The outcome of the surgical repair of multiple ventricular septal defects was satisfactory. Although the sandwich technique is simple and effective, the use of numerous felt patches disturbed the movement of the interventricular septum. An effort should be made to close the muscular ventricular septal defect directly to avoid postoperative cardiac dysfunction. Large apical ventricular septal defects, especially those located just underneath the moderator band, are considered suitable for the sandwich technique.

A two-month-old male infant with tetralogy of Fallot underwent a right-sided modified Blalock-Taussig shunt using a 4 mm expanded polytetrafluoroethylene graft through a right thoracotomy. Five months later, the patient developed otitis media, followed by repeated relapses of pneumonia and fever of unknown origin. Multidetector-row computed tomography and angiography, performed at 12 months of age, revealed a pseudoaneurysm of the subclavian artery at the insertion of the modified Blalock-Taussig shunt. After 20 days of antibiotic therapy, the pseudoaneurysm and infected graft were successfully resected through a median sternotomy approach. This report describes the treatment strategy of this rare but potentially fatal complication after a modified Blalock-Taussig shunt operation.

Loss of μ-crystallin causes PPARγ activation and obesity in high-fat diet-fed mice. (μ-crystallin(CRYM)の欠損が高脂肪食負荷マウスで PPARγの活性化と肥満を誘発する。 ) (論文の内容の要旨) 〔背景と目的〕 肥満はエネルギー貯蓄と消費のバランスの崩れがその発症要因となる。甲状腺ホルモンは脂肪の産生と消費を調節すること によりエネルギー貯蓄−消費のバランスを司っている。 μ-crystallin (CRYM) は細胞内で甲状腺ホルモン(T3)と結合することで細胞 内の T3 の働きを調節する蛋白である。CRYM が 2 型糖尿病合併肥満患者の白色脂肪内で減少している、CRYM が骨格筋の働き を調整している、といった近年の報告を踏まえ、我々は CRYM がエネルギー代謝に関与しているとの仮説を立てた。CRYM の 全身欠損(KO)マウスを用いて CRYM が高脂肪食負荷下でエネルギー代謝へどのような影響を与えるか解明することを目的とし た。 〔方法〕 8 週齢の野生型マウスと CRYM KO マウスに対して、10 週間の 60％高脂肪食を与えた。体重および空腹時血糖値を 2 週間ご とに測定し、並行して摂餌量も測定した。負荷 10 週目に内臓脂肪、耐糖能、肝臓を評価した。内臓脂肪を重量測定と組織切片 による脂肪細胞のサイズで評価した。耐糖能をグルコース腹腔内投与試験、インスリン腹腔内投与試験、islet 単離刺激試験で 評価した。肝臓を重量測定及び組織切片での脂肪滴サイズの比較、real time PCR を用いた炎症、脂肪合成、PPAR の遺伝子発現 量の違いで評価した。統計学的処理は、PASW statistics (v18.0)を用いて、2 群間の差を Mann-Whitney U test で確認し、P 値 0.05 未満を有意差ありとした。 〔結果〕 野生型マウスに比べ CRYM KO マウスは、負荷後 8 週から体重、内臓脂肪が有意に上昇し、摂餌量も一貫して多い傾向を認 めた。脂肪については内臓脂肪(精巣周囲、後腹膜)の重量、および精巣周囲内臓脂肪の組織切片による脂肪細胞面積の有意な 増大を認めた。空腹時の血糖に差はなかったが、ブドウ糖負荷により耐糖能の低下を認めた。インスリン投与によるインスリ ンに対する反応、膵臓からラ氏島を分離してブドウ糖刺激に対するインスリン分泌を確認したが、有意な差は認められなかっ た。 肝臓は重量に差はなく、 CRYM KO マウスで組織切片での脂肪滴が有意な増加を認めた。 肝臓の遺伝子発現量解析で、 CRYM KO マウスでは炎症に関連する Tnf-α、核内転写因子の Ppar γと脂肪産生に関連する Acc1 の有意な上昇を認めた。 〔考察〕 甲状腺ホルモンの細胞内結合蛋白である CRYM を欠損させたマウスにおいて、高脂肪食の負荷は肥満を引き起こし、脂肪の 増加及び脂肪細胞の肥大化、耐糖能の低下、脂肪細胞及び肝臓での炎症系遺伝子の活性化を認めた。さらには肝臓で Ppar γと Acc1 遺伝子の有意な増加を認め、脂質産生と脂肪の蓄積に CRYM が抑制的に働いている可能性を示した。 白色脂肪について、T3 はノルエピネフリンの末梢での産生を刺激することで、脂肪分解増加や白色脂肪減少をおこす。既報 で LXR(Liver X receptor)βが皮下脂肪の甲状腺ホルモン発現量を調整し、白色脂肪量を調整することが報告されており、CRYM

Given that factors affecting renal function remain unknown, this study aimed to identify key predictors of estimated glomerular filtration rate (eGFR) deterioration, which is a representative of renal function decline in older adults with type 2 diabetes (T2DM). In an exploratory prospective observational study, we enrolled 268 Japanese people with T2DM aged ≥20 years who were followed up at Shinshu University Hospital. Among those, 112 eligible individuals aged ≥65 years were included in the present study. Factors associated with 3-year changes in eGFR (ΔeGFR) and eGFR deterioration (ΔeGFR < 0) were identified using bivariate and multivariable analyses. Regarding baseline values of the subjects, the mean age was 73.5 years, mean blood pressure was 131/74 mm Hg, mean hemoglobin A1c was 7.1%, mean eGFR was 62.0 mL/min/1.73 m 2 , mean urinary albumin excretion was 222.6 mg/gCre, and mean serum uric acid (UA) was 5.5 mg/mL. In bivariate analysis, the 3-year change in UA (ΔUA) levels was significantly correlated with ΔeGFR (r = −0.491, P < .001), but the baseline UA was not (r = 0.073, P = .444). Multiple linear regression analysis revealed that ΔUA was a significant negative predictor of ΔeGFR in the model that included sex, age, body mass index, serum albumin, and ΔUA as explanatory variables. Moreover, multiple logistic regression analysis demonstrated that ΔUA had a positive association with ΔeGFR <0 (odds ratio 2.374; 95% confidence interval 1.294–4.357). Thus, future renal function decline can be predicted by ΔUA but not by baseline UA in older adults with T2DM. Further research is needed to determine whether lowering the serum UA level can prevent eGFR decline.

The mechanism whereby 17β-estradiol (E2) mediates insulin gene transcription has not been fully elucidated. In this study, exposure of hamster insulinoma (HIT-T15) cells to 5 × 10 −9 to 1 × 10 −7 M E2 led to a concentration-dependent decrease of insulin mRNA levels. Transient expression of the estrogen receptor (ER) in HIT-T15 cells revealed that estrogen receptor α (ERα) repressed transcription of the rat insulin II promoter in both ligand-dependent and ligand-independent manners. The N-terminal A/B domain of ERα was not required for either activity. However, the repression was absent with mutated ER lacking the DNA-binding domain. Moreover, introducing mutations in the D-box and P-box of the zinc finger of ER (C227S, C202L) also abolished the repression. Deletion of the insulin promoter region revealed that nucleotide positions − 238 to − 144 (relative to the transcriptional start site) were needed for ER repression of the rat insulin II gene. PDX1- and BETA2-binding sites were required for the repression, but an estrogen response element-like sequence or an AP1 site in the promoter was not involved. In conclusion, we found that estrogen repressed insulin mRNA expression in a beta cell line. In addition, the ER suppressed insulin gene transcription in a ligand-independent matter. These observations suggest ER may regulate insulin transcription by indirect genomic signaling. Electronic supplementary material The online version of this article (10.1007/s11626-019-00328-5) contains supplementary material, which is available to authorized users.