Biomedical subjects

G Nicoletti

Publications and source records attributed to G Nicoletti.

At least 145 records · Page 8Linked to original sources

PubMed1993

Uncoupling of growth inhibition and differentiation in dexamethasone-treated human rhabdomyosarcoma cells.

The effects of dexamethasone, a synthetic glucocorticoid, and of N,N-dimethylformamide on in vitro growth and differentiation and on proto-oncogene expression of human rhabdomyosarcoma cells were studied. RD/18 clone cells (derived from the embryonal rhabdomyosarcoma cell line RD) treated with 100 nM dexamethasone showed an almost complete block of differentiation: about 5% myosin-positive cells were observed after 2 weeks of culture in dexamethasone-supplemented differentiation medium, compared to 20% of untreated cultures. Dexamethasone also induced a 20-30% growth inhibition and a more flattened morphology. The treatment with N,N-dimethylformamide induced a significantly increased proportion of myosin-positive cells (reaching about 30%) and a 40% growth inhibition. Induction of differentiation inversely correlated with the levels of c-myc proto-oncogene expression: after a 2 week culture dexamethasone-treated cells showed the highest c-myc expression and N,N-dimethylformamide-treated cells the lowest. Culture conditions per se down-modulated c-erbB1 and up-regulated c-jun expression, with no relationship to the differentiation pattern. Other proto-oncogenes were not expressed (c-sis, N-myc, c-mos, c-myb) or were not modulated (c-fos, c-raf). Therefore dexamethasone and N,N-dimethylformamide, both causing a decreased growth rate, showed opposing actions on myogenic differentiation and on c-myc proto-oncogene expression of human rhabdomyosarcoma cells.

Cell Count↗

PubMed1993

Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transfected tumour cells.

Transfection of murine metastatic B78H1 cells (derived from B16 melanoma) with a syngeneic H-2Kb gene was used to study the effect of Major Histocompatibility Complex (MHC) gene products on tumour cell adhesion to endothelial cells and matrix proteins and the involvement in the metastatic process. H-2Kb-expressing transfectants showed a reduced adhesion to endothelial surfaces of different origin (four murine endotheliomas and human umbilical vein endothelial cells) when compared to parental B78H1 cells and to controls transfected with pSV2neo alone. On the average a 50-70% reduction in adhesion to endothelial cells was observed among H-2Kb transfectants. H-2Kb transfectants had a reduced expression of the alpha 4 integrin subunit, moreover the adhesion of Neo-transfected clones to endothelial cells was reduced to the levels of H-2Kb transfectants by antibodies directed against the beta 1 subunit and the endothelial VCAM-1 molecule, thus suggesting an impairment of the VLA-4/VCAM-1 interaction in H-2Kb transfectants. Adhesion to extracellular matrix components was also strongly decreased: in general the adhesion of H-2Kb cells showed a 50-75% inhibition with respect to Neo or parental controls. The highest difference was observed in adhesion to vitronectin and laminin, the lowest in adhesion to fibronectin. Reduction in adhesive properties of H-2Kb-expressing transfectants could be involved in the reduced metastatic ability, evaluated by means of intravenous injection of cells: H-2Kb transfectants yielded less than ten lung colonies, while all controls produced more than 100. Our data indicate that expression of a single class I MHC gene can significantly alter the metastatic phenotype of MHC-negative tumour cells and this could be related to a general alteration of tumour cell adhesive interactions.

Animals↗

PubMed1993

The effect of cefepime on some immune parameters in vitro: lack of interference with mitogen-induced lymphoproliferation, immunoglobulin synthesis, IFN-gamma and IL-2 secretion and IL-2 receptor expression.

The possible interference of the novel antibiotic cefepime (CPE) with some functions of the immune system was investigated in vitro. Peripheral blood mononuclear cells (PBMC) cultured in the presence of drug concentrations ranging from 25 to 100 micrograms/ml normally maintained their responsiveness to polyclonal (PHA, Con A, PWM) mitogenic stimulation in regard to proliferative response, IgM and IgG synthesis and IFN-gamma and IL-2 secretory capacity. Moreover, PHA-induced expression of IL-2 receptors was comparable in PBMCs cultured in the presence or absence of CPE. Taken together, these data suggest that CPE does not interfere, at this specific level, with T- and B-cell mediated functions in vitro.

Adult↗

PubMed1993

Efficacy of azithromycin compared with spiramycin in the treatment of odontogenic infections.

Sixty patients with acute odontogenic infections were randomly allocated to oral treatment with azithromycin 500 mg/day once-daily for three days (n = 30) or spiramycin 3,000,000 units three-times daily for seven days (n = 30). Baseline and post-treatment oral specimens were collected from patients to test for pathogenic bacteria. Aerobic bacteria were tested using the Kirby-Bauer disc diffusion method, and anaerobic bacteria with a broth microdilution method, for their susceptibility to azithromycin and spiramycin. A greater incidence of resistance was found in the spiramycin group than in the azithromycin group. The bacteriological assessment showed that the normal balance of microflora was re-established in 67% of patients treated with azithromycin vs 53% in the group treated with spiramycin. Clinical cure was higher in the azithromycin treatment group (97%) compared with the spiramycin group (73%). These results indicate that three-day azithromycin, possibly because of its unusual pharmacokinetics, is more effective than seven-day spiramycin in the treatment of odontogenic infections.

Azithromycin↗

PubMed1992

Susceptibility of frequent urinary pathogens to fosfomycin trometamol and eight other antibiotics: results of an Italian multicenter survey.

In order to assess the resistance profile for fosfomycin trometamol after several years of clinical use in Italy, this study has explored the susceptibility to fosfomycin and eight other antibacterial drugs of 6,021 strains isolated from 23,816 urines during 1990 in three teaching hospitals located in Genoa, Parma and Catania. Gram-negative strains, notably Escherichia coli (41.6%), were primarily involved. Amoxicillin was the least active compound with resistance in 41.4% of the isolates. Fosfomycin showed the lowest rate of resistance in both gram-negative (2.8%) and gram-positive (2.1%) pathogens. This was followed by norfloxacin with a resistance rate of 11.8% and netilmicin with 12.2%. These results indicate that fosfomycin-trometamol may continue to be used in single-dose treatment of urinary tract infections even in the absence of microbiological data since the prevalence of resistance to the drug is, at present, so low that therapeutic failure is highly improbable.

Anti-Bacterial Agents↗

PubMed1992

Induction of myogenic differentiation in human rhabdomyosarcoma cells by ionising radiation, N,N-dimethylformamide and their combination.

Differentiation-inducing ability of gamma-radiation, N,N-dimethylformamide and their combination has been tested on human rhabdomyosarcoma RMZ-RC2 clone cells. Ionising radiation at 2-5 Gy doses induced a more differentiated morphology, with the appearance of an increased proportion of multinuclear myotube-like cells, and a significant increase in myosin-positive and multinuclear cells. Radiation appeared to act by inducing de novo differentiated elements. N,N-dimethylformamide was able to induce an increased myosin expression, but did not affect multinuclear cell proportion. The combined treatment (ionising radiation and N,N-dimethylformamide) resulted in an additive increase in the proportion of myosin-positive cells, approaching 25-35%, but de novo differentiated elements were not increased above the levels obtained with irradiation alone.

Cell Differentiation↗

PubMed1992

Control of H-2 expression in transformed nonhaemopoietic cells by autocrine interferon.

The relationship between autocrine interferon (IFN) production and the expression of class I Major Histocompatibility Complex (MHC) membrane glycoproteins in vitro was investigated in a panel of murine transformed cells of nonhaemopoietic origin. The panel included 11 cell lines of H-2Kb haplotype derived from fibrosarcomas, carcinomas and melanoma, and from transformed fibroblasts. IFN activity was detected in the conditioned medium of nine cell lines; fibrosarcomas were among the high IFN producers, while the non-producers were a melanoma clone and a lung carcinoma cell line. A significant correlation was found between IFN production and the expression of H-2K/D glycoproteins, thus suggesting that long-term maintainment of MHC glycoprotein expression in vitro could be mediated by self produced IFN. Two IFN producer cell lines, MN/MCA1 and R80/17, were cultured in the presence of a blocking antiserum against IFN-alpha/beta: a significant decrease in H-2b expression was observed, thus indicating the existence of an autocrine IFN circuit. Taken together these findings suggest that release of IFN is a frequent event among transformed nonhaemopoietic cells, and that self-produced IFN contributes to the regulation of MHC antigen levels in solid tumours.

Carcinoma↗

PubMed1992

Microbiological considerations of the etiological agents of lower respiratory tract infections.

One hundred eight-four sputum specimens from the same number of patients with lower respiratory tract infections were examined to determine the bacterial count and the relationship between the microorganisms isolated and the presumptive pathology. The sputa were subdivided into three groups; "high probability", "low probability", and "contaminated sputa", following the criteria of the microscopic readings: sputum with more than 25 white cells and low numbers of squamous epithelial cells represents true lower respiratory tract infections (high probability); those with fewer than 25 white cells represent non-bacterial infections or non-infected sputa (low probability) while sputa with more than 25 squamous cells per field represent contaminated specimens (contaminated sputa). Statistical analysis was carried out to correlate these data. Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, and Streptococcus pyogenes showed significant differences in the three groups considered.

Gram-Negative Bacteria↗

PubMed1992

TNF impairs in vivo and in vitro natural killer (NK) susceptibility of B16 melanoma cells.

Tumour necrosis factor alpha (TNF) is a multipotent cytokine which affects many biological properties of both normal and neoplastic cells. Here we show that treatment with TNF reduces B16-A melanoma cell susceptibility to normal and in vivo- and in vitro-activated NK cell-mediated killing. This resistance is associated with an enhancement of B16-A metastatic potential in normal syngeneic mice, but not in anti-asialo GM1-treated animals, further supporting the NK dependence of TNF-induced enhancement of metastatic ability. A significant increase of MHC class I expression on B16-A murine melanoma cells is observed after TNF treatment. In all these effects TNF interacts positively with interferon gamma (IFN gamma). Taken together, these results indicate that TNF treatment negatively affects the susceptibility of B16-A murine melanoma to NK effectors in vivo and in vitro. This decreased susceptibility may be related, at least in part, to enhanced expression of MHC class I antigens on tumour cells.

Animals↗

PubMed1992

In vitro activity of a new broad-spectrum, beta-lactamase-stable oral cephalosporin, cefixime, in comparison with other drugs, against Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pneumoniae.

Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991. Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin. Cefixime inhibits 90% of S. pneumoniae, H. influenzae and H. parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l. It inhibits 90% of M. catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l. In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains). In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M. catarrhalis, the authors observed different indications in the guidelines for ampicillin. Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp. and M. catarrhalis (TEM and ROB in Haemophilus strains and BRO in M. catarrhalis). In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections.

Administration, Oral↗

PubMed1992

Bactericidal activity and postantibiotic effect of cefdinir (Cl 983, FK 482) against selected pathogens.

The bactericidal activity and the postantibiotic effect (PAE) of cefdinir (Cl 983, FK 482) (CDR), were determined against Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis and Escherichia coli (5 strains each) in comparison to erythromycin (E), cotrimoxazole (SXT) and amoxicillin-clavulanic acid (AMC). Kinetic studies of kill showed that CDR was rapidly bactericidal at concentrations 2 and 4 times the minimum inhibitory concentration (MIC): a reduction of 99.9% in CFU values was observed after 6-8 h for many of the isolates tested. As expected, a PAE was observed when S. aureus was treated with CDR at MIC (range of individual values for 5 strains 0.8-1.5 h) and 4 x MIC (range 1.1-1.4 h). Moreover, CDR showed a significant PAE at both its MIC and 4 x MIC against S. pneumoniae (range 0.5-1.0 h and 0.9-1.1 h), H. influenzae (range 0.4-0.7 h and 0.4-0.8 h), B. catarrhalis (range 0.5-0.7 h and 0.65-0.95 h) and E. coli (range 0.5-0.6 h and 0.5-0.7 h). The good bactericidal activity and the significant PAE of CDR against Gram-positive and Gram-negative bacteria (including respiratory pathogens) are a promising indication for the clinical efficacy of this cephalosporin in several bacterial infections.

Amoxicillin↗

PubMed1992

[Roxithromycin in dental infections].

Roxithromicin is a semisynthetic macrolide antibiotic, with similar antibacterial activity to erythromycin. It is characterized by an excellent pharmacokinetic profile and a good tissue penetration. Particularly at the dose of 300 mg per day the dental tissue diffusion is extremely good, and this is important to oppose the oral cavity infections. Oral cavity infections can be either odontogenic or non odontogenic. Odontogenic infections are typically primary and are caused by commensal bacteria (oral Streptococci, Bacteroides sp., Veillonella sp. and Fusobacterium sp.). The antibacterial spectrum of roxithromycin is very large and includes many of the most frequent strains responsible for oral cavity infections. A very interesting characteristic of roxithromycin is its penetration in macrophages (uptake) that allow a more rapid inhibition of bacterial activity. To evaluate the clinical efficacy and tolerance of roxithromycin in the treatment of odontogenic infections, an open study was performed. This study evaluated both the microbiological and clinical aspects. Thirty patients (21 females and 9 males) who had not been previously treated with antibiotic or antibacterial drugs, affected by infective dysodontiasis, gingivitis and periodontal diseases, received 300 mg per day (once a day) of roxithromycin for an average period of 6 days. The symptomatology considered was: intumescence, redness, pain, lymphangitis and presence of trismus. Clinical symptomatology was assessed at the start and at the end of the treatment. The symptomatological improvement due to roxithromycin was rapid and very effective. After 6 days of therapy, the improvement was statistically significant (p < 0.01) compared to basal conditions. No adverse reactions or side-effects were complained during the study. No changement were detected in laboratory parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Preliminary evaluation of immunoadjuvant activity of an orally administered glucan extracted from Candida albicans.

The immunoadjuvant activity of an orally administered glucan (Glucanil, Gluimmun) was investigated in mice. Glucan was extracted from Candida albicans ATCC 20955 and purified by an alkali-acid and detergent treatment. In this study the chronic intravenous infection with Candida albicans (treated or not with amphotericin B) or Staphylococcus aureus was the experimental model. Moreover the production of interleukin-2 was evaluated in treated animals. Oral treatment with glucan at 1 mg/mouse/day repeated doses, starting from 10 days before the experimental infection, significantly increased polymorphonuclear leukocytes and peripheral monocytes number. A significant increase in number and in vitro candidacidal activity was also observed for alveolar macrophages. The resistance towards systemic infection with Candida albicans or Staphylococcus aureus increased, significantly reducing the growth of microorganisms in the kidneys of infected animals. Glucan significantly increased the candidacidal spleen cells activity and synergized with amphotericin B chemotherapeutic action. Higher doses (eg. 2 or 5 mg/mouse) were not effective. A 10 days oral treatment with 1 mg/mouse/d significantly increased the interleukin-2 production. Toxicological studies showed that glucan is highly tolerated.

Adjuvants, Immunologic↗

PubMed1991

Karyotypic characterization of a new human embryonal rhabdomyosarcoma cell line.

Chromosomal analysis of an advanced recurrent rhabdomyosarcoma of the embryonal type was performed on cell cultures in the 9th passage of in vitro cultivation. This tumor showed a modal karyotype of 54 and was characterized by multiple numerical and structural chromosome abnormalities, all present in high frequencies. Abnormalities observed in 100% of the cells included a der(1) chromosome with a short unidentified insertion between q31 and q32; a der(1) chromosome, arising from insertion at the same breakpoint of a longer segment with a duplicated 1q31 band and translocation of 13q23----qter to 1p36, a deleted tetrasomic 13q23----qter, and a der(4) chromosome showing 1p36----pter translocated to 4p13. Other common abnormalities included trisomy of chromosomes 8, 13, and 9p, deletions of chromosomes 6, 10, 11, and 12, and presence of marker chromosomes. Characterization of the established line at the 38th passage evidenced the persistence of both the modal karyotype and all the numerical and structural abnormalities previously found. The results of this study provide further evidence of the major involvement of alterations in chromosome 1 in the progression of rhabdomyosarcoma.

Child↗

PubMed1991

Immunological and non-immunological influence of H-2Kb gene transfection on the metastatic ability of B16 melanoma cells.

The H-2b-negative B78HI clone (derived from B16 melanoma) was transfected with the H-2Kb gene; 4 cell clones expressing membrane H-2Kb antigens and 2 control clones (transfected with pSV2neo alone) were used for studies of metastatic ability, immunogenicity, NK sensitivity and homotypic adhesion. The experimental metastatic capacity of H-2Kb transfectants in syngenic mice was greatly diminished in comparison with control and parent cells. Both immune-mediated and intrinsic properties of transfectants correlated with their lower metastatic ability. A cell-mediated cytotoxic response was induced by repeated in vivo immunizations of syngeneic mice followed by in vitro restimulation of effectors when transfectants (but not controls) were used as immunizers and as targets. Moreover, homotypic adhesion of H-2Kb transfectants was significantly lower than that of controls. Sensitivity to NK cells of transfectants was not decreased in comparison to H-2-negative controls. It is known that in vitro treatment with IFN-gamma of H-2-positive B16 melanoma cells induces a simultaneous increase in H-2 expression and in experimental metastasis; treatment of H-2Kb transfectants with IFN-gamma induced a higher Kb expression, but no increase in metastatic ability, thus suggesting that the IFN-sensitive component that mediates enhancement of metastasis is not H-2Kb.

Animals↗

PubMed1991

Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria.

Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E.coli. The bacterial [3H]diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli [3H]diazepam binding are those that are active in displacing [3H]benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligand spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed.

Animals↗

PubMed1991

In vitro differentiation of rhabdomyosarcomas induced by nickel or by Moloney murine sarcoma virus.

In vitro cultures and clonal derivatives have been established from rat rhabdomyosarcomas induced by Moloney-Murine Sarcoma Virus (MSV) or by nickel sulfide; differentiation ability has been studied as expression of desmin, embryonic and adult myosin isoforms, alpha-actin isoforms and cellular fusion. The two rhabdomyosarcoma models showed different levels of myogenic differentiation. Multinucleated myotube-like structures were frequently observed in cultures derived from nickel-induced tumours. Desmin was present in 50-80% of cells and embryonic myosin in up to 10%. In MSV-tumour-derived cultures and in their metastases or clonal derivatives two cell types are present in different ratios: spindle-shaped cells, adherent to plastic surfaces, and rounded cells, loosely attached or floating free in the medium. These cultures showed features of myogenic differentiation (10-80% desmin-positive cells), but embryonic myosin expression and production of multinucleated myotube-like structures were very rare events. Cultures from autochthonous lymph node and lung metastatic cells showed similar patterns of differentiation. Retinoic acid increased differentiated features (myotube formation and embryonic myosin expression) only in nickel-induced rhabdomyosarcoma cells. The two models described here mimic the heterogeneity in differentiation pattern found among human rhabdomyosarcomas. Myogenic differentiation ability was retained at a good level by nickel-induced tumours, whereas it was strongly impaired in MSV-induced tumours.

Animals↗

PubMed1991

New epidemiological data on resistance to netilmicin and other aminoglycosides.

In previous investigations we considered the increasing resistance of Gram-negative organisms to aminoglycosides over time. We therefore performed further studies to evaluate eventual variations in the incidence of bacterial resistance to aminoglycosides over the last four years. We tested Gram-negative microorganisms recently isolated from pathological materials of various clinical origins with gentamicin, amikacin, tobramycin and netilmicin. Our data show evidence that there was no significant increasing resistance to aminoglycosides, and that netilmicin continues to be active as an anti-Gram-negative antibiotic.

Amikacin↗