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Biomedical subjects

A Fusco

Publications and source records attributed to A Fusco.

At least 235 records · Page 13Linked to original sources

A retrovirus carrying the polyomavirus middle T gene induces acute thrombocythemic myeloproliferative disease in mice.

Mice inoculated with an artificially constructed retrovirus carrying the middle T gene of polyomavirus develop acute myeloproliferative disease with severe thrombotic and hemorrhagic disorder and impaired platelet function. The megakaryocytic lineage appears to be a target for polyoma-murine leukemia virus infection and middle T gene expression. This newly described disease represents a unique model system for studying disorders of the megakaryocytic lineage.

Adenosine Triphosphate↗

Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression.

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

Animals↗

Elevated levels of a specific class of nuclear phosphoproteins in cells transformed with v-ras and v-mos oncogenes and by cotransfection with c-myc and polyoma middle T genes.

Transformation of a rat thyroid epithelial cell line (FRTL5-C12) with Kirsten and Harvey murine sarcoma viruses (carrying the ras oncogenes) results in elevated levels of three perchloric acid-soluble nuclear phosphoproteins. These three proteins are also induced to high levels in the PC-C13 thyroid epithelial cell line when transformed by the myeloproliferative sarcoma virus (carrying the v-mos oncogene) and when transformed by transfection with the c-myc proto-oncogene followed by infection with the polyoma leukaemia virus (PyMuLV) carry the polyoma middle T antigen gene. Neither c-myc or PyMuLV alone induced high levels of the three nuclear proteins. Untransformed thyroid fibroblasts have high levels of two of the three proteins and can be transformed by PyMuLV alone resulting in the appearance of the third protein. Transformation with Harvey sarcoma virus also results in the induction of the third protein. The three phosphoproteins have been purified by h.p.l.c. and shown to be related to the HeLa protein HMGI already described. The results of these studies indicate that elevated levels of these HMGI-like proteins are associated with neoplastic transformation and/or with an undifferentiated phenotype.

Animals↗

Eicosanoids as immunomodulators of penetration by Schistosome cercariae.

To infect a definitive host, schistosome cercorioe must identify and penetrate intact skin. This involves complex biochemical and morphological changes over a fairly brief time (48 hours), and possibly offers a potential point of intervention against infection. Attempts to define a vaccine against the invading organisms have so far been unsuccessful, but unravelling the complex biochemical interactions of schistosome penetration and transformation seems to suggest possible pharmacological or immunopharmacological interventions against these initial stages of infection.

Journal Article↗

One- and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes.

A system of epithelial cells is described in which it is possible to study the number and the nature of genes capable of conferring the malignant phenotype. Two fully differentiated, hormone-responsive cell lines from rat thyroid glands are presented which are susceptible to one-step or two-step transformation upon infection with several murine acute retroviruses. After infection, both cell lines became independent from their thyrotropic hormone requirement for growth. However, complete transformation was achieved with one of the cell lines (FRTL-5 Cl 2), whereas the other cell line (PC Cl 3) failed to grow in agar and to give rise to tumors in vivo. The latter cell line was susceptible to complete transformation upon cooperation of the v-ras-Ha and the human c-myc oncogenes.

Animals↗

Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans.

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.

Animals↗

Histone and nonhistone proteins from normal and virus-transformed rat thyroid epithelial cells.

The histone and nonhistone nuclear proteins extracted by different methods from nuclei of normal and virus-transformed rat thyroid epithelial cells (FRTL5 cell line) were studied by polyacrylamide gel electrophoresis in acetic acid/urea and in SDS and by autoradiography. The results have shown that some of these proteins have an higher level of phosphorylation in virus-transformed than in normal cells; moreover, an higher amount of three proteins (C, D, and E), which in normal cells are not detectable at least as Coomassie staining, was found. These proteins, extractable with perchloric acid, are suggested to belong to the High Mobility Group (HMG proteins) and to play some regulatory role.

Animals↗

Multipotential hemopoietic cell lines isolated from stem cell cultures infected with Friend virus complex (MuLV + F-SFFV) show presence of MuLV but not F-SFFV.

The only factor-dependent or factor-independent hemopoietic murine stem cell lines which can be permanently maintained in vitro are cell lines which originate from bone marrow cultures of congenic mice differing in the Fv-2 locus infected with Friend spleen focus forming virus (F-SFFV) in conjunction with either Rauscher or Friend helper virus (R-MuLV or F-MuLV). We determined the viral state of these cells by restriction enzyme analysis, measurement of SFFV and MuLV related RNA, immunoprecipitation analysis of viral related proteins and biological activity to test whether integration and expression of R-MuLV or F-SFFV are obligatory. All stem cell lines (SUT, JUT, 416B) showed expression of MuLV coded proteins or virus but SFFV was not found in these cell lines. A two-fold difference of RNA hybridizing with SFFV-specific cDNAs observed in stem cells of Fv-2rr and of Fv-2ss genotype is in agreement with data published earlier.

Animals↗

Sperm maturation in human semen: role of transglutaminase-mediated reactions.

A Ca2+-dependent, transglutaminase-like activity has been detected both free in the human seminal plasma and bound on the spermatozoon surface. A marked variability of the two enzymatic activities in the semen of different normal subjects was observed; but limited changes occurred in various ejaculates of the same individual. Moreover, we report evidence of the ability of several seminal plasma proteins to act as acyl donor substrates for endogenous transglutaminase, whereas human ejaculated spermatozoa have been shown to possess polyamine-binding sites specifically involved in transglutaminase-catalyzed reactions. It is postulated that semen transglutaminase may play a role in suppressing sperm antigenicity and in the male gamete's acquiring biological features of a fully differentiated and fertile cell.

Adult↗

[Effects of enzymatic deglycosylation of human goiter thyroglobulin on its immunochemical properties].

Thyroglobulin (Tg), isolated from soluble iodoproteins by ammonium sulphate fractionation, was enzymatically deglycosylated in vitro and analyzed by polyacrylamide gel electrophoresis, double immunodiffusion and non-commercial RIA. Carbohydrate and iodine content was chemically determined. By PAAGE deglycosylated Tg (dTg) showed the appearance of a major band in the 12S region and three slower migrating bands corresponding to higher aggregates than 19S Tg. In immunodiffusion by testing native and deglycosylated Tg against anti-native Tg antiserum it was shown the appearance of a spur of native on deglycosylated Tg. By RIA of native and deglycosylated Tg against anti-deglycosylated Tg antiserum it was shown a minor binding capacity of the anti-deglycosylated antibody against native Tg at high dilutions. The results demonstrate that the enzymatic deglycosylation release almost all the carbohydrates of goiter Tg and that the removal of the carbohydrates of Tg produces a loss of antigenic determinants of the molecule.

Electrophoresis, Polyacrylamide Gel↗