1,721,243 research outputs found
HIV-1-Related mechanisms of suppression of CD34+ hematopoietic progenitors
No full textPeripheral blood cytopenias and bone marrow abnormalities are frequently observed in HIV-1-seropositive subjects. Two major mechanisms have been proposed to explain the hematopoietic failure often observed in patients with advanced HIV-1 disease: (i) infection of cells composing the bone marrow microenvironment with a deranged production of hematopoietic growth factors; (ii) direct suppression of hematopoietic progenitor cells mediated by HIV-1 virions and/or viral proteins. In vivo and in vitro experimental evidence supports a combination of both mechanisms. In fact, it has been shown that: (i) infection with HIV-1 and/or exposure of bone marrow accessory cells to envelope glycoprotein 120 (env gp 120) increases the production of inhibitory cytokines such as tumor necrosis factor alpha; (ii) a subset of CD34+ hematopoietic progenitor cells co-expresses the CD4 antigen and may be infected in vivo with HIV-1; (iii) HIV-1 virions or immune complexes containing env gp 120 are able to induce apoptosis of uninfected CD34+ hematopoietic progenitors. This last inhibitory effect appears to be mediated by the upregulation of transforming growth factor beta 1, which is endogenously produced by hematopoietic progenitors. Both the load and the biological characteristics of the virus play an important role in causing these suppressive effects, since different HIV-1 isolates display varying abilities to suppress hematopoiesis, and some isolates are not cytopathic at all
Nuclear protein kinase isoforms and apoptosis
No full textThe process of apoptosis is regulated at multiple levels through phosphorylation by several different protein kinases. The protein kinase C (PKC) family of isozymes have been shown to exert both inhibitory and stimulatory influences on apoptosis. During the apoptotic process phosphorylative events are known to occur also at the nuclear level. Evidence suggests that PKC isoforms play a key role in some steps that lead to nuclear disassembly during the execution phase of apoptosis. This review highlights the recent progress made in determining the roles played by individual PKC nuclear isoforms in the control of apoptosis
La ceroplastica anatomica del Settecento. Racconto di una mostra
No full textIn 2016 an exhibition on the anatomical waxes of the University of Ferrara was organized by SMA (Museum System of the University). This exhibition displayed the models of the human body which were produced at the end of the 18th century by Giovanni Tumiati and Giuseppe Chiappi for the former’s teaching of obstetrics and which have been restored in the last few years thanks to a collaboration between the Universities of Ferrara and Cagliari. The restoration of the models and the preparation of the exhibition have been the occasion for some important discoveries on the characteristic traits of the models and their makers
Prereplicative increase of nuclear matrix-bound DNA polymerase-alpha and primase activities in HeLa S3 cells following dilution of long-term cultures.
No full textWe investigated the association of DNA polymerase and DNA primase activity with the nuclear matrix in HeLa S3 cells diluted with fresh medium after having been cultured without any medium change for 7 days. Flow cytometric analysis demonstrated that just before dilution about 85\% of the cells were in the G1 phase of the cycle, whereas 8\% were in the S phase. After dilution with fresh medium, 18-22 h were required for the cell population to attain a stable distribution with respect to the cell cycle. At that time, about 38\% of the cells were in the S phase. DNA polymerase and DNA primase activity associated with the nuclear matrix prepared from cells just before dilution represented about 10\% of nuclear activity. As judged by [3H]-thymidine incorporation and flow cytometric analysis, an increase in the number of S-phase cells was evident at least 6 h after dilution. However, as early as 2 h after dilution into fresh medium, a striking prereplicative increase of the two activities was seen in the nuclear matrix fraction but not in cytosol or isolated nuclei. Both DNA polymerase and primase activities bound to the matrix were about 60\% of nuclear activity. Overall, the nuclear matrix was the cell fraction where the highest induction (about 10-fold) of both enzymatic activities was seen at 30 h after dilution, whereas in cytosol and isolated nuclei the increase was about two- and fourfold, respectively. Typical immunofluorescent patterns given by an antibody to 5-bromodeoxyuridine were seen after dilution. These findings, which are at variance with our own previous results obtained with cell cultures synchronized by either a double thymidine block or aphidicolin exposure, strengthen the contention that DNA replication is associated with an underlying nuclear structure and demonstrate the artifacts that may be generated by procedures commonly used to synchronize cell cultures
Transfer of liposome encapsulated carboxyfluorescein to isolated nuclei
No full textThe interaction between phosphatidylcholine vesicles and isolated rat liver nuclei has been examined by studying the uptake of the fluorophore carboxyfluorescein. The kinetics of transfer of the dye, analyzed by flow cytofluorimetry with a Fluorescence Activated Cell Sorter (FACS IV), indicate an efficient delivery to the nucleoplasm. The results reflect a liposome-nuclear membrane interaction which may contribute to the processes which underlie our previously described morphological and functional changes in isolated nuclei treated with phospholipids
Lipid-F1 nucleohistone interactions
No full textHigh concentrations of phospholipids determine destabilization of F1 histone-DNA complex at the weight ratios, histone:DNA, 0.8:1 and 1:1, but low concentrations cause only negligible destabilization. Cholesterol at high weight ratios has little effect on nucleohistone stability. Only linolenic acid of the fatty acids used reproduces similar changes in the thermal stability of F1 histone-DNA complex as phospholipids. The type of interaction of phospholipids with the F1 histone-DNA complex is analyzed, and the involvement of phospholipids in DNA replication in vivo is discussed
Inhibition of purified CD34+ hematopoietic progenitor cells by HIV-1 is mediated by endogenous TGF-beta 1.
No full textHuman CD34+ hematopoietic progenitor cells, stringently purified from the peripheral blood of 20 normal donors, showed an impaired survival and clonogenic capacity after exposure to either heat-inactivated human immunodeficiency virus (HIV) 1 (strain IIIB) or cross-linked envelope gp120. Cell cycle analysis, performed at different times in serum-free liquid culture, showed an accumulation in G0/G1 in HIV-1- or gp120-treated cells and a progressive increase of cells with subdiploid DNA content, characteristic of apoptosis. In blocking experiments with anti-transforming growth factor (TGF) beta 1 neutralizing serum or TGF-beta 1 oligonucleotides, we demonstrated that the HIV-1- or gp120-mediated suppression of CD34+ cell growth was almost entirely due to an upregulation of endogenous TGF-beta 1 produced by purified hematopoietic progenitors. Moreover, by using a sensitive assay on the CCL64 cell line, increased levels of bioactive TGF-beta 1 were recovered in the culture supernatant of HIV-1/gp120-treated CD34+ cells. Anti-TGF-beta 1 neutralizing serum or TGF-beta 1 oligonucleotides were also effective in inducing a significant increase of the plating efficiency of CD34+ cells, purified from the peripheral blood of three HIV-1-seropositive individuals, suggesting that a similar mechanism may be also operative in vivo. The relevance of these findings to a better understanding of the pathogenesis of HIV-1-related cytopenias is discussed
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