Azacitidine Treatment Following Intensive Chemotherapy with Daunorubicin and Cytarabin for Acute Transformation in Myelodysplastic/Myeloproliferative Neoplasms

Article信州医学雑誌 62(3):167-172(2014)journal articl

Attaining Complete Remission May Confer a Better Outcome after Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute B-cell Lymphoblastic Leukemia

Introduction : Treatment outcome of adult patients with acute B-cell lymphoblastic leukemia (ALL) is suboptimal even after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To maximize the efficacies of this treatment strategy, risk stratification is crucial. Methods : We retrospectively collected clinical data of the adult patients with allo-HSCT for ALL at a single insitiution in Japan between 2003 and 2022. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS), progression-free survival (PFS) and GVHD-free-and-relapse-free survival (GRFS) at 3 years. Results : A total of 58 patients were included with 34 females and a median age of 39. Sixty-two percent of patients harbored high-risk cytogenetic features or Philadelphia chromosome (Ph). Hematologic complete response (CR) rate was 93 ％ after a first induction, but 75.9 ％ were in CR at allo-HSCT. Blinatumomab was used in 1.7 ％ of patients. A chimeric mRNA had been detected in 4 of 26 patients at allo-HSCT. The 3-year OS, PFS and GRFS were 72.7 ％, 54.7 ％ and 46.2 ％, respectively. Pre-transplantation CR was an independent risk factor. Discussion/Conclusions : Our results imply that a better OS may potentially be achieved by improved pretransplantation CR rate with more frequent application of novel agents.Article信州医学雑誌 71(5) : 257-267, (2023)journal articl

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

STAT3 gene mutations and their association with pure red cell aplasia in large granular lymphocyte leukemia

Large granular lymphocyte leukemia (LGLL) has been morphologically characterized as a group of lymphoproliferative diseases that include T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of natural killer cells (CLPD-NK). We investigated mutations in the Src homology 2 (SH2) domain of the signal transducer and activator of transcription 3 (STAT3) gene in Asian cohorts of T-LGLL and CLPD-NK (n=42 and 11, respectively). Two mutations, Y640F and D661Y, were identified using direct sequencing or allele-specific (AS) PCR. Y640F and D661Y mutations were found in seven and 18 patients, respectively. Two patients were positive for both mutations. Frequencies of STAT3 mutations in T-LGLL and CLPD-NK were 47.6% and 27.2%, respectively. Pure red cell aplasia (PRCA) was associated with the mutations (P=0.005). The mutations were persistently found at stable levels in some patients after more than 5years using AS-quantitative PCR. The results of the present study indicate that the SH2 domain of the STAT3 gene is frequently mutated in Asian T-LGLL and CLPD-NK, and that PRCA is closely correlated with the mutations. SH2 domain of the STAT3 gene is frequently mutated in Asian T cell large granular lymphocyte leukemia and chronic lymphoproliferative disorders of NK cells. Pure red cell aplasia is closely associated with the mutations.ArticleCANCER SCIENCE. 105(3):342-346 (2014)journal articl

Improved Thermal Performance of Combined Convection and Radiation Using Room Air Conditioner

This study aims to evaluate the indoor thermal environment within a detached residence in summer by applying combined convection and radiation air conditioning system using the refrigerant gas of room air conditioners (RACs). First, field measurements were performed in a detached residence at Hiroshima, Japan, in July and August 2021. Consequently, PMV values were generally maintained within the comfortable range during air-conditioning operation. The amount of heat generated by convection (via the RAC indoor unit) Qc and that by radiation (via the radiation panel) Qr were determined as 426 and 259 W, respectively, and the overall heat generated Qtotal was determined as 685 W. Applying the CFD model, thermal environment was compared varying the ratio between Qc and Qr with a constant Qtotal of 685 W. Results showed that the synergistic operation of a RAC and a radiant panel presented more comfortable PMV values than that of a single RAC application. Furthermore, the airflow from the RAC decreased with an increase in Qr ratio, and the chilled radiant panel provided a cooling effect around the dining area, where the airflow of the RAC was inadequate, thereby improving the thermal comfort

Reducing energy consumption of heat pumps by introducing a thermal energy storage system

We proposed a short-term thermal energy storage system by applying Phase Change Materials (PCMs) in air ducts connected to an indoor air conditioning unit within a ceiling space. PCM tubes were arranged in a staggered layout in the air duct and cooled by chilled air from the air conditioning unit during “charging” mode, whereas the PCM tubes released cold energy to the room space without operation of the compressor during “discharging” mode. The charging mode allowed for an increase in the partial load ratio of the heat pump to prevent low-efficiency operation at <20% load, which can increase seasonal energy efficiency. We constructed an energy simulation program, where the heat exchange coefficient between the PCM tubes and air was varied with airflow rate and the temperature difference between the PCM and air, in accordance with results from CFD analysis. Switching between the charging and discharging modes was based on the outlet temperature (Tout) and 30% of the rated capacity of the indoor unit (Lr). The heat balance between the charging and discharging modes was improved by this change to the system control. A higher load factor and higher COP resulted in a 7.6% reduction in energy consumption

Computational fluid dynamics analysis in the ductless whole-house air conditioning system

Recently, the heat load for space heating in residential houses has been reduced as airtightness, and thermal insulation performance has been improving even in moderate climate regions of Japan. In such situations, the heat load can be handled by one room air-conditioner with high energy efficiency. We report the results of computational fluid dynamics (CFD) analysis of an indoor thermal environment and the airflow distribution during the space heating operation in a ductless house air conditioning system, in which heated air from a room air conditioner installed in a thermal-insulated basement space is distributed throughout the building using air inlets on the floor in each story and open-door rooms without ductworks. To determine the adequate size and position of the air inlets on the floor in this heating system, we evaluated the air circulation performance for changes in the conditions of the air inlets by CFD analysis for a standard two-storey house model in Japan. The results suggest that the air temperature distribution is markedly different in the size and position of the air inlets on the floor. Large volumes of airflow through the openings in the building resulted in maintaining the rooms at a temperature range of 17 to 24 degrees uniformly. These results also provide information for system and building designs for effective space heating and for proper usage when choosing to open or close air inlets in the operational phase

Molecular Mechanism of Spectral Tuning by Chloride Binding in Monkey Green Sensitive Visual Pigment

The visual pigments of the cones perceive red, green, and blue colors. The monkey green (MG) pigment possesses a unique Cl− binding site; however, its relationship to the spectral tuning in green pigments remains elusive. Recently, FTIR spectroscopy revealed the characteristic structural modifications of the retinal binding site by Cl− binding. Herein, we report the computational structural modeling of MG pigments and quantum-chemical simulation to investigate its spectral redshift and physicochemical relevance when Cl− is present. Our protein structures reflect the previously suggested structural changes. AlphaFold2 failed to predict these structural changes. Excited-state calculations successfully reproduced the experimental red-shifted absorption energies, corroborating our protein structures. Electrostatic energy decomposition revealed that the redshift results from the His197 protonation state and conformations of Glu129, Ser202, and Ala308; however, Cl− itself contributes to the blueshift. Site-directed mutagenesis supported our analysis. These modeled structures may provide a valuable foundation for studying cone pigments