Biomedical subjects

G Nicoletti

Publications and source records attributed to G Nicoletti.

At least 19 recordsLinked to original sources

PubMed1995

Systemic effects of cytokines released by gene-transduced tumor cells: marked hyperplasia induced in small bowel by gamma-interferon transfectants through host lymphocytes.

Cells transduced with cytokine genes are currently used to enhance the anti-tumor and immunomodulatory effects of these molecules in cancer therapy. The sustained release of cytokine thus obtained can perturb many homeostatic systems of the host. We have previously shown that the murine mammary adenocarcinoma TS/A transfected with the murine gamma-interferon (IFN-gamma) gene stimulates a strong immune response that impairs tumor growth. Mice bearing tiny tumors have serum IFN-gamma levels constantly exceeding 100 IU/ml. Therefore, we asked which systemic effects can be triggered in mice by such transfectants. BALB/c mice bearing tumors produced by clone 16.6000 cells (which release 6,000 IU/ml of IFN-gamma in culture) were compared to normal mice and to mice with tumors produced by parent cells transfected with the neomycin resistance gene (NEO cells, no IFN-gamma release). Histological studies revealed a marked hyperplasia of small bowel in mice bearing 16.6000 tumors; the villi and crypts of these mice were > 1.5 times longer than those of normal mice and of mice bearing NEO tumors. In vivo administration of bromodeoxyuridine evidenced a 2.5-3 times increase in the proliferative score of the intestinal crypts of mice bearing 16.6000 tumors compared to control mice. No intestinal alterations were observed in nude mice bearing 16.6000 tumors. T lymphocytes thus appear to play a causal role in this phenomenon.

Adenocarcinoma↗

PubMed1995

The subacute levodopa test for evaluating long-duration response in Parkinson's disease.

The clinical relevance of a long-duration response (LDR) to levodopa therapy in Parkinson's disease (PD) has not been widely recognized. In 25 patients with moderate PD, we measured LDR on motor function after short periods of treatment with levodopa (subacute tests). Each subacute test lasted 15 days and consisted of the oral administration of levodopa at various interdose intervals (IDIs) of 48, 24, 12, 8, 6, and 5 hours. The goal for a subacute test was to achieve a satisfactory antiparkinsonian effect before the last levodopa dose (day 15), i.e., an LDR greater than 50% of the maximal response following an acute levodopa test (LDR-endpoint). Twenty-one patients (84%) reached the LDR-endpoint. The IDI at which levodopa was administered clearly differentiated patients who were otherwise clinically indistinguishable when evaluated at baseline off medication or after an acute levodopa test. The IDI schedule that produced a satisfactory LDR was specific for each patient, since longer DIs failed to produce the required LDR, and a shorter IDI schedule (resulting in larger cumulative dosage of levodopa) did not significantly enhance the response. Also, the LDR decay rate after discontinuation of treatment was individual for each patient and independent of the cumulative amount of levodopa administered. Both the IDI schedule and the LDR decay rate may reflect the ability of nigrostriatal neurons to store and to release dopamine formed from the exogenous precursor. The assessment of the LDR to levodopa by subacute tests is useful for establishing the appropriate dose of the drug, as well as for developing levodopa sparing strategies in PD patients.

Aged↗

PubMed1995

Aflatoxin M1 in human breast milk samples from Victoria, Australia and Thailand.

This study examined the exposure of infants to aflatoxin M1 (AFM1) and of lactating mothers to aflatoxin B1 (AFB1), using AFM1 in breast milk as a biomarker for exposure to AFB1. An enzyme-linked immunosorbent assay was modified for the analysis of AFM1 in breast milk samples from 73 women from Victoria for comparison with breast milk samples from Thailand (n = 11). The results were compared with those obtained by HPLC. AFM1 was detected in 11 samples from Victoria and five samples from Thailand at median concentrations of 0.071 ng/ml (range 0.028 to 1.031 ng/ml) and 0.664 ng/ml (range 0.039 to 1.736 ng/ml), respectively. Levels of AFM1 in Thai milk samples were significantly higher than those in milk samples from Victoria.

Aflatoxin B1↗

PubMed1995

Redundancy of autocrine loops in human rhabdomyosarcoma cells: induction of differentiation by suramin.

Three human rhabdomyosarcoma cell lines were used to investigate the presence of autocrine loops based on the production of insulin-like growth factor (IGF)-II, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)/transforming growth factor (TGF)-alpha and of their corresponding receptors, and whether these loops affect cell proliferation and myogenic differentiation. Two cell lines, RD/18 and CCA, deriving from tumours of the embryonal histotype, showed the presence of both growth factors and receptors which make possible three different autocrine loops, while the alveolar RMZ-RC2 cell line lacked that based on the EGF receptor. Culture of rhabdomyosarcoma cells in the presence of specific blocking antibodies, directed to a component of single autocrine loops, inhibited cell proliferation (up to 50%), without inducing myogenic differentiation. Suramin, a drug which non-selectively interferes with the binding of growth factors to their cellular receptors, was used to block all the autocrine loops simultaneously. In CCA and RMZ-RC2 cells suramin was able to induce a significant increase (up to 3-fold) in the proportion of myosin-positive cells over control cultures. Therefore rhabdomyosarcoma cells of embryonal and alveolar histotype can show a redundancy of growth-sustaining autocrine loops. Suramin could interfere with them by acting on both growth inhibition and induction of myogenic differentiation.

Base Sequence↗

PubMed1995

Transduction of genes coding for a histocompatibility (MHC) antigen and for its physiological inducer interferon-gamma in the same cell: efficient MHC expression and inhibition of tumor and metastasis growth.

The mouse mammary carcinoma TS/A, of BALB/c (H-2d) origin, was transfected with the murine interferon-gamma (IFN-gamma) gene (Int. J. Cancer 55: 320, 1993). We used IFN-gamma transfectants as recipients for a second round of transfections with murine allogeneic class I histocompatibility (H-2b) genes that are modulated by IFN. Transfectants with either gene alone, as well as parent TS/A cells (TS/A-pc), were used as controls. Only double transfectants expressed high levels of the allogeneic H-2b genes, while in H-2b single transfectants the expression was very low (but was induced by treatment with exogenous IFN-gamma). The tumorigenic potential of IFN-gamma or H-2b single transfectants was reduced in comparison to TS/A-pc. IFN-gamma+H-2Kb double transfectants were almost nontumorigenic, while IFN-gamma+H-2Db clones gave rise to tumors in about one-half of mice. The experimental metastatic ability of all IFN-gamma+H-2b double transfectants was very low. IFN-gamma single transfectants were known to induce a strong macrophage response in the host. The expression of allogeneic H-2 antigens added a T-lymphocyte-mediated response that accounted for the lower tumorigenicity of double transfectants. These results show that it is possible to steer the immune response evoked by tumor cells for therapeutic purposes. Moreover, the high H-2 expression obtained in IFN-gamma+H-2b double transfectants suggests that single IFN-gamma transfectants are ideal recipients for all IFN-sensitive genes. This approach can be used also for other general-purpose inducers of gene expression.

Animals↗

PubMed1995

In-vitro antimycoplasmal activity of flurithromycin.

The in vitro activity of flurithromycin, a 14-membered macrolide drug, was found to be similar to that of erythromycin against 41 strains of Mycoplasma spp. and 100 strains of Ureaplasma urealyticum. All 28 strains of Mycoplasma hominis were uniformly resistant to both macrolides with MICs > 256 mg/L, U. urealyticum showed intermediate resistance with MIC50s of 0.5 and 1 mg/L for erythromycin and flurithromycin, respectively, whereas the ten strains of Mycoplasma pneumonia were susceptible to < or = 0.03 mg/L of both macrolides.

Enterococcus faecalis↗

PubMed1995

Levels of flurithromycin in female genital tissue.

The levels of flurithromycin in gynecological tissue in 20 female patients were studied after preoperative administration. The tissue flurithromycin levels obtained were comparable to those obtained in serum at 3 and 4 h but were frequently higher than those in serum at 6 and 12 h. Flurithromycin reached the highest concentrations in ovary at 4 h and in endometrium at 6 h.

Anti-Bacterial Agents↗

PubMed1995

Comparative effects of amitriptyline and amineptine in patients affected by anxious depression.

In a double-blind, placebo-controlled study, the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action, amitriptyline and amineptine, was investigated in patients affected by anxious depression. Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder (DSM-III-R) and meeting additional operational clinical criteria such as anxiety, trepidation, restlessness, early and/or late insomnia, impulsivity, hostility, dysphoria, compulsivity, hyperperspiration, palpitation, pollakiuria and phobias were included. They were randomly assigned to three groups (n = 22) and treated either with placebo, amitriptyline (up to 100 mg/day) or amineptine (up to 200 mg/day) for 6 weeks. Patients showed better response to amitriptyline, a preferential inhibitor of serotonin reuptake, than to amineptine, a selective inhibitor of dopamine reuptake. The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression.

Adolescent↗

PubMed1995

Enterococci: susceptibility patterns and therapeutic options.

Enterococci do not possess the common virulence factors found in many other bacteria, but they have a number of other characteristics which make them particularly pathogenic. These organisms are intrinsically resistant to a number of antimicrobial agents, including beta-lactams (penicillins and cephalosporins), polymyxins and the lincosamides. They are also tolerant to the bactericidal activity of penicillins and glycopeptides, and some of the group have acquired resistance to a number of other clinically important antimicrobial agents including ampicillin, aminoglycosides, chloramphenicol and erythromycin. Numerous national and international studies have demonstrated the changes in the antibiotic resistance of enterococci. Many strains now exhibit multiple drug resistance, the most important being high-level resistance to streptomycin and gentamicin. Organisms exhibiting this high-level resistance are usually resistant to all synergistic combinations of beta-lactam antibiotics and aminoglycosides. Ampicillin-resistant strains are now emerging, some of which are beta-lactamase producers. While resistance to glycopeptides remains rare, it is increasing dramatically in many areas of the world. As nosocomial isolates of enterococci have displayed resistance to essentially every useful antimicrobial agent, it is likely to become increasingly difficult to treat and control enterococcal infections. The glycopeptide antibiotics vancomycin and, particularly, teicoplanin are the only alternatives currently available. Although a bactericidal combination of antibiotics appears necessary only in endocarditis and meningitis and although knowledge of the prevalence of resistant strains can be used to guide the selection of appropriate therapy, optimal regimens for the treatment of infections caused by multiresistant strains have yet to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Resistance, Microbial↗

PubMed1994

Biologic characterization of pleural metastases from lung adenocarcinoma: description of the new DV90 cell line.

AIMS AND BACKGROUND: The characterization of pleural metastases from lung adenocarcinoma is often limited to single biologic features. METHODS: The present paper describes the cellular kinetic parameters, as well as immunocytochemical, ultrastructural and genetic characteristics of the new DV90 cell line, established from the pleural effusion of a stage IV lung adenocarcinoma. RESULTS: The cell line has a diploid DNA content, a doubling time of 24 h and 7% cloning efficiency, it is tumorigenic in nude mice. Ultrastructural investigation revealed the typical features of lung adenocarcinoma; the diagnosis was confirmed by its immunohistochemical reactivity with a panel of monoclonal antibodies specifically capable of identifying adenocarcinoma cells. Genetic analysis revealed a 46 X, -Y, +8, der (6)t(6?)(q27;?) karyotype and hyperexpression of the protein codified by genes Her2/Neu and p53. CONCLUSION: The importance of multidisciplinary biologic characterization in identifying the origin and biological behavior of pleural metastases deriving from lung adenocarcinoma is discussed.

Adenocarcinoma↗

PubMed1994

H-2Kb and H-2Db gene transfections in B16 melanoma differently affect non-immunological properties relevant to the metastatic process. Involvement of integrin molecules.

Modification of non-immunological cell adhesion properties plays a major role in the decrease in metastatic ability observed after transfection of the H-2Kb gene in H-2-negative B16-derived melanoma clone cells. To investigate the role played by different class-I major histocompatibility complex (MHC) genes on non-immunological properties relevant for metastasis, transfection with the H-2Db gene alone or in conjunction with the H-2Kb gene was performed. H-2Db gene transfection did not modify either metastatic potential or non-immunological cell adhesion properties. Double KbDb transfectants showed a decreased metastatic ability when compared to control clones and to Db transfectants; a decrease in homotypic adhesive ability was also observed, even though not in all clones studied: therefore expression of the Db gene is also relevant. The mechanisms of homotypic cell adhesion were studied and found to be dependent upon temperature and divalent cations. Adhesion was partially inhibited by an antiserum directed against the beta 1 integrin subunit, whereas anti-alpha IIb beta 3 was ineffective. Cell pre-treatment with anti-beta 1 serum reduced metastatic ability. A decreased expression of alpha 4 and alpha 6 integrin subunits was observed in Kb clones, whereas no difference in the levels of some homophilic cell adhesion molecules, such as N-CAM and alpha IIb beta 3, was found. Adhesion required the activity of tyrosine kinases, as suggested by the decreased adhesive properties and impaired metastatic ability of cells pre-treated with the tyrosine-kinase-inhibitor genistein. These results are compatible with involvement of integrin molecules of the beta 1 family in the adhesive ability of these cells. Our data show that: (a) immunological and non-immunological effects of MHC transfection are correlated and depend on the class-I gene used, suggesting that MHC gene therapy can be highly successful only if appropriate MHC genes are transfected; (b) non-immunological cell-adhesion properties modified after MHC transfection could be related to an impairment of integrin-mediated adhesive interactions.

Animals↗

PubMed1994

In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922.

The in vitro activities of rufloxacin and its metabolite, MF 922, were compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline against Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, and Ureaplasma urealyticum. Rufloxacin, MF 922, and ciprofloxacin shared similar activities against all mycoplasmas tested. (MICs for 90% of isolates tested [MIC90s], 0.5 to 4 micrograms/ml. Ofloxacin had the lowest MIC90s for U. urealyticum, M. fermentans, and M. hominis (MIC90s, 0.25 to 1 micrograms/ml) and erythromycin had the lowest MIC90 for M. pneumoniae (MIC90, 0.004 micrograms/ml).

Anti-Infective Agents↗

PubMed1994

[Microbiological aspects of antibiotics with immunomodulating action].

Through the introduction of a 7-mercapto-1,3-thiazole chain at position 3' of the dihydrothiazine ring, cefodizime, which is structurally similar to cefotaxime, has acquired a number of remarkable immunomodulatory properties while retaining a potent antimicrobial spectrum of activity. Cefodizime penetrates in fact readily through the bacterial cell wall and interacts with its molecular targets in such a way that at high concentrations cell death and lysis are rapidly induced. Its spectrum of action encompasses the Enterobacteria, Neisseriae, Haemophilus, Moraxella catarrhalis, methicillin-susceptible staphylococci and streptococci, with pneumococci included. Cefodizime is devoid of useful potency against Pseudomonas, Acinetobacter and enterococci. Given the wide occurrence of strains synthesizing beta-lactamases in several primary pathogens of community-acquired and nosocomial infections, the complete stability of cefodizime towards the most prevalent of these hydrolytic enzymes (TEM-1, TEM-2, SHV-1, BRO-1 and the staphylococcal penicillinases) seems reassuring. Only a few chromosomally-coded and extended spectrum beta-lactamases produced by gram-negative microorganisms inactivate the new cephalosporin. Since the distribution of pathogens carrying these enzymes depends on the local trends of antibacterial consumption and cannot be easily predicted, a large multicenter study in Italy has recently assessed the antibacterial potency of cefodizime, in comparison with suitable drugs, on 1985 selected nosocomial strains. In this survey cefodizime was more effective in vitro than amoxicillin-clavulanate, gentamicin and piperacillin while being substantially similar in the rates of eradication of gram-negative and gram-positive organisms to other third generation cephalosporins like ceftazidime and ceftriaxone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

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↗

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↗