Small airway disease associated with Sjögren’s syndrome: Clinico-pathological correlations

SummaryBackgroundRelationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögren’s syndrome have remained unclear.Subjects and methods: We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögren’s syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögren’s syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores.ResultsBronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögren’s syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF50, MEF25 and air trapping.ConclusionsConstrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögren’s syndrome

Induction of macrophage migration inhibitory factor precedes the onset of acute tonsillitis.

We investigated the serum macrophage migration inhibitory factor (MIF) levels of palmoplantar pustulosis patients, before and after the tonsillar provocation test. Higher serum MIF levels of palmoplantar pustulosis patients were decreased after the tonsillar provocation test (n=29). To confirm these phenomena, two patients with acute tonsillitis had their changes in body temperature, C-reactive protein (CRP) and serum MIF levels examined during the course of their illness. Surprisingly, increased MIF preceded fever and CRP elevation, and MIF subsequently decreased at the onset of fever and CRP elevation. Since MIF is an initiator of other proinflammatory cytokines, we suggest that the induction of MIF may precede other inflammatory conditions

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

P2 hierarchy ノ カンゼン WKB カイセキ

京都大学0048新制・論文博士博士(理学)乙第12110号論理博第1493号新制||理||1475(附属図書館)UT51-2007-Q827京都大学大学院理学研究科数学・数理解析専攻(主査)准教授 竹井 義次, 教授 岡本 久, 教授 向井 茂学位規則第4条第2項該当Doctor of ScienceKyoto UniversityDA

二成分高分子系における共連続相分離構造の界面曲率に関する研究

京都大学0048新制・論文博士博士(工学)乙第10314号論工博第3488号新制||工||1163(附属図書館)UT51-2000-C81(主査)教授 橋本 竹治, 教授 粷谷 信三, 教授 田中 文彦学位規則第4条第2項該当Doctor of EngineeringKyoto UniversityDA

Small-angle scattering tomography of precipitation-hardened multilayer Al/Al-Zn/Al model alloys

Tomographic images constructed from small-angle X-ray scattering (SAXS) intensities utilizing microbeams have been examined for a model multilayered aluminum alloy sample heat-treated to form spatially modulated composition and microstructures. Spatial distributions of composition and precipitation microstructure have been examined by one-dimensional scanning SAXS measurements and two-dimensional tomographic images of attenuation parameters and integrated intensity of SAXS intensity. Reconstructed images using the integrated intensity reflected the distribution of precipitates in terms of their volume fraction over the sample inside the sample, and agreed with more detailed analysis made in the one-dimensional case