Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptor γ (PPARγ), whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB) and/or c-Jun amino-terminal kinase (JNK). In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies

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

Xanthogranulomatous Pyelonephritis with Incomplete Double Ureter

Introduction. Xanthogranulomatous pyelonephritis (XGP) is a type of chronic renal inflammation that usually occurs in immunocompromised middle-aged women with chronic urinary tract infection or ureteral obstruction induced by the formation of ureteral stones. XGP with an incomplete double ureter is extremely rare. Case Presentation. A 76-year-old woman was referred to our department to undergo further examination for a left renal tumor that was detected by ultrasonography. Dynamic contrast computed tomography (CT) revealed an enhanced tumor in the upper renal parenchyma. Laparoscopic radical nephrectomy was performed based on a preoperative diagnosis of renal cell carcinoma. Histological sections showed the aggregation of foam cells; thus, XGP was diagnosed. Conclusion. We herein report a rare case of XGP in the upper pole of the kidney, which might have been associated with an incomplete double ureter

The Reduction of State Anxiety by Clearing a Space : An Empirical Study with Graduate School Students

Clearing A Space（以下CAS）はフォーカシング簡便法の最初のステップとして位置づけられており、フォーカシングをするための準備段階として考えられてきた。しかし、フォーカシング研究が展開するにつれてCASを単独で取り扱った研究や事例報告が数多くなされ、CASの有効性が示されてきた。しかしそれらの研究はほとんどが事例研究であり、実証研究は、集団法によるCASを除くとほとんどみられないのが現状である。そこで本研究では、フォーカサーとリスナーのペアによるCASの効果を質問紙によって検討することを目的とした。CAS前後の新版STAI得点の比較では、状態不安得点の有意な低下が認められ（ W+=–2.936, p<.01, N=11）（（t 10）=7.142, P<.01, N=11）、CASの抗状態不安効果が確認された。また、CASの効果にはどのような要素が関連しているのかを検討するために、STAI以外にFMSとYG性格検査や、セッションの逐語記録などの録音データを用いて探索的な研究を行った。これらの結果、CASセッション全体にかかる時間が多い群が、少ない群よりも有意に状態不安が低減していることが分かり、問題や気がかりと距離を取り終えた後のからだの感覚をじっくり味わう時間をとることが状態不安の低減に役立つと考えられた。Clearing A Space (CAS), the first step of Focusing Short Form, was originally developed as a preparation for Focusing. A number of research studies and case studies have demonstrated the effectiveness of CAS, but empirical studies on CAS are limited. This study was aimed at measuring the effects of CAS by statistical comparison of responses to psychological questionnaires. It was found that state anxiety as measured by STAI decreased significantly (W+=-2.936, p<.01,N=11), (t(10)=7.142, P<.01, N=11) following CAS sessions, demonstrating that CAS reduces state anxiety. In addition to STAI, FMS, Yatabe-Guilford Personality Inventory, and verbatim records of sessions were used to explore what factors may be related to the effects of CAS. It was found that state anxiety in a group of subjects who took more time for CAS showed more reduction in state anxiety when compared to a group of subjects who took less time. It was thought that savoring and staying with the cleared space after CAS may enhance the reduction of state anxiety

高齢の非代償性心不全患者において、非心血管疾患、特に感染症は重要な死因である

BACKGROUND:Despite marked improvements in treatment strategies for heart failure (HF), the mortality rate of elderly patients with HF is still high. Detailed causes of death have not been fully understood.METHODS AND RESULTS:We studied 459 consecutive patients with acute decompensated HF (ADHF) emergently admitted to our hospital from 2007 to 2011. Patients were divided into 2 groups: <75 years old (younger group; n = 225) and ≥75 years old (elderly group; n = 234). All-cause death, cardiovascular death, and noncardiovascular death were assessed as adverse outcomes. Compared with the younger group, the elderly group was characterized by a higher proportion of women and hypertensive patients and higher left ventricular ejection fraction. During a mean follow-up of 20.7 months, a total of 174 patients (37.9%) died. All-cause death was significantly higher in the elderly group than in the younger group (46.6% vs 28.9%; P < .0001), and this difference was caused by an increase in noncardiovascular deaths (20.9% vs 9.3%; P < .001), especially deaths due to infection (10.7% vs 4.0%; P < .01). Cardiovascular deaths did not differ between the 2 groups.CONCLUSIONS:Noncardiovascular deaths, most of which were caused by infection, were frequent among elderly patients with ADHF.博士（医学）・甲第629号・平成27年3月16日Copyright © 2014 Elsevier Inc. All rights reserved

胎盤増殖因子の可溶性Fms様チロシンキナーゼ-1に対する血中濃度比の上昇は安定冠動脈疾患患者における有害事象発症の予測因子である

OBJECTIVE: To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis. METHODS: We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years. RESULTS: A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10(-2)) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10(-2)) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE.博士（医学）・甲615号・平成26年3月17日発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.2169/internalmedicine.52.9073

可溶性Flt-1産生低下は、心筋リモデリングおよび心不全増悪に寄与する

Soluble fms-like tyrosine kinase-1 (sFlt-1), an endogenous inhibitor of vascular endothelial growth factor and placental growth factor, is involved in the pathogenesis of cardiovascular disease. However, the significance of sFlt-1 in heart failure has not been fully elucidated. We found that sFlt-1 is decreased in renal failure and serves as a key molecule in atherosclerosis. In this study, we aimed to investigate the role of the decreased sFlt-1 production in heart failure, using sFlt-1 knockout mice. sFlt-1 knockout mice and wild-type mice were subjected to transverse aortic constriction and evaluated after 7 days. The sFlt-1 knockout mice had significantly higher mortality (52% versus 15%; P=0.0002) attributable to heart failure and showed greater cardiac hypertrophy (heart weight to body weight ratio, 8.95±0.45 mg/g in sFlt-1 knockout mice versus 6.60±0.32 mg/g in wild-type mice; P<0.0001) and cardiac dysfunction, which was accompanied by a significant increase in macrophage infiltration and cardiac fibrosis, than wild-type mice after transverse aortic constriction. An anti–placental growth factor–neutralizing antibody prevented pressure overload–induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Moreover, monocyte chemoattractant protein-1 expression was significantly increased in the hypertrophied hearts of sFlt-1 knockout mice compared with wild-type mice. Monocyte chemoattractant protein-1 inhibition with neutralizing antibody ameliorated maladaptive cardiac remodeling in sFlt-1 knockout mice after transverse aortic constriction. In conclusion, decreased sFlt-1 production plays a key role in the aggravation of cardiac hypertrophy and heart failure through upregulation of monocyte chemoattractant protein-1 expression in pressure-overloaded heart.博士（医学）・乙第1384号・平成28年11月24日© 2016 American Heart Association, Inc.The definitive version is available at " https://doi.org/10.1161/HYPERTENSIONAHA.116.07371

JAK2 V617F-Dependent Upregulation of PU.1 Expression in the Peripheral Blood of Myeloproliferative Neoplasm Patients

Myeloproliferative neoplasms (MPN) are multiple disease entities characterized by clonal expansion of one or more of the myeloid lineages (i.e. granulocytic, erythroid, megakaryocytic and mast cell). JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in such tumor cells and have been incorporated into the diagnostic criteria published by the World Health Organization since 2008. However, the mechanism by which these mutations contribute to MPN development is poorly understood. We examined gene expression profiles of MPN patients focusing on genes in the JAK–STAT signaling pathway using low-density real-time PCR arrays. We identified the following 2 upregulated genes in MPN patients: a known target of the JAK–STAT axis, SOCS3, and a potentially novel target, SPI1, encoding PU.1. Induction of PU.1 expression by JAK2 V617F in JAK2-wildtype K562 cells and its downregulation by JAK2 siRNA transfection in JAK2 V617F-positive HEL cells supported this possibility. We also found that the ABL1 kinase inhibitor imatinib was very effective in suppressing PU.1 expression in BCR-ABL1-positive K562 cells but not in HEL cells. This suggests that PU.1 expression is regulated by both JAK2 and ABL1. The contribution of the two kinases in driving PU.1 expression was dominant for JAK2 and ABL1 in HEL and K562 cells, respectively. Therefore, PU.1 may be a common transcription factor upregulated in MPN. PU.1 is a transcription factor required for myeloid differentiation and is implicated in erythroid leukemia. Therefore, expression of PU.1 downstream of activated JAK2 may explain why JAK2 mutations are frequently observed in MPN patients

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in 2018

While primary percutaneous coronary intervention (PCI) has significantly contributed to improve the mortality in patients with ST segment elevation myocardial infarction even in cardiogenic shock, primary PCI is a standard of care in most of Japanese institutions. Whereas there are high numbers of available facilities providing primary PCI in Japan, there are no clear guidelines focusing on procedural aspect of the standardized care. Whilst updated guidelines for the management of acute myocardial infarction were recently published by European Society of Cardiology, the following major changes are indicated; (1) radial access and drug-eluting stent over bare metal stent were recommended as Class I indication, and (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. Although the primary PCI is consistently recommended in recent and previous guidelines, the device lag from Europe, the frequent usage of coronary imaging modalities in Japan, and the difference in available medical therapy or mechanical support may prevent direct application of European guidelines to Japanese population. The Task Force on Primary Percutaneous Coronary Intervention of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has now proposed the expert consensus document for the management of acute myocardial infarction focusing on procedural aspect of primary PCI