母子分離ストレスが報酬探索行動に及ぼす影響と側坐核におけるドーパミンD1受容体のDNAのメチル化機構を介した発現変化について

Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual’s life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS + SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS + SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS + SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward-seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens (NAc). MS + SI female mice had significantly lower D1 receptor mRNA and protein levels than controls, whereas the expression of TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels were unchanged in MS + SI male mice. When attempting to elucidate the mechanism underlying downregulation of the D1 receptor in the NAc of MS + SI females, we found hypermethylation of the Drd1a promoter region. These results suggest that early-life stress affects reward-seeking behavior in female mice, which may be associated with the downregulation of D1 receptor in the NAc via epigenetic modification of its promoter region.博士（医学）・甲第672号・平成29年6月28日Copyright © 2017 Elsevier B.V. All rights reserved

Ｌ-フェニルアラニンの水和クラスター形成におけるコンフォマー特異性

2006年分子構造総合討論会, 2006年9月20日-23日, グランシップ(静岡), 2B0

ノウソッチュウ ノ イリョウ レンケイ : ケンナンブ イリョウ ノ カイゼン オ メザシテ

Background : Cerebrovasucular disease have been known as“brain attack”since introduction of the treatment with recombinant tissue plasminogen activator against cerebral infarction. Emergent transport of apoplexy patients to hospitals with stroke care unit is needed. But nowadays, shortage of doctors appeared in Kaifu county of Tokushima Prefecture. Objectives : The aim of this study was to clarify problems on patients with apoplexy in this district. Methods : Three representative clinical cases are presented. Results : They were suffered from acute cerebral infarction, subarachnoid hemorrhage, or chronic cerebral infarction complicated with aspiration pneumonia and bed-sores. Conclusions : In order to treat patients with cerebrovasucular diseases effectively in this district, organic and friendly co-operation among doctors of stroke care units, physicians belonging to the Tokushima Medical Association, and staffs of the geriatric health service facilities is needed

ジョウチョウカンマク ジョウミャク ケッセンショウ ノ イチレイ

We report a case of superior mesenteric vein thrombosis successfully saved by resection of enteral necrosis. A ６７ years-old man who admitted for abdominal pain was diagnosed with acute enterocolitis and treated. After two days, abdominal pain increased and abdominal CT revealed superior mesenteric vein thrombosis. He was referred to the department of surgery. We conducted emergency operation. During surgery, bloody ascites and the enteral necrosis about５０cm in length was confirmed. The necrotic ileum was resected and an end-to-end anastomosis was performed. Immediately after surgery, we started anticoagulation therapy. The patient recoverd well and was discharged on POD３２． In a slow pattern like this case, we should suspect superior mesenteric vein thrombosis and diagnose by abdominal CT

ダイチョウ ガン ニ タイスル 5 FU アイソボリン リョウホウ デ コウカ ガ ミトメラレタ 2レイ

We report 2 cases of rectal cancer responding to postoperative chemotherapy with 5-fluorouracil and isovorin. Case 1 : A 60 years-old woman underwent low-anterior resection for rectal cancer in 1994 and partial right lung resection for metastatic lung cancer in 1998. She underwent chemotherapy with 5-fluorouracil and isovorin for mediastinal lymph node metastasis and high score of serum CEA in 2000. After the chemotherapy, the lymph node shrank and serum CEA normalized. Case 2 : A 75 years-old woman underwent low-anterior resection and hysterectomy for rectal cancer with multiple lung metastasis in 2000. She underwent postoperative chemotherapy with 5-fluorouracil and isovorin for metastatic lung cancer. The lung tumor shrank and serum CEA decreased. Chemotherapy with 5-fluorouracil and isovorin seemed to be effective for advanced colon cancer. We should reconfirm the effectiveness and improve the directions for use

Hydration profiles of aromatic amino acids : conformations and vibrations of L-phenylalanine–(H2O)n clusters

IR-UV double resonance spectroscopy and ab initio calculations were employed to investigate the structures and vibrations of the aromatic amino acid, L-phenylalanine–(H2O)n clusters formed in a supersonic free jet. Our results indicate that up to three water molecules are preferentially bound to both the carbonyl oxygen and the carboxyl hydrogen of L-phenylalanine (L-Phe) in a bridged hydrogen-bonded conformation. As the number of water molecules is increased, the bridge becomes longer. Two isomers are found for L-Phe–(H2O)1, and both of them form a cyclic hydrogen-bond between the carboxyl group and the water molecule. In L-Phe–(H2O)2, only one isomer was identified, in which two water molecules form extended cyclic hydrogen bonds with the carboxyl group. In the calculated structure of L-Phe–(H2O)3 the bridge of water molecules becomes larger and exhibits an extended hydrogen-bond to the π-system. Finally, in isolated L-Phe, the D conformer was found to be the most stable conformer by the experiment and by the ab initio calculation.The authors would like to acknowledge the support from the Grant-in-Aids for Scientific Research (18205003) by the Ministry of Education, Science, Sports, and Culture, Japan and from the French-German CNRS-DFG binational project. T. E. gratefully acknowledges financial support from Satake foundation