Term delivery choriocarcinoma patient with brain and lung metastases successfully treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy.

It is well known that antecedent term delivery and metastasis to sites other than the lungs and vagina are high risk factors for patients with gestational trophoblastic neoplasia. Here we report on a patient with choriocarcinoma who presented with brain and lung metastases after term delivery and was treated by EMA-CO chemotherapy. A 31-year-old woman delivered a healthy infant at term. Frequent episodes of hemoptysis occurred beginning 3 weeks after the delivery. On admission to our hospital, she had lesions in the uterus, lungs and brain as well as motor aphasia and hemiplagia. The pretreatment beta-hCG level was 21,000 ng/ml and the WHO score was 16 (high-risk group). The EMA-CO regimen was administrated as first-line chemotherapy and the patient achieved complete remission after 7 courses. Treatment was terminated after 11 courses and maintained with etoposide (25 mg/day) for 6 months. The patient has remained in complete remission for more than 16 years without other adjuvant therapies. We believe that EMA-CO can currently be considered the regimen of first choice for most high-risk patients with gestational trophoblastic neoplasia in view of its effectiveness and excellent tolerability.</p

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発生の場における蛹コミットメントと予定細胞死の内分泌支配

金沢大学理学部本研究期間に次のことを明らかにした。(1)ホルモン濃度変化。幼若ホルモンとエクジステロイドの体液濃度の詳細な変化を、ラジオイムノアッセイにより測定した。幼若ホルモンは3〜蛹期まで12時間おき。エクジステロイドは4〜蛹化まで2時間間隔の測定。(2)翅成虫原基の蛹コミットメント。翅成虫原基で蛹コミットメントが生じる時期を5令脱皮後16時間までと確定した。また、この時期のコミットメントにはエクジステロイドは必要ないこと、幼若ホルモンは単独ではコミットメントを抑制するものの20-ヒドロキシエクジソン(20E)存在化では抑制効果を失うこと、翅成虫原基での20E感受性は4令head capsule slippage(HCS)の頃に現れ、脱皮に向かって強くなること、等を明らかにした。ホルモンの応答を全くもたない4令初期の翅成虫原基を、ホルモンフリー条件で前培養後20Eでチャレンジすると蛹コミットメントが誘導できた。この時の幼若ホルモン感受性は高く、培養下で生理的濃度で強く抑制させた。これらの結果、翅成虫原基の蛹コミットメントの進行は、翅成虫原基の幼若ホルモン応答能の急激な低下と密接な関係があることがわかった。(3)前部絹糸腺の予定細胞死。前部絹糸腺の予定細胞死を培養下で20Eを加えることにより再現した。この時の細胞死の進行を数値化した。細胞死に必要な遺伝子発現の時間を調べた結果、20E投与後8時間で死の実行に必要な遺伝子の転写は完了し、18時間で翻訳が完了した。しかし20Eは42時間必要であった。これは20Eの膜受容体の存在を示唆している。また、20Eチャレンジにより発現する遺伝子をDD鵬により7つクローニングした。現在その機能解析が進行中である。Present research determined and showed the followings during the propqsed period.(1) Hormone titer : Hemolymph juvenile hormone and ecdysteroid titers were determined every 12 h for JH during a period from third stadium to pupation and every 2 h for ecdysteroids from 4th stadium through pupation.(2) Pupal commitment of for wing discs : The change in commitment in wing discs was found to be finished for 16 h after last larval ecdysis. 20-Hydroxyecdyosne did not accelerate the rate of the change and JH failed to suppress the change at a physiological dose. JH also did not affect the change in commitment by. 20E. The change in commitment may be initiated at the time of head capsule slippage (HCS). After HCS, the discs became responsive dramatically to 20E while lost their responsiveness to JH. The discs of early 4th stadium, that were not pupally committed by 20E in vitro, were able to be pupally committed by two step incubation, first with no hormone followed by 20E challenge. In such conditions, the discs were pupally committed and the commitment was strongly suppressed by JH at a concentration lower than physiological one.(3) Programmed cell death of anterior silk gland : Apoptosis of anterior silk gland is induced by 20E in vitro. After 20E challenge, gene expression and protein synthesis necessary for the death were completed within 8 and 18 h, respectively. Nevertheless, 20E must be present for 42 h for completion of the death. Along with other evidence, 20E was suggested to act after 18 h through a membrane-bound receptor and the second messenger is cyclic AMP. Seven early genes have been cloned and five of them exhibited homology of known genes in other animals but two did not possess open reading frame. Analysis of their function is under progress.研究課題/領域番号:09440273, 研究期間(年度):1997 – 1999出典：研究課題「発生の場における蛹コミットメントと予定細胞死の内分泌支配 」課題番号09440273（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-09440273/094402731999kenkyu_seika_hokoku_gaiyo/）を加工して作

Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1890号 , 学位授与年月日 : 平成19年9月28日, 学位授与大学 : 金沢大学, 主査教授 : 山本 博, 副査教授 : 山岸 正和 , 中尾 眞

Middle-aged Japanese women are resistant to obesity-related metabolic abnormalities

金沢大学医薬保健研究域医学系We attempted to determine sex differences in obesity-related metabolic abnormalities in a relatively large middle-aged Japanese population. The study population consisted of 2935 men and 1622 women who were 35 to 59 years old. Metabolic abnormalities were determined using the Japanese criteria for metabolic syndrome, and we evaluated the number of metabolic abnormalities discriminated by waist circumference. In men, the mean number of metabolic abnormalities increased as the waist circumference increased. In women, although the mean number of metabolic abnormalities increased as the waist circumference increased, the mean number was less than 1 even in those with a waist circumference of at least 95 cm. According to the receiver operating characteristic curve, the cutoff levels yielding the maximal sensitivity plus specificity for predicting the prevalence of one or more obesity-related metabolic abnormalities were 80 cm in men and 73 cm in women. However, the positive predictive value was as low as 28.8% in men and 7.1% in women, which may not be suitable for a screening test, especially in women. Middle-aged Japanese women seem to be resistant to obesity-induced metabolic abnormalities, and waist circumference would not effectively predict the existence of metabolic syndrome. In setting the cutoff points in guidelines, a greater emphasis should be placed on the absolute risk of having abnormalities or diseases. © 2009 Elsevier Inc. All rights reserved

Cores and pH-dependent Dynamics of Ferredoxin-NADP+ Reductase Revealed by Hydrogen/Deuterium Exchange

This research was originally published in the Journal of Biological Chemistry. Young-Ho Lee, Kosuke Tamura, Masahiro Maeda, Masaru Hoshino, Kazumasa Sakurai, Satoshi Takahashi, Takahisa Ikegami, Toshiharu Hase, and Yuji Goto. Cores and pH-dependent Dynamics of Ferredoxin-NADP+ Reductase Revealed by Hydrogen/Deuterium Exchange. J. Biol. Chem. 2007; 282, 5959-5967. © the American Society for Biochemistry and Molecular Biolog

Simulations of Surface X-ray Diffraction from a Monolayer 4He Film Adsorbed on Graphite

We carried out simulations of crystal truncation rod (CTR) scatterings, i.e., one of the surface X-ray diffraction techniques with atomic resolution, from a monolayer He film adsorbed on graphite. Our simulations reveal that the 00L rod scatterings from the He monolayer exhibit notable intensity modifications for those from a graphite surface in the ranges of approximately L = 0.6 - 1.7 and L = 2.2 - 3.5. The height of the He monolayer from the graphite surface largely affects the CTR scattering profiles, indicating that CTR scatterings have enough sensitivities to determine the surface structure of the various phases in the He layer. In particular, in the incommensurate solid phase, our preliminary experimental data show the intensity modulations that are expected from the present simulations.Comment: 6 pages, 4 figures, to be published in JPS Conf. Pro

Fat-free mass and calf circumference as body composition indices to determine non-exercise activity thermogenesis in patients with diabetes

Aims/Introduction: To investigate the clinical and anthropometrical parameters that are associated with non-exercise activity thermogenesis that is composed of basal energy expenditure (BEE) and diet-induced thermogenesis (DIT) in patients with diabetes. Materials and Methods: Body composition was assessed using bioelectrical impedance, and BEE and DIT were measured using indirect calorimetry in 40 Japanese patients with diabetes. Results: BEE correlated positively with bodyweight, body mass index, fat mass, and fat-free mass, and correlated negatively with age in both men and women. In multivariate logistic regression analysis, BEE correlated positively with both fat mass and fat-free mass independently of sex and age. In addition, DIT correlated positively with bodyweight, body mass index, fat mass and fat-free mass, and correlated negatively with age in women, but not men. Fat-free mass contributed to DIT at least partly, and an aging-related decrease in DIT was observed. The best anthropometric parameter that reflected fat mass and fat-free mass was hip circumference (HC) and calf circumference (CC), respectively, in both men and women. Indeed, both HC (men β = 0.600, P < 0.001; women β = 0.752, P < 0.001) and CC (men β = 0.810, P = 0.012; women β = 0.821, P = 0.002) were correlated with BEE independently of age and sex. In addition, CC (β = 0.653, P = 0.009), but not HC was correlated with DIT significantly only in females, independently of age. Conclusions: HC reflects fat mass and was positively associated with BEE, but not with DIT. In contrast, CC reflects fat-free mass, and was positively associated with BEE in both men and women, and with DIT in women. © 2015 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd

Tumor necrosis factor-α-induced production of plasminogen activator inhibitor 1 and its regulation by pioglitazone and cerivastatin in a nonmalignant human hepatocyte cell line

金沢大学大学院医学系研究科環境社会医学Plasminogen activator inhibitor 1 (PAI-1) is an important mediator of atherosclerosis and liver fibrosis in insulin resistance. Circulating levels of PAI-1 are elevated in obese individuals, and PAI-1 messenger RNA is significantly higher in the livers of obese type 2 diabetic individuals than in nonobese type 2 diabetic individuals. To address the mechanism underlying the up-regulation of hepatic PAI-1 in obesity, we tested the effects of tumor necrosis factor α (TNF-α), an important link between obesity and insulin resistance, on PAI-1 production in the nonmalignant human hepatocyte cell line, THLE-5b. Incubation of THLE-5b cells with TNF-α stimulated PAI-1 production via protein kinase C-, mitogen-activated protein kinase-, protein tyrosine kinase-, and nuclear factor-κB-dependent pathways. A thiazolidinedione, pioglitazone, reduced TNF-α-induced PAI-1 production by 32%, via protein kinase C- and nuclear factor-κB-dependent pathways. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin inhibited TNF-α-induced PAI-1 production by 59%, which was reversed by coincubation with mevalonic acid. In conclusion, obesity and TNF-α up-regulation of PAI-1 expression in human hepatocytes may contribute to the impairment of the fibrinolytic system, leading to the development of atherosclerosis and liver fibrosis in insulin-resistant individuals. A thiazolidinedione and a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor may thus be candidate drugs to inhibit obesity-associated hepatic PAI-1 production. © 200