Thermodynamic data for pure gold were critically assessed using an extended Einstein model from 0 K for the crystalline FCC_A1 phase and a two state model for the liquid phase. During the assessment, ...careful critical evaluation of the experimental data on thermodynamic properties of solid (FCC_A1) and liquid phases was carried out. Due to the fact that there is a large scatter in the experimental data for crystalline gold in the temperature range between 200 K and the melting point, we carried out additional ab initio calculations of the thermodynamic properties. In order to fulfil the need for a precise evaluation of So298.15 we needed to use an additional technique using multiple Einstein functions, which allows the experimental heat capacity and enthalpy data for the solid phase to be approximated accurately from 0 K up to the melting point. It was found during the data analysis that there is a large scatter in experimental data for the enthalpy of fusion and the liquid phase.
•Thermodynamic data for solid and liquid Au were assessed from 0 K.•Ab-initio simulations to define the Cp for solid gold were carried out.•Multiple Einstein functions were used for a precise evaluation of So298.•An extended Einstein model was used for the crystalline phase.•Two-state model was used for the liquid phase.
We studied suppressor potential of myeloid-derived suppressor cells (MDSC) in multiple myeloma patients, including before and after mobilization of hematopoietic stem cells (HSC), by evaluating the ...expression of arginase-1 (Arg1), indolamine-2,3-dioxygenase (IDO), and PD-L1 in MDSC subsets. The study included 20 multiple myeloma patients in remission, 5 patients with progression, as well as 10 sex-and age-matched healthy donors. The expression of Arg1, IDO, and PD-L1 in circulating granulocytic MDSC (G-MDSC, Lin
–
HLA-DR
–
CD33
+
CD66b
+
), monocytic MDSC (M-MDSC, CD14
+
HLA-DR
low/–
), and early-stage MDSC (E-MDSC, Lin
–
HLA-DR
–
CD33
+
CD66b
–
) was evaluated by flow cytometry. Multiple myeloma patients in remission were characterized by reduced expression of Arg1 in M-MDSC in comparison with donors. The expression of Arg1 in M-MDSC depended on the number of induction therapy lines performed and was significantly lower in patients who received ⩾2 lines and responded with remission. Patients with multiple myeloma progression (resistant to therapy) showed significantly increased expression of Arg1 and PD-L1 in M-MDSC, as well as increased expression of Arg1 in E-MDSC. After G-CSF-induced mobilization of HSC, the content of circulating Arg1-expressing M-MDSC increased significantly. Considering the presence of MDSC in apheresis products, MDSC suppressive activity is discussed as a factor affecting the outcomes of autologous HSC transplantation in multiple myeloma patients.
All types of immune cells are involved in the pathogenesis of multiple myeloma (MM). Granulocytic (G-MDSCs) and monocytic myeloid-derived suppressor cells (M-MDSCs) have significant protumor effects. ...The T cell immune response may be reduced due to the development of T cell exhaustion, characterized by the expression of inhibitory receptors PD-1, TIM-3, etc. Granulocyte colony-stimulating factor (G-CSF) supports the generation and expansion of MDSCs and can influence the functional properties of T cells. The purpose of our work was to investigate the possible effect of stimulation with G-CSF drugs on the induction of PD-1 and TIM-3 expression by T cells in patients with MM. The study included 40 patients with MM who underwent mobilization of hematopoietic progenitor cells with G-CSF drugs (5 mcg/kg/day) for 4-5 days. Content of CD4 + PD-1 + , CD4 + TIM-3 + , CD8 + PD-1 + , CD8 + TIM-3 + T cells, Lin-HLA-DR-CD33 + CD66b + G-MDSCs, and CD14 + HLA-DR - M-MDSCs was assessed before the start of a course of G-CSF injections (n = 33), after a course of G-CSF on the first day of separation of hematopoietic progenitor cells (n = 28) and after 3-6 months (n = 40) by flow cytometry. The relative content of G-MDSCs and M-MDSCs was significantly higher in patients with MM after a course of G-CSF. After 3-6 months, the content of G-MDSCs and M-MDSCs decreased to the initial values. After the course of G-CSF, an increase in the content of CD4 + PD-1 + T cells was noted compared to the values before the study. After 3-6 months, the content of this population did not differ from the initial values. The relative numbers of CD4 + TIM-3 + , CD8 + PD-1 + , and CD8 + TIM-3 + T cells did not change after a course of G-CSF. There were no significant correlations between the content of the populations of MDSCs and T cells expressing PD-1 and TIM-3 after a course of G-CSF. Mobilization of hematopoietic stem cells by G-CSF in patients with MM is accompanied by a transient increase in MM populations and an isolated increase in CD4 + PD-1 + T cells.
The avoidance of immune surveillance by malignant plasma cells (PCs) in multiple myeloma (MM) is mediated by different mechanisms, among which an induction of T cell exhaustion and expansion of ...myeloid-derived suppressor cells (MDSCs) appear to play substantial roles, but it is still a lack of data on possible MDSC-mediated induction of T cell exhaustion. The aim of the present work was to evaluate possible relationship between frequencies of MM PCs, MDSCs and phenotypically exhausted PD-1
+
and TIM-3
+
T cells in bone marrow (BM) samples and peripheral blood (PB) of MM patients at various disease stages. Peripheral blood (n = 88) and BM samples (n = 56) were obtained from MM patients (newly diagnosed (n = 6), patients in remission (n = 71) and with progressive disease (n = 11)). Frequencies of T cells expressing checkpoint receptors PD-1 and TIM-3, polymorphonuclear MDSCs (PMN-MDSCs, Lin
-
CD14
-
HLA-DR
-
CD33
+
CD15
+
/CD66b
+
), monocyte MDSCs (M-MDSCs, CD14
+
HLA-DR
low/-
), early MDSCs (E-MDSCs, Lin
-
HLA-DR
-
CD33
+
CD15
-
/CD66b
-
), and MM PCs (CD45
dim
CD38
+
CD138
+
CD56
+
CD19
-
CD117
+
CD27
-
CD81
-
) were assessed with flow cytometry. Circulating and BM-resident PD-1
+
/TIM-3
+
T cell subsets, BM E-MDSCs, as soon as MM PCs and serum beta2-microglobulin (B2-M) levels were gradually increased in patients at different stages. Despite that, there were no associations between the markers of tumor load and the studied cell subsets. In patients in remission, BM PMN-MDSCs negatively correlated with CD4
+
T cells, CD4
+
PD-1
+
and CD8
+
TIM-3
+
T cell subsets; there were positive correlations between BM E-MDSCs and CD4
+
PD-1
+
TIM-3
+
cells and PB M-MDSCs and CD8
+
PD-1
+
and (as a trend) CD8
+
TIM-3
+
T cells. We found no associations for the samples of patients at diagnosis and with progression. We can conclude that a possible mutual influence of malignant PCs, MDSCs and PD-1
+
/TIM-3
+
T cells is nonlinear, especially during a manifest tumor growth at diagnosis and progression. The detected negative correlations between resident PMN- MDSCs and T cell subsets might be associated with MDSC suppressive function, affecting both predominantly activated PD-1
+
cells and exhausted TIM-3
+
subsets. The positive correlations between BM E-MDSCs and CD4+PD-1
+
TIM-3
+
cell subset and circulating M-MDSCs and PD-1
+
and TIM-3
+
CD8
+
T cells might confirm an ability of MDSCs to induce T cell exhaustion.
Introduction
. Myeloid-derived suppressor cells (MDSCs) play an important role in restriction of the immune response and are associated with a poor prognosis in cancer. Mobilization of hematopoietic ...stem cells (HSCs) before high-dose chemotherapy (HCT) with autologous HSC transplantation (auto-HSCT) is accompanied by a signifcant increase in MDSC counts in peripheral blood and apheresis product of multiple myeloma (MM) patients. However, quantitative changes of these cells at the post-transplant and their role at the immune recovery remain unexplored.
The study was aimed
to analyze the dynamics of circulating MDSC counts and the expression of suppressor molecule arginase-1 in patients with MM in the frst 12 months after HCT and auto-HSCT and evaluate association between MDSCs and transplantation outcomes.
Material and Methods
. The study included 44 MM patients who underwent HCT and auto-HSCT. The relative number of granulocytic MDSCs (G-MDSCs), monocytic MDSCs (M-MDSCs), and early-stage MDSCs (E-MDSCs), as well as the expression of arginase-1 in each of MDSC subsets was evaluated by fow cytometry in patient peripheral blood samples.
Results. At the engraftment (day +12 – +16, leukocytes >1×10
9
/l), M-MDSC relative count was increased (p
U
=0.038), as well as the relative (p
U
=0.003) and absolute (p
U
˂
0.0001) counts of G-MDSCs, decreasing after 6 months down to pre-transplant values (рU=0.007, рU=0.024 and рU=0.02, respectively) and remaining at the same level at the 12-month follow-up period. The absolute count of E-MDSCs by the time of the engraftment decreased transiently (p
U
=0.004 vs before HCT), gradually recovering by 12-month follow-up (p
U
=0.032 vs day +12 – +16). The remission within 12 months in the group with G-MDSCs˂0.17 % at the engraftment was observed in 67 ± 11 % of patients, with G-MDSCs >0.17 % – in 94 ± 6 % of patients (p=0.049). During the 12-month post-transplant, the number of M-MDSCs expressing arginase-1 has been increasing, with a tendency to lower values at the engraftment in patients with early MM relapse (p
U
=0.09).
Conclusion
. The association of early MM relapse after auto-HSCT with the lower count of G-MDSCs and the lower count of arginase-1
+
M-MDSCs at the engraftment suggests that MDSCs is involved in the restriction of homeostatic proliferation as a factor for more effective immune recovery.
A critical assessment of the thermodynamic and phase diagram data for the crystalline and liquid phases of the Ge-O system at ambient pressures has been carried out to provide a set of parameters ...which can be used as a basis for the calculation of ternary and multicomponent phase equilibria. The phase diagram reported by Massalski (Binary Alloy Phase Diagrams, ASM International, Materials Park,
1990
) does not correctly reproduce the rather limited experimental information for the system. There is some inconsistency between the rather more extensive experimental thermodynamic data for the three phases of GeO
2
stable at ambient pressures.
This work describes the specific features of the influenza virus circulating in the period from October 2015 to March 2016 in 10 cities of Russia, the basic laboratories of CEEI at the D.I. Ivanovsky ...Institute of Virology “Federal Research Centre of Epidemilogy and Microbiology named after the honorary academician N.F. Gamaleya” of the Ministry of Health of the Russian Federation. The increase in the morbidity caused by influenza viruses was detected in January-February 2016. The duration of the morbidity peak was 4-5 weeks. The most vulnerable group included children at the age from 3 to 6; a high rate of hospitalization was also detected among people at the age of 15-64 (65%). In clinic symptoms there were middle and severe forms with high frequency of hospitalization as compared with the season of 2009-2010, but much higher in comparison with the season of 2014-2015. Some of the hospitalized patients had virus pneumonias, half of which were bilateral. Among these patients, 10% were children; 30%, adults. The mortality in the intensive care unit of the hospital was 46%. Almost all lethal cases were among unvaccinated patients in the case of late hospitalization and without early antiviral therapy. The predominance of the influenza A(H1N1)09pdm virus both in the Russian Federation and the major part of the countries in the Northern hemisphere was noted. The results of the study of the antigenic properties of influenza strains of A(H1N1)pdm09 virus did not reveal any differences with respect to the vaccine virus. The sequencing data showed the amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in genes encoding internal proteins (PA, NP, M1, NS1). Strains were sensitive to oseltamivir and zanamivir and maintained resistance to rimantadine. The participation of non-influenza ARI viruses was comparable to that in preliminary epidemic seasons.
The peculiarities of the influenza viruses circulation in 2012-2013 are discussed. The results were obtained in 10 cities of Russia, where basic laboratories of the Influenza Ecology and Epidemics ...Center of on the basis of Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, are situated. The increasing rate of the ARD morbidity caused by influenza viruses was observed in January-March 2013. The highest indices of the morbidity were detected during 6-7 weeks with the following decreasing rate till threshold levels to week 14. The influenza A (H1N1) pdm09, A (H3N2), and B viruses were the cause of the epidemic, but their activity differed over areas of Russia. The results of study of the antigenic and genetic properties of the influenza strains demonstrated closed relatives with respect to vaccine strains. In addition, some heterogeneity of the circulating strains and their drift variants were found as well. All tested strains were sensitive to oseltamivir (excluding one A (H1N1) pdm09 strain), zanamivir, arbidol, and remained resistant to rimantadine. The ratio of the ARD viruses was comparable with the last epidemic seasons.
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