Preleukemia: hematological disorders prior to onset of leukemia

Published data on Japanese leukemia patients with a preleukemic hematological disorder were assessed. The reexamined cases were from the &#34;Japona Centra Revuo Medicina&#34; reported during the period from 1952 to 1971. Among preleukemic hematological disorders, hypoplastic anemia was the most frequently reported (41 of 62 cases). These &#34;hypoplastic preleukemia&#34; patients were rather elderly and terminated mostly in atypical myelocytic leukemia. The chief hematological feature of the hypoplastic preleukemia cases was the coexistence of a relative erythroid hyperplasia and a slight increase of myeloblasts in the bone marrow that was unusual in hypoplastic anemia. The presence of pancytopenia and hypocellular marrow with a relative erythroid hyperplasia combined with a slight increase of myeloblasts probably indicates hypoplastic preleukemia that terminates later in acute leukemia.</p

Constructing Machine-learned Interatomic Potentials for Covalent Bonding Materials and MD Analyses of Dislocation and Surface

As machine learning potentials for molecular dynamics (MD) simulations, Spectral Neighbor Analysis Potential (SNAP) and quadratic SNAP (qSNAP) were constructed for silicon (Si) and silicon carbide (SiC). The reproducibility of the basic material properties about perfect crystal, free surface and dislocation cores in Si and 3C-SiC was investigated. The coefficients of SNAP and qSNAP were optimized using liner regression to present energy and force obtained by DFT. In addition, hyperparameters (cutoff length and weights for optimization, here) were determined using genetic algorithm to reproduce elastic moduli obtained by DFT. Lattice constant and elastic moduli of Si crystal by MD using our SNAP or qSNAP agree well with the values of DFT, and they have higher accuracy than those by any empirical potential. Additionally, melting point and specific heat at constant pressure were calculated by MD correctly. Especially in qSNAP of Si, the surface energy of {100} and {111} planes and the reconstructed {100} surface structure were almost reproduced. For 3C-SiC, SNAP reproduces lattice constant and elastic moduli of DFT. Furthermore, edge dislocation cores were generated successfully. However, the potentials we constructed have insufficient reproducibility in the plastic region, so it is necessary to continue development

Antitumor activity of neocarzinostatin, effect on Rauscher leukemia in mice

Neocarzinostatin (NCS), an antibiotic with a high molecular weight, showed an inhibittory effect on Rauscher mouse leukemia. In normal mice, no significant changes were found in peri· pheral blood pictures except a tendency of lymphocytopenia, when O. 05mg/kg/day and O.50mg/kg/day of NCS were injected intraperi. toneally to two groups of mice for three days. On the other hand, peripheral nucleated cells of Rauscher leukemic mice decreased after intraperitoneal administration of NCS in a dose over O.25mg/kg/day for three days. The cells affected by NCS were mainly erythroblasts and smudged cells. Spleens of Rauscher leukemic mice treated with NCS have been reduced in weight, and histological examinations of livers showed a signicant decrease of infiltrating cells. In three groups treated with 0.25mg/kg/day of NCS for seven days, O.25mg/kg/day for three days and O.50mg/kg/day for three days, the.5()% survival time was longer than in the control group. Particularly, the 50% survival time in Rauscher leukemic mice treated with 0.50 mg/kg/day for three days was over twice that of the control group.</p

Remarkable Alteration of PD-L1 Expression after Immune Checkpoint Therapy in Patients with Non-Small-Cell Lung Cancer: Two Autopsy Case Reports

Pembrolizumab is an immune checkpoint inhibitor (ICI), currently recommended as thefirst-line treatment for patients with advanced non-small-cell lung cancer (NSCLC) showing 50% expression of programmed death-ligand 1 (PD-L1). Previously it was reported that platinum-based chemotherapy may change PD-L1 expression in solid cancers. However, no reports addressing alteration of PD-L1 expression after ICI therapy in NSCLC are available so far. The patients wereJapanesemales 83 and 87 years old,whowere diagnosedwithNSCLC based on the transbronchial lung biopsies showing sarcomatoid feature with high PD-L1 expression. They received Pembrolizumab,however, passed awaywith disease progression on day 27 and day 9, respectively. PD-L1, PD1, andCD8 antibodies were applied to pretreatment tumor biopsies and autopsy specimens. Immunoexpression of all themarkers was evaluated using Aperio ImageScope. We found that PD-L1 expression decreased significantly from 75.6% to 13.2% and from 100% to 58.8%, in patients 1 and 2, respectively. This alteration was less prominent in the perinecrotic tumor area. A considerable decrease of PD-L1 score was linked with a little effect of Pembrolizumab in our patients. This association might be one of the contributing mechanisms of resistance to ICI and needs further investigation in large-scale studies

Huggable Communication Medium Maintains Level of Trust during Conversation Game

There have been several attempts in recent years to develop a remote communication device using sensory modalities other than speech that would induce a user’s positive experience with his/her conversation partner. Specifically, Hugvie is a human-shaped pillow as well as a remote communication device enabling users to combine a hugging experience with telecommunication to improve the quality of remote communication.The present research is based on the hypothesis that using Hugvie maintains users’level of trust toward their conversation partners in situations prone to suspicion. Thelevel of trust felt toward other remote game players was compared between participants using Hugvie and those using a basic communication device while playing a modified version of Werewolf, a conversation-based game, designed to evaluate trust. Although there are always winners and losers in the regular version of Werewolf, the rules were modified to generate a possible scenario in which no enemy was present among the players and all players would win if they trusted each other. We examined the effect of using Hugvie while playing Werewolf on players’ level of trust toward each other and our results demonstrated that in those using Hugvie, the level of trust toward other players was maintained

Spatially resolved metabolic distribution for unraveling the physiological change and responses in tomato fruit using matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI–MSI)

Information on spatiotemporal metabolic behavior is indispensable for a precise understanding of physiological changes and responses, including those of ripening processes and wounding stress, in fruit, but such information is still limited. Here, we visualized the spatial distribution of metabolites within tissue sections of tomato (Solanum lycopersicum L.) fruit using a matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI–MSI) technique combined with a matrix sublimation/recrystallization method. This technique elucidated the unique distribution patterns of more than 30 metabolite-derived ions, including primary and secondary metabolites, simultaneously. To investigate spatiotemporal metabolic alterations during physiological changes at the whole-tissue level, MALDI–MSI was performed using the different ripening phenotypes of mature green and mature red tomato fruits. Although apparent alterations in the localization and intensity of many detected metabolites were not observed between the two tomatoes, the amounts of glutamate and adenosine monophosphate, umami compounds, increased in both mesocarp and locule regions during the ripening process. In contrast, malate, a sour compound, decreased in both regions. MALDI–MSI was also applied to evaluate more local metabolic responses to wounding stress. Accumulations of a glycoalkaloid, tomatine, and a low level of its glycosylated metabolite, esculeoside A, were found in the wound region where cell death had been induced. Their inverse levels were observed in non-wounded regions. Furthermore, the amounts of both compounds differed in the developmental stages. Thus, our MALDI–MSI technique increased the understanding of the physiological changes and responses of tomato fruit through the determination of spatiotemporally resolved metabolic alterations

Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation

Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXα. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-1 gene expression by polymerase chain reaction and HO-1 localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-1 gene expression levels significantly increased after I/R. In addition, HO-1 levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-1 gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO-1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-1 gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage