Interleukin-2 stimulates the colony-forming activity of in vitro irradiated bone marrow

The data are presented on the stimulatory effect of interleukin-2 on the formation of spleen exocolonies from bone marrow irradiated in vitro with doses of 0.5 to 2.5 Gy. It is suggested that the effect observed is associated with the increased proliferation of CFUs survived after irradiation.     

High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans

We compared male-reproductive-tract polypeptides of Drosophila melanogaster and D. simulans by using two-dimensional gel electrophoresis. Approximately 64% of male-reproductive-tract polypeptides were identical between two randomly chosen isofemale lines from these two species, compared with 83% identity for third-instar imaginal wing-disc polypeptides. Qualitatively similar differences were found between reproductive tracts and imaginal discs when D. sechellia was compared with D. melanogaster and with D. simulans. When genic polymorphism was taken into account, approximately 10% of male- reproductive-tract polypeptides were apparently fixed for different alleles between D. melanogaster and D. simulans; this proportion is the same as that found for soluble enzymes by one-dimensional gel electrophoresis. Strikingly, approximately 20% of male-reproductive- tract polypeptides of either D. melanogaster or D. simulans had no detectable homologue in the other species. We propose that proteins of the Drosophila male reproductive tract may have diverged more extensively between species than have other types of proteins and that much of this divergence may involve large changes in levels of polypeptide expression.      

Changes in the concentration of serum fibronectin in irradiated animals

A study of the level of fibronectin in blood serum of Wistar rats at different times after gamma-irradiation (7.5 Gy) has demonstrated a considerable increase in its concentration after 3 days. This increase is a function of radiation dose absorbed (within the range from 1 to 10 Gy). The most pronounced changes are observed with serious and extremely serious forms of acute radiation sickness. The administration of cycloheximide 48 h after irradiation removes completely the increase in the level of blood serum fibronectin.     

Microelectrode studies of the active Na transport pathway of frog skin

When the outer surface of short-circuited frog skin was penetrated with microelectrodes, stable negative potentials that averaged near -100 mV were recorded consistently, confirming the results of Nagel (W. Nagel. 1975. Abstracts of the 5th International Biophysics Congress, Copenhagen. P-147.). The appearance of these stable potentials, V(O), concurrent with the observations that (a) a high resistance outer barrier R(O) accounting for approximately 75 percent or more of the transcellular resistance of control skins had been penetrated and that (b) 10(-5) M amiloride and reduced [Na] outside caused the values of V(O) to increase towards means value near -130 mV while the values of percent R(O) increased to more than 90 percent. It was of relationships were the same as the values of E(1) observed in studies of the current-voltage relationships were the same as the values of E’(1) defined as the values of voltage at the inner barrier when the V(O) of the outer barrier was reduced to zero by voltage clamping of the skins. Accordingly, these data are interpreted to mean that the values of E(1), approximately 130 mV, represent the E(Na) of the sodium pump at the inner barrier. 2,4-DNP was observed to decrease the values of transepithelial voltage less than E(1) the V(O) was negative. These data can be interpreted with a simple electrical equivalent circuit of the active sodium transport pathway of the frog skin that includes the idea that the outer membrane behaves as an electrical rectifier for ion transport.     

A comparative evaluation of the changes in the duration of "hexenal sleep" in acute radiation and combined radiation-thermal lesions]

In experiments with Wistar rats it was found that the increase in the length of the "hexenal dream" during the first week after the effect of a mixture of radiation and heat is much more pronounced than that observed after exposure to radiation alone and independent of the severity of a radiation component (gamma radiation, 4, 6 and 7.5 Gy). The peculiarities revealed in the hypnotic effect of hexenal develop against the background of the postirradiation aggravation of hypoalbuminemia and decrease in the liver ATP.     

Role of interleukin-6 (IL-6) in the pathogenesis of combined radiation/thermal injuries

Combined injury such as whole body gamma-irradiation at the dose of 7 Gy+10% body surface full-thickness thermal burn were investigated in (CBA x C57BL6)F1 mice. Enhanced level of IL-6 in mice serum at 6-24 hs following combined injury was established. The potential inhibiting activity of pentoxifylline (POF) as an influence to IL-6 levels, and measure of several acute phase response signs has been evaluated. It was established, that single POF injection don't modify IL-6 production, don't change leukocytosis and early hyperfermentemia (as alaninaminotransferase levels indicated). But serum albumin content was increased after preliminary POF administration to mice with combined injury. On the other side, mouse anti-IL-6 monoclonal antibodies administration increased 30-days animal survival up to 60% while 100% lethality was registered in untreated mice. Possible anti-inflammatory inactivity reasons of POF under combined injury conditions are discussed in this article, and important role of IL-6 hyperproduction in combined injury outcomes burden is suggested.     

Cytokine production by different population of macrophages following radiation or combined radiation injury

Male mice (CBA x C57BL6)F1 were used for the experiments throughout this study. The levels of spontaneous and LPS-stimulated cytokines production (IL-1 beta, IL-6 and TNF-alpha) by peritoneal, splenic, and bone marrow macrophages were evaluated by means of enzyme-linked immunosorbent assay at 3, 6, 24, 48 and 72 hours after irradiation alone or combined injury (irradiation + thermal burn). The results suggest that macrophages, harvested from the main mice hematopoietic organs (bone marrow, spleen), did not increase cytokines production within the first three days following the 7 Gy gamma-irradiation or combined injury. Peritoneal macrophages revealed a capacity to enhance IL-6 and IL-1 production versus normal healthy mice. There were no significant differences of cytokine-producing activity if macrophages were harvested from irradiated or combined injured mice.     

Direct intracardiac injection of umbilical cord-derived stromal cells and umbilical cord blood-derived endothelial cells for the treatment of ischemic cardiomyopathy

The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of cardiovascular disease, which produces high rates of morbidity and mortality. A therapeutic option that has emerged in the last decade is cell therapy. The aim of this study was to compare the effect of transplanting human umbilical cord-derived stromal cells (UCSCs), human umbilical cord blood-derived endothelial cells (UCBECs) or a combination of these two cell types for the treatment of ischemic cardiomyopathy (IC) in a Wistar rat model. IC was induced by left coronary artery ligation, and baseline echocardiography was performed seven days later. Animals with a left ventricular ejection fraction (LVEF) of ≤40% were selected for the study. On the ninth day after IC was induced, the animals were randomized into the following experimental groups: UCSCs, UCBECs, UCSCs plus UCBECs, or vehicle (control). Thirty days after treatment, an echocardiographic analysis was performed, followed by euthanasia. The animals in all of the cell therapy groups, regardless of the cell type transplanted, had less collagen deposition in their heart tissue and demonstrated a significant improvement in myocardial function after IC. Furthermore, there was a trend of increasing numbers of blood vessels in the infarcted area. The median value of LVEF increased by 7.19% to 11.77%, whereas the control group decreased by 0.24%. These results suggest that UCSCs and UCBECs are promising cells for cellular cardiomyoplasty and can be an effective therapy for improving cardiac function following IC.     

Some consequences of systemic inflammatory response in the pathogenesis of aggravation of outcomes of combined radiation and thermal injuries

Experiments were executed on (CBA x C57BL6) F1 male mice. Animals were subjected to the total body irradiation with a dose 7 Gy or combine radiation-thermal injury (CRTI), when irradiated animals were additionally subjected to a thermal burn of 10% of the body surface. Some signs of systemic inflammatory response were investigated in these two compared groups. It was established that the period of substantial increasing of the mortality in animals with CRTI (from 7th till 15th day) was characterized with expressed postradiation leikopenia and thrombocytopenia, was accompanied by hypoalbuminemia and hyperfibrinogenemia with a moderate raise in serum ALT activity. From all investigated hematological and biochemical parameters, at CRTI only plasma level of fibrinogen statistically differed from that in a group of the irradiated mice without a burn. It is suggested that endogenous infection and bacterial toxins are important at the pathogenesis of hyperfibrinogenemia and aggravation of CRTI outcomes by the 30-days survival criteria.     

Most nuclear systemic autoantigens are extremely disordered proteins: implications for the etiology of systemic autoimmunity

Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies in normal individuals.