Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events

Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms

ボウサイ キョウイク ニ カンスル ショウガッコウ キョウイン ヨウセイ カテイ ガクセイ ノ イシキ : コクサイ キョウイク キョウリョク ニオケル ニホン ノ ヒカク ユウイセイ オ ゼンテイ トシテ

The purposes of this paper are two-hold：（1） to point out the Japanese comparative advantages and issues of disaster prevention education for the international community, （2） to investigate characteristics of prospective elementary school teachers\u27 awareness in disaster prevention education. For these purposes, firstly, we arrange the circumstances and results of patrimony about disaster prevention education in recent years. Secondly, a questionnaire survey was conducted on 113 prospective primary teachers （undergraduate students）. The results indicated three main points：（a） although disaster prevention education must be a comparative advantage, there are a lot of tasks such as curriculum development in a teacher training. （b） Prospective elementary school teachers have interest in disaster reduction education to study professional issues. （c） Six factors extracted from their consciousness by factor analysis, and highly technical factors had positively affected confidence in judgment, instructions under disaster, development of pupil\u27s independence during usual activity

D-dimer trends predict recurrent stroke in patients with cancer-related hypercoagulability

Abstract Introduction: In patients with cancer-associated hypercoagulability (CAH)-related stroke, D-dimer trends after anticoagulant therapy may offer a biomarker of treatment efficacy. The purpose of this study was to clarify the association between D-dimer trends and recurrent stroke after anticoagulant therapy in patients with CAH-related stroke. Methods: We performed retrospective cohort study of consecutive patients with CAH-related stroke at two stroke centers from 2011 through 2020. The ratio of post-treatment to pre-treatment D-dimer levels (post/pre ratio) was used as an indicator of D-dimer trends after anticoagulant therapy. Fine–Gray models were used to evaluate the association between post/pre ratio and recurrent stroke. Results: Among 360 acute ischemic stroke patients with active cancer, 73 patients with CAH-related stroke were included in this study. Recurrent stroke occurred in 13 patients (18%) during a median follow-up time of 28 days (interquartile range, 11–65 days). Multivariate analysis revealed that high post/pre ratio was independently associated with recurrent stroke (per 0.1 increase: hazard ratio 2.20, 95% confidence interval 1.61–3.01, p=0.012). Discussion and Conclusion: D-dimer levels after anticoagulant therapy were associated with recurrent stroke in CAH-related stroke patients. Patients with neutral trends in high D-dimer levels after anticoagulant therapy were at high risk of recurrent stroke

RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules

AbstractHuman RSV causes an annual epidemic of respiratory tract illness in infants and in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses include inhibition of type I IFN mRNA transcription and blocking signal transduction of JAK/STAT family members. The suppressor of cytokines signaling (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and block the activation of the JAK/STAT signaling pathway. To evaluate the potential of SOCS molecules to subvert the innate immune response to RSV infection, eight SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells. Suppression of SOCS1, SOCS3 and CIS by short interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore, inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing STAT1/2 phosphorylation. These results suggest that RSV infection escapes the innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in epithelial cells

産後うつとボンディングの関連の経産による変化: 子どもの健康と環境に関する全国調査からの経時的な結果より

富山大学・富医薬博乙77号・土田 暁子・2020/11/25関連論文Tsuchida A, Hamazaki K, Matsumura K, Miura K, Kasamatsu H, Inadera H; Japan Environment and Children\u27s Study (JECS) Group. Changes in the association between postpartum depression and mother-infant bonding by parity: Longitudinal results from the Japan Environment and Children\u27s Study. J Psychiatr Res. 2019 Mar;110:110-116. doi: 10.1016/j.jpsychires.2018.11.022. Epub 2018 Nov 28. PMID: 30616158.富山大

Involvement of Girdin in the Determination of Cell Polarity during Cell Migration

Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement

Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones

The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

publication en ligne. Article dans revue scientifique avec comité de lecture. nationale.National audienceThe human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology

Sudden Onset of Brain Metastasis despite the Use of Vemurafenib for Another Metastatic Lesion in Malignant Melanoma Patients

Vemurafenib is an inhibitor of the BRAF mutation and has been approved by the Food and Drug Administration as a treatment option for patients with unresectable melanoma without brain metastasis. In the literature, vemurafenib has been reported to be also effective against brain metastasis. We encountered 3 cases with brain metastasis on vemurafenib therapy. In these cases, vemurafenib was clinically effective against metastatic lesions other than those in the brain. The brain lesions developed after the metastatic lesion had occurred. Therefore, we assume that the melanomas of the patients acquired resistance against vemurafenib. The brain metastases were treated with the cyberknife. Patients 1 and 2 without LDH elevation are still alive, but patient 3 with abnormal LDH elevation died despite the treatment. We need to carefully follow patients on vemurafenib therapy because brain metastasis can suddenly occur even if the metastatic lesion has decreased clinically. The therapeutic effect of vemurafenib against brain metastasis is poor in cases with LDH elevation

Successful Treatment of Sudden Hepatitis Induced by Long-Term Nivolumab Administration

Immune checkpoint inhibitors have drastically changed in the treatment of many kinds of malignancies, especially malignant melanoma. The focus of the recent experiments has not only been on their efficacy but also immune-related adverse events (irAEs). We report a case of fulminant hepatitis due to nivolumab. In this case, the patient had undergone long-term nivolumab therapy. He did not complain of any symptoms but his liver enzyme levels were extremely elevated (grade 4). We promptly decided to start oral corticosteroids in the patient. His liver function rapidly improved. The dose of corticosteroids was gradually reduced. Our case demonstrates that sudden onset fulminant hepatitis can occur despite the safe use of long-term nivolumab therapy. The irAE can improve rapidly with proper corticosteroid treatment. This report will be useful for the physicians who always use immune checkpoint inhibitors