Clinical training in department of general dentistry at Tokyo Dental College Chiba Hospital

A compulsory postgraduate clinical training program was established in April 2006 in Japan, and an applicants-only postgraduate training program 9 years ago at Tokyo Dental College. In addition, a training program was also established in the Department of General Dentistry at Tokyo Dental College Chiba Hospital in April 2002. The curriculum consists of training in the outpatient clinic and the following: 1) clinical training (preparation of written treatment plans, simulation practice, submission of evaluation sheets, and submission of training journals), 2) tutorials, and 3) case reports. In 1), trainees write treatment plans for new patients, discuss them with their instructor, perform simulation practice using dummies based on those discussions, submit evaluation sheets and training journals concerning treatment, and receive their instructor's assessment. In 2), trainees are divided into small groups, independently study themes they have chosen, and present the results. In 3), they orally report cases they have treated and receive evaluation by other trainees and instructors in general discussion meetings. In addition, a course was also established at the Department of General Dentistry, Tokyo Dental College Chiba Hospital in April 2002. We report the training curriculum of this course.     

Radiosynthesis and evaluation of [11C]YM-202074 as a PET ligand for imaging the metabotropic glutamate receptor type 1

IntroductionDeveloping positron emission tomography (PET) ligands for imaging metabotropic glutamate receptor type 1 (mGluR1) is important for studying its role in the central nervous system. N-cyclohexyl-6-{[N-(2-methoxyethyl)-N-methylamino]methyl}-N-methylthiazolo[3,2-a]benzimidazole-2-carboxamide (YM-202074) exhibited high binding affinity for mGluR1 (K_i=4.8 nM), and selectivity over other mGluRs in vitro. The purpose of this study was to label YM-202074 with carbon-11 and to evaluate in vitro and in vivo characteristics of [¹¹C]YM-202074 as a PET ligand for mGluR1 in rodents.Methods[¹¹C]YM-202074 was synthesized by N-[¹¹C]methylation of its desmethyl precursor with [¹¹C]methyl iodide. The in vitro and in vivo brain regional distributions were determined in rats using autoradiography and PET, respectively.Results[¹¹C]YM-202074 (262–630 MBq, n=5) was obtained with radiochemical purity of >98% and specific activity of 27–52 GBq/μmol at the end of synthesis, starting from [¹¹C]CO₂ of 19.3–21.5 GBq. In vitro autoradiographic results showed that the high specific binding of [¹¹C]YM-202074 for mGluR1 was presented in the cerebellum, thalamus and hippocampus, which are known as mGluR1-rich regions. In ex vivo autoradiography and PET studies, the radioligand was specifically distributed in the cerebellum, although the uptake was low. Furthermore, the regional distribution was fairly uniform in the whole brain by pretreatment with JNJ16259685 (a mGluR1 antagonist). However, radiometabolite(s) was detected in the brain.ConclusionsFrom these results, especially considering the low brain uptake and the influx of radiometabolite(s) into brain, [¹¹C]YM-202074 may not be a useful PET ligand for in vivo imaging of mGluR1 in the brain.     

Fabrication of scaffold‐free contractile skeletal muscle tissue using magnetite‐incorporated myogenic C2C12 cells

We have fabricated a functional skeletal muscle tissue using magnetite‐incorporated myogenic cell line C2C12 and a magnetic field. Magnetite‐incorporated C2C12 cells were patterned linearly on a monolayer of fibroblast NIH3T3 cells, using a magnetic field concentrator. After induction of differentiation, the C2C12 cells fused and formed multi‐nucleated myotubes. The 3T3 layer became detached in a sheet‐like manner after cultivation in differentiation medium for 5–8 days. When two separate collagen films were placed on a culture dish as tendon structures, a cylindrical construct was formed. Histological observation of the fabricated cylindrical tissue revealed the presence of multinucleate cells within it. Immunofluorescence staining of the construct showed the presence of sarcomere structures within the construct. Western blot analysis showed that muscle proteins were expressed in the construct. When the construct was stimulated with electric pulses, it exhibited active tension of approximately 1 µ N. These results demonstrate that functional skeletal muscle tissue was formed through magnetic force‐based tissue engineering. This is the first report of fabrication of skeletal muscle tissue with active tension‐generating capability using magnetic force‐based tissue engineering. The scaffold‐free skeletal muscle tissue engineering technique presented in this study will be useful for regenerative medicine, drug screening or use as a bio‐actuator. Copyright © 2010 John Wiley & Sons, Ltd.     

Surgical strategy of brain tumors adjacent to the optic radiation using diffusion tensor imaging-based tractography

The present study evaluated the efficacy of diffusion tensor imaging (DTI)-based tractography in the surgery of brain tumors adjacent to the optic radiation. Of the 14 surgical cases included, 11 had metastatic brain tumors and 3 cerebral gliomas. Additionally, 4 of the 14 patients had pre-operative visual field defects, while the remaining 10 patients experienced no visual impairment. The optic radiations on the lesion side were evident in all 14 patients. On the basis of these tractographic findings, we employed optimal surgical approaches in each patient to avoid injury to the eloquent neural structures, including optic radiation, during surgery. Successful surgical resection was performed in all 14 patients. Of the 14 patients, 2 with visual field defects during the pre-operative period showed improvement in their visual field, and the remaining 12 patients experienced no visual deterioration. DTI-based tractography thus is a feasible modality for the surgical planning of brain lesions adjacent to the optic radiation.     

Synergistic antitumor effects of FGFR2 inhibitor with 5‐fluorouracil on scirrhous gastric carcinoma

Scirrhous gastric carcinoma (SGC) carries the highest mortality because of a frequent metastasis to lymph node (LN). S1, a 5‐fluorouracil (5‐FU) analog, is clinically available for gastric cancer at an advanced stage. Fibroblast growth factor receptor 2 (FGFR2) is required for the proliferation of SGC. The objective of this study is to clarify the benefit of a combination of S1 and kinase inhibitors including FGFR2 inhibitor Ki23057 in gastric cancer. OCUM‐2MLN and KATO‐III were derived from SGC. MKN‐7 and MKN‐74 were derived from non‐SGC. MTT assay was used to examine the growth‐inhibitory activity of 5 small‐synthetic molecules including Ki23057, Sunitinib, Glivec, Lapatinib or SU11274, in cells cultured with 5‐FU. Combination effects of 5‐FU with Ki23057 on proliferation, apoptosis and mRNA expression were examined. S1 and/or Ki23057 were administered to murine models of SGC created by the orthotopic inoculation of OCUM‐2MLN cells. Ki23057 at 100 nM significantly (p < 0.01) inhibited the proliferation and decreased the phosphorylation of FGFR2 in SGC cells, but not in non‐SGC. Ki23057 showed synergistic antitumor effects for SGC cells in combination with 5‐FU using CalcuSyn analysis, but Sunitinib, Glivec, Lapatinib and SU11274 did not. The combination of Ki23057 and 5‐FU decreased DPD expression and increased apoptosis rates and p21 expression level of SGC cells. The combined administration of S1 and Ki23057 significantly (p < 0.05) decreased orthotopic tumors as well as LN metastasis more effectively than S1 alone. These findings suggested that the combined treatment with 5‐FU and Ki23057 produced synergistic antitumor effects and is therapeutically promising for SGC treatment.