Acute myeloid leukemia (AML) is the most common form of acute leukemia diagnosed in adults. Despite advances in medical care, the treatment of AML still faces many challenges, such as treatment-related toxicities, that limit the use of high-intensity chemotherapy, especially in elderly patients. Currently, various immunotherapeutic approaches, that is, CAR-T cells, BiTEs, and immune checkpoint inhibitors, are being tested in clinical trials to prolong remission and improve the overall survival of AML patients. However, early reports show only limited benefits of these interventions and only in a subset of patients, showing the need for better patient stratification based on immunological markers. We have therefore developed and optimized a 30-color panel for evaluation of effector immune cell (NK cells, γδ T cells, NKT-like T cells, and classical T cells) infiltration into the bone marrow and analysis of their phenotype with regard to their differentiation, expression of inhibitory (PD-1, TIGIT, Tim3, NKG2A) and activating receptors (DNAM-1, NKG2D). We also evaluate the immune evasive phenotype of CD33+ myeloid cells, CD34+CD38-, and CD34+CD38+ hematopoietic stem and progenitor cells by analyzing the expression of inhibitory ligands such as PD-L1, CD112, CD155, and CD200. Our panel can be a valuable tool for patient stratification in clinical trials and can also be used to broaden our understanding of check-point inhibitory networks in AML.

• MeSH
• Leukemia, Myeloid, Acute * immunology   pathology   MeSH
• Killer Cells, Natural immunology   MeSH
• Bone Marrow * pathology   immunology   MeSH
• Humans MeSH
• Flow Cytometry methods   MeSH
• T-Lymphocytes immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Publikace se zaměřuje na dějiny České společnosti biotypologické, konstitučního lékařství, antropometrie a eugeniky v Československu v letech 1937-1959. Určeno odborné veřejnosti.; Publikace se zabývá vznikem, činností a zánikem České společnosti biotypologické a pronikáním vědy o lidské konstituci do československé medicíny v období od poloviny 30. do konce 50. let 20. století. Biotypologie neboli věda o lidské konstituci vycházela z ambice klasifikovat každého jedince na základě jeho morfologických a fyziologických vlastností ve vztahu k ideálně stanovenému konstitučnímu typu. Byla založena na přesvědčení o pevné korelaci mezi fyzickou podobou, psychickými vlastnostmi a mentálními schopnostmi člověka a na snaze o zobecnění individuálních vlastností, matematické typizaci a odvozování funkce z tvaru. Biotypologové si slibovali poznání nejskrytějších zákoutí lidské individuality, a tím i získání přehledu o vlastnostech, schopnostech a zdravotním potenciálu populace. Mělo jít o výchozí bod pro racionální a efektivní lékařskou péči a pro výchovu, výběr a vhodné pracovní umístění člověka v podmínkách masové výroby. Mimořádný ohlas a podporu tento výzkum získával v baťovském Zlíně. Jako příklad dobového ozdravného vědeckého programu a sociálního inženýrství v medicíně je příběh České společnosti biotypologické také příběhem nebezpečného sebevědomí a ambicí integrovat lékařskou péči do politické správy společnosti.

• MeSH
• Anthropology, Physical history   MeSH
• Anthropometry history   MeSH
• History, 20th Century MeSH
• Eugenics history   MeSH
• Personality MeSH
• Societies, Medical history   MeSH
• Body Constitution MeSH
• Check Tag
• History, 20th Century MeSH
• Publication type
• Monograph MeSH
• Geographicals
• Czechoslovakia MeSH

• Conspectus
• Antropologie
• NML Fields
• antropologie
• dějiny lékařství

We constructed recombinant vaccinia viruses (VACVs) coexpressing the insulin-like growth factor-binding protein-3 (IGFBP-3) gene and the fusion gene encoding the SigE7Lamp antigen. The expression of the IGFBP-3 transgene was regulated either by the early H5 promoter or by the synthetic early/late (E/L) promoter. We have shown that IGFBP-3 expression regulated by the H5 promoter yielded higher amount of IGFBP-3 protein when compared with the E/L promoter. The immunization with P13-SigE7Lamp-H5-IGFBP-3 virus was more effective in inhibiting the growth of TC-1 tumors in mice and elicited higher T-cell response against VACV-encoded antigen than the P13-SigE7Lamp-TK(-) control virus. We found that high-level production of IGFBP-3 enhanced virus replication both in vitro and in vivo, resulting in more profound antigen stimulation. Production of IGFBP-3 was associated with a higher adsorption rate of P13-SigE7Lamp-H5-IGFBP-3 to CV-1 cells when compared with P13-SigE7Lamp-TK(-). Intracellular mature virions (IMVs) of the IGFBP-3-expressing virus P13-SigE7Lamp-H5-IGFBP-3 have two structural differences: they incorporate the IGFBP-3 protein and they have elevated phosphatidylserine (PS) exposure on outer membrane that could result in increased uptake of IMVs by macropinocytosis. The IMV PS content was measured by flow cytometry using microbeads covered with immobilized purified VACV virions.

• MeSH
• Antigens, Viral immunology   MeSH
• Insulin-Like Growth Factor Binding Protein 3 genetics   immunology   MeSH
• Immunization methods   MeSH
• Human papillomavirus 16 genetics   immunology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Papillomavirus E7 Proteins genetics   immunology   MeSH
• Promoter Regions, Genetic MeSH
• Virus Replication immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Antibody Formation MeSH
• Vaccination methods   MeSH
• Viral Vaccines immunology   pharmacology   MeSH
• Vaccinia virus genetics   immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Respiration MeSH
• Gases administration & dosage   metabolism   MeSH
• Diving physiology   trends   MeSH

• MeSH
• Anesthesia methods   adverse effects   utilization   MeSH
• Electrocardiography methods   utilization   MeSH
• Financing, Organized MeSH
• Heart Function Tests methods   utilization   MeSH
• Cardiovascular System physiopathology   drug effects   MeSH
• Horses MeSH
• Death, Sudden, Cardiac etiology   prevention & control   MeSH
• Models, Theoretical MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

• MeSH
• Accreditation MeSH
• Libraries, Medical MeSH

• MeSH
• Electromagnetic Fields MeSH
• Radiologic Health legislation & jurisprudence   MeSH
• Occupational Exposure MeSH
• Threshold Limit Values MeSH
• Environmental Exposure MeSH
• Geographicals
• Czech Republic MeSH

• MeSH
• Electromagnetic Fields adverse effects   MeSH
• Risk Assessment MeSH
• Humans MeSH
• Central Nervous System Neoplasms etiology   MeSH
• Central Nervous System Diseases etiology   MeSH
• Telephone MeSH
• Check Tag
• Humans MeSH

• MeSH
• Anti-Asthmatic Agents therapeutic use   MeSH
• Asthma classification   physiopathology   MeSH
• Bronchial Hyperreactivity MeSH
• Hyperventilation MeSH
• Humans MeSH
• Airway Obstruction MeSH
• Ventilation-Perfusion Ratio MeSH
• Status Asthmaticus physiopathology   MeSH
• Check Tag
• Humans MeSH

• MeSH
• Electromagnetic Fields MeSH
• Risk Assessment MeSH
• Hearing Disorders MeSH
• Telephone MeSH
• Carcinogenicity Tests MeSH
• Radiation adverse effects   MeSH