心筋再生医療を目的とした心筋に内在する心筋組織幹細胞・心筋前駆細胞同定の試み

金沢大学附属病院ラット心筋梗塞モデルで、BrdUラベリングによりDNA合成能を有する心筋細胞を同定し、リン酸化HistoneH3(増殖細胞マーカー),Nestin(未分化細胞マーカー)に対する特異抗体を用いて免疫染色を施行した。また心筋組織を左室自由壁(梗塞境界〜梗塞領域),心室中壁(非梗塞領域)に分け,コラゲナーゼ処理にて心筋細胞を単離し塗抹標本を作製,核の数及び心筋細胞の大きさを計測した。実験動物は生後8週体重250gの雄ウィスターラットを使用,左小開胸下に左冠動脈を結紮し心筋梗塞モデルを作成,冠動脈結紮群(MI群:n=4),非結紮群(N群:n=4)とした.1週間後BrdUを腹腔内投与(50mg/kgを4時間毎24時間)し心摘出.摘出心は輪状に切除し病理組織切片を作成した.結果はBrdUの免疫染色では,MI群の梗塞境界領域で心筋細胞の核陽性像を一組織切片に平均4.8個認めた.N群では心筋細胞の核陽性像は認めなかった.Nestinの免疫染色ではMI群梗塞境界領域の心筋細胞で瘢痕組織を取り囲むように陽性像が認められた.連続切片にてBrdU陽性の心筋細胞はリン酸化HistoneH3及びNestinに陽性であることが確認できた.塗抹標本では48%が単核,50%が二核の心筋細胞で,両群とも左室自由壁,心室中壁でその割合に差は認めなかった.心筋細胞の大きさは心室中隔の単核細胞ではN/MI群:1695±692/1974±689μm2.二核細胞ではN/MI群:2104±924/2387±809μm2.左室自由壁の単核細胞ではN/MI群:1893±588/1723±608μm2,二核細胞ではN/MI群:2091±609/2326±679μm2であった.心室中壁で生じる梗塞後の単核心筋細胞の肥大化は左室自由壁では認めず,大きさは小さいまま維持された.以上より,ラットを用いた実験で心筋梗塞境界領域にBrdUにラベルされるDNA合成能を有する心筋細胞の存在を確認した.また,成体心筋組織中に内在する心筋組織幹細胞,前駆細胞の存在可能性を示唆する所見として梗塞境界〜梗塞領域では単核で小さい心筋細胞が維持されていることを確認した.研究課題/領域番号:13877213, 研究期間(年度):2001 – 2002出典：「心筋再生医療を目的とした心筋に内在する心筋組織幹細胞・心筋前駆細胞同定の試み」研究成果報告書　課題番号13877213（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/grant/KAKENHI-PROJECT-13877213 ）を加工して作

CDDP耐性細胞の細胞膜メチオニン能動輸送に及ぼすcDDPの影響: cDDPの細胞内分布と葉酸代謝修飾の定量的評価

金沢大学附属病院ヒト胃癌由来のMKN-28、MKN-45と大腸癌由来のSW-48、HCT-15を用いて実験を行つた。各細胞を、プレートに付着した状態と培養液中に浮遊した状態でcDDP(5μM、10μM)に接触させた。接触時間は12ないし24時間とした。その後、Metの細胞内へのuptake\u27を^C-Metを用いて測定した。細胞がプレートに付着した状態では、cDDPの濃度や接触時間に関わらず、MetのuptakeはMKN-45において最も抑制されていた。特に24時間接触の後は、72%のMetのuptake阻害が観察された。また、24時間接触後はSW-48においても54%のMetのuptake阻害が観察された。しかし、これらの結果からcDDPによる細胞膜中性アミノ酸transporter阻害作用は、従来の定説より遥かに軽微であるものと思われた。さらに、^3H-dThdのuptakeを同様に測定した。なお、^C-Metと^3H-dThdのuptakeは生細胞数にて補正した。dThdのuptakeをみると、12時間接触、24時間接触ともにMKN-45で最も抑制されていたが、Metのuptake阻害と比較するとその阻害率は低率であった(22.2%vs45.4%、39,8% vs 71.6%)。細胞が培養液中に浮遊した状態では、いずれの細胞においてもcDDPによるMetのuptake阻害は認められなかった。以上より、(1)cDDPによるMetの細胞内取込み阻害作用は、多種の細胞において認められるものではなく、またその程度も軽微であるものと思われた。(2)特定の細胞(MKNー45)では、dThdのuptakeによって補正した後も明らかなcDDPによるMetのuptake阻害が認められた。(3)cDDPによるMetのuptake阻害は、いずれの細胞においても接着状態でのみ認められた。研究課題/領域番号:07671295, 研究期間(年度):1995-1997出典：研究課題「CDDP耐性細胞の細胞膜メチオニン能動輸送に及ぼすcDDPの影響: cDDPの細胞内分布と葉酸代謝修飾の定量的評価」課題番号07671295（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/grant/KAKENHI-PROJECT-07671295/）を加工して作

消化器癌化学療法の効果的かつ安全な施行 : 癌の化学療法施行医に求められる知識と対策

金沢大学医学部附属病院外科学会抄

Early patency rate and fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms

ObjectivesThe present study analyzes the early patency of intercostal artery reconstruction, using graft interposition and aortic patch anastomosis, and determines the fate of reattached intercostal arteries after repair of thoracoabdominal aortic aneurysms.MethodsWe selected 115 patients (mean age, 63 ± 15 years; range, 19-83 years; male, n = 83) treated by thoracoabdominal aortic aneurysm repair with 1 or more reconstructed intercostal arteries at the Kobe University Graduate School of Medicine between October 1999 and December 2012. The intercostal arteries were reconstructed using graft interposition (n = 66), aortic patch anastomosis (n = 42), or both (n = 7).ResultsThe hospital mortality rate was 7.8% (n = 9). Eleven patients (9.6%) developed spinal cord ischemic injury (permanent, n = 6, transient, n = 5). The average number of reconstructed intercostal arteries per patient was 3.0 ± 1.5 (1-7), and 345 intercostal arteries were reattached. The overall patency rate was 74.2% (256/345) and that of aortic patch anastomosis was significantly better than that of graft interposition (90.8% [109/120] vs 65.3% [147/225], P < .01), but significantly worse for patients with than without spinal cord ischemic injury (51.9% [14/27] vs 76.1% [242/318], P = .01). There was no patch aneurysm in graft interposition during a mean of 49 ± 38 (range, 2-147) postoperative months, but aortic patch anastomosis including 4 intercostal arteries became dilated in 2 patients.ConclusionsAortic patch anastomosis might offer better patency rates and prevent spinal cord ischemic injury compared with graft interposition. Although aneurysmal changes in intercostal artery reconstructions are rare, large blocks of aortic wall reconstruction should be closely monitored

Effect of atherothrombotic aorta on outcomes of total aortic arch replacement

ObjectiveThe effect of an atherothrombotic aorta on the short- and long-term outcomes of total aortic arch replacement, including postoperative neurologic deficits, remains unknown. We evaluated this relationship and also elucidated the synergistic effect of multiple other risk factors, in addition to an atherothrombotic aorta, on the neurologic outcome.MethodsA group of 179 consecutive patients undergoing total aortic arch replacement were studied. An atherothrombotic aorta was present in 34 patients (19%), more than moderate leukoaraiosis in 71 (39.7%), and significant extracranial carotid artery stenosis in 27 (15.1%). In-hospital deaths occurred in 2 patients, 1 (2.9%) of 34 patients with and 1 (0.7%) of 145 patients without an atherothrombotic aorta (P = .26). Permanent neurologic deficits occurred in 4 (2.2%) and transient neurologic deficits in 17 (9.5%) patients. Multivariate analysis demonstrated that the risk factors for transient neurologic deficits were an atherothrombotic aorta (odds ratio, 4.4), extracranial carotid artery stenosis (odds ratio, 5.5), moderate/severe leukoaraiosis (odds ratio, 3.6), and cardiopulmonary bypass time (odds ratio, 1.02). To calculate the probability of transient neurologic deficits, the following equation was derived: probability of transient neurologic deficits = {1 + exp [7.276 − 1.489 (atherothrombotic aorta) − 1.285 (leukoaraiosis) − 1.701 (extracranial carotid artery stenosis) − 0.017 (cardiopulmonary bypass time)]}−1. An exponential increase occurred in the probability of transient neurologic deficits with presence of an atherothrombotic aorta and other risk factors in relation to the cardiopulmonary bypass time. Survival at 3 years after surgery was significantly reduced in patients with vs without an atherothrombotic aorta (75.0% ± 8.8% vs 89.2% ± 3.1%, P = .01).ConclusionsPatients with an atherothrombotic aorta and associated preoperative comorbidities might be predisposed to adverse short- and long-term outcomes, including transient neurologic deficits

DUT Temperature Coefficient and Power Cycles to Failure

We demonstrated power cycling tests with different temperature coefficient samples and shown that cycles to failure strongly depends upon the coefficient. The test samples are investigated by SAT before and after the failure. As a result, we clarified the relationship between the DUT temperature coefficient and failure mechanism. The temperature coefficient is extremely important as a parameter for power cycle tests. High temperature coefficient can lead shorter cycles to failure by thermal runaway before bonding wire disconnection. We also proposed a new method to control temperature coefficient of DUT with gate voltage clamping to drain voltage.33rd International Symposium on Power Semiconductor Devices and ICs (ISPSD 2021), 30th of May and 3rd of June, 2021, Full Virtual Conferenc

Outcome of elective total aortic arch replacement in patients with non–dialysis-dependent renal insufficiency stratified by estimated glomerular filtration rate

ObjectiveLittle is known about the impact of preoperative renal function stratified by estimated glomerular filtration rate (eGFR) on outcomes of total aortic arch replacement (TAR). The current study addressed this issue and identified a cutoff value of eGFR for the requirement of postoperative renal replacement therapy.MethodsFrom January 2000 to May 2011, 229 consecutive patients who did not require preoperative hemodialysis were retrospectively studied after elective TAR. Patients were grouped into the following categories: those with normal renal function (eGFR >90 mL/min/1.73 m2; n = 11) and those with mild (eGFR, 60-90 mL/min/1.73 m2; n = 86), moderate (eGFR, 30-59 mL/min/1.73 m2; n = 111), or severe (eGFR <30 mL/min/1.73 m2; n = 21) renal dysfunction. Linear trend tests demonstrated that the lower categories of eGFR were associated with a higher age, hypertension, coronary artery disease, peripheral arterial disease, and a higher EuroSCORE II.ResultsThe overall hospital mortality was 2.2%. A lower categories of eGFR were an independent risk factor for hospital mortality (odds ratio, 0.91; P = .002) and postoperative renal replacement therapy (odds ratio, 0.94; P < .002). A cutoff value for the requirement of postoperative renal replacement therapy was 26.0 mL/min/1.73 m2. Patients in the lower categories of eGFR had significantly higher hospital mortality (P = .03) and more morbidities, such as renal replacement therapy (P < .01), postoperative permanent neurologic deficits (P = .013), and prolonged mechanical ventilatory support (P < .01). Midterm survival and freedom from major adverse cerebrocardiovascular events were worse across the levels of the lower categories of eGFR.ConclusionsPreoperative eGFR is a strong predictor of short- and midterm outcomes in contemporary TAR

Proto-oncogene, Pim-3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad-mediated apoptosis

金沢大学がん研究所がん病態制御We previously observed that Pim-3 with serine/threonine kinase activity, was aberrantly expressed in malignant lesions of endoderm-derived organs, liver and pancreas. Because Pim-3 protein was not detected in normal colon mucosal tissues, we evaluated Pim-3 expression in malignant lesions of human colon, another endoderm-derived organ. Pim-3 was detected immunohistochemically in well-differentiated (43/68 cases) and moderately differentiated (23/41 cases) but not poorly differentiated colon adenocarcinomas (0/5 cases). Moreover, Pim-3 proteins were detected in adenoma (35/40 cases) and normal mucosa (26/111 cases), which are adjacent to adenocarcinoma. Pim-3 was constitutively expressed in SW480 cells and the transfection with Pim-3 short hairpin RNA promoted apoptosis. In the same cell line, a pro-apoptotic molecule, Bad, was phosphorylated at Ser112 and Ser 136 sites of phosphorylation that are representative of its inactive form. Ser112 but not Ser136 phosphorylation in this cell line was abrogated by Pim-3 knockdown. Furthermore, in human colon cancer tissues, Pim-3 co-localized with Bad in all cases (9/9) and with phospho-Ser112 Bad in most cases (6/9). These observations suggest that Pim-3 can inactivate Bad by phosphorylating its Ser112 in human colon cancer cells and thus may prevent apoptosis and promote progression of human colon cancer. © 2007 Japanese Cancer Association

下咽頭頸部食道癌手術における吻合の工夫とT-Eシャント,および甲状腺温存の意義(下咽頭頸部食道癌,一般演題,第61回日本消化器外科学会定期学術総会)

金沢大学医学部附属病院外科学会抄