[Successful treatment of acute promyelocytic leukemia with all-trans retinoic acid on hemodialysis for acute renal failure].

All-trans retinoic acid (ATRA) is used as standard induction therapy for acute promyelocytic leukemia (APL), but it is contraindicated for patients on hemodialysis. We present a case of a patient with APL on hemodialysis, intubated, and with marked disseminated intravascular coagulation (DIC) who was successfully treated with ATRA. A 49-year-old man was transferred to our hospital and admitted into the intensive care unit due to renal dysfunction, DIC, and pneumonia. Promyelocytes were noted in the peripheral blood, and he was diagnosed with APL after bone-marrow examination. Because of renal dysfunction, only Ara-C was used but with a reduced dose. The patient's condition improved, and he was extubated and withdrawn from dialysis on the 5th day of hospitalization. The patient suffered from APL syndrome during induction therapy, which necessitated ATRA withdrawal and steroid administration. Remission was achieved after induction therapy, and the patient is currently on maintenance therapy. There are few cases of patients with APL on hemodialysis who were treated with ATRA; hence, it is necessary to review the treatment plan for these patients.

Use of mTRAQ derivatization reagents on tissues for imaging neurotransmitters by MALDI imaging mass spectrometry: the triple spray method.

During drug development, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry is used for visually elucidating the distribution of substances such as biomarkers, candidate compounds, and metabolites in the tissues. However, it is difficult to make relative comparisons between tissue sections and there are still many challenges. Here, we report a new method of "triple spray" for the comparison of analyte distribution in multiple tissue slices. This method targets amino acids and amines, and it incorporates the application of the internal standard in the on-tissue derivatization step. With further development, it has the potential to alleviate problems caused by the matrix effect. Initially, we measured three serial sections of rat brain to verify the efficacy of this method. In the hypothalamus, where gamma-aminobutyric acid (GABA) is known to be present in high concentration, the GABA levels of the three serial section showed little variation (CV = 1.62%). Subsequently, we compared the GABA level in the brain between stroke-prone spontaneous hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats with three individuals each. It showed significant differences between these models at the pre-selected region of interest (p < 0.05). Our results show that the triple spray allows for relative comparison among multiple tissue slices with high reproducibility. Graphical abstract.

An In Vitro Human Liver Model by iPSC-Derived Parenchymal and Non-parenchymal Cells.

During liver development, hepatoblasts and liver non-parenchymal cells (NPCs) such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) constitute the liver bud where they proliferate and differentiate. Accordingly, we reasoned that liver NPCs would support the maturation of hepatocytes derived from human induced pluripotent stem cells (hiPSCs), which usually exhibit limited functions. We found that the transforming growth factor ß and Rho signaling pathways, respectively, regulated the proliferation and maturation of LSEC and HSC progenitors isolated from mouse fetal livers. Based on these results, we have established culture systems to generate LSECs and HSCs from hiPSCs. These hiPSC-derived NPCs exhibited distinctive phenotypes and promoted self-renewal of hiPSC-derived liver progenitor cells (LPCs) over the long term in the two-dimensional culture system without exogenous cytokines and hepatic maturation of hiPSC-derived LPCs. Thus, a functional human liver model can be constructed in vitro from the LPCs, LSECs, and HSCs derived from hiPSCs.