, linear regression expressions that represented changes in gum color were derived. The color scale was developed using these regression expressions. Thirty-two chewed gums were evaluated using colorimeter and were assessed three times using the color scale by six dentists aged 25–27 (mean, 25.8) years, six preclinical dental students aged 21–23 (mean, 22.2) years, and six elderly individuals aged 68–84 (mean, 74.0) years. The intrarater and interrater reliability of evaluations was assessed using intraclass correlation coefficients. Validity of the method compared with a colorimeter was assessed using Spearman’s rank correlation coefficient. All intraclass correlation coefficients were > 0.90, and Spearman’s rank-correlation coefficients were > 0.95 in all groups. These results indicated that the evaluation method of the color-changeable chewing gum using the newly developed color scale is reliable and valid.departmental bulletin pape
The choroid plexus (CP) is present on the ventricular walls of the brain, produces cerebrospinal fluid (CSF), contains many blood vessels, and is a major functional component of the blood–CSF barrier. The CP is an important site in the pathophysiology of various neurological diseases, including Alzheimer’s disease and meningeal amyloidosis. We performed gene silencing in the CP in vivo by using an antisense oligonucleotide (ASO). A short ASO of length 12 nucleotides was intravenously injected into rats. The ASO was not delivered to neurons or glia in the central nervous system, but was successfully delivered into the CP, and resulted in a significant reduction of endogenous target gene expression in epithelial cells within the CP. Although the mechanism of uptake of the ASO by the CP was not elucidated, the ASO bound to albumin in vivo, and the distribution of ASO delivery was similar to that of albumin delivery. These findings suggest that we inhibited target gene expression in the epithelial cells of the CP via albumin-ASO conjugates. This strategy should be useful for investigations of the function of CP, and for the development of new gene-silencing therapies for diseases with pathophysiology related to the CP.departmental bulletin pape
The long QT syndrome type 2 (LQT2) is inheritable life threatening arrhythmic disorder and one of the most common genetic variants in long QT syndrome. There are some indications for treatment of the patients with LQT2 but it is impossible to completely prevent fatal arrhythmia. To develop novel therapy for the patients with LQT2, it has been desired to generate disease-specific and patient-specific disease model. Human induced pluripotent stem (iPS) cells are somatic cell-derived pluripotent stem cells with infinite proliferation ability and multipotency. Patient-specific iPS cells can be derived from patient somatic cells, have all genomic information encoded in patient’s genome including mutation and all SNPs, and can be ideal disease models of the patients. To generate disease model for LQT2 by iPS cells, we should firstly generate iPS cells from the patient with LQT2 and confirm the genomic mutation in iPS cells. In this study, we showed the successful generation of iPS cells from a patient with KCNH2 G603D mutation. The patient specific iPS cells properly expressed stem cell markers, such as NANOG and OCT3/4. We also confirmed that the KCNH2 G603D (G1808A) mutation was taken over in patient specific iPS cells. These patient-specific iPS cells may contribute to the future analysis for disease pathogenesis and drug innovation.departmental bulletin pape
The aim of this study was to determine transport of lidocaine ions through a hairless rat skin in vivo and to compare the efficacy of alternating current (AC) with that of direct current (DC) iontophoresis (IOP). We measured the concentration of lidocaine transported through a cellophane membrane or a hairless rat dorsal skin applying either AC-IOP or DC-IOP. The results revealed that lidocaine concentration increased in a time-dependent manner in vitro in both DC-IOP and AC-IOP. However, the in vivo study showed different tendencies in lidocaine concentration. In the DC-IOP group, lidocaine concentration reached its maximum 20 min after current application and then decreased rapidly; the AC-IOP group showed an increase in lidocaine concentration in a time-dependent manner. There were no side effects such as electrical burns in the rats. In conclusion, AC can be applied for long periods and DC for short periods, or their application time can be appropriately scheduled. Our study also suggests the mechanism by which voltage waveforms affect the skin when applied by IOP. In the future, these findings will be a solid foundation for developing various kinds of medical equipment such as scheduled drug delivery system that can easily deliver various types of drug.departmental bulletin pape
During the past 10 years, residency training in otorhinolaryngology-head and neck surgery (ORL-HNS) in Japan, especially at university hospitals, has emphasized subspecialization, resulting in insufficiencies in basic surgical techniques with an extreme bias toward acquiring subspecialty surgical case experience. To address this problem, we developed a target-oriented program intended to achieve a more balanced approach to surgical training and performed a 1-year trial of the program at the Jikei University School of Medicine. Fourteen residents with 1 to 4 years of ORL-HNS experience completed the trial. Each resident’s competencies in six basic surgical procedures were assessed on the basis of the number of cases handled by the resident, and each resident’s case selection bias after implementation of the target-oriented training was examined. The case selection bias in the trial group residents was reduced and their balance in case experience was shown to be improved in comparison with that in control group residents who were trained in the conventional way. In addition, opinion surveys of the participants and supervising otorhinolaryngologists (trainers) indicated that they felt that the new training system had been effective in improving the balance in case experience and improving motivation, and creating greater awareness of training goals and progress.departmental bulletin pape
Chronic subdural hematoma (CSDH) is prevalent among elderly populations worldwide, and its mysterious pathogenesis has been discussed in the literature for decades. The issues remaining to be solved in regard to CSDH include the initiating events; the bleeding into the subdural space and the formation of the outer and inner membranes, its development; increase and liquefaction of hematoma, the optimal treatments, and the natural history. The pathophysiology is becoming more clear due to recent findings from computed tomography studies and human models of CSDH. In this work, we review previous studies on CSDH and present a new integrated concept about the development of this common condition after head injuries.departmental bulletin pape
We examined the changes in psychological distress and quality of life (QOL) during the perioperative period in oral cancer patients undergoing surgery and investigated the relationship between patient's psychological distress and QOL. Methods. Fifty patients participated. The Hospital Anxiety and Depression Scale (HADS; Japanese version), as a psychological test and the Functional Assessment of Cancer Therapy General (FACT-G); and Head and Neck (FACT-H&N), as quality of life (QOL) surveys were administered preoperatively, after surgery, and 1 month after leaving the hospital. Results. Anxiety was highest pre-operation and depression was highest post-operation, but improvements in both were seen post-discharge. At the pre-operation time point, anxiety and depression low-score groups had significantly high scores on Emotional well-being and Functional well-being. At the post-operation time point, anxiety and depression low-score groups had significantly high scores on all QOL subscales. Conclusion. Providing psychological support while considering anxiety might be particularly useful preoperatively whereas providing psychological support while considering depression might be particularly useful postoperatively.departmental bulletin pape
We employed a questionnaire survey to assess attitudes toward informed consent (IC) among hospital doctors. Based on the result of the correlation analysis, the following two hypotheses were identified. The first hypothesis is that “the doctor’s belief that the patient’s self-determination is possible promotes cure of illness by obtaining IC.” The second hypothesis is that “the doctor’s belief that the patient’s self-determination is possible has a positive influence on patient’s quality of life by obtaining IC.” We clarified the rationale for explaining these two hypotheses by applying cross tabulation analysis, discriminant analysis and principal component analysis (PCA). The doctors were divided into two groups in terms of their position on the patient’s self-determination. One group of doctors believed the possibility of patient’s self-determination, and the other did not. Through our statistical analyses, the characteristics that discriminate these two groups were identified. It was revealed that the former group placed a great importance on the hospitality value, while the latter placed an importance on the service value. Agreement or rejection of the concept of IC has been demonstrated as a key distinguishing factor between the two groups. The results of PCA showed that the doctor’s belief on the patient’s self-determination in obtaining IC had a significant effect on medical outcomes, and the two above-mentioned hypotheses were revealed.departmental bulletin pape