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216 result(s) for "Tsushima, Yoshito"
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Gadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway
Gadolinium (Gd)-based contrast agents (GBCAs) are chemicals injected intravenously during magnetic resonance imaging to enhance the diagnostic yield. Repeated use of GBCAs causes their deposition in the brain. Such deposition may affect various neuronal cells, including astrocytes. In this study, we examined the effect of GBCAs (Omniscan, Magnescope, Magnevist, and Gadovist) on astrocyte migration, which is critical for formation of neurons during development and maintaining brain homeostasis. All GBCAs increased cell migration and adhesion with increased actin remodelling. Knockdown of integrin αvβ3 by RNAi or exposure to integrin αvβ3 inhibitor reduced astrocyte migration. GBCAs increased phosphorylation of downstream factors of αvβ3, such as FAK, ERK1/2, and Akt. The phosphorylation of all these factors were reduced by RNAi or integrin αvβ3 inhibitor. GBCAs also increased the phosphorylation of their downstream factor, Rac1/cdc42, belonging to the RhoGTPases family. Coexposure to the selective RhoGTPases inhibitors, decreased the effects of GBCAs on cell migration. These findings indicate that GBCAs exert their action via integrin αvβ3 to activate the signaling pathway, resulting in increased astrocyte migration. Thus, the findings of the study suggest that it is important to avoid the repeated use of GBCAs to prevent adverse side effects in the brain, particularly during development.
Diagnostic value of “hyperdense consolidation sign” as a characteristic new computed tomography sign of diffuse alveolar hemorrhage
Diffuse alveolar hemorrhage (DAH) is an uncommon but life-threatening condition. Although DAH must be distinguished from other lung diseases, no specific computed tomography (CT) signs of DAH have been reported. This study aimed to evaluate the diagnostic value of “hyperdense consolidation” CT sign. We retrospectively evaluated non-contrast CT findings of 25 DAH patients and age- (≤ 2 years) and sex-matched controls with symptoms of dyspnea and hypoxemia. Two radiologists compared the two groups for the presence of hyperdense consolidation signs in lung parenchyma, defined as consolidation that visually contains areas with higher density than the aorta in the specific narrow window setting (window level = 35 Hounsfield units [HU], width = 80 HU) with a mediastinal filter. The sensitivity, specificity, positive- and negative-predictive values of the hyperdense consolidation sign for detection of DAH were 32.0%, 100%, 100%, and 59.5% with perfect interobserver agreement (к = 1.00). The hyperdense consolidation sign was found to be a highly specific sign for DAH.
ABO Blood Groups, Lipids, and Coronary CT Imaging in A Japanese Single-Center Cohort
Background and Objectives: Non-O ABO blood groups have been linked to higher coronary risk, plausibly via hemostatic and lipid pathways. However, evidence in Japanese populations and imaging-defined disease is limited. We examined whether ABO status relates to serum lipids and coronary CT imaging findings in Japanese adults. Materials and Methods: We reviewed adults who underwent coronary CT angiography (CCTA) at our institution. After prespecified exclusions, 865 patients comprised the imaging cohort. For lipid analyses, we excluded patients receiving lipid-lowering therapy at the time of blood sampling, leaving 636 patients (lipid subset). ABO blood group was obtained from the medical record as recorded at registration (patient-reported) and was not re-confirmed by laboratory testing for this study. Outcomes were any coronary artery calcium (Agatston score > 0) and ≥50% luminal stenosis on CCTA. Results: In the lipid subset (n = 636), coronary calcium was present in 44–54% of patients across the four ABO groups and did not differ across groups (p = 0.33). Among assessable scans in the imaging cohort, ≥50% stenosis did not differ across the four ABO groups. In multivariable models (n = 636), older age, male sex, hypertension, and diabetes were independently associated with both outcomes (CAC presence and ≥50% stenosis) (all p < 0.05). For ≥50% stenosis, higher High-Density Lipoprotein-cholesterol (HDL-C) was additionally associated with lower odds (p < 0.05). ABO status (O vs. non-O) was not independently associated with either outcome. Conclusions: In Japanese adults undergoing CCTA, type O blood was tied to lower HDL-C and higher diastolic pressure—features that track with cardiometabolic risk—yet ABO type did not independently relate to coronary calcium or CT-defined stenosis once standard risk factors were considered. These data suggest that, in this setting, ABO adds little beyond conventional risk profiling.
Safety and Efficacy of Aortic Vs Internal Iliac Balloon Occlusion for Cesarean Delivery in Coexisting Placenta Accreta and Placenta Previa
PurposeTo investigate safety and efficacy of intra-aortic balloon occlusion (IABO) versus internal iliac artery balloon occlusion (IIABO) for cesarean delivery in coexisting placenta accreta and placenta previa.Materials and MethodsFrom 2006 to 2019, 60 pregnant women who had undergone preoperative IABO (n = 28) and IIABO (n = 32) for cesarean delivery in coexisting placenta accreta and placenta previa were retrospectively identified, and their medical records and relevant imaging were reviewed.ResultsMaternal characteristics (age, gravidity, previous cesarean delivery, gestational age, and neonatal weight) were similar in both groups. Estimated blood loss, volume of blood transfusion, length of hospitalization, and rate of hysterectomy were not significantly different between the groups. Operation time (the duration of cesarean delivery and hysterectomy, p < 0.05), total time of balloon occlusion (p < 0.01), and fetal radiation dose (p < 0.001) in the IABO group were less than in the IIABO group. No severe complications related to the balloon occlusion procedure were noted in either group.ConclusionIABO and IIABO are safe and effective options for cesarean delivery in patients with combined placenta accreta and placenta previa. The average operation time, balloon occlusion time, and fetal radiation dose in patients with IABO are less than in patients with IIABO. There were no complications related to balloon occlusion of the aorta or internal iliac artery.
Contrast-induced anaphylaxis: does it occur in the medical environment and is it being responded to appropriately?
PurposeTo analyze the appropriateness of primary response for anaphylaxis due to iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCA).Materials and methodsThis retrospective study included all patients in whom intravenous contrast agents (five types of ICMs and four types of GBCAs) were administered at our hospital between April 2016 and September 2021. For the patients who developed anaphylaxis, we obtained data on the time records of contrast injection, anaphylaxis onset, and intramuscular adrenaline (epinephrine) administration.ResultsOf the 76,555 ICM and 30,731 GBCA administrations, anaphylaxis occurred in 49 cases (0.05%), and in 48 cases (98.0%) the onset was within 30 min after administration with widely distributed times (median, 7.5 min; interquartile range, 4.5–10.8 min; max, 26 min). Intramuscular adrenaline administration was performed in 43 cases (87.8%), and this was done within five minutes after the onset in 37 cases (75.5%). Only in 24 cases (49.0%), there were time records of both the onset and adrenaline administration (if performed).ConclusionAnaphylaxis occurred within 30 min after contrast injection in the majority of the cases, but times were widely distributed. Only in 75.5% of cases, appropriate primary treatment was performed, and the importance of keeping exact time records in patients’ charts should be re-emphasized.
Innovative Use of a Coaxial Double-Balloon Catheter System for Treating Gastric Varices
Herein, we present the case of a 52-year-old female with a history of hepatic surgery who developed gastric varices. Owing to the risk of rupture, a balloon-occluded retrograde transvenous obliteration (BRTO) procedure was performed using a coaxial double-balloon catheter system. Subsequently, the outer balloon catheter was advanced into the gastrorenal shunt. However, venography failed to visualize the varices. Attempts to advance the inner catheter into the varices have been unsuccessful. The inner catheter was advanced into the left gastric vein, establishing a closed circuit around the gastric varices using an outer balloon catheter. A sclerosing agent was subsequently injected through the gap between the outer and inner balloon catheters and via the outer balloon catheter, successfully embolizing the gastric varices. The coaxial double-balloon catheter system is a viable and effective method for treating gastric varices, particularly in cases where traditional BRTO techniques may be challenging owing to their complex vascular anatomy.
High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells
Programmed death ligand 1 (PD-L1) expression on the surface of cancer cells affects the efficacy of anti-PD-1/PD-L1 immune checkpoint therapy. However, the mechanism underlying PD-L1 expression in cancer cells is not fully understood, particularly after ionizing radiation (IR). Here, we examined the impact of high linear energy transfer (LET) carbon-ion irradiation on the expression of PD-L1 in human osteosarcoma U2OS cells. We found that the upregulation of PD-L1 expression after high LET carbon-ion irradiation was greater than that induced by X-rays at the same physical and relative biological effectiveness (RBE) dose, and that the upregulation of PD-L1 induced by high LET carbon-ion irradiation was predominantly dependent on ataxia telangiectasia and Rad3-related (ATR) kinase activity. Moreover, we showed that the downstream signaling, e.g. STAT1 phosphorylation and IRF1 expression, was upregulated to a greater extent after high LET carbon-ion irradiation than X-rays, and that IRF1 upregulation was also ATR dependent. Finally, to visualize PD-L1 molecules on the cell surface in 3D, we applied immunofluorescence-based super-resolution imaging. The three-dimensional structured illumination microscopy (3D-SIM) analyses revealed substantial increases in the number of presented PD-L1 molecules on the cell surface after high LET carbon-ion irradiation compared with X-ray irradiation.
Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations
Gadolinium (Gd)-based contrast agents (GBCAs) are chemicals injected intravenously during magnetic resonance imaging (MRI) to enhance the diagnostic yield. The repeated use of GBCAs can cause their deposition in the brain, including the cerebellum. Such deposition may affect various cell subsets in the brain and consequently cause behavioral alterations due to neurotoxicity. Caution should thus be exercised in using these agents, particularly in patients who are more likely to have repeated enhanced MRIs during their lifespan. Further studies are required to clarify the toxicity of GBCAs, and potential mechanisms causing neurotoxicity have recently been reported. This review introduces the effects of GBCAs in the cerebellum obtained from in vitro and in vivo studies and considers the possible mechanisms of neurotoxicity involved.
Quantification of liver fat fraction using T1-weighted mDixon MRI in young patients with ataxia telangiectasia undergoing whole-body MRI: an exploratory study
Background Ataxia–telangiectasia (A–T) is an inherited multiorgan disorder with onset in childhood. Liver involvement, with steatosis and subsequent fibrosis, is increasingly recognized in children and young people with A–T. Purpose To evaluate feasibility of T1-weighted two-point mDixon MRI for identification of liver steatosis in children with A–T and conduct exploratory analysis of relationships between MRI-quantified liver fat fraction and clinical and laboratory measures. Study type Post hoc analysis of prospectively collected research data. Population 16 participants (8 female) with A–T aged 4.8–16.6 years. Field strength/sequence 3.0-T, two-point T1-weighted mDixon. Assessment Participants underwent whole-body MRI including T1-weighted mDixon. Water/fat signal percentage images were generated. Hepatic T1 fat fraction (T1-FF) was calculated from regions-of-interest placed in the right anterior, right posterior and left hepatic lobes. T1-FF > 5.56% was used as the diagnostic criterion for hepatic steatosis. Statistical tests Group comparisons of variables between participants with and without previous diagnosis of liver steatosis were made using independent sample Mann–Whitney U. Associations between T1-FF and age, neurological severity and of liver function tests were tested with Spearman correlation. Statistical significance was pre-specified as p < 0.05. Results Analyzable T1-weighted mDixon data was available for 11 participants. Five MRI datasets were discarded due to motion artefact (n = 3) or incorrect archiving of the original water image (n = 2). Median liver T1-FF was 11.3% (4.7–49.7%), and 10/11 (91%) of participants had evidence of steatosis. Participants with previous diagnosis of steatosis had higher T1-FF than those without (median 32.7% [9.7–49.7%], versus 10.3% [4.7–11.3%], p  = 0.030). T1-FF correlated most strongly with alanine transaminase (r = 0.76, p  = 0.007) and γ-glutamyltransferase (r = 0.76, p  = 0.006). Conclusion T1-weighted mDixon MRI is feasible for detecting steatosis in children with A–T, although motion artefacts reduced data completeness. MRI-quantified liver T1-FF correlates with markers of liver health. We found higher prevalence of liver steatosis using T1-weighted mDIXON than previously reported in pediatric A–T cohorts.
Effect of type 2 diabetes on Gd-EOB-DTPA uptake into liver parenchyma: replication study in human subjects
Purpose Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is a contrast agent for magnetic resonance imaging (MRI), which specifically taken up by hepatocytes through organic anion-transporting polypeptides (OATPs). Previous research in mice has shown that type 2 diabetes is associated with reduced uptake of Gd-EOB-DTPA into the liver parenchyma, reflecting reduced expression of OATP. Since considerable differences in OATP expression exist between mice and humans, human studies are necessary to clarify the effect of diabetes to Gd-EOB-DTPA uptake. The purpose of this study was to validate the effect of diabetes to Gd-EOB-DTPA liver uptake by a confirmatory study in humans. Methods Patients who underwent Gd-EOB-DTPA-enhanced MRI were retrospectively reviewed and divided into two groups: severe or uncontrolled diabetic group (patients with insulin therapy and/or HbA1c ≥ 8.4%) and the control group. Liver-to-spleen ratio (LSR) and relative enhancement of the liver (REL) were calculated to represent Gd-EOB-DTPA liver uptake. Results A total of 94 patients fulfilled the criteria. The severe or uncontrolled diabetic group ( n  = 15) showed significantly lower LSR (1.74 ± 0.26 vs. 1.98 ± 0.31, p  = 0.007) and REL (0.69 ± 0.23 vs. 0.87 ± 0.31, p  = 0.005), compared to the control group ( n  = 79). Conclusion Our study revealed decreased uptake of Gd-EOB-DTPA into liver parenchyma in the severe or uncontrolled diabetic patients. Further studies to determine the impact of the reduced liver enhancement on clinical diagnostic practice will be needed. Graphic abstract