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result(s) for
"Fukuda, Hitoshi"
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CD146 is highly expressed in glioma stem cells and acts as a cell cycle regulator
by
Kawanishi, Yu
,
Nakajo, Takahito
,
Fukui, Naoki
in
Apoptosis
,
Brain cancer
,
Brain Neoplasms - metabolism
2019
Introduction
CD146 is highly expressed in various malignant tumors and contributes to their malignancy phenotype, which involves metastatic and tumorigenic activity. However, studies on the expression and function of CD146 in brain tumors are limited.
Methods
We over-expressed or knocked-down CD146 in both conventionally cultured glioma cells and tumor spheres (TS). The distribution of glioma cells and their stem cells in different cell cycle phases was analyzed by flow cytometry using the stem cell marker CD133 and the glial precursor marker A2B5. CD146 expression was immunohistochemically examined in glioma tissues.
Results
The majority of glioma stem cells (GSCs) expressing CD133 were also CD146-positive. CD146 knockdown in GSCs significantly compromised cell growth. Cell cycle analysis revealed that most of the CD146 and CD133 double-positive cells were in the G2/M phase. Ectopic expression of CD146 in parental glioma cells resulted in cell cycle arrest of most differentiated cells in G0/G1 phase. In contrast, ectopic expression of CD146 in GSCs resulted in an increase in the number of CD133-positive cells in the G2/M phase. Furthermore, CD146 knockdown reduced the number of CD133-positive cells in the G2/M phase, which was consistent with effects of cell growth inhibition. Immunohistochemical analysis revealed that CD146 expression was significantly upregulated in World Health Organization (WHO) Grade III and IV glioma and positively correlated with CD133 expression.
Conclusions
CD146 is mainly expressed in dividing GSCs and may be a potential target for eradicating glioma stem cells.
Journal Article
Impact of areal socioeconomic status on prehospital delay of acute ischaemic stroke: retrospective cohort study from a prefecture-wide survey in Japan
2023
ObjectivesTo examine whether the Areal Deprivation Index (ADI), an indicator of the socioeconomic status of the community the patient resides in, is associated with delayed arrival at the hospital and poor outcomes in patients with acute ischaemic stroke from a prefecture-wide stroke database in Japan.DesignRetrospective study.SettingTwenty-nine acute stroke hospitals in Kochi prefecture, Japan.ParticipantsNine thousand and six hundred fifty-one patients with acute ischaemic stroke who were urgently hospitalised, identified using the Kochi Acute Stroke Survey of Onset registry. Capital and non-capital areas were analysed separately.Primary and secondary outcome measuresPrehospital delay defined as hospital arrival ≥4-hour after stroke onset, poor hospital outcomes (in-hospital mortality and discharge to a nursing facility) and the opportunities of intravenous recombinant tissue plasminogen activator (rt-PA) and endovascular reperfusion therapy.ResultsIn the overall cohort, prehospital delay was observed in 6373 (66%) patients. Among individuals residing in non-capital areas, those living in municipalities with higher ADI (more deprived) carried a significantly higher risk of prehospital delay (per one-point increase, OR (95% CI) 1.45 (1.26 to 1.66)) by multivariable logistic regression analysis. In-hospital mortality (1.45 (1.02 to 2.06)), discharge to a nursing facility (1.31 (1.03 to 1.66)), and delayed candidate arrival ≥2-hour of intravenous rt-PA (2.04 (1.30 to 3.26)) and endovascular reperfusion therapy (2.27 (1.06 to 5.00)), were more likely to be observed in the deprived areas with higher ADI. In the capital areas, postal-code-ADI was not associated with prehospital delay (0.97 (0.66 to 1.41)).ConclusionsLiving in socioeconomically disadvantaged municipalities was associated with prehospital delays of acute ischaemic stroke in non-capital areas in Kochi prefecture, Japan. Poorer outcomes of those patients may be caused by delayed treatment of intravenous rt-PA and endovascular reperfusion therapy. Further studies are necessary to determine social risk factors in the capital areas.Trial registration numberThis article is linked to a clinical trial to UMIN000050189, No.: R000057166 and relates to its Result stage.
Journal Article
Impact of subcallosal artery origin and A1 asymmetry on surgical outcomes of anterior communicating artery aneurysms
2021
Background
Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery.
Methods
A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (
n
= 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches,
n
= 92).
Results
In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0 mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19–38.5;
p
= 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings.
Conclusion
Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.
Journal Article
Impact of Aneurysm Projection on Intraoperative Complications During Surgical Clipping of Ruptured Posterior Communicating Artery Aneurysms
2016
Abstract
BACKGROUND:
Surgical clipping of ruptured posterior communicating artery (PCoA) aneurysms is a well-established procedure to date. However, preoperative factors associated with procedure-related risk require further elucidation.
OBJECTIVE:
To investigate the impact of the direction of aneurysm projection on the incidence of procedure-related complications during surgical clipping of ruptured PCoA aneurysms.
METHODS:
A total of 65 patients with ruptured PCoA aneurysms who underwent surgical clipping were retrospectively analyzed from a single-center, prospective, observational cohort database in this study. The aneurysms were categorized into lateral and posterior projection groups, depending on direction of the dome. Characteristics and operative findings of each projection group were identified. We also evaluated any correlation of aneurysm projection with the incidence of procedure-related complications.
RESULTS:
Patients with ruptured PCoA aneurysms with posterior projection more likely presented with good-admission-grade subarachnoid hemorrhage (P = .01, χ2 test) and were less to also have intracerebral hematoma (P = .01). These aneurysms were found to be associated with higher incidence of intraoperative rupture (P = .02), complex clipping with fenestrated clips (P = .02), and dense adherence to PCoA or its perforators (P = .04) by univariate analysis. Aneurysms with posterior projection were also correlated with procedure-related complications, including postoperative cerebral infarction or hematoma formation (odds ratio, 5.87; 95% confidence interval, 1.11-31.1; P = .04) by multivariable analysis.
CONCLUSION:
Ruptured PCoA aneurysms with posterior projection carried a higher risk of procedure-related complications of surgical clipping than those with lateral projection.
Journal Article
Formation of Amino Acids and Carboxylic Acids in Weakly Reducing Planetary Atmospheres by Solar Energetic Particles from the Young Sun
2023
Life most likely started during the Hadean Eon; however, the environmental conditions which contributed to the complexity of its chemistry are poorly known. A better understanding of various environmental conditions, including global (heliospheric) and local (atmospheric, surface, and oceanic), along with the internal dynamic conditions of the early Earth, are required to understand the onset of abiogenesis. Herein, we examine the contributions of galactic cosmic rays (GCRs) and solar energetic particles (SEPs) associated with superflares from the young Sun to the formation of amino acids and carboxylic acids in weakly reduced gas mixtures representing the early Earth’s atmosphere. We also compare the products with those introduced by lightning events and solar ultraviolet light (UV). In a series of laboratory experiments, we detected and characterized the formation of amino acids and carboxylic acids via proton irradiation of a mixture of carbon dioxide, methane, nitrogen, and water in various mixing ratios. These experiments show the detection of amino acids after acid hydrolysis when 0.5% (v/v) of initial methane was introduced to the gas mixture. In the set of experiments with spark discharges (simulation of lightning flashes) performed for the same gas mixture, we found that at least 15% methane was required to detect the formation of amino acids, and no amino acids were detected in experiments via UV irradiation, even when 50% methane was used. Carboxylic acids were formed in non-reducing gas mixtures (0% methane) by proton irradiation and spark discharges. Hence, we suggest that GCRs and SEP events from the young Sun represent the most effective energy sources for the prebiotic formation of biologically important organic compounds from weakly reducing atmospheres. Since the energy flux of space weather, which generated frequent SEPs from the young Sun in the first 600 million years after the birth of the solar system, was expected to be much greater than that of GCRs, we conclude that SEP-driven energetic protons are the most promising energy sources for the prebiotic production of bioorganic compounds in the atmosphere of the Hadean Earth.
Journal Article
Flexible endoscopically assisted evacuation of acute and subacute subdural hematoma through a small craniotomy: preliminary results
2018
BackgroundThe first choice to treat acute subdural hematoma (SDH) is a large craniotomy under general anesthesia. However, increasing age or comorbid burden of the patients may render invasive treatment strategy inappropriate. These medically frail patients with SDH may benefit from a combination of small craniotomy and endoscopic hematoma removal, which is less invasive and even available under local anesthesia. Although hematoma evacuation with a rigid endoscope for acute or subacute SDHs has been reported in the literature, use of a flexible endoscope may have distinct advantages. In this article, we attempted to clarify the utility of small craniotomy evacuation with a flexible endoscope for acute and subacute SDH in the elderly patients.MethodBetween November 2013 and September 2016, a total of 17 patients with acute SDH (15 patients), subacute SDH (1 patient), or acute aggravation of chronic SDH (1 patient) underwent hematoma evacuation with a flexible endoscope at our hospital and were enrolled in this retrospective study. Either under local or general anesthesia, the SDH was removed with a flexible suction tube with the aid of the flexible endoscope through the small craniotomy (3 × 4 cm). Hematoma evacuation rate, improvement of clinical symptoms, and procedure-related complications were evaluated.ResultsHematoma evacuation rate was satisfactory, and statistically significant clinical improvement was observed in postoperative Glasgow Coma Scale in all cases compared to the preoperative assessment. No procedure-related hemorrhagic complications were observed.ConclusionsThe results reported here suggest that small craniotomy evacuation with a flexible endoscope is a safe, effective, and minimally invasive treatment for acute and subacute SDH in selected cases.
Journal Article
Added value of anxiolytic benzodiazepines in predictive models on severe delirium in patients with acute decompensated heart failure: A retrospective analysis
by
Ishida, Tomoaki
,
Okamoto, Manami
,
Miyamura, Mitsuhiko
in
Alanine
,
Alanine transaminase
,
Anxiety disorders
2021
Delirium in patients with acute decompensated heart failure (ADHF) is associated with poor clinical outcomes. Although some medications have been reported as risk factors for delirium, their impact on patients with ADHF is still unclear. This study aimed to determine the association of specific medication use with delirium and their additive predictive value in models based on conventional risk factors.
In this single-center, retrospective study, 650 patients treated for ADHF were included. Fifty-nine patients (9.1%) had delirium. In multivariate analysis, anxiolytic benzodiazepines [odds ratio (OR): 6.4, 95% confidence interval (CI): 2.8-15], mechanical ventilation or noninvasive positive pressure ventilation (OR: 6.0, 95% CI: 2.9-12), depression (OR: 3.2, 95% CI: 1.5-6.5), intensive care or high care unit admission (OR: 2.9, 95% CI: 1.5-5.6), male sex (OR: 2.0, 95% CI: 1-3.7), and age (OR: 1.1, 95% CI: 1-1.1) were independently associated with severe delirium. The predictive model that included anxiolytic benzodiazepines had a significantly better discriminatory ability for the incidence of severe delirium than the conventional model.
The use of anxiolytic benzodiazepines was independently correlated with severe delirium, and their use in models based on conventional risk factors had an additive value for predicting delirium in patients with ADHF.
Journal Article
Choice of Treatment Modality and Validity of Direct Surgery for Complex Posterior Inferior Cerebellar Artery-Related Aneurysms
by
Nonaka, Motonobu
,
Fukui, Naoki
,
Ueba, Tetsuya
in
Aneurysms
,
Care and treatment
,
Combination therapy
2025
Background/Objectives: Complex aneurysms of the posterior inferior cerebellar artery (PICA) remain challenging because of their deep location, variable morphology, and proximity to critical neurovascular structures. Although endovascular therapy is preferred, its feasibility is limited in wide-necked, fusiform, or dissecting lesions. We describe our tertiary referral hospital single-center experience with tailored microsurgical and endovascular strategies—emphasizing occipital artery–PICA (OA-PICA) bypass, transcondylar fossa craniotomy, and cerebellomedullary fissure opening—and analyze perioperative factors that influence outcome. Methods: All consecutive patients treated for PICA origin or distal-PICA aneurysms between January 2021 and April 2025 were retrospectively reviewed. Demographics, aneurysm characteristics, procedure type, antithrombotic regimen, complications, diffusion-weighted MRI findings, and 3-month modified Rankin Scale scores were collected. Results: Twelve aneurysms (mean age 61.4 ± 15.2 years; 8 women) were treated: trapping + OA-PICA bypass in 5, direct clipping in 2, flow diverter in 1, endovascular parent artery occlusion in 2, coil embolization in 1, and a hybrid bypass-plus-coil strategy in 1. Two cases were ruptured aneurysms. Perioperative aspirin was used in 2/5 bypass cases; heparin was added in one hybrid case. Asymptomatic PICA-territory infarcts occurred in the three bypasses performed without antiplatelet therapy (one with intra-anastomotic thrombus). No leaks or subcutaneous collections of cerebrospinal fluid were encountered, and no graft occlusions were observed. At 3 months, 9/12 patients achieved a good outcome (mRS 0–2); among them, only one patient with subarachnoid hemorrhage (SAH) experienced postoperative worsening of the mRS. Two cranial nerve palsies (one permanent, one transient) and one wound site hematoma (heparin-associated) resolved without sequelae. Conclusions: Meticulous operative planning allows safe treatment of complex PICA aneurysms. Perioperative aspirin appears beneficial for OA-PICA bypass, whereas perioperative heparin increases bleeding risk. Individualized selection of endovascular, microsurgical, or combined strategies yields favorable early neurological outcomes in this demanding subset of cerebrovascular disease.
Journal Article
Non-Saccular Aneurysm Shape as a Poor Prognostic Factor in Younger Patients with Spontaneous Subarachnoid Hemorrhage
2025
Background/Objectives: Non-saccular aneurysms are a rare subtype of intracranial aneurysms with complex morphologies. Although treatment strategies for ruptured non-saccular and saccular aneurysms differ significantly, large-scale comparisons of the outcomes between the two types remain limited. We aimed to compare the clinical characteristics, procedure-related complications, and functional outcomes between patients with subarachnoid hemorrhage (SAH) caused by non-saccular or saccular aneurysms. Methods: We retrospectively analyzed 1176 consecutive patients with aneurysmal SAH from a population-based stroke registry in Kochi Prefecture, Japan. Aneurysms were classified as saccular or non-saccular based on the morphology, and clinical variables, radiological features, and treatment modalities were compared. Additionally, 840 patients who underwent intervention for their aneurysms within 3 days of onset were further investigated to evaluate the impact of the non-saccular aneurysm shape on poor functional outcomes, defined as a modified Rankin Scale score ≥ 3 at discharge. Results: Non-saccular aneurysms were more common in younger patients and located in the posterior circulation. Procedure-related ischemic complications were more likely to occur in non-saccular aneurysms than in saccular aneurysms (odds ratio [OR]: 2.57, 95% confidence interval [CI]: 1.56–4.97, p < 0.001). In a multivariable logistic regression analysis, a non-saccular morphology was an independent risk factor of poor outcomes (OR: 2.92, 95% CI: 1.34–6.32, p = 0.007) after adjustment for potential confounders. Interaction and subgroup analyses revealed that the negative effects of non-saccular aneurysms on functional outcomes were more prominent in younger patients aged ≤ 60 years. Conclusions: Non-saccular aneurysms are independently associated with ischemic complications and poor outcomes after SAH, particularly in younger patients.
Journal Article