Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238 bp deletion, and a compound heterozygous FGA1238 bp deletion and novel FGA c.54+3A > C substitution

We identified two afibrinogenemic girls in two Japanese families and performed molecular analysis to clarify the mechanisms of fibrinogen defects. Genetic analyses were performed by PCR amplification of the fibrinogen gene and DNA sequence analysis. To analyze the mechanisms of mature fibrinogen defects in plasma, we cloned minigenes from the proposita's PCR-amplified DNA, transfected them into CHO cells, and sequenced the cDNA amplified with the RT reaction followed by PCR. Sequence analyses indicated that one was caused by a homozygous 1238 bp deletion of the fibrinogen A alpha-chain gene (FGA Delta 1238) and the other was a compound heterozygous FGA Delta 1238 and novel FGA c.54+3A > C substitution. The minigene corresponding to FGA Delta 1238 generates two aberrant mRNAs, both of which may induce a frameshift and terminate prematurely. In contrast, the minigene corresponding to FGA c.54+3A > C generates two aberrant mRNAs, one of which may induce a frameshift and terminate prematurely, and the other uses a cryptic 5' splice site in exon 1, resulting in the deletion of six amino acids in signal peptides. Molecular analyses of both genetic variants suggest that the lack of a mature A alpha-chain, impaired assembly, and/or secretion of the fibrinogen molecule may lead to afibrinogenemia.ArticleINTERNATIONAL JOURNAL OF HEMATOLOGY. 96(1):39-46 (2012)journal articl

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis

Background: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). Methods: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. Results: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. Conclusions: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course

Real-time nanodiamond thermometry probing in vivo thermogenic responses

蛍光ナノダイヤモンドを用いた量子温度計により動物個体の発熱を捉えることに成功. 京都大学プレスリリース. 2020-09-25.Get diamonds, take temperature. 京都大学プレスリリース. 2020-10-06.Real-time temperature monitoring inside living organisms provides a direct measure of their biological activities. However, it is challenging to reduce the size of biocompatible thermometers down to submicrometers, despite their potential applications for the thermal imaging of subtissue structures with single-cell resolution. Here, using quantum nanothermometers based on optically accessible electron spins in nanodiamonds, we demonstrate in vivo real-time temperature monitoring inside Caenorhabditis elegans worms. We developed a microscope system that integrates a quick-docking sample chamber, particle tracking, and an error correction filter for temperature monitoring of mobile nanodiamonds inside live adult worms with a precision of ±0.22°C. With this system, we determined temperature increases based on the worms’ thermogenic responses during the chemical stimuli of mitochondrial uncouplers. Our technique demonstrates the submicrometer localization of temperature information in living animals and direct identification of their pharmacological thermogenesis, which may allow for quantification of their biological activities based on temperature

Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature

Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL

Strukturierung des Unterrichts anhand der Lehrer:innenfragen. Perspektiven der Jugyo Kenkyu

Analog zum Leipziger Ansatz der qualitativen Unterrichtsforschung stellt das Team der Hiroshima Universität sein spezifisches Vorgehen der Lesson Study vor. Auf der Basis der normativen Lesson Study mit Fokus auf die Gruppenbildung im Klassenzimmer zeigt die Analyse ihre Praxisnähe und moniert ein gewisses Defizit der Untersuchungsmaterialien, die aus dem Kontext der qualitativen Unterrichtsforschung bereitgestellt wurden. Die forschungsmethodologische Differenz zeigt sich darin, dass der Fokus auf die Lehrer:innenfrage im qualitativen Zugang Prozesse der Offenheit und Lenkung und in der Jugyo Kenkyu Strukturen der Gruppenbildung in den Blick rückt. (DIPF/Orig.

Identification of candidate molecular targets of the novel antineoplastic antimitotic NP-10

We previously reported the identification of a novel antimitotic agent with carbazole and benzohydrazide structures: N′-[(9-ethyl-9H-carbazol-3-yl)methylene]-2-iodobenzohydrazide (code number NP-10). However, the mechanism(s) underlying the cancer cell-selective inhibition of mitotic progression by NP-10 remains unclear. Here, we identified NP-10-interacting proteins by affinity purification from HeLa cell lysates using NP-10-immobilized beads followed by mass spectrometry. The results showed that several mitosis-associated factors specifically bind to active NP-10, but not to an inactive NP-10 derivative. Among them, NUP155 and importin β may be involved in NP-10-mediated mitotic arrest. Because NP-10 did not show antitumor activity in vivo in a previous study, we synthesized 19 NP-10 derivatives to identify more effective NP-10-related compounds. HMI83-2, an NP-10-related compound with a Cl moiety, inhibited HCT116 cell tumor formation in nude mice without significant loss of body weight, suggesting that HMI83-2 is a promising lead compound for the development of novel antimitotic agents

Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis

Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC

Effect of Environmental Change while Climbing Mt. Daisen on Forced Vital Capacity and Forced Expiratory Volume % in Young Women

The aim of the present study was to clarify the effects of environmental change while climbing Mt. Daisen on forced vital capacity and forced expiratory volume % in young women in summer. Seven healthy Japanese women (age: 22.6 ± 4.2 years) volunteered to climb Mt. Daisen (1,709m), located in Tottori prefecture, in August. Participants\u27 expiratory forced vital capacity (FVC), forced expiratory volume % (FEV_%) and arterial oxygen saturation (SpO_2) were measured at 4 points (Ground: 10m, Rest point: 780m, Summit: 1,709m, Goal point: 780m). The measurements were conducted soon after the subjects\u27 arrival at each point. The degree of dyspnea sensation was measured at Ground, Rest point, Goal point and at each station. There were no significant changes in FVC. FEV_% at the summit was significantly lower than at the Ground and Rest point. No significant differences were found in SpO_2 at each measuring point. The degree of dyspnea sensation at each station soon after the subjects\u27 arrival was significantly higher than those at the Rest point. The results of this study indicated mild airway contraction induced by stresses on the respiratory system from increasing exercise intensity during an ascent of Mt. Daisen

Highly Stretchable Stress-Strain Sensor from Elastomer Nanocomposites with Movable Cross-links and Ketjenblack

Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress- strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices