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Biomedical subjects

G Fiorucci

Publications and source records attributed to G Fiorucci.

At least 37 records · Page 2Linked to original sources

Posttranscriptional regulation of beta interferon expression in erythroid Friend cells treated with gamma interferon.

Treatment of Friend erythroleukemia cells (FLC) with gamma interferon (IFN-gamma) in the presence of anti-IFN-beta antibodies reduces the effectiveness of the antiviral state and the induction of 2'-5'-oligoadenylate synthetase activity, indicating that the antiviral activity of IFN-gamma in FLC is in part mediated by the production of IFN-beta. Accordingly, IFN-gamma induces a less pronounced antiviral state in FLC resistant to IFN-alpha/beta than in wild-type cells. Moreover, while results of run-on assays indicate that both IFN-alpha and -beta genes are constitutively transcribed in these cells, FLC treatment with IFN-gamma induces only IFN-beta mRNA accumulation. These results indicate that posttranscriptional mechanisms are involved in the regulation of IFN-beta and -alpha expression by IFN-gamma. The low amounts of the induced IFN-beta synergize with IFN-gamma in mounting the potent antiviral effect.

2',5'-Oligoadenylate Synthetase↗

Nutritional status of the elderly V). Dietary and biochemical data and anthropometry of noninstitutionalized elderly in Perugia at the eleventh year follow-up.

The nutritional status of 93 noninstitutionalized elderly of the city of Perugia, mostly of them examined longitudinally, was assessed at the eleventh year follow-up. Diet is still rather rich and unbalanced. Alcohol intake in men is very high. Biological dietary errors have an impact on the nutritional status, particularly for folates, of the individual. But in this regard it is interesting to note that in some cases vitamin and mineral nutriture has improved at this follow-up. In addition the distribution of malnutrition is rather different from that of the previous follow-up. As on previous occasions, no correlation was observed between vitamin intake and corresponding nutritional status (with the exception of riboflavin). Obesity is rather common among women; men present a higher muscular area and hand muscular strength. The clinical evaluation of nutritional status evidences principally changes which are mostly ascribable to old age. Among the pathologies, chronic ischemic heart disease, hypertension, chronic respiratory diseases, osteoarthrosis and diabetes occur most frequently.

Aged↗

A full-length murine 2-5A synthetase cDNA transfected in NIH-3T3 cells impairs EMCV but not VSV replication.

Treatment of cells with interferons (IFNs) induces resistance to virus infection. The 2'-5'oligo A (2-5A) synthetase/RNase L is one of the pathways leading to translation inhibition induced by IFN treatment. A murine cDNA encoding the 43-kDa 2-5A synthetase was cloned and sequenced. NIH-3T3 cell clones transfected with this cDNA expressed the enzymatic activity to various extents and exhibited resistance to encephalomyocarditis virus (EMCV) but not to vesicular stomatitis virus replication. The specific resistance to EMCV can be attributed to 2-5A synthetase.

2',5'-Oligoadenylate Synthetase↗

Spectrum of biological activity of interferons.

The interferons comprise a group of proteins first identified by their ability to protect cells against virus infections but also capable of influencing cellular physiology. They are synthesized and secreted by a variety of cell types in response to various inducers. Their effects include antiviral action, inhibition of cell proliferation, modulation of cell differentiation and activation of various cell types in immune system. This review aims to summarize the current state of biology of interferon action with special emphasis on those aspects related to the use of these molecules in antitumoral therapy. The antitumor effects of IFNs results from pleiotropic IFN activity exerted either directly on tumor cells (i.e. antiproliferative effects, effects on oncogene expression, on cell differentiation and enhanced expression of cell surface antigens), or via indirect effects (i.e. activation of effector mechanisms of the host as modulation of the expression of the major histocompatibility antigens, effects on macrophages, NK, T and B cells).

Animals↗

Interferons in cell growth and development.

Interferons (IFNs), besides inducing an antiviral state in uninfected cells, are also natural regulatory molecules. They play a key role in the regulation both of cell growth and differentiation, and of development. Up- or down-regulation of oncogenes by IFNs may be one of the mechanisms by which these molecules affect cell physiology. The list of IFN-inducible proteins continues to grow rapidly and future research should identify among these the mediators of the biological effects of IFNs.

Animals↗

Natural resistance in mice against Friend cells injected intravenously. III. Comparison between in vivo and in vitro passaged interferon-sensitive (745) and interferon-resistant (3Cl8) cell clones.

In vitro (FLC-Vt) or in vivo (FLC-V) passaged Friend erythroleukaemia cells of DBA/2 origin were tested for susceptibility to natural resistance (NR) in vivo or to NK cell activity in vitro. Scarcely oncogenic FLC-Vt cells were highly susceptible to in vivo NR (measured as rapid organ clearance or growth inhibition in lethally irradiated mice) or to in vitro NK attack. Conversely, highly oncogenic FLC-V cells were weakly susceptible to NR and to NK as well. These data seem to point out that natural immunity, which is up-regulated by endogenous or exogenous interferons, can play a significant role in surveillance against mouse leukaemic cells of retrovirus origin.

Animals↗

All three human ras genes are expressed in a wide range of tissues.

We examined the expression of the ras gene family (Ha-ras, Ki-ras, N-ras) in human fetal tissues (14 week) and in several human tumor cell lines. Dot blot hybridization showed that the three ras genes were expressed in all of the samples analysed, with a range of expression between 10 and 180 molecules/cell. There was no correlation between levels of expression of ras genes and the type of ras gene activated in different tumor types.

Embryo, Mammalian↗

Detection of a transforming gene in spontaneous reticulum cell sarcoma of SJL/J mice: genetically linked and host-dependent neoplasia.

Spontaneous reticulum cell sarcoma (RCS) tumor induction occurs in 90% of SJL/J mice of 8-13 months of age. Tumor induction and growth has been shown to be under the influence of both H-2 and non-H-2 genes as well as the presence of an intact host T-cell system. We postulated that cellular oncogenes may play a role in the induction, growth, and characteristics of RCS. DNA-mediated gene transfer protocols were adopted to investigate the presence of transforming genes in DNA from RCS of SJL/J mice. High molecular weight DNA was isolated from these tumors as well as from brains and livers of control tumor-free SJL/J mice and transfected into NIH-3T3 mouse and F2408 rat fibroblast cell lines. Foci of transformed cells with a peculiar round morphology were scored in both rat and mouse cultures given tumor DNA, but not in those receiving DNA from normal tissues. DNA from first-cycle transformants was transfected in further cycles of transfection, giving rise to foci with similar morphological appearances and growth properties. These experiments suggest that a transforming gene, present in RCS spontaneous tumors, is involved in the malignant conversion of the transfected normal fibroblasts. The implication of these results with respect to the induction and growth properties of RCS is discussed.

Animals↗

Reduced maturation of Friend virus in adhesive mutants of Friend leukemia cells.

The replication of Friend Leukemia virus (FLV) has been investigated in adhesive clones (FF) of Friend Leukemia cells which were selected via cultivation on top of human fibroblast monolayers. In these adhesive clones a shut-down of FLV production is observed under conditions of culture confluency; this finding is not due either to a reduced number of cell divisions nor to a defective expression of FLV genome as assessed by Northern blot and immunofluorescence studies. Ultrastructural studies showed that virus budding and release into the medium is not detectable under these conditions. Conversely, in confluent FF cell monolayers abundant imperfect type-A enveloped particles were visible, possibly originating from stacks of granular endoplasmic reticulum with thickened membranes. It is postulated that the reduced virus production in adhesive FF monolayers is due to as yet undetermined events taking place during virus maturation at a time coincident with that of cell-cell adhesion under conditions of culture confluency.

Animals↗

Biodegradability of inhaled organic particles in patients with chronic bronchitis.

2 h after the inhalation of monodispersed 99mTc-labeled autologous spherocytes and of commercial human albumin microspheres (HAM), 7 patients with chronic bronchitis underwent bronchofibroscopy. The fate of organic particles along the tracheobronchial tree was verified by scanning electron microscopy and the proteolytic activity (trypsin and PZ peptidase) in mucus samples was assessed. Significant proteolytic activity was detected in bronchial secretions. Thereafter in vitro digestion of labeled spherocytes and HAM was verified after exposure to increasing concentrations of trypsin. While in vitro a similar time-course of tryptic digestion of both particles was observed, in vivo spherocytes seem to be less vulnerable to enzymatic digestion. These findings add another unexpected variable, which may influence the reproducibility of radioaerosol lung mucociliary clearance measurements, and improve its standardization.

Aerosols↗

Friend murine leukemia virus and spleen focus-forming virus expression in highly malignant interferon-sensitive and interferon-resistant Friend leukemia cells.

Analysis of expression of the Friend murine leukemia virus (F-MuLV) and of the spleen focus forming virus (SFFV) has been undertaken in highly malignant interferon (IFN)-sensitive (745) and IFN-resistant (3Cl-8) Friend leukemia cells (FLC), serially passaged intraperitoneally in DBA/2 mice. In vivo passaged 745 cells, as well as the clones derived thereof, did not release Friend virus (FV). Western blot analysis of the plasma membrane fractions of the virus nonproducer 745 cells revealed the lack of gp69/70 glycoprotein expression. At least 10 intraperitoneal passages of virus producer in vitro passaged of virus producer in vitro passaged 745 cells were necessary to obtain the selection of the virus nonproducer phenotype. In contrast in vivo passaged 3Cl-8 cells continued to produce FV even after 100 in vivo passages and expressed gp69/70 antigens to a similar extent as the original in vitro passaged FLC. The expression of F-MuLV and SFFV RNAs in virus producer and virus nonproducer FLC clones has been investigated by means of Northern blot technique using probes specific for either F-MuLV or SFFV. No F-MuLV specific RNA sequences were detected in virus nonproducer 745 clones. SFFV specific RNA transcripts and gp52/55 glycoprotein production could be revealed in all the FLC tested. Southern blot analysis showed the presence of F-MuLV specific sequences in the cellular DNA of virus nonproducer 745 clones. As both in vivo passaged F-MuLV producer 3Cl-8 and F-MuLV nonproducer 745 cells were equally barely immunogenic and highly malignant when injected into syngeneic DBA/2 mice, these results indicate that F-MuLV expression does not result per se in a high immunogenic potential of tumor cells. For the time being, as a specific property of 3Cl-8 versus 745 cells is the interferon-resistant phenotype, it is tempting to speculate that the selection of virus nonproducer cell variants after in vivo passages of interferon-sensitive 745 cells could depend on the presence of low levels of endogenous interferon in normal young mice.

Animals↗

Immunofluorescence study of thymuses of mice given Friend leukemia virus: conventional vs monoclonal antibodies.

In the course of a study of the early effects of Friend Leukemia Virus (FLV) infection in thymus structure and function, evidence of early localization of infectious FLV in the thymic type I and type II epithelio-reticular cells of susceptible mice was obtained. Such evidence was based upon bio-assay, ultrastructural and immunofluorescence observations. As for the latter, conventional monospecific sera against FLV p30 and gp70 antigens as well as two distinct monoclonal antibodies recognizing FLV gp70 epitopes were employed. Both monoclonal antibodies stained with a granular pattern the cytoplasm of type I and II epithelio-reticular cells from susceptible mice injected with live FLV. On the contrary, conventional monospecific sera diffusely stained the cytoplasm of all epithelio-reticular cells of the thymus, independently of mice inoculation with and susceptibility to virus, possibly recognizing tissue-associated normal mouse antigens and/or cross-reacting antigens of other ecotropic viruses.

Animals↗

[Radioimmunoassay of high specificity for vincristine].

The authors set up a simple and fairly rapid radioimmunoassay for vincristine, that shows a good sensitivity, precision and specificity. In particular, the higher specificity in comparison with other similar dosage techniques is likely due to the marked specificity of the used anti-vincristine serum, which displays a low interference even by molecules with a vincristine-like structure. Therefore, the suggested radioimmunoassay technique seems quite suitable for studying vincristine pharmacokinetics and for monitoring blood levels of this alkaloid in treated patients.

Evaluation Studies as Topic↗

Transcriptional induction of H2 (class I) antigens and beta 2 microglobulin by interferon-gamma in interferon-sensitive and interferon-resistant Friend leukemia cells.

The effect of interferons (IFNs) type I (alpha/beta) and type II (gamma) on the stimulation of H2-Dd (class I) and beta 2 microglobulin genes transcription was analysed in IFN-sensitive (w.t.) and IFN-resistant Friend erythroleukemia cells (FLC). Type I IFN enhances the expression of H2-Dd and beta 2 microglobulin genes in w.t. FLC but does not modulate the expression of these genes in clones resistant to IFN-alpha/beta. IFN type II treatment of w.t. and IFN-alpha/beta resistant cell lines results in an increased expression of H2-Dd and beta 2 microglobulin genes, while being ineffective in the cell clone resistant to both types of IFNs. In this cell system the effect(s) of IFN type II is in part mediated by the induction of IFN-beta. The results reported in the present paper suggest that the IFN-gamma is able per se to increase the expression of H2-Dd and beta 2 microglobulin genes; since a reduced but clearly evident stimulation of the expression of these genes was observed in the FLC clone totally resistant to type I IFN.

Animals↗