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Tubulointerstitial Nephritis Complicated with Primary Sjogren’s Syndrome under Treatment for Type 2 Diabetes Mellitus

2012年全国高分子材料科学与工程研讨会

作者：潘鹏举 Masahiro Fujita mizuo maeda 浙江大学化工系化学工程联合国家重点实验室 Bioengineering Laboratory RIKEN

利用ATRP和点击化学,合成了线性和星形的聚异丙基丙烯酰胺（PNIPAAm）/DNA的共聚物,并且研究了其在水溶液中的胶束化行为。与PNIPAAm均聚物相比,亲水性DNA链段的引入使PNIPAAm在水溶液中的最低临界溶解温度（LCST）升高,相转变过程中焓... 详细信息

利用ATRP和点击化学,合成了线性和星形的聚异丙基丙烯酰胺（PNIPAAm）/DNA的共聚物,并且研究了其在水溶液中的胶束化行为。与PNIPAAm均聚物相比,亲水性DNA链段的引入使PNIPAAm在水溶液中的最低临界溶解温度（LCST）升高,相转变过程中焓变减小。在LCST温度以上,PNIPAAm-co-DNA共聚物发生胶束化,形成了以PNIPAAm疏水性链段为核、ssDNA亲水性链段为壳的胶束粒子。共聚物的组成和拓扑结构是影响胶束粒子尺寸和结构的主要因素。该类DNA修饰的软纳米粒子在水溶液中的稳定性对目标ssDNA的序列非常敏感,在基因检测中将有潜在的应用前景。

关键词： DNA 聚异丙基丙烯酰胺原子转移自由基聚合点击化学胶束

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Open Journal of Nephrology 2012年第4期2卷 105-108页

作者： Shinichi Antoku Hiroyuki Ito mizuo Mifune Hiroko Nawata Masahiro Kato Department of Diabetes Metabolism and Kidney DiseaseEdogawa HospitalTokyoJapan Department of Internal Medicine Edogawa HospitalTokyoJapan Department of Neurology Edogawa HospitalTokyoJapan

Tubulointerstitial nephritis complicated by primary Sj?gren’s syndrome in a patient under treatment for type 2 diabetes mellitus was diagnosed in the early stage of the disease by renal biopsy. The symptoms of primary Sj?gren’s syndrome, such as thirst and polydipsia, were masked by the characteristic symptoms of type 2 diabetes mellitus. An association between sicca symptoms and diabetes mellitus (types 1 and 2) has been previously reported. Hence, it is possible that there are common underlying immunological mechanisms between primary Sj?gren’s syndrome and diabetes mellitus of both types. Intervention with steroids in a timely manner appears to have prevented or slowed the progression of re- nal impairment.

关键词： Tubulointerstitial Nephritis Sjogren’s Syndrome Type 2 Diabetes Mellitus

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用环状糊精作口臭除臭剂

江苏食品与发酵 1983年第2期 46-49页

作者： mizuo Yajima 吕庆林江苏省食品发酵研究所

本发明是关于用环状糊精(以下略为 CD)作有效成份的口臭除臭剂的。有一些食物在咽下之后很长时间内,其强烈的恶臭气味往往在呼气中残留着。产生这样一些恶臭气味的食物包括某些液体、大蒜、鱼和韭菜。另一种情况是烟鬼因尼古丁所造成的... 详细信息

本发明是关于用环状糊精(以下略为 CD)作有效成份的口臭除臭剂的。有一些食物在咽下之后很长时间内,其强烈的恶臭气味往往在呼气中残留着。产生这样一些恶臭气味的食物包括某些液体、大蒜、鱼和韭菜。另一种情况是烟鬼因尼古丁所造成的臭气味。当人们会面对,臭气味会引起不愉快的感觉,造成烦恼。因此,人们已经开发和使用了若干种除臭剂。普通的除臭剂一般含有香料作为其有效成份。在这些类型的除臭剂中,其除臭效应是基于香料的遮蔽作用。因此,从本质上来说,臭气中的恶臭物质并未除去,所以普通除臭剂的作用是不十分满意的。

关键词：除臭剂有效成份 CD 苹果布丁环状糊精口臭

Frequent Copy Gain of the <i>MET</i>Gene in Hypopharyngeal and Laryngeal Cancer in the Japanese Population

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Journal of Cancer Therapy 2015年第12期6卷 1093-1102页

作者： Ken Akashi Yasuhiro Ebihara Go Omura Yuki Saito Masafumi Yoshida mizuo Ando Takahiro Asakage Tatsuya Yamasoba Yoshinori Murakami Division of Molecular Pathology Institute of Medical Science The University of Tokyo Tokyo Japan Department of Otolaryngology-Head and Neck Surgery The University of Tokyo Tokyo Japan Department of Head and Neck Surgery Saitama Medical University International Medical Center Saitama Japan Department of Head and Neck Surgery Tokyo Medical and Dental Graduate School of Medicine Tokyo Japan

Molecular targeting therapy to specific genetic alterations has not been established in head and neck squamous cell carcinoma (HNSCC) except for cetuximab treatment. To characterize alterations of actionable oncogenes in HNSCC, we examined the gain of copy and mutation of the MET gene in 54 Japanese HNSCC. Copy gain of the MET was analyzed by droplet digital PCR (ddPCR) and quantitative real time PCR (qPCR) using 2 distinct fragments of the gene, and mutation was examined in exons 14 - 19 of MET by Sanger sequencing. Both ddPCR and qPCR showed significantly correlated results in copy number at two distinct fragments of the MET gene (R = 0.96 and R = 0.78), although ddPCR gave more significant and sensitive results. Copy gain of the MET was detected in 10 of 54 (19%) HNSCCs and more frequently observed in tumors of the hypopharynx (4 of 12;33%) or larynx (5 of 13;38%) than those of the oral cavity (1 of 21;4%) or oropharynx (0 of 8;0%), suggesting the existence of site-specific features in the oncogenic mechanisms of HNSCCs. Copy gain of the MET was also observed preferentially in older patients, although no correlation in other parameters, including clinical stages and overall or recurrence-free survival, was observed. On the other hand, of the two HNSCCs in which nucleotide substitution was detected, one was R1040Q in exon 15 with unknown function, and the other was a silent mutation in exon16. These results suggest that copy gain of the MET can provide an indicator for treatment with tyrosine kinase inhibitors for MET in a subset of hypopharyngeal or laryngeal cancer.

关键词： Head and Neck Squamous Cell Carcinoma MET Copy Gain Mutation Molecular Targeting Therapy

Reduced endogenous insulin secretion in diabetic patients with low-titer positive antibodies against GAD

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Journal of Diabetes Mellitus 2012年第1期2卷 96-100页

作者： Yuichiro Takeuchi Hiroyuki Ito Koshiro Oshikiri Shinichi Antoku Mariko Abe mizuo Mifune Michiko Togane Masahiro Kato Department of Diabetes Metabolism and Kidney Disease Edogawa Hospital Tokyo Japan

Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. The endogenous insulin secretion was estimated on the basis of the C-peptide immunoreactivity from a 24 h urine collection (uCPR). Clinical variables were compared between patients negative for the GAD antibody (GAD antibody titer < 1.5 U/mL), a low-titer positive GAD antibody (1.5 U/mL ≤ GAD antibody titer < 10 U/mL) and a high-titer positive GAD antibody (10 U/mL ≤ GAD antibody titer). Results: The low and high-titer positive GAD antibodies were found in 25 and 10 patients, respectively. The uCPR was significantly lower in both the patients with a low (37 ± 33 ug/24h) and high-titer (39 ± 27 ug/24h) positive GAD antibodies than in those negative for GAD antibodies (71 ± 52 ug/24h). The uCPR level was significantly lower in the low-titer positive GAD antibody group (29 ± 22 ug/24h) than in the negative group (67 ± 55 ug/24h) among the patients not taking insulin secretagogues. The difference disappeared in the subjects taking insulin secreagogues. In the stepwise multiple regression analysis, a low-titer positive GAD antibody was independently associated with the uCPR level. Conclusions: Endogenous insulin secretion is reduced in diabetic patients positive for GAD antibodies, even if the titer is low. Earlier initiation of insulin therapy might therefore protect the pancreatic β-cell function in diabetic patients with a low-titer positive GAD antibody.

关键词： GAD Antibody Endogenous Insulin Secretion Urinary C-Peptide SPIDDM LADA

Superior Retinacular Artery Did Not Occlude in a Rat Model of the Non-Traumatic Osteonecrosis of the Femoral Head

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Open Journal of Orthopedics 2016年第6期6卷 144-149页

作者： Shunichiro Okazaki Satoshi Nagoya Junya Shimizu Nobuyuki Takahashi Keisuke mizuo Hideki Hyodoh Kenji Tateda Ima Kosukegawa Satoshi Watanabe Toshihiko Yamashita Department of Musculoskeletal Biomechanics and Surgical Development Sapporo Medical University Sapporo Japan Department of Legal Medicine Sapporo Medical University Sapporo Japan Department of Orthopedic Surgery Sapporo Medical University Sapporo Japan

Non-traumatic osteonecrosis of the femoral head (ONFH) is believed to be avascular necrosis. Certainly, a disruption of a supplying artery induces necrosis in the supplying artery-dominant region. However, when an abnormality such as cell apoptosis, or another reason, is developed in the supplying artery-dominant region, it induces a disruption of the supplying artery. Therefore, to prove that ONFH is avascular necrosis, it is necessary to demonstrate the disruption of the supplying artery prior to histological osteonecrosis development. Here we investigate histologically, using a rat model, whether disruption of the supplying artery occurs before the initial development of ONFH following corticosteroid treatment. Rats were given imiquimod and methylprednisolone, and were sacrificed 1, 2, 3, 7 or 14 days after the last injection. At the sacrifice, the rat was perfused with 20 ml black Indian ink through the left ventricle. ONFH was observed in the Imiquimod + Methylprednisolone group at 7 and 14 days. The osteonecrotic area was not stained with perfused black Indian ink. However, the lateral portion of the femoral head near the superior retinacular artery was stained with the ink. In conclusion, the present study shows that the superior retinacular artery did not occlude before the initial development of ONFH histologically in rats.

关键词： Osteonecrosis of the Femoral Head Corticosteroid Rat Avascular

The number of antihypertensive agents simply reflects the grade and the risk of atherosclerosis in patients with type 2 diabetes mellitus

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Journal of Diabetes Mellitus 2013年第4期3卷 161-167页

作者： Hiroyuki Ito Mariko Abe Masahiro Shinozaki Takashi Omoto Shinya Nishio Masahide Furusho Shinichi Antoku mizuo Mifune Michiko Togane Tsutomu Sanaka Department of Diabetes Metabolism and Kidney Disease Edogawa Hospital Tokyo Japan Lifestyle-Related Disease and CKD Center Edogawa Hospital Tokyo Japan

Aims: The associations between the number of antihypertensive agents being taken by type 2 diabetic patients and 1) the grade of atherosclerosis according to non-invasive surrogate markers for atherosclerosis and 2) the other risk factor for atherosclerosis, were cross-sectionally investigated. Methods: The association between the blood pressure control and the clinical characteristics was evaluated in 1359 patients with type 2 diabetes mellitus. Results: The number of antihypertensive agents was 1.5 ± 1.4 (2.0 ± 1.2 among the 990 patients with hypertension). The proportion of patients taking no antihypertensive agents was 29%, 22% were taking one, 29% were taking two and 21% of the patients were taking three or more antihypertensive agents. The value of the ankle-brachial pressure index significantly decreased with the increase in the number of antihypertensive agents even if the blood pressure was corrected to the target value. The values of brachial-ankle pulse wave velocity and carotid intima-media thickness were also increased. The prevalence of risk factors for atherosclerosis, such as obesity, hyperlipidemia, chronic kidney disease, hyperuricemia and anemia was significantly elevated with the number of agents. Conclusions: The number of antihypertensive agents simply reflects the grade and risk of atherosclerosis in patients with type 2 diabetes mellitus.

关键词： Hypertension Antihypertensive Agents Intima-Media Thickness Ankle-Brachial Pressure Index Pulse Wave Velocity

High Incidence of Null-Type Mutations of the <i>TP</i>53 Gene in Japanese Patients with Head and Neck Squamous Cell Carcinoma

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Journal of Cancer Therapy 2014年第7期5卷 664-671页

作者： Yasuhiro Ebihara Miwako Iwai Ken Akashi Takeshi Ito Go Omura Yuki Saito Masafumi Yoshida mizuo Ando Takahiro Asakage Tatsuya Yamasoba Yoshinori Murakami Department of Otolaryngology—Head and Neck Surgery The University of Tokyo Tokyo Japan Division of Molecular Pathology Institute of Medical Science The University of Tokyo Tokyo Japan

Objective: Molecular targeting therapy has not been generally established in head and neck squamous cell carcinoma (HNSCC) except for cetuximab treatment for targeting epidermal growth factor receptor (EGFR). We analyzed alterations of the TP53, KRAS2, and EGFR genes in Japanese HNSCC to identify subpopulations of tumors potentially susceptible or not susceptible to specific therapy based on their genetic alterations. Materials and Methods: A total of 56 Japanese subjects were included in this study. Genomic DNA of exons 5 - 9 of the TP53, exons 1 and 2 of the KRAS2, exons 19 - 22 of the EGFR, and their flanking sequences were amplified by polymerase chain reaction (PCR) followed by direct sequencing. Splicing variants of EGFR were examined by reverse transcription (RT)-PCR. Results: Mutations of the TP53 and KRAS genes were detected in 25 (45%) and 2 (4%) of 56 HNSCC cases, respectively, while neither mutation nor splicing variant of EGFR was observed. The TP53 mutation did not correlate with clinical stages or primary sites of the tumors. The patterns of nucleotide substitutions specific to HNSCC were not observed. However, the incidence of null-type mutations of the TP53, which cannot be detected as abnormal by conventional immunohistochemical (IHC) studies, was significantly higher (10/25;40%) than that of HNSCC reported in other countries. Conclusion: Frequent TP53 mutations, especially null-type mutations, but infrequent or no alterations of the KRAS and EGFR suggest that the sequencing analysis of theTP53 mutation rather than IHC analysis of p53 provides a potentially useful marker to predict the response of HNSCC to chemotherapy or radiotherapy.

关键词： Head and Neck Squamous Cell Carcinoma TP53 Mutation KRAS EGFR Molecular Marker

牛乳蛋白与过敏儿童患者血清特异性IgE结合情况的检测与分析

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中国农业大学学报 2017年第9期22卷 40-44页

作者：石径周亚迪罗永康江米足中国农业大学食品科学与营养工程学院北京100083 北京双娃乳业有限公司北京100102 浙江大学附属儿童医院杭州310001

研究牛乳蛋白过敏儿童血清中对4种主要乳蛋白过敏原的抗体特异性情况。采用间接酶联免疫吸附法测定乳过敏儿童血清中4种乳蛋白过敏原特异性IgE抗体。结果显示,乳过敏儿童血清中α-乳白蛋白和β-乳球蛋白的特异性IgE比例较高,特异性IgE... 详细信息

研究牛乳蛋白过敏儿童血清中对4种主要乳蛋白过敏原的抗体特异性情况。采用间接酶联免疫吸附法测定乳过敏儿童血清中4种乳蛋白过敏原特异性IgE抗体。结果显示,乳过敏儿童血清中α-乳白蛋白和β-乳球蛋白的特异性IgE比例较高,特异性IgE阳性率分别可达44.3%和39.3%,其次α-酪蛋白和β-酪蛋白特异性IgE阳性率为31.2%和36.1%。研究结果表明,乳过敏儿童对4种乳蛋白过敏原都有一定比例的特异性IgE抗体,其中α-LA和β-LG的阳性率较高,是乳蛋白过敏儿童的主要过敏原蛋白,大部分乳过敏儿童不止对1种乳蛋白过敏。

关键词：牛乳蛋白过敏儿童特异性IgE 过敏原