Dual-alkylator Conditioning Regimen with Busulfan and Melphalan for Bone Marrow Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelofibrosis : The Results of a Retrospective Study at a Single Institution in Japan

Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant morbidity and mortality, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative approach. While the optimal conditioning regimen before allo-HSCT for MF patients remains to be determined, recent studies have suggested that a thiotepa-busulfan-containing dual-alkylator regimen, FBT regimen, may be associated with favorable outcomes. In Japan, however, thiotepa is not indicated for MF. Here we describe the results of 6 cases of MF treated with melphalan-busulfan containing dual-alkylator regimen, FBM regimen, followed by their first allo-HSCT at a single institution. Neutrophil and platelet engraftment was achieved in all patients. And a full donor chimerism was confirmed in all patients at ＋30 days after allo-HSCT. The relatively small size and short observation period of our study make it difficult to draw a definitive conclusion ; however, our results suggest that a dualalkylator regimen of FBM may be a candidate for an conditioning for allo-HSCT for MF, which should be verified with a large cohort of patients.Article信州医学雑誌 71(6) : 393-402, (2023)journal articl

Serum uric acid distribution according to SLC22A12 W258X genotype in a cross-sectional study of a general Japanese population

<p>Abstract</p> <p>Background</p> <p>Although <it>SLC22A12 258X </it>allele was found among those with hypouricemia, it was unknown that serum uric acid distribution among those with <it>SLC22A12 258X </it>allele. This study examined serum uric acid (SUA) distribution according to <it>SLC22A12 </it>W258X genotype in a general Japanese population.</p> <p>Methods</p> <p>Subjects were 5,023 health checkup examinees (3,413 males and 1,610 females) aged 35 to 69 years with creatinine < 2.0 mg/dL, who were participants of a cohort study belonging to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). <it>SLC22A12 </it>W258X was genotyped with a polymerase chain reaction with confronting two-pair primers.</p> <p>Results</p> <p>The genotype frequency was 4,793 for <it>WW</it>, 225 for <it>WX</it>, and 5 for <it>XX</it>, which was in Hardy-Weinberg equilibrium (p = 0.164) with <it>X </it>allele 0.023 (95% confidence interval [0.021-0.027]). Mean (range) SUA was 6.2 (2.1-11.4) mg/dL for <it>WW</it>, 3.9 (0.8-7.8) mg/dL for <it>WX</it>, and 0.8 (0.7-0.9) mg/dL for <it>XX </it>among males, and 4.5 (1.9-8.9) mg/dL, 3.3 (2.0-6.5) mg/dL, and 0.60 (0.5-0.7) mg/dL among females, respectively. Six individuals with SUA less than 1.0 mg/dL included two males with <it>XX </it>genotype, one male with <it>WX </it>genotype, and three females with <it>XX </it>genotype. Subjects with <it>WX </it>genotype were 14 (77.8%) of 18 males with a SUA of 1.0-2.9 mg/dL, and 28 (34.6%) of 81 females with the same range of SUA. The corresponding values were 131 (25.1%) of 522 males and 37 (3.5%) of 1,073 females for SUA 3.0-4.9 mg/dL, and 8 (0.4%) of 2,069 males and 5 (1.1%) of 429 females for SUA 5.0-6.9 mg/dL. The <it>X </it>allele effect for SUA less than 3 mg/dL was significantly (p < 0.001) higher in males (OR = 102.5, [33.9-309.8]) than in females (OR = 25.6 [14.4-45.3]).</p> <p>Conclusions</p> <p>Although <it>SLC22A12 </it>W258X was a determining genetic factor on SUA, SUA of those with <it>WX </it>genotype distributed widely from 0.8 mg/dL to 7.8 mg/dL. It indicated that other genetic traits and/or lifestyle affected SUA of those with <it>WX </it>genotype, as well as those with <it>WW </it>genotype.</p

Cellular Basis of Tissue Regeneration by Omentum

The omentum is a sheet-like tissue attached to the greater curvature of the stomach and contains secondary lymphoid organs called milky spots. The omentum has been used for its healing potential for over 100 years by transposing the omental pedicle to injured organs (omental transposition), but the mechanism by which omentum helps the healing process of damaged tissues is not well understood. Omental transposition promotes expansion of pancreatic islets, hepatocytes, embryonic kidney, and neurons. Omental cells (OCs) can be activated by foreign bodies in vivo. Once activated, they become a rich source for growth factors and express pluripotent stem cell markers. Moreover, OCs become engrafted in injured tissues suggesting that they might function as stem cells

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

Psychological Distress among Caregivers for Patients Who Die of Cancer: A Preliminary Study in Japan

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