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Biomedical subjects

G Falcone

Publications and source records attributed to G Falcone.

At least 73 records · Page 4Linked to original sources
PubMed1989

Mechanisms other than polyclonal B cell activation possibly involved in Epstein-Barr virus-induced autoimmunity.

In order to verify whether Epstein-Barr virus (EBV)-induced polyclonal B cell activation is the major cause of autoimmunity during infectious mononucleosis (IM), we have investigated, by immunoblotting, the fine specificity of anti-smooth muscle autoantibodies (autoAbs) in the sera of IM patients. Furthermore, we have isolated a number of in vivo infected EBV-positive cell lines from a patient with IM and compared the reactivity of the secreted immunoglobulins (Igs) with that of serum autoAbs. The reactivity of anti-smooth muscle autoAbs was found to be closely restricted to three proteins of approximate molecular weights 54, 52 and 48 kD. Furthermore, none of 48 EBV-positive B cell lines shared any reactivity with serum autoantibodies. Taken together, these results suggest that EBV-induced autoimmunity is not a consequence of a random activation of B cells, but a specific phenomenon, requiring mechanisms other than polyclonal B cell activation.

Antibody Specificity↗
PubMed1989

[A rare case of massive osteolysis (Ghoram's syndrome)].

The authors report a case of massive osteolysis of the right shoulder in a woman aged 53 years, characterised by progressive evolution with spontaneous arrest 8 months after onset. The diagnosis of Ghoram's syndrome was based on a histologic examination revealing evident vascular neoformation, radiographic and clinical evolution.

Diagnosis, Differential↗
PubMed1988

Specific viral oncogenes cause differential effects on cell-to-cell communication, relevant to the suppression of the transformed phenotype by normal cells.

We have studied growth regulation in mixed cultures of normal and oncogene-transformed 3T3 cells. The NIH 3T3 cells transformed by myc, src, and ras showed comparable cloning efficiency in semisolid medium. However, when they were plated on plastic with an excess of normal mouse embryo fibroblasts, BALB/c 3T3 ClA31-1-1, ras- and src-transformed cells were able to form distinct foci on the layer of density-arrested normal cells, whereas myc-transformed cells lacked this ability. In order to determine whether suppression or expression of the transformed phenotype could be correlated with the ability of the different cell populations to communicate, gap-junctional intercellular communication (IC) was measured by the Lucifer yellow dye transfer assay in coculture of normal and transformed cells. The dye was observed to spread from BALB/c 3T3 to myc-NIH 3T3 cells, indicating the presence of IC between these two cell types. In contrast no passage of Lucifer yellow was observed between src-NIH 3T3 or ras-NIH 3T3 and BALB/c 3T3. Addition of a phorbol ester tumor promoter, phorbol-12,13-didecanoate, efficiently rescued proliferation and focus formation by myc-transformed cells. The tumor promoter was able to inhibit IC in BALB/c 3T3 cells, although this response greatly varied among the different oncogene transformed clones. Tumorigenicity in nude mice strongly correlated with growth behavior in vitro: myc-transformed cells were either nontumorigenic or slowly tumorigenic, and src- and ras-transformed cells were highly tumorigenic. These data suggest an important role of IC in modulating abnormal growth behavior in vitro and in vivo.

Animals↗
PubMed1988

Differential influence of adjacent normal cells on the proliferation of mammalian cells transformed by the viral oncogenes myc, ras and src.

We investigated the role of adjacent normal cells in the modulation of focal outgrowth of mammalian fibroblasts transformed by different viral oncogenes (myc, src and ras). NIH3T3 cells transformed by these three oncogenes were derived by transfection or infection and showed comparable cloning efficiencies in semi-solid medium. However, upon replating in liquid medium a small number of transformed cells together with a vast excess of normal mouse embryo fibroblasts C3H10T1/2, ras- and src-transformed cells were able to overgrow the monolayer and formed distinct foci, whereas myc-transformed cells lacked this ability. Conditioned medium from normal cells did not affect the proliferation of myc-transformed cells at clonal density. Addition of phorbol ester tumour promoters, either at the time of plating or as late as after one week, efficiently rescued focus formation by myc-transformed cells. In contrast, when myc-transformed cells were cultivated alone, their clone size and cloning efficiency were slightly reduced by the addition of tumour promoters. These results indicate that cell-cell contacts between transformed cells and adjacent normal cells specifically inhibit the growth of myc- but not of ras- or src-transformed cells. The ability of tumour promoters and phospholipase-C to rescue the focus forming ability of myc-transformed cells is consistent with the possibility that activation of protein-kinase C is involved in the clonal expansion of 'suppressed' myc-bearing cells.

Animals↗
PubMed1987

Partial transformation of mouse fibroblastic and epithelial cell lines with the v-myc oncogene.

To investigate the role of the myc gene in mammalian cell transformation, plasmid constructs containing the v-myc oncogene and a co-selectable G418 resistance marker were introduced into both mouse fibroblasts (NIH-3T3) and bladder epithelial cells (BBN3 and BBN7). After transfection or microinjection of DNA, no transformed foci could be detected on confluent monolayers but, when the cells were cultured under conditions in which individual cells were allowed to grow and form colonies, morphological transformation was observed. Unlike ras-transformed NIH-3T3 cells, v-myc-transformed cells were unable to grow in serum-free medium and therefore still required exogenous growth factors. v-myc-transformed NIH-3T3 cells were poor at forming foci when co-cultivated with untransformed cells; however, the efficiencies could be increased by addition of EGF to the medium. Both v-myc-transformed fibroblasts and epithelial cells acquired the ability to grow in soft agar, though at efficiencies lower than the corresponding ras transformants. Subcutaneous inoculation of v-myc-transformed NIH-3T3 cells into nude mice resulted in no tumours within 6 weeks. After protracted periods (2-3 months) a few tumours were detected, but at a frequency barely above that for spontaneous tumour formation. Epithelial cells transformed by v-myc were either non-tumorigenic or gave a very low incidence of tumours. We conclude that the v-myc oncogene induces morphological changes and anchorage independence in immortal mouse fibroblasts and epithelial cell lines but further events are required for the cells to become tumorigenic.

Animals↗
PubMed1987

Azthreonam in the treatment of urinary tract infection: evaluation of efficacy, renal effects and nephrotoxicity.

The efficacy, renal effects and nephrotoxicity of a short course of treatment with azthreonam were evaluated in 11 adult patients with urinary tract infection. Azthreonam was administered for 5 days at a daily dose adjusted to the residual renal function of the patients. In the pre-treatment period, during treatment and 10 days after completion of therapy, urine cultures, urinalysis and routine renal function tests (clearance of creatinine, urea and uric acid) were performed and urinary enzymes (alanine-aminopeptidase, gamma-glutamyl-transpeptidase, N-acetyl-beta-D-glucosaminidase, lysozyme) were determined. Renal haemodynamics (glomerular filtration rate and effective renal plasma flow) were measured in the pretreatment period and on the 5th day of therapy. The results confirm the efficacy of azthreonam for treatment of urinary tract infection. Results of renal function tests and measurements of urinary enzymes remained unchanged during and after treatment with azthreonam. These data support the conclusion that azthreonam is an effective antimicrobial agent which does not influence renal function or cause nephrotoxic effects.

Adult↗
PubMed1986

Human monoclonal antibody to purified protein derivative of tuberculin produced by hybrids constructed with Epstein-Barr virus-transformed B lymphocytes and mouse myeloma cells.

A method of producing human monoclonal antibody by combining somatic cell hybridization technology with the capability of Epstein-Barr virus (EBV) to transform human B lymphocytes is described. Peripheral blood lymphocytes from a donor with positive tuberculin skin test reaction were transformed by EBV and then tested for antibody production to mycobacterial purified protein derivative (PPD) by an enzyme-linked immunosorbent assay. Two EBV-transformed lymphoblastoid cell lines making IgM antibodies to PPD were obtained. One of these cell lines was fused by polyethylene glycol with a murine hypoxanthine-guanine phosphoribosyl transferase-deficient myeloma cell line that had been selected for resistance to ouabain. The human-mouse hybrids were selected in ouabain-containing HAT medium and 11 heterohybridomas producing IgM antibody to PPD were obtained. One of these was cloned by limiting dilution with efficiency at least 20-fold higher than parent EBV-transformed cell line. Heterohybridoma subclones reached levels of IgM antibody as high as 75.0 micrograms/ml of culture medium, whereas IgM production of EBV-transformed B cell clones ranged between 3.0 and 4.0 micrograms/ml.

Animals↗
PubMed1985

Distinctive effects of the viral oncogenes myc, erb, fps, and src on the differentiation program of quail myogenic cells.

The relationship between susceptibility to transformation in vitro by different oncogenes and terminal differentiation was analyzed in embryonic quail myogenic cells. Infection with Rous sarcoma virus (RSV), Fujinami sarcoma virus (FSV), avian erythroblastosis virus (AEV), and the avian myelocytomatosis virus MC29 led to rapid and massive transformation. Transformed cells had distinctive morphological alterations, increased proliferation rates, and the ability to grow in agar suspension. Furthermore, homogeneously transformed cultures failed to fuse into multinucleated myotubes and to express muscle-specific genes. However, cloned populations of RSV-, FSV-, and AEV-transformed myogenic cells could, under appropriate culture conditions, partially differentiate into atypical "revertant" myotubes. In contrast, competence for terminal differentiation was completely and irreversibly suppressed on transformation by MC29. The specificity of action of a given oncogenic sequence on the inhibition of differentiation was further studied by using conditional and nonconditional transformation mutants. Myogenic cells infected with temperature-sensitive (ts) mutants of RSV and FSV exhibited a fully reversible block of differentiation after shift to restrictive temperature, while cells infected with ts34 AEV were not temperature sensitive for differentiation. Cultures infected with the partially transformation-defective mutant of MC29 td10H were morphologically transformed and acquired anchorage independence for proliferation but maintained a residual competence for terminal differentiation.

Alpharetrovirus↗
PubMed1985

Polyclonal B cell activators inhibit contact sensitivity to oxazolone in mice by potentiating the production of anti-hapten antibodies that induce T suppressor lymphocytes acting through the release of soluble factors.

Polyclonal B cell activators (PBAs) such as purified protein derivative, lipopolysaccharide, Staphylococcus aureus strain Cowan I (StaCwI), and Pseudomonas aeruginosa inhibit contact sensitivity to oxazolone in mice when given 24 h before sensitization. This suppression, transferable from immunodepressed animals to oxazolone-sensitized recipients with immune serum, has been shown to be due to the early appearance of anti-hapten antibodies. These antibodies elicit T suppressor cells which release soluble factor(s) capable of inhibiting the passive transfer of contact sensitivity.

Animals↗