Scintigraphic studies on the etiology of Ampulla Cardiomyopathy

SummaryBackgroundAlthough there are many reports on Ampulla Cardiomyopathy, its etiologic mechanisms are not well known.AimEtiology of Ampulla Cardiomyopathy was investigated by myocardial scintigraphy with various nuclear tracers.Subjects and methodsIn nine patients with Ampulla Cardiomyopathy, myocardial scintigraphy was performed at acute, subacute and chronic phases. Total defect score (TDS) of tallium-201 (Tl) or technetrium-99m sestamibi (MIBI) myocardial perfusion and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) scintigraphies was calculated. Cardio-mediastinal ratio (H/M) and washout rate (WR) of early and delayed images of iodine-123-meta-iodobenzylguanidine (MIBG) scintigraphy were also calculated. The patients in whom TDS of myocardial perfusion scintigraphy at acute phase was 0, were classified into group N (n=5) and those with TDS≥1 into group D (n=4).ResultsTDS of BMIPP at acute, subacute and chronic phases was higher in D than in N; 28.8±10.3 vs. 7.2±4.7 (p=0.0039), 15.5±2.1 vs. 1.0±0.8 (p<0.0001) and 2.7±1.2 vs. 0 (p=0.05), respectively. WR of MIBG at acute phase was also higher in D (50.3±5.7% vs. 36.6±10.5%, p=0.05). H/M (dH/M) on the delayed images and WR at chronic phase were not different between the two groups. H/M (eH/M) on the early images was lower in D. Blood noradrenaline (ng/ml) at acute phase was higher in D than in N (1.21±0.55 vs. 0.45±0.33, p<0.05). Left ventricular ejection fraction (LVEF) was decreased in both at acute phase but it was lower in D than in N (48.1±3.7% vs. 69.9±9.7%, p<0.05) at subacute phase.ConclusionThese findings suggest that the etiology of Ampulla Cardiomyopathy is neurologically stunned myocardium induced by coronary microcirculatory disorder.Due to the significant amount of time that was necessary for normalization of wall motion in the D group, myocardial scintigraphy is believed to be also useful in assessment of severity

Angioscopic Evaluation of Neointimal Coverage of Coronary Stents

Drug-eluting stents (DES) reduce coronary restenosis significantly; however, late stent thrombosis (LST) occurs, which requires long-term antiplatelet therapy. Angioscopic grading of neointimal coverage of coronary stent struts was established, and it was revealed that neointimal formation is incomplete and prevalence of LST is higher in DES when compared to bare-metal stents. It was also observed that the neointima is thicker and LST is less frequent in paclitaxel-eluting and zotarolimus-eluting stents than in sirolimus-eluting stents. Many new stents were devised and they are now under experimental or clinical investigations to overcome the shortcomings of the stents that have been employed clinically. Endothelial cells are highly anti-thrombotic. Neo-endothelial cell damage is considered to be caused by friction between the cells and stent struts due to the thin neointima between them which might act as a cushion. Therefore, development of a DES that causes an appropriate thickness (around 100 μm) of the neointima is a potential option with which to prevent neo-endothelial cell damage and consequent LST while preventing restenosis

Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study

Background Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. Methods A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. Results The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. Conclusions Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

若年層による「ケータイメール」のメディア実践に関する調査研究 : 二重の脱コンテクスト性という技術的特性を受けて

本稿は、大学生・専門学校生といった若年世代が、携帯電話のメール機能である「ケータイメール」というメディアをいかに意味づけ、利用しているかといり「メディア実践」の現状を明らかにしょうとする調査研究である。研究手法としては、まず、メディアの歴史的系譜、他メディアとの相互メディア的状況をふまえ、ケータイメールの技術的特性について「理論的分析」をおこなった。そうした特性を受けて、利用者がいかなるメディア実践をおこなっているのか、専門学校生等を対象に「質的・量的アンケート調査」を行っており、この双方の擦り合わせをすることで、「考察」として結んでいる。「理論的分析」では、ケータイメールは電子テキストメディアやモバイル・パーソナルメディアとして多様なメディア特性を有するなかでも、特に身体性の希薄化による「コミュニケーション上の手がかり (コンテクスト) の欠如」と「利用コンテクストの制約からの解放」という「二重の脱コンテクスト性」をもっことに注目した。「調査結果」としては、ケータイメールのメディア実践の現状について、「ケータイメールのコミュニケーション的メディア特性」、「他メディアとの使い分け状況」、「関係性への影響」といり三方向から理解した。ケータイメールは、コミュニケーションする上での「気楽さ」、「手軽さ」、「使い勝手のよさ」から、用件伝達に優れた適性を有するものの、それに限らず、コンサマトリーなやりとりも含めた幅広いロミュニケーション内容に利用されていた。「考察」では、「二重の脱コンテクスト性」というメディア特性を有するケータイメールを使って、特にコンサマトリーなコミュニケーションを実現するためには、「コンテクストの創造・付与」とい巧意味で、利用者のより主体的な関与が求められてい喝ことを指摘した。 This paper is a study which investigates the current "Media-Practices" of how youths give meaning to the media of cell phone texting and how they use it. For this study, first theoretical analysis was performed about the technical characteristics of cell phone texting, based on the historical genealogy of this media and the situation of inter-media. Secondly, qualitative /quantitative surveys were conducted on vocational school students to investigate what the media habits of the users under the conditions of such technical characteristics. By making theoretical analysis and surveys negotiate, conclusions of the problem were drawn. With theoretical analysis, it was noted that cell phone texting had the media-characteristic of "double de-context nature", which means that communications by this media lack the key to analogue communication (context) and also are released from traditional physical restrictions. As a conclusion, it should be pointed out that users were asked for more independent and active participation of the media, in the sense of "creating and granting of contexts" in order to communicate intimately by using the cell phone texting

Molecular imaging of low-density lipoprotein in human coronary plaques by color fluorescent angioscopy and microscopy.

OBJECTIVES: Low-density lipoprotein (LDL) is an important risk factor for coronary artery disease. However, its localization in human coronary plaques is not well understood. The present study was performed to visualize LDL in human coronary artery wall. METHODS: (1) The fluorescence characteristic of LDL was investigated by color fluorescent microscopy (CFM) with excitation at 470-nm and emission at 515-nm using Nile blue dye (NB) as a biomarker. (2) Native LDL in 40 normal segments, 42 white plaques and 35 yellow plaques (20 with necrotic core) of human coronary arteries was investigated by color fluorescent angioscopy (CFA) and CFM. RESULTS: (1) NB elicited a brown, golden and red fluorescence characteristic of LDL, apolipoprotein B-100, and lysophosphatidylcholine/triglyceride, respectively. (2) The % incidence of LDL in normal segments, white, and yellow plaques was 25, 38 and 14 by CFA and 42, 42 and 14 by CFM scan of their luminal surface, respectively, indicating lower incidence (p<0.05) of LDL in yellow plaques than white plaques, and no significant differences in detection sensitivity between CFA and CFM. By CFM transected surface scan, LDL deposited more frequently and more diffusely in white plaques and yellow plaques without necrotic core (NC) than normal segments and yellow plaques with NC. LDL was localized to fibrous cap in yellow plaques with NC. Co-deposition of LDL with other lipid components was observed frequently in white plaques and yellow plaques without NC. CONCLUSIONS: (1) Taken into consideration of the well-known process of coronary plaque growth, the results of the present study suggest that LDL begins to deposit before plaque formation; increasingly deposits with plaque growth, often co-depositing with other lipid components; and disappears after necrotic core formation. (2) CFA is feasible for visualization of LDL in human coronary artery wall