Ca2+-activated Cl− Current from Human Bestrophin-4 in Excised Membrane Patches

Bestrophins are a newly discovered family of Cl− channels, some members of which are activated by intracellular Ca2+. So far, all studies were carried out with whole-cell recordings from plasmid-transfected cultured cells, so it is unclear whether Ca2+ activates bestrophin through a metabolic mechanism or in a more direct way. We report here experiments that addressed this question with excised, inside-out membrane patches. We chose human bestrophin-4 (hBest4) for heterologous expression because it gave particularly large Cl− currents when expressed, thus allowing detection even in excised membrane patches. hBest4 gave a negligible Cl− current in a Ca2+-free solution on the cytoplasmic (bath) side, but produced a Cl− current that was activated by Ca2+ in a dose-dependent manner, with a K1/2 of 230 nM. Thus, Ca2+ appears to activate the bestrophin Cl− channel without going through a freely diffusible messenger or through protein phosphorylation. Because the activation and deactivation kinetics were very slow, however, we cannot exclude the involvement of a membrane-associated messenger

Aquaporin-11: A channel protein lacking apparent transport function expressed in brain

BACKGROUND: The aquaporins are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two recently described aquaporins, numbers 11 and 12, appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. RESULTS: We report on the characterization of Aquaporin-11 (AQP11). AQP11 RNA and protein is found in multiple rat tissues, including kidney, liver, testes and brain. AQP11 has a unique distribution in brain, appearing in Purkinje cell dendrites, hippocampal neurons of CA1 and CA2, and cerebral cortical neurons. Immunofluorescent staining of Purkinje cells indicates that AQP11 is intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the plasma membrane failed to transport water, glycerol, urea, or ions. CONCLUSION: AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily. Further studies are necessary to elucidate the role of AQP11 in the brain

冠動脈高度石灰化病変に対するスコアリングバルーンラクロスNon-Slip Elementを用いた冠動脈形成術－光干渉断層法による有用性の評価

Percutaneous coronary intervention (PCI) for heavily calcified lesions is challenging because these lesions are resistant to balloon dilatation and stenting. Lacrosse non-slip element (NSE) may have the potential to dilate heavily calcified lesions. We aimed to investigate predictors of successful lesion modification using Lacrosse NSE angioplasty via optical coherence tomography (OCT)-guided PCI. We investigated 32 patients with severe target lesion calcification treated with OCT-guided PCI. Successful lesion modification was defined as the complete fracture of calcification after Lacrosse NSE angioplasty. Before PCI, 172 segments with calcification were identified. After pre-dilatation using Lacrosse NSE, successful lesion modification was achieved in 117 segments (68.0%). Calcification was significantly thinner in successfully disrupted segments than in non-disrupted segments (p < 0.001). Calcification angle tended to be larger in disrupted than in non-disrupted segments (p = 0.08). Convex types were less frequently observed in disrupted than in non-disrupted segments (p < 0.001). At minimal lumen area sites, 26 segments (81.3%) were successfully modified. Similar to the overall results, the disrupted group had significantly thinner calcification than the non-disrupted group (p < 0.001). The angle of the calcified plaque was similar between the 2 groups (p = 0.39). Convex-type calcifications were less frequently observed in the disrupted group than in the non-disrupted group (p = 0.05). Receiver-operating characteristic curve analysis showed that calcification thickness < 565 μm was the best predictor of completely disrupted calcification. The thickness and shape of calcifications were predictors of successful lesion modification after Lacrosse NSE angioplasty.博士（医学）・乙第1426号・平成31年3月15日© Japanese Association of Cardiovascular Intervention and Therapeutics 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular intervention and therapeutics. The final authenticated version is available online at: http://dx.doi.org/10.1007/s12928-018-0553-6

Rare Concurrence of Apical Hypertrophic Cardiomyopathy and Effusive Constrictive Pericarditis

A 78-year-old man with a history of pulmonary tuberculosis was referred for preoperative evaluation of cardiac function. Echocardiography and cardiac cine magnetic resonance imaging (MRI) indicated apical hypertrophic cardiomyopathy (HCM), a thickened visceral pericardium, and a large pericardial effusion. Cardiac late gadolinium-enhanced MRI revealed pericardial inflammation or fibrosis. Apical HCM with concurrent effusive constrictive pericarditis was diagnosed. Further studies are required to elucidate the pathophysiology of this condition

Dual-single photon emission computed tomography and contrast-enhanced magnetic resonance imaging to evaluate dissimilar features of apical hypertrophic cardiomyopathy

Apical hypertrophic cardiomyopathy (HCM) is an uncommon variant of HCM characterized by hypertrophy located in the left ventricular apex that occurs at a rate of about 30% in the Japanese population. Although the prognosis of most patients with apical HCM is relatively benign, it can be poor if apical left ventricular aneurysms develop. However, the mechanism of aneurysmal formation is unclear. We describe two patients with apical HCM and dissimilar findings in 201Thallous chloride (201TlCl) and 123I-betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) dual single-photon emission computed tomography (dual-SPECT), but no myocardial fibrosis on contrast-enhanced magnetic resonance images (MRI). One had apparently normal myocardial perfusion and metabolism, whereas the other had exercise-induced myocardial ischemia and impaired myocardial metabolism. These findings indicated that even apical HCM without myocardial fibrosis is pathophysiologically heterogeneous. Apical HCM has been evaluated by either dual-SPECT or cardiac MRI, but not by both. Thus, a combination of imaging modalities is apparently essential for elucidating the pathophysiology of apical HCM. These dissimilar findings in dual-SPECT might be important in identifying patients with apical HCM who are at high risk of forming aneurysms. (Cardiol J 2010; 17, 3: 306-311

OCT で検出された冠動脈のlipid-richプラークに対する至適薬物療法施行後の臨床経過

Background: The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques (LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT). Methods and Results: Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and 64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12); the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01). Conclusions: A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.博士（医学）・甲第869号・令和5年3月15

経皮的冠動脈インターベンションにおけるステント血栓症発症に特徴的なステント留置後の光干渉断層法の冠動脈内の所見

Background:The association between unfavorable post-stent optical coherence tomography (OCT) findings and subsequent stent thrombosis (ST) remains unclear. This study investigated the ST-related characteristics of post-stent OCT findings at index percutaneous coronary intervention (PCI). Methods and Results:Fifteen patients with ST onset after OCT-guided PCI (ST group) were retrospectively enrolled. Post-stent OCT findings in the ST group were compared with those in 70 consecutive patients (reference group) without acute coronary syndrome onset for at least 5 years after OCT-guided PCI. The incidence of acute myocardial infarction (AMI) was higher in the ST than reference group (60.0% vs. 17.1%, respectively; P=0.0005). The incidence of incomplete stent apposition (93.3% vs. 55.7%; P=0.0064), irregular protrusion (IP; 93.3% vs. 62.8%; P=0.0214), and thrombus (93.3% vs. 51.4%; P=0.0028) was significantly higher in the ST than reference group. The maximum median (interquartile range) IP arc was significantly larger in the ST than reference group (265° [217°–360°] vs. 128° [81.4°–212°], respectively; P180° was significantly higher in the ST than reference group (100% vs. 58.3%, respectively; P=0.0265). Conclusions:IP with a large arc was a significant feature on post-stent OCT in patients with ST.博士（医学）・甲第868号・令和5年3月15

Synchronous neuroendocrine tumors in both the pancreas and ileum: A case report

AbstractIntroductionAlthough it is well-known that in multiple endocrine neoplasia type 1 (MEN 1) disease, multiple endocrine lesions frequently occur, synchronous or metachronous neuroendocrine tumors (NETs) in non-MEN 1 patients are extremely rare.Presentation of caseAn asymptomatic 72-year-old woman with an ileal NET was referred to our hospital. Abdominal computed tomography revealed another circular tumor within the pancreatic head. She was classified as a non-MEN 1 patient. An operative procedure was performed with a preoperative diagnosis of synchronous NET, which was confirmed by pathological examination.DiscussionBoth morphologic and immunophenotypic findings were different between in the ileum and pancreas. Therefore, it was reasonable to consider that both tumors were primary tumors. The synchronous occurrence of these tumors is unusual, and it may be considered as a chance occurrence.ConclusionWe here report the first case of synchronous pancreatic NET and ileal NET in a non-MEN 1 patient