Search

Supplemental material, sj-docx-1-cix-10.1177_11769351221085064 for Using Natural Language Processing Techniques to Detect Adverse Events From Progress Notes Due to Chemotherapy by Yukinori Mashima, Takashi Tamura, Jun Kunikata, Shinobu Tada, Akiko Yamada, Masatoshi Tanigawa, Akiko Hayakawa, Hirokazu Tanabe and Hideto Yokoi in Cancer Informatics

Objective. Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T-cell infiltration into target tissues, but the specific cytokines, receptors, and T-cell populations remain largely unidentified. Role of the potent chemokine CXCL12 and its receptor CXCR4 in T-cell autoimmune response was examined using alymphoplasia (aly)/aly mice, a Sjögren’s syndrome (SS) model. Methods. T-cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunological analysis. In vitro migration assay was used to assess T-cell migratory activity toward several chemokines. Gene expression of chemokine receptors, and transforming growth factor (TGF)β receptors was measured with quantitative reverse transcription-polymerase chain reaction. The CXCR4 antagonist AMD3100 was administered to the aly/aly mice to evaluate its suppressive effect on autoimmune lesions. Results. Effector memory T (TEM) cells derived from aly/aly mice demonstrated higher in vitro migratory activity toward CXCL12 than aly/+ TEM cells. CXCL12 expression was specifically upregulated in the SS target cells of aly/aly mice. TEM cells from RelB−/− mice, but not nuclear factor (NF)-κB1−/− mice, also showed high migratory activity toward CXCL12, implicating a nonclassical NF-κB2/RelB pathway in the regulation of TEM cell migration. TEM cells from aly/aly mice also overexpressed TGFβ receptors I and II. The CXCR4 antagonist AMD3100 suppressed autoimmune lesions in aly/aly mice by reducing TEM cell infiltration. Conclusion. Our results suggest that the NF-κB2/RelB pathway regulates T-cell migration to autoimmune targets through TGFβ/TGFβR-dependent regulation of CXCL12−CXCR4 signaling. This suggests that these signaling pathways are potential therapeutic targets for treating autoimmune diseases.

The maternal immune system during pregnancy is largely changed to maintain immune tolerance against the embryo. Although thymus tissues, which generate T cells, are also dynamically altered during pregnancy, the precise phenotype of thymic T cells and gene alteration in thymus tissues remain to be completely elucidated. In this study, we performed a comprehensive analysis of gene expression and assessed T-cell phenotypic changes in the thymus of mice during pregnancy. Thymus tissues of female C57BL/6 mice during pregnancy were resected to investigate T-cell phenotypes using flow cytometric and immunofluorescence analyses and gene expression using a DNA microarray. Decreased weight of thymus tissues was observed during gestation. Cell numbers of total populations of thymic T cells in pregnant mice were significantly decreased compared with those in non-pregnant mice. DNA microarray and RT-PCR analyses revealed several upregulated genes in the thymus tissues of pregnant mice. Among them, the insulin growth factor-binding protein 5 (IGFBP5) was the most upregulated gene, and its increased protein expression of macrophages was confirmed by immunofluorescence analysis. In summary, a unique change in gene expression was observed in transient atrophy of thymus tissues during pregnancy. The change in gene expression, including that in IGFBP5 of macrophages, may influence thymic differentiation of T cells to maintain an immunological tolerance during pregnancy.

Objective: Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor (MOT) characterized by sheets and lobules of vacuolated and clear cells. To understand the biology of CCOC, we established a new cell line, CCOC-T, with EWSR1-ATF1 fusion gene from a mandible tumor with distant metastasis and characterized this cell line. Materials and methods: To detect the EWSR1-ATF1 fusion gene, we used three CCOC cases, including the present case, by RT-PCR and FISH analysis. We characterized established CCOC-T cells by checking cell growth, invasion and the expression of odontogenic factors and bone-related factors. Moreover, the gene expression profile of CCOC-T cells was examined by microarray analysis. Results: Histologically, the primary tumor was comprised of cords and nests containing clear and squamoid cells separated by fibrous septa. In addition, ameloblastomatous islands with palisaded peripheral cells were observed, indicating probable odontogenic origin. This tumor expressed the fusion gene EWSR1-ATF1, which underlies the etiology of hyalinizing clear cell carcinoma (HCCC) and potentially that of CCOC. We found a breakpoint in the EWSR1-ATF1 fusion to be the same as that reported in HCCC. Established CCOC-T cells grew extremely slowly, but the cells showed highly invasive activity. Moreover, CCOC-T cells expressed bone-related molecules, odontogenic factors, and epithelial mesenchymal transition (EMT)-related molecules. Conclusion: To the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT.

Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth.

原著, 入院中の学童の母親を対象に看護師が実施するケアについて、母親と看護師の認識と期待に違いがあるかを明らかにすることを目的に質問紙調査を実施した。分析対象は、入院している学童の母親80名と学童が入院中の病棟の看護師239名とした。学童の条件は、小学1～6年生、病状が比較的安定し、トイレへの移動が可能であることとした。説明や精神的な支援などから構成される母親へのケア7項目に関して、実践状況に関する母親と看護師の認識、母親がケアをどの程度期待しているかと母親の期待がどの程度あると看護師が推測するかも調査し、母親と看護師の回答の差異について分析した。その結果、母親への声かけ、母親の体調の気遣い、子どもの症状に対応できる情報提供では、看護師からケアを受けていると認識する母親は少なかった。体調の気遣いは、期待する母親も少なかった。看護師が、母親への関わりを工夫する必要性や、母親のニーズに応じた情報を提供する重要性が示唆された。

Background Nanomaterials are widely used in various fields. Although the toxicity of carbon nanotubes (CNTs) in pulmonary tissues has been demonstrated, the toxicological effect of CNTs on the immune system in the lung remains unclear. Methods and finding In this study, exposure to Taquann-treated multi-walled CNTs (T-CNTs) was performed using aerosols generated in an inhalation chamber. At 12 months after T-CNT exposure, alveolar inflammation with macrophage accumulation and hypertrophy of the alveolar walls were observed. In addition, fibrotic lesions were enhanced by T-CNT exposure. The macrophages in the bronchoalveolar lavage fluid of T-CNT-exposed mice were not largely shifted to any particular population, and were a mixed phenotype with M1 and M2 polarization. Moreover, the alveolar macrophages of T-CNT-exposed mice produced matrix metalloprotinase-12. Conclusions These results suggest that T-CNT exposure promoted chronic inflammation and fibrotic lesion formation in profibrotic macrophages for prolonged periods.

When pDHA4, a vector carrying all five pfaA-pfaE genes responsible for docosahexaenoic acid (DHA; 22:6) biosynthesis in Moritella marina MP-1, was coexpressed in Escherichia coli with the individual pfaA-pfaD genes for eicosapentaenoic acid (EPA; 20:5) biosynthesis from Shewanella pneumatophori SCRC-2738, both polyunsaturated fatty acids were synthesized only in the recombinant carrying pfaB for EPA synthesis. Escherichia coli coexpressing a deleted construct comprising pfaA, pfaC, pfaD and pfaE for EPA and pfaB for DHA produced EPA and DHA. Both EPA and DHA were detected in bacteria that inherently contained pfa genes for DHA. These results suggest that PfaB is the key enzyme determining the final product in EPA or DHA biosynthesis.