Experession of human interleukin-10 inEscherichia coli cells

The human interleukin-10 gene has been synthesized by the chemical enzymatic method. Vectors for cytoplasmic and periplasmic expression of recombinant interleukin-10 have been obtained inE. coli cells. A high level of protein expression was found to be characteristic of only recombinant strains producing interleukin-10 as “fused” protein (fused with the N-terminal fragment of interleukin-3). Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 3, pp. 324–327, March, 1995 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences). (Address for correspondence: Nauchnyi Pr. 8, 117246 Moscow, fax 331-01-01.     

Immunocytotherapy. A new trend in fetal tissue transplantation

The clinical applications of theoretical immunology are not numerous. The authors demonstrate present-day immunocytotherapeutic approaches to fetal tissue transplantation widely used in medicine. Results of therapy by injections of lymphokine-activated killer cells in combination with interleukin-2, T-cell vaccines, and genetically transformed T cells are presented. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 4, pp. 412–415, April, 1994     

Stem hematopoietic cells with inserted foreign gene: Proliferative activity and proliferative potential in the long term after transplantation into irradiated mice

The transfer of the human adenosine deaminase gene to murine stem hematopoietic cells is performed on an irradiated sublayer of a long-term bone marrow culture by the conventional method of retroviral transduction with cytokines and by stimulation of stem cells without cytokines. The efficiency of gene transfer into colony-forming units (CFUs) with the aid of cytokines is 72% and without them it is 50%. In irradiated mice reconstituted with the retrovirus-infected bone marrow cells the donor hematopoietic activity is preserved during a 1-year period. The proliferative activity of CFUs of chimeric cells 6 months after the reconstitution was the same and did not depend on the mode of gene transfer. The spleen repopulation activity is lowered in all the groups of chimeric mice 6–12 months after reconstitution. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 6, pp. 648–650, June, 1994 Presented by A. I. Vorob'ev, Member of the Russian Academy of Medical Sciences     

Transplantation of human fetal tissue in hematology

Intravenous transplantation of human fetal tissue, notably of the liver and thymus, is used in emergency hematological states: aplastic anemia and acute leukemia. The strong manifestation of “graft-versus-host” disease proved unexpected. Fetal donor hepatic cells stimulate hemopoiesis in the recipient. In some cases true cellular chimerism has been observed, specifically when a transplant of human fetal tissue (THFT) to a fetus with prenatal pathology was performedin utero. In gene therapy attempts have been made to infuse hemopoietic stem cells intravenously or to introduce the adenosine aminase gene into leukocytes of patients with a deficiency of this enzyme. Treatment using transplantation of human fetal tissue will help solve the problem of HLA-histocompatibility and will make gene therapy more widely applicable. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 4, pp. 375–377, April, 1994     

Regression and stabilization of advanced murine atherosclerotic lesions: a comparison of LDL lowering and HDL raising gene transfer strategies

Both reductions in atherogenic lipoproteins and increases in high-density lipoprotein (HDL) levels may affect atherosclerosis regression. Here, the relative potential of low-density lipoprotein (LDL) lowering and HDL raising gene transfer strategies to induce regression of complex murine atherosclerotic lesions was directly compared. Male C57BL/6 LDL receptor (LDLr)^−/− mice were fed an atherogenic diet (1.25% cholesterol and 10% coconut oil) to induce advanced atherosclerotic lesions. A baseline group was killed after 6 months and remaining mice were randomized into a control progression (Adnull or saline), an apolipoprotein (apo) A-I (AdA-I), an LDLr (AdLDLr), or a combined apo A-I/LDLr (AdA-I/AdLDLr) adenoviral gene transfer group and followed-up for another 12 weeks with continuation of the atherogenic diet. Gene transfer with AdLDLr decreased non-HDL cholesterol levels persistently by 95% (p < 0.001) compared with baseline. This drastic reduction of non-HDL cholesterol levels induced lesion regression by 28% (p < 0.001) in the aortic root and by 25% (p < 0.05) in the brachiocephalic artery at 12 weeks after transfer. Change in lesion size was accompanied by enhanced plaque stability, as evidenced by increased collagen content, reduced lesional macrophage content, a drastic reduction of necrotic core area, and decreased expression of inflammatory genes. Elevated HDL cholesterol following AdA-I transfer increased collagen content in lesions, but did not induce regression. Apo A-I gene transfer on top of AdLDLr transfer resulted in additive effects, particularly on inflammatory gene expression. In conclusion, drastic lipid lowering induced by a powerful gene transfer strategy leads to pronounced regression and stabilization of advanced murine atherosclerosis.     

Dissociation of E∶T conjugates upon activation of human natural killers by factors acting at the “lethal blow” stage

It is demonstrated that in the presence of human recombinant γ-interferon and C-reactive protein the activity of natural killers increases 9–43%, whereas the number of effector:target cell conjugates formed at the stage of recognizing and binding of target cells decreases 14–80%. There is a weak positive correlation (ρ=0.35) between the activity of natural killers and the number of effector:target cell conjugates. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 280–285, March, 1994     

Wild-type apo A-I and apo A-IMilano gene transfer reduce native and transplant arteriosclerosis to a similar extent

Apolipoprotein (apo) A-I_Milano is an apo A-I mutant characterized by a cysteine for arginine substitution at position 173. Apo A-I_Milano carriers have much less atherosclerosis than expected from their low plasma high-density lipoprotein cholesterol levels, suggesting that this mutant may have superior atheroprotective properties. Here, we compare the effect of hepatocyte-directed gene transfer of wild-type human apo A-I and human apo A-I_Milano on endothelial progenitor cell (EPC) biology and on the progression of native atherosclerosis and allograft vasculopathy in C57BL/6 apo E^−/− mice. Human apo A-I and apo A-I_Milano transfer resulted in an equivalent increase of EPC number and function as well as EPC incorporation and endothelial regeneration in allografts and inhibited the progression of native atherosclerosis and allograft vasculopathy to a similar extent. In conclusion, the current head-to-head comparison indicates that human apo A-I_Milano transfer is not superior compared to wild-type human apo A-I transfer. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Polyunsaturated phosphatidylcholine micelle-induced decrease of atherogenicity of the serumin vitro

It is shown that polyunsaturated phosphatidylcholine administered in micelles stabilized by a plant-derived glycoside prevents the accumulation of cholesterol by cells incubated in atherogenic serum and, moreover, in certain cases causes a 1.4–1.5-fold drop of intracellular cholesterol as compared to control cells. The optimum antiatherogenic effect was achieved when using a micelle concentration of 100–200 μg/ml and an incubation time of at least 4 hours. The antiatherogenic effect was analogous to the effect of high density serum lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5 pp. 497–501, May, 1995 Presented by Yu. M. Lopukhin, Member of the Russian Academy of Medical Sciences     

Stimulation of proliferative activity of human natural killers (CD16+CD56+ cells) by recombinant interleukin-3in vitro

The proliferative activity of human natural killers (CD16⁺CD56⁺ cells) in the presence of 100 and 1000 IU/ml human recombinant interleukin-3 is investigatedin vitro. It is shown that recombinant interleukin-3 reliably enhances natural killer proliferation, causing a 9–15.2-fold increase of³H-thymidine uptake by CD16⁺CD56⁺ cells both in complete culture medium and in conditioned medium. The effect of the factor is 3.9–6.4 and 3.6–8.9-fold more potent than that of recombinant interleukin-2 and granulocyte-macrophage colony-stimulating factor, respectively, in the same doses. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 4, pp. 409–412, April, 1995 Presented by S. V. Prozorovskii, Member of the Russian Academy of Medical Sciences     

S100β protein stimulates regeneration of the rabbit cornea

The effect of S100β protein on the processes of wound repair in the rabbit cornea is studied. Subconjunctival injection of the protein is found to promote favorable and rapid healing of the corneal injury, evidence of which is early epithelization, a drop of the index of migrating inflammatory cells, and prevention of the development of fibrous subepithelial tissue. Translated fromByulleten' Eksperimental'noi biologii i Meditsiny, Vol. 118, N ^o , 7, pp. 98–101, July, 1994     

Expression of the c-myc and Ca-ATPase genes in cardiac muscle during adaptation to repeated stress

In the course of adaptation to repeated stress, the expression of the proto-oncogene c-myc found to increase much more rapidly than that of the Ca-ATPase gene. It is suggested that an increase in the level of c-myc expression may activate the structural Ca-ATPase gene and possibly also the heat-shock proteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 2, pp. 124–126, February, 1994     

Opioid peptides improve human fetal nervous tissue survival after cryopreservation in culture

The study was carried out on the 18–20-week human fetal brain by culturing organotypic and dissociated cells of the cerebral cortex and the corpora quadrigemina area. Tissue viability was assessed from the formation of growth cones and neuroglial bundles, as well as of glial cell formation. The study showed that after tissue freezing in organotypic cultures, viable cells were detected in not more than 10% of grafts. The addition of opioid peptides noticeably (by 1.3–2 times) increased the number of surviving cells. This regularity was not observed in dissociated cultures. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 4, pp. 408–411, April, 1994     

Fibronectin as a compensating factor in the natural cytotoxicity system in interferon-dependent immunodeficiency

The cytotoxicity of natural killer cells (NK) against³H-uridine-labeled target cells (TC, human erythromyeloleukosis cells K-562) and the intensity of conjugate formation in the NK:TC system in the presence of γ-interferon, C-reactive protein, and human fibronectin are studiedin vitro in 14 patients with multiple sclerosis. It is shown that γ-interferon and C-reactive protein decrease the cytotoxic activity of NK with a simultaneous stimulation of conjugate formation in the NK:TC system. The correlation between the studied parameters becomes weaker. Human fibronectin induces collateral changes in the activity of NK and in the number of effector:target conjugates formed in the natural cytotoxicity reaction. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 7, pp. 67–70, July, 1994     

Effect of monochromatic red and near-infrared light on the adhesive properties of the cell membrane: Dependence on wavelength

Changes in the adhesive properties of the cell membrane after irradiation of HeLa cells with monochromatic visible and near-infrared radiation (λ=580–860 nm, i=1.3 W/m², t=40 sec, D=52 J/m²) are assessed as the number of adherent cells. Three spectral regions (600–625 nm, 645–700 nm, and 720–860 nm) with the maximums near wave-lengths 620, 680, 750, and 825 nm are identified, where the adhesive properties of the cell membrane are observed to be enhanced. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 6, pp. 670–672, June, 1994 Presented by V. P. Solov'ev, Member of the Russian Academy of Medical Sciences     

Expression of the human α-1-antitrypsin gene in heterologous mammalian cells

A genetic-engineering construction is developed containing the full-size cDNA of human α-1-antitrypsin, controlled by the promotor and enhancer elements from cytomegalovirus. It is shown that, after transfection with this recombinant DNA, it is properly expressed in heterologous animal cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, vol. 117, N ^o 2, pp. 166–167, Feburary, 1993 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences     

The contribution of individual and pairwise combinations of SNPs in the APOA1 and APOC3 genes to interindividual HDL-C variability

Apolipoproteins (apo) A-I and C-III are components of high-density lipoprotein-cholesterol (HDL-C), a quantitative trait negatively correlated with risk of cardiovascular disease (CVD). We analyzed the contribution of individual and pairwise combinations of single nucleotide polymorphisms (SNPs) in the APOA1/APOC3 genes to HDL-C variability to evaluate (1) consistency of published single-SNP studies with our single-SNP analyses; (2) consistency of single-SNP and two-SNP phenotype–genotype relationships across race-, gender-, and geographical location-dependent contexts; and (3) the contribution of single SNPs and pairs of SNPs to variability beyond that explained by plasma apo A-I concentration. We analyzed 45 SNPs in 3,831 young African–American (N=1,858) and European–American (N=1,973) females and males ascertained by the Coronary Artery Risk Development in Young Adults (CARDIA) study. We found three SNPs that significantly impact HDL-C variability in both the literature and the CARDIA sample. Single-SNP analyses identified only one of five significant HDL-C SNP genotype relationships in the CARDIA study that was consistent across all race-, gender-, and geographical location-dependent contexts. The other four were consistent across geographical locations for a particular race–gender context. The portion of total phenotypic variance explained by single-SNP genotypes and genotypes defined by pairs of SNPs was less than 3%, an amount that is miniscule compared to the contribution explained by variability in plasma apo A-I concentration. Our findings illustrate the impact of context-dependence on SNP selection for prediction of CVD risk factor variability.Electronic Supplementary Material Supplementary material is available in the online version of this article at CHRISTINE M. BROWN received her B.S. in Zoological Anthropology from the University of Michigan, Ann Arbor, MI, and is currently working towards her Masters degree in Epidemiology in the School of Public Health. She is presently a Research Associate in the Dept. of Human Genetics at the University of Michigan, Ann Arbor, MI.CHARLES F. SING received his Ph.D. in Statistics and Genetics from North Carolina State University in Raleigh, NC. He is currently a Professor in the Dept. of Human Genetics at the University of Michigan, Ann Arbor, MI.     

Effect of complexes of apolipoprotein A-I with tetrahydrocortisol and pregnenolone on protein biosynthesis in rat hepatocytes culture

Complexes of apolipoprotein A-I with tetrahydrocortisol and pregnenolone exhibit high biological activity and increase the rate of protein biosynthesis in the culture of rat hepatocytes. An important role in this process is played by reduced Δ⁴-3-keto group in the A-ring of steroid hormones. A complex of apolipoprotein A-I and pregnenolone modulated the rate of protein biosynthesis in liver cells. Hence, the observed changes are not organ-specific for this steroid. Our results suggest that this mechanism of regulation play an important role in intracellular regeneration and proliferation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 9, pp. 264–266, September, 2007     

Characteristics of high-density lipoprotein binding sites in cultured parenchymal,endothelial, and Kupffer's cells from rat liver

Liver endothelial cells posses surface high-affinity binding sites for HDL₃, whose affinity is 4 times higher than that of the sites on hepatocytes and Kupffer's cells. The maximal number of high-affinity binding sites on endothelial cells is 437 ng/mg protein, which surpasses this parameter on the hepatocyte surface several times. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 268–270, March, 1994     

Blast transformation of lymphocytes and the activity of natural killer cells in the presence of γ-globulinin vitro

The cytotoxic activity of natural killer cells against³H-uridine-labeled target cells (human erythromyeloleukosis cells K-562) and the intensity of spontaneous blast transformation are studiedin vitro in the presence of human serum γ-globulin. It is shown that spontaneous blast transformation is 49–51% due to the presence of aggregated γ-globulin, while the aggregate-free γ-globulin fraction does not induce this reaction. The cytotoxic activity of natural killer cellsin vitro declines in the presence of native γ-globulin, which is related to the influence of aggregated γ-globulin, the intensity of whose formation may increase upon a manyfold decrease in the γ-globulin content of the preparation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 625–630, December, 1994     

Role of mast cells in reparative processes in inflammation

Using the model of acute infectious peritonitis in rats, it is shown that inflammation induced in the absence of mast cells is characterized by marked inhibition of reparative processes. The most significant accumulation of functionally active fibroblasts and the development of granulations and young connective tissue in the mesentery occur 5–10 days after flogogen injection in the natural development of inflammation and after 10–20 days in the absence of mast cells. The data suggest that under natural conditions mast cells directly or indirectly stimulate reparative processes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 3, pp. 262–265, March, 1995 Presented by E. D. Gol'dberg, Member of the Russian Academy of Medical Sciences