190 research outputs found

    Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria

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    Urticarial rash observed in cryopyrin-associated periodic syndrome (CAPS) caused by nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3 (NLRP3) mutations is effectively suppressed by anti–interleukin (IL)-1 treatment, suggesting a pathophysiological role of IL-1β in the skin. However, the cellular mechanisms regulating IL-1β production in the skin of CAPS patients remain unclear. We identified mast cells (MCs) as the main cell population responsible for IL-1β production in the skin of CAPS patients. Unlike normal MCs that required stimulation with proinflammatory stimuli for IL-1β production, resident MCs from CAPS patients constitutively produced IL-1β. Primary MCs expressed inflammasome components and secreted IL-1β via NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain when stimulated with microbial stimuli known to activate caspase-1. Furthermore, MCs expressing disease-associated but not wild-type NLRP3 secreted IL-1β and induced neutrophil migration and vascular leakage, the histological hallmarks of urticarial rash, when transplanted into mouse skin. Our findings implicate MCs as IL-1β producers in the skin and mediators of histamine-independent urticaria through the NLRP3 inflammasome

    Phase separation of a ternary lipid vesicle including n-alkane: Rugged vesicle and bilayer flakes formed by separation between highly rigid and flexible domains

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    We investigate the phase separation of a ternary lipid bilayer including n-alkane and construct the ternary phase diagram. When a certain proportion of a long n-alkane is mixed with a binary mixture of lipids, which exhibit the disordered liquid-crystalline phase and the ordered gel phase at room temperature, we observed the characteristic morphology of bilayers with phase separation. The ordered bilayer forms flat and rigid domains, which is connected or rimmed with flexible domains in the disordered phase. The asymmetric emergence of the phase separation region close to the ordered phase side is interpreted based on the almost equal distribution of the n-alkane to the ordered and disordered phase domains

    The Efficacy of Neoadjuvant Androgen Deprivation Therapy as a Prostate Volume Reduction before Brachytherapy for Clinically Localized Prostate Cancer

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    From September 2003 to December 2005, 188 patients who visited our hospital and allied institutions for the purpose of prostate brachytherapy were administrated hormonal therapy for volume reductions before brachytherapy. The pretreatment and posttreatment of prostate volume using a transrectal ultrasound volumetric study and the types and duration of hormonal therapy were analyzed. We administered 91 patients with Luteinizing hormone-releasing hormone (LH-RH) agonist, 49 patients with anti-androgen (bicaltamide/flutamide), and 48 patients with maximum androgen blockade (MAB). The duration of the hormonal therapy was 1-3 months for 49 patients, 4-6 months for 59 patients, 7-9 months for 40 patients, 10-12 months for 32 patients, and over 13 months for 8 patients. Before the initiation of hormonal therapy, the mean prostate volume was 35.12 ml (11.04-78.71 ml), and the average of prostate volume before and after hormonal therapy was 36.79 ml and 24.79 ml, respectively (a 32.4% reduction). The prostate volume reduction rate was 32.0% for the LH-RH agonist only, 18.1% for the anti-androgen only and 41.2% for the MAB. No statistically significant difference was observed for the duration of hormonal therapy between 3 groups. A three-month course of the neoadjuvant LH-RH agonist indicated a sufficient volume reduction effectiveness for a large prostate volume.</p

    Novel method for rapid fluorescence in-situ hybridization of ALK rearrangement using non-contact alternating current electric field mixing

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    Echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase gene (EML4-ALK) rearrangement is a key driver mutation in non-small cell lung cancer (NSCLC). Although Break-Apart ALK fluorescence in situ hybridization (FISH) is a reliable diagnostic method for detecting ALK gene rearrangement, it is too costly and time-consuming for use as a routine screening test. Our aim was to evaluate the clinical utility of a novel rapid FISH (RaFISH) method developed to facilitate hybridization. RaFISH takes advantage of the non-contact mixing effect of an alternating current (AC) electric field. Eighty-five specimens were used from patients diagnosed with NSCLC identified immunohistochemically as ALK 0, (1/2+) or (3+). With RaFISH, the ALK test was completed within 4.5 h, as compared to 20 h needed for the standard FISH. Although RaFISH produced results more promptly, the staining and accuracy of the ALK evaluation with RaFISH was equal to the standard. We found 97.6% agreement between FISH and RaFISH based on the status of the ALK signals. These results suggest RaFISH could be used as a clinical tool to promptly determine ALK status

    Novel method for rapid in-situ hybridization of HER2 using non-contact alternating-current electric-field mixing

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    Human epidermal growth factor receptor 2 (HER2)-targeted agents are an effective approach to treating HER2-positive breast cancer patients. However, the lack of survival benefit in HER2-negative patients as well as the toxic effects and high cost of the drugs highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel rapid dual in-situ hybridization (RISH) method developed to facilitate hybridization. The method takes advantage of the non-contact mixing effect of an alternating current (AC) electric field. One hundred sixty-three specimens were used from patients diagnosed with primary breast cancers identified immunohistochemically as HER2 0/1(+), (2+) or (3+). The specimens were all tested using conventional dual in-situ hybridization (DISH), DISH with an automated slide stainer, and RISH. With RISH the HER2 test was completed within 6 h, as compared to 20-22 h needed for the standard protocol. Although RISH produced results more promptly using smaller amounts of labeled antibody, the staining and accuracy of HER2 status evaluation with RISH was equal to or greater than with DISH. These results suggest RISH could be used as a clinical tool to promptly determine HER2 status

    Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors

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    The study of genetic alterations and molecular biology in central nervous system (CNS) tumors has improved the accuracy of estimations of patient prognosis and tumor categorization. Therefore, the updated 2021 World Health Organization (WHO) classification includes various diagnostic genes, molecules, and pathways for diagnosis, as well as histological findings. These findings are expected both to have diagnostic applications and to facilitate new targeted therapies that target tumor-specific genetic changes and molecular biology. Intramedullary spinal cord tumors (IMSCTs) are rare CNS tumors that are difficult to treat because they occur in eloquent areas. Although the genetic underpinnings of IMSCTs remain unclear compared to their intracranial counterparts, the genetic characteristics of these tumors are gradually being revealed. Here, we describe the major changes in the new 2021 WHO classification and review the major types of IMSCTs, with an emphasis on their clinical features and genetic alterations

    Effect on impact properties of adding tantalum to V-4Cr-4Ti ternary vanadium alloy

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    Four V-Ta-4Cr-4Ti quaternary alloys containing different quantities of Ta were investigated to determine the effect of Ta content on the Charpy impact properties. Five button-shaped ingots of the V-4Cr-4Ti ternary alloy and V-xTa-4Cr-4Ti quaternary alloys (x = 3, 9, 15, and 22 wt.%) were fabricated on a laboratory scale by using non-consumable arc-melting in an argon atmosphere. Charpy impact tests were conducted at temperatures ranging from 77 K to 293 K using an instrumented impact tester. Both the upper shelf energy and the ductile–brittle transition temperature increased with increasing Ta content. The addition of 3 wt.% Ta resulted in solid solution strengthening without any degradation of the Charpy impact properties. Thus, the addition of 3 wt.% Ta (V-3Ta-4Cr-4Ti) is an appropriate amount to use in blanket structural materials for nuclear fusion reactors. The spectra of TEM-EDS for V-3Ta-4Cr-4Ti quaternary alloy indicate that there is no significant enrichment of Ta in the matrix as compared with that in the precipitate. However, thermal aging may result in the formation of the Laves phase, causing the degradation of Charpy impact properties. The characterization of precipitates, thermal aging, and creep tests of the V-3Ta-4Cr-4Ti quaternary alloy need to be investigated to determine the optimum Ta content
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