Publications by authors named "Y Shimada"

3,164 Publications

  • Page 1 of 1

A capsule-associated gene of , , is involved in pH homeostasis.

Microbiology (Reading) 2021 Jun;167(6)

Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585, Japan.

The gene is known to be involved in capsule formation in the basidiomycete yeast . A null mutant of , Δ, lacks a capsule around the cell wall and its acidic organelles are not stained with quinacrine. In order to clarify whether the Cap64 protein indeed maintains vacuole or vesicle acidification, so that the vesicle containing the capsule polysaccharide or DBB substrate are transported to the cell membrane side, the relationship between and intracellular transport genes and between and enzyme-secretion activity were analysed. Laccase activity was higher in the Δ strain than in the wild-type strain, and the transcriptional levels of and were also higher in the Δ strain than in the wild-type strain. The intracellular localization of the Cap64 protein was analysed by overexpressing an mCherry-tagged Cap64 and observing its fluorescence. The Cap64 protein was accumulated within cells in a patch-like manner. The quinacrine-stained cells were observed to analyse the acidified cell compartments; quinacrine was found to be accumulated in a patch-like manner, with the patches overlapping the fluorescence of CAP64-mCherry fusion protein. Quinacrine was thus accumulated in a patch-like fashion in the cells, and the mCherry-tagged Cap64 protein position was consistent with the position of quinacrine accumulation in cells. These results suggest that might be involved in intracellular acidification and vesicle secretion via exocytosis.
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http://dx.doi.org/10.1099/mic.0.001029DOI Listing
June 2021

Endotyping in Heart Failure - Identifying Mechanistically Meaningful Subtypes of Disease.

Circ J 2021 Jun 8. Epub 2021 Jun 8.

Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center.

Endotyping is an emerging concept in which diseases are classified into distinct subtypes based on underlying molecular mechanisms. Heart failure (HF) is a complex clinical syndrome that encompasses multiple endotypes with differential risks of adverse events, and varying responses to treatment. Identifying these distinct endotypes requires molecular-level investigation involving multi-"omics" approaches, including genomics, transcriptomics, proteomics, and metabolomics. The derivation of these HF endotypes has important implications in promoting individualized treatment and facilitating more targeted selection of patients for clinical trials, as well as in potentially revealing new pathways of disease that may serve as therapeutic targets. One challenge in the integrated analysis of high-throughput omics and detailed clinical data is that it requires the ability to handle "big data", a task for which machine learning is well suited. In particular, unsupervised machine learning has the ability to uncover novel endotypes of disease in an unbiased approach. In this review, we will discuss recent efforts to identify HF endotypes and cover approaches involving proteomics, transcriptomics, and genomics, with a focus on machine-learning methods.
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http://dx.doi.org/10.1253/circj.CJ-21-0349DOI Listing
June 2021

Cardiac and Echocardiographic Markers in Cryptogenic Stroke with Incidental Patent Foramen Ovale.

J Stroke Cerebrovasc Dis 2021 Jun 6;30(8):105892. Epub 2021 Jun 6.

Department of Neurology, Juntendo University Urayasu Hospital, Chiba, Japan. Electronic address:

Objective: Some cardiac abnormalities could be a substrate for potential embolic source in cryptogenic stroke (CS). We evaluated whether cardiac and echocardiographic markers were associated with CS in patients with incidental patent foramen ovale (PFO) as defined using the Risk of Paradoxical Embolism (RoPE) score.

Materials And Methods: Among 677 patients enrolled in a multicenter observational CS registry, 300 patients (44%) had PFOs detected by transesophageal echocardiography. They were classified into probable PFO-related stroke (RoPE score>6, n = 32) and stroke with incidental PFO (RoPE score≤6, n = 268) groups, and clinical characteristics, laboratory findings, cardiac and echocardiographic markers (i.e. brain natriuretic peptide, left atrial [LA] diameter, ejection fraction, early transmitral flow velocity/early diastolic tissue Doppler imaging velocity [E/e'], LA appendage flow velocity, spontaneous echo contrast, atrial septal aneurysm, substantial PFO, and aortic arch plaques), stroke recurrence, and excellent outcome (modified Rankin scale score <2) at discharge were compared. Risk factors for low RoPE scores were determined using multiple logistic regression analysis.

Results: Higher brain natriuretic peptide levels (p = 0.032), LA enlargement (p < 0.001), higher E/e' (p = 0.001), lower LA appendage flow velocity (p < 0.001), non-substantial PFO (p = 0.021), and aortic arch plaques (p = 0.002) were associated with the low RoPE score group. Patients with high RoPE scores had excellent outcomes (58% versus 78%, p = 0.035). LA enlargement (age- and sex-adjusted odds ratio, 1.15; 95 % confidence interval, 1.00-1.32; p = 0.039) was an independent predictor of low RoPE scores.

Conclusions: Abnormal cardiac substrate could be associated with CS occurrence in a subset of patients with PFO. Patients with CS who had incidental PFO may be at risk of cardioembolism.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105892DOI Listing
June 2021

The impact of pathological lymph node metastasis with lymphatic invasion on the survival of patients with clinically node-negative non-small cell lung cancer: A multicenter study.

Lung Cancer 2021 May 29;158:9-14. Epub 2021 May 29.

Department of Thoracic Surgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Objectives: Lymphatic vessel invasion (Ly) plays a crucial role in pathological lymph node metastasis (pN), and we consider pN + Ly + disease to indicate a high affinity for the lymphatic system. This study evaluated the outcomes of patients with clinically node-negative (N0) non-small cell lung cancer (NSCLC) who presented with pN + with Ly+.

Materials And Methods: This retrospective study evaluated 1775 patients with clinically N0 stage I-III NSCLC who underwent R0 anatomical resection and systematic lymph node dissection at three institutions between January 2010 and December 2017. Patients were classified into four groups according to their pN and Ly statuses. Univariable and multivariable analyses were performed to identify factors associated with poor recurrence-free survival (RFS) and pN + Ly+.

Results: Kaplan-Meier curves revealed that the 5-year RFS rates were 90.8 % for pN-Ly- patients, 55.6 % for pN-Ly + patients, 63.4 % for pN + Ly- patients, and 41.3 % for pN + Ly + patients. Distant and lymph node recurrences were more common in the pN + Ly + group, relative to in the pN-Ly- and pN-Ly + groups (both p < 0.001). Multivariable analyses revealed that pN and Ly statuses were independently associated with RFS, while the solid tumor size and maximum standardized uptake value were independently associated with pN + Ly + status. The proportion of pN + Ly + disease was 17.2 % in patients with a solid-part size of > 1.80 cm and a SUVmax of > 3.55.

Conclusion: pN and Ly statuses were independent prognostic factors in patients with clinically N0 stage I-III NSCLC. Diseases presenting with pN + with Ly + were associated with increased rates of distant and lymph node recurrence.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.029DOI Listing
May 2021

An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke.

Thromb Haemost 2021 Jun 2. Epub 2021 Jun 2.

Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.

Background: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism.

Methods: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age.

Results: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (P<0.001) and higher extent of NETosis (P=0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, P=0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 min, 95% CI: 0.6-21.1 min, P=0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (P<0.001) and were associated with poorer functional outcomes (adjusted common OR: 0.49, 95% CI: 0.24-0.99).

Conclusions: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.
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http://dx.doi.org/10.1055/a-1522-4507DOI Listing
June 2021