Pathological sequelae of blood transfusion during hypothermia

Under analysis was the influence of two factors--blood loss (intraoperative and postoperative) and blood substitution--upon the frequency of postoperative complications in patients with acquired mitral heart diseases operated upon under conditions of non-perfusion hypothermia. A conclusion is made that hemotransfusion during operations performed under conditions of "dry" heart and non-perfusion hypothermia should be performed but in anemia threatening by hemic hypoxia.     

Hierarchies in eukaryotic genome organization: Insights from polymer theory and simulations

Eukaryotic genomes possess an elaborate and dynamic higher-order structure within the limiting confines of the cell nucleus. Knowledge of the physical principles and the molecular machinery that govern the 3D organization of this structure and its regulation are key to understanding the relationship between genome structure and function. Elegant microscopy and chromosome conformation capture techniques supported by analysis based on polymer models are important steps in this direction. Here, we review results from these efforts and provide some additional insights that elucidate the relationship between structure and function at different hierarchical levels of genome organization.     

Characteristics of humoral immunity to rubella virus in residents of Moscow in 1998-1999]

A total of 400 blood samples were collected from residents of Moscow in 1998-1999, 369 from adults aged mainly 19-31 years and from children aged 5-12 years. The mean incidence of antirubella antibody was 76.5%; the value varied in different age groups. The highest percentage of antibody detection was observed in men aged 19-25 years (91.8%) and the lowest in pregnant women aged 18-38 years (66-67%). Estimation of antihemagglutinin titers in international Units showed that antibody titer 1:40 and higher protected from infection; such titers were detected in 73.6% examinees. In pregnant women the level of immunological defense was very low (only 56%), which necessitates urgent vaccination of adolescent girls and young women. The results of EIA were compatible with the results of indirect hemagglutination test (IHAT), but EIA was much more sensitive in cases with low titers of IHAT.     

Recipient humoral immunity against leukoreduced allogeneic platelets is suppressed by aminoguanidine, a selective inhibitor of inducible nitric oxide synthase

Leukoreduced allogeneic platelet transfusions have been previously shown to initially stimulate an in vitro cellular cytotoxicity and subsequently Induce the formation of immunoglobulin G (IgG) antidonor alloantibodies. To further characterize these responses and determine if they are related, recipient BALB/c H-2d mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10(8) C57BL/6 H2b platelets. In control, non-AMG-treated mice, transfusion significantly (P < .01) increased serum levels of interferon-gamma (IFN-gamma) by day 1 posttransfusion (PT). IFN-gamma returned to pretransfusion levels by day 3 PT, and its production was not affected by AMG treatment. Serum interleukin-4 (IL-4), on the other hand, was undetectable before and during the transfusion protocol. By day 3 PT, recipient spleen cells could mediate in vitro anti-P815 (auto), anti-EL4 (allo), and anti-R1.1 (third-party MHC) cytotoxicity, and these responses were maximal by day 7 PT. Concurrently, a significant reduction in the vitro ability of recipient splenocytes to respond to Concanavalin A (ConA) was observed; this was not seen with lipopolysaccharide (LPS) stimulation. Elevated levels of NO2- were found in the ConA culture supernatants from transfused mice at day 3 PT. Serum antidonor alloantibodies were detected by the fifth platelet transfusion. AMG treatment of recipient mice significantly inhibited the transfusion. Induced cytotoxicity and ConA-stimulated NO2- production, and restored ConA-induced proliferation to normal levels. AMG appeared to selectively inhibit platelet-induced alloantibody production in that it did not affect antibody production induced by transfusions with 10(5) allogeneic leukocytes or by immunization with a foreign protein antigen, human gamma globulin, in adjuvant therapy. These results indicate that an in vivo AMG-sensitive mechanism is essential for recipients to initiate a humoral IgG immune response against allogeneic platelets.     

Effect of microgravity on glial cell line‐derived neurotrophic factor and cerebral dopamine neurotrophic factor gene expression in the mouse brain

Mice were exposed to 1 month of space flight on the Russian biosatellite BION‐M1 to determine its effect on the expression of genes involved in the maintenance of the mouse brain dopamine system. The current article focuses on the genes encoding glial cell line‐derived neurotrophic factor (GDNF) and cerebral dopamine neurotrophic factor (CDNF). Space flight reduced expression of the GDNF gene in the striatum and hypothalamus but increased it in the frontal cortex and raphe nuclei area. At the same time, actual space flight reduced expression of the gene encoding CDNF in the substantia nigra but increased it in the raphe nuclei area. To separate the effects of space flight from environmental stress contribution, we analyzed expression of the investigated genes in mice housed for 1 month on Earth in the same shuttle cabins that were used for space flight and in mice of the vivarium control group. Shuttle cabin housing failed to alter the expression of the GDNF and CDNF genes in the brain structures investigated. Thus, actual long‐term space flight produced dysregulation in genetic control of GDNF and CDNF genes. These changes may be related to downregulation of the dopamine system after space flight, which we have shown earlier. © 2015 Wiley Periodicals, Inc. Significance: Our results provide the first evidence of microgravity effects on expression of the GDNF and CDNF neurotrophic factor genes. A considerable decrease in mRNA level of GDNF and CDNF in the nigrostriatal dopamine system was found. Because both GDNF and CDNF play a significant role in maintenance and survival of brain dopaminergic neurons, we can assume that this dysregulation in genetic control of GDNF and CDNF genes in substantia nigra could be among the reasons for the deleterious effects of space flight on the dopamine system.     

Hemoglobin M equon beta 41 (C7) phenylalanine leads to tyrosine

A severe hemolytic crisis was observed in a 34-yr-old female of English- Irish extraction following a viral illness treated with acetaminophen. Heinz bodies and heat instability were present only during a transient hemolytic event. A challenge dose of acetaminophen caused no detectable hematologic abnormality. Structural studies of the hemoglobin during hemolysis and again after complete recovery localized the abnormality to tryptic peptide beta Tp-5, and automated sequencing of I 125-labeled beta chains indicated a replacement of phenylalanine (C7) beta 41 by tyrosine. Substitution of the next residue, phenylalanine (CD1) beta 42 by serine (Hb Hammersmith), has resulted in chronic severe Heinz body hemolytic anemia. The lack of chronic anemia in the present disorder may reflect the different relationships of beta41 and beta 42 and/or the similarities in volume and hydrophobicity of tyrosine and phenylalanine. It is suggested that substitution of tyrosine for phenylalanine in Hb Mequon may disturb the critical environment around the heme group and render it susceptible to oxidative denaturation in the presence of infections and/or drugs.