ABSTRACT
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-DRlow/-), 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.
Subject(s)
Multiple Myeloma , Myeloid-Derived Suppressor Cells , Humans , B7-H1 Antigen/genetics , Multiple Myeloma/therapy , HLA-DR AntigensABSTRACT
We showed that inhibition of cytokine production by bone marrow adherent cells and their soluble products is a mechanism of regulation of cytokine-producing activity of bone marrow erythrokaryocytes under normal conditions.
Subject(s)
Bone Marrow Cells/metabolism , Cytokines/metabolism , Erythrocytes/metabolism , Chemotactic Factors/metabolism , Glycophorins/metabolism , Granulocyte Colony-Stimulating Factor/metabolism , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Interleukin-13/metabolism , Interleukin-17/metabolism , Interleukin-1beta/metabolism , Interleukin-4/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Macrophage Inflammatory Proteins/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In human cells, expression of IL-4 gene involves alternative mRNA splicing. IL-4delta2 splice variant is an antagonist of full-length IL-4 protein and blocks its effect on the functional activity of immunocompetent cells. The effect of recombinant IL-4delta2 on cytokine-producing activity of human peripheral blood mononuclear cells is shown for the first time.
Subject(s)
Interleukin-4/pharmacology , Leukocytes, Mononuclear/drug effects , Alternative Splicing , Cell Proliferation/drug effects , Humans , Immunoglobulin E/biosynthesis , Immunoglobulin E/blood , In Vitro Techniques , Interleukin-4/genetics , Interleukin-6/biosynthesis , Interleukin-6/blood , Interleukin-6/genetics , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Recombinant Proteins/pharmacologyABSTRACT
AIM: To analyse the results of diagnosis and treatment of patients with aquired aplastic anemia (AA) in one center. MATERIAL AND METHODS: All AA patients, diagnosed and treated in one clinic in 1998-2005, were included in the trial. In severe and very severe AA (SAA/VSAA) the patients (n = 19) received combined immunosuppressive therapy (IST) with antithymocytic globulin (ATG) and cyclosporin A (CsA), in non-severe AA (NSAA) the patients (n = 9) were given monotherapy with CsA. Allogenic transplantation of bone marrow (alloTBM) was made in 4 young patients with SAA/VSAA. RESULTS: The diagnosis of AA was established in 33 patients (19 males and 14 females): NSAA in 9, SAA in 19, VSAA in 5, idiopathic--in 26, posthepatic--in 5, associated with pregnancy--in 2 patients. Age median was 20 years (13-53). The clone of paroxysmal nocturnal hemoglobinuria (PNH) was identified in 7 of 33 patients (21%), antigen HLA-DRB1 *15 in 6 of 11 patients (55%). In median of 26-month follow-up 31 patients (94%) were alive. In IST, complete or partial remissions were obtained in 88% patients. Median of the interval to achievement of transfusion independence made up 2.5 months. All the patients after alloTBM are in complete remission, chronic extensive transplant against host reaction was observed in one case. CONCLUSION: Introduction of updated protocols provides long-term survival of more than 80% AA patients. To optimize treatment outcomes, it is necessary to include newly diagnosed AA patients into ongoing multicenter studies.
Subject(s)
Anemia, Aplastic/diagnosis , Anemia, Aplastic/therapy , Bone Marrow Transplantation , Immunosuppression Therapy , Anemia, Aplastic/drug therapy , Antilymphocyte Serum/therapeutic use , Combined Modality Therapy , Cyclosporine/therapeutic use , Female , Humans , Immunosuppressive Agents , Male , Treatment OutcomeABSTRACT
The subject of the case study was blood of 8 fish species. It was examined within the ABO system. 68 tests of stains of fish blood mixed with human blood were made. It was shown as possible to differentiate between human blood and fish blood in mixed stains.
Subject(s)
ABO Blood-Group System , Blood Grouping and Crossmatching , Blood Stains , Fishes/blood , Animals , HumansABSTRACT
Fragments of the bones, nails, and teeth were examined in 12 forensic biological departments of bureaus for forensic medical expert evaluation of the Russian Federation. A total of 790 experiments were carried out with 145 bones, 5 teeth, and nails from 12 cadavers. In the overwhelming majority of cases the experiments were carried out with control investigations of blood, hair, salivary, and sweat samples. Modifications of the absorption-elution method were used to detect the AB0 antigens, these modifications involving all stages of the test (fixation, fat extraction, medium for elution, reagents, time factors in absorption and elution, etc.). Analysis of the data permitted the authors to make some conclusions and offer recommendations for practical biological experts.
