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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Management control and operative budget at a radiology center].

The laws reforming the National Health Service (SSN) (DL 30.12.92 n. 502 converted into DL 7.12.93 n.517) strongly modify the operation rules of the local sociosanitary units (USL) and imply that the rules themselves be reorganized with flexible and agile organization systems, introducing, in addition, a budget system as a tool for programming and checking the results. The essential elements for management evaluation are: -an accurate accounting system for every department, based on a detailed analysis of the productive factors directly used; -a survey of the activity data with uniform and established indices. This work deals with a radiology department as a responsible unit belonging to Imola State Administration. It is an intermediate service as its activity is for both in- and outpatients. To calculate the cost of the service provided to users and to define the use of resources, inpatients and outpatients costs were included. This involves adding the cost of the examinations requested of the intermediate service, that is, the radiology department. The operative tool used to ascribe the cost of these demands to the departments needs a transfer cost system showing the increasing value of the number of services that the intermediate service gives the final user. To evaluate the activity of the radiology department, we tried to identify an index of respective complexity for every examination: a figure which allows us to express the use of resources according to the complexity of the services given and to turn the number of examinations into significant activity.

Budgets↗
PubMed1996

[Clinical experience with the use of implantable vascular systems in advanced heart failure].

BACKGROUND: Patients with end-stage cardiomyopathy frequently require acute or chronic infusional treatments and long hospitalization. Availability of a simple and safe vascular access is a true necessity for these patients, especially in case of inotropic or diuretic outpatient treatment. In this study we have evaluated the usefulness and the applicability of implantable vascular access in the management of end-stage cardiomyopathy. Technical problems and both short and long term complications have been analysed. METHODS: Nineteen implantable vascular system (16 Port-A-Cath, Pharmacia; 3 Celsite, Bruneau) have been implanted in a group of 15 patients with end-stage cardiomyopathy. All patients had been previously hospitalized and needed prolonged infusional therapy. Implantation was performed in local anaesthesia with technique derived from pace-maker implantation. RESULTS: All the interventions were well tolerated, average procedural time was 30 min (range 20-60 min). No procedural complications occurred. Re-implantation of the system was required in 2 patients due to catheter thrombosis, In 1 patient due to catheter rupture caused by wrong positioning of infusion needle, and in 1 patient due to inflammatory reaction. In 2 further cases catheter thrombosis was treated with local infusion of urokinase. In 1 patient the catheter was repositioned after dislocation. The average in situ permanence of the systems was 8 months (range 15 day-18 months). CONCLUSIONS: Vascular implantable systems have proved useful and easily applf1p4e in the management of patients with end stage cardiomyopathy. After training some of the implied complications are easily avoidable. The use of this device has concurred to reduce duration and frequency of hospitalizations.

Adult↗
PubMed1996

[Use of a digital radiology system with phosphors in the assessment of thoracic diseases in bedside radiography].

We report our experience with a storage phosphor radiography system; to assess both the image resolution and the dynamic range of the system, a phantom simulating chest average density was used. Finally, we investigated the system impact on portable chest radiographs. The radiographs were taken on 35 x 43 cm phosphor plates, with 80 kV, 3 mAs and focus-film distance of 130 cm. The phosphor plates were scanned with a 75 microns laser beam, postprocessed with the system software and, finally, printed on a 20 x 25 cm film. As reported by other Authors, the storage phosphor system showed similar spatial resolution to conventional radiography (2.5 lp/mm for 35 x 43 cm films and 4.5 lp/mm for 20 x 25 cm films), a wide dynamic range always allowing correcting exposure, but increased noise; these features allow film density optimization even in such "critical" situations and bedside radiographs. Pneumonia, pneumothorax, emphysema, pleural effusions and catheters or tubes positioning were always easily depicted. In our experience, the phosphor plate storage system exhibits many advantages over conventional radiography, namely image postprocessing, the opportunity to choose between several sizes of laser films and finally, the possibility of linking the system to a network and possibly to a digital archive. The main drawbacks of the system are its increased noise and, at present, with the available hardware, slow plate reading.

Humans↗
PubMed1995

N-acetylcysteine-promoted survival of PC12 cells is glutathione-independent but transcription-dependent.

Our prior work established that comparable concentrations of N-acetylcysteine (NAC) both block the proliferation of PC12 cells and prevent death of trophic factor-deprived sympathetic neurons and PC12 cells. The present work addresses several aspects of the mechanisms of these actions. NAC increases intracellular levels of glutathione (GSH) by approximately 10-fold in PC12 cells. However, blockade of this increase by treatment with buthionine sulfoximine did not affect either promotion of survival or inhibition of DNA synthesis. Thus, these actions of NAC are independent of its effects on intracellular GSH. NAC's actions in our system do not appear to be dependent on its anti-oxidant/radical scavenger properties, but may be due to its activity as a reductant. Consistent with this, several other reducing agents, the most effective of which was 2,3-dimercaptopropanol, mimicked NAC in blocking DNA synthesis and suppressing death of PC12 cells and sympathetic neurons. Finally, we observed that in striking contrast to nerve growth factor and a number of other trophic agents, the survival-promoting effects of NAC on PC12 cells are blocked by actinomycin D. This suggests that NAC may act by inducing specific gene expression.

Acetylcysteine↗
PubMed1995

Gene therapy in peripheral blood lymphocytes and bone marrow for ADA- immunodeficient patients.

Adenosine deaminase (ADA) deficiency results in severe combined immunodeficiency, the first genetic disorder treated by gene therapy. Two different retroviral vectors were used to transfer ex vivo the human ADA minigene into bone marrow cells and peripheral blood lymphocytes from two patients undergoing exogenous enzyme replacement therapy. After 2 years of treatment, long-term survival of T and B lymphocytes, marrow cells, and granulocytes expressing the transferred ADA gene was demonstrated and resulted in normalization of the immune repertoire and restoration of cellular and humoral immunity. After discontinuation of treatment, T lymphocytes, derived from transduced peripheral blood lymphocytes, were progressively replaced by marrow-derived T cells in both patients. These results indicate successful gene transfer into long-lasting progenitor cells, producing a functional multilineage progeny.

Adenosine Deaminase↗
PubMed1995

Down-regulation of interleukin 6 receptor alpha chain in interleukin 6 transduced melanoma cells causes selective resistance to interleukin 6 but not to oncostatin M.

The cytokines interleukin 6 (IL-6) and oncostatin M are able to inhibit the growth of cell lines obtained from early but not advanced melanomas. Resistant cell lines have frequently been found to produce IL-6. Acquisition of IL-6 resistance and the relationship between resistance and endogenous IL-6 production are poorly defined phenomena. We have characterized a panel of melanoma cell lines for susceptibility to IL-6 and oncostatin M and have generated lines that acquired resistance to IL-6 by IL-6 cDNA transduction. These lines retained the previous oncostatin M sensitivity, suggesting that the alpha chain of IL-6 receptor (IL-6R alpha) is involved in the acquisition of resistance. In fact transduced cells lost the ability to bind 125I-IL-6 and to release soluble IL-6R alpha in culture. Moreover, addition of soluble recombinant IL-6R alpha were able to restore IL-6 sensitivity in association with IL-6 production. On the contrary, naturally IL-6 resistant melanoma cell lines were not inhibited by treatment with recombinant soluble IL-6R alpha in association with endogenously produced or recombinant IL-6. These results demonstrate that down-regulation of IL-6 receptor is only one of different mechanisms that are responsible of IL-6 resistance in melanoma cells.

Cell Division↗
PubMed1995

Prevention of apoptotic neuronal death by GM1 ganglioside. Involvement of Trk neurotrophin receptors.

We have used serum-deprived cultures of wild type and genetically modified PC12 cells to investigate the molecular mechanisms by which monosialoganglioside (GM1) rescues neuronal cells from apoptotic death elicited by withdrawal of trophic support. Our findings indicate that GM1-promoted survival can be mediated in part by the Trk NGF receptor as well as by TrkB, and potentially by tyrosine kinase receptors for additional neurotrophic growth factors. Experiments employing K-252a, an inhibitor of Trk kinases, and PC12 cells overexpressing a dominant inhibitory form of Trk both indicate that a portion of the survival-promoting activity of GM1 is evoked by receptor dimerization and autophosphorylation. In consonance with this we find that GM1 stimulates Trk tyrosine autophosphorylation and Trk-associated protein kinase activity. These observations may provide a mechanism to account for the reported in vitro and in vivo trophic actions of GM1.

Animals↗
PubMed1995

A retroviral vector containing a muscle-specific enhancer drives gene expression only in differentiated muscle fibers.

Genetically modified myogenic cells have a number of potentially relevant applications for gene therapy of genetic defects. Retroviral vectors proved to be a safe and efficient tool to transfer and express genes into satellite cells and their differentiated progeny, although muscle-specific regulation of the transferred gene is very difficult to achieve in a conventional vector framework. We modified a Moloney murine leukemia virus (MoMLV)-derived retroviral vector containing a bacterial beta-galactosidase (beta-Gal) reporter gene by inserting a muscle creatinine kinase (MCK) enhancer element into the U3 region of the viral long terminal repeat (LTR). The resulting vector (mLBSN) was transferred into cells of different histological origin, including undifferentiated murine and human myogenic cells, which were unable to express the transgene at detectable levels. Instead, gene expression from the modified LTR was obtained in a mouse myogenic cell line and in human primary satellite cells upon induction of differentiation into myotubes in culture, and correlated with the activation of the muscle differentiation program. beta-Gal-negative, mLBSN-transduced human satellite cells were also transplanted into the quadricep muscle of immunodeficient mice, where activation of the transgene expression was observed in vivo after differentiation and fusion into muscle fibers. These results show that retroviral vectors carrying LTRs modified in the enhancer sequences may be used to target tissue- and differentiation-specific gene expression into the muscle. For practical purposes, satellite cells engineered by muscle-specific retroviral vectors might represent an effective tool to deliver expression of a given gene product specifically into the muscle tissue, avoiding undesired protein accumulation in mononucleated cells. More generally, this type of vector might be useful whenever regulated expression of a transferred gene is necessary in a target cell or tissue.

Animals↗
PubMed1995

Oligoclonal CD8 lymphocytes from persons with asymptomatic human immunodeficiency virus (HIV) type 1 infection inhibit HIV-1 replication.

CD8 lymphocytes from asymptomatic human immunodeficiency virus (HIV) type 1-infected patients can suppress virus production from infected CD4 cells. Suppressive activity is separate and distinct from cytotoxic T lymphocyte (CTL) reactivities and is likely mediated by a soluble factor(s). The majority of HIV-1 suppression studies have been done in the context of bulk CD8 cell cultures. In this study, viral suppression was characterized by clonal populations of CD8 cells derived from HIV-1-infected patients. Most of the suppressive clones were devoid of detectable CTL reactivity against env-, gag-, pol-, and nef-expressing targets. Among the suppressive clones derived from an individual patient, a marked heterogeneity was evident with respect to phenotypic markers, cytokine production, and T cell receptor V beta expression. These results suggest that noncytolytic virus suppression is oligoclonal in nature. Clones provide tools for future studies aimed at understanding the mechanism of suppression and identifying the suppressive factor.

CD8-Positive T-Lymphocytes↗
PubMed1995

CD40 signalling in ileal Peyer's patch B cells: implications for T cell-dependent antigen selection.

The ileal Peyer's patch (PP) plays a central role in B cell development in young sheep and it is hypothesized that this B cell development occurs independent of extrinsic antigen and T cells. Therefore, it was of interest to examine ileal PP follicular (iPf) B cell responses to CD40 ligand, a molecule integral to T cell-dependent B cell development. A variable level of CD40 expression was detected on a subpopulation of iPfB cells and J558L cells, expressing a membrane form of mouse CD40 ligand (mCD40L), interacted specifically with the CD40 molecule on iPfB cells. In response to mCD40L the non-S phase iPfB cells were rescued from apoptotic cell death and there was a marked proliferative response but viable cell number remained relatively constant. The mCD40L also induced decreased cytoplasmic cAMP levels, blocked anti-Ig-induced iPfB cell death and induced functional IL-2 receptor expression on a subpopulation of iPfB cells. Many of the mCD40L-induced responses of iPfB cells were similar to those reported for germinal centre and immature B cells, and indicated that cognate T cell-B cell interaction could influence iPfB cell proliferation and differentiation. Finally, that mCD40L induced iPfB cell activation and differentiation was evident as increased expression of CD5, the BAQ44A molecule, the CACT65A molecule and the expansion of surface IgG1+ B cells. These mCD40L-induced phenotypic changes were also observed on subpopulations of freshly isolated iPfB cells and jejunal PP follicular B cells. However, few iPfB cells had a phenotype similar to that observed in co-culture with mCD40L and this suggested that T cell-dependent B cell development may play a minor role in ileal PP B cell development. The possible significance of CD40 signalling is discussed in terms of the selection of iPfB cells during development.

Animals↗
PubMed1995

IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp).

CD8+ cytotoxic T lymphocytes are an important component in the immunologic control of human viral diseases. IL-7, a stromal cell-derived cytokine, has been demonstrated to enhance both anti-tumour and anti-viral CTL as well as lymphokine-activated killer (LAK) activity. We studied the ability of IL-7 to support the activation and the growth of in vitro antigen-specific CTL precursors (CTLp) present in peripheral blood mononuclear cells (PBMC) from HIV-infected patients. Results from these studies demonstrate that inclusion of IL-7 in a vaccinia/HIV-1 vector-based stimulation strategy greatly augmented overall CTL reactivities, whereas addition of IL-7 to unstimulated cultures failed to induce any significant anti-viral cytolytic activity. In four of six patients, HIV-specific lytic activities were significantly higher in cultures stimulated with antigen plus IL-7 compared with in vitro stimulation (IVS) with antigen alone. Cytotoxic activity was principally mediated by CD8+ effector cells, and CD3+/CD8+ cell expansion was increased by 2.7-fold in the presence of IL-7. In PBMC from seronegative donors, IL-7 enhanced anti-vaccinia CTL activities with less effect on cell proliferation. Furthermore, anti-gag CTL frequencies determined by limiting dilution analysis were increased by 2- and 10-fold in two asymptomatic patients following IVS plus IL-7 compared with antigen stimulation alone. Cytofluorimetric analysis revealed that IL-7 preferentially expanded CD8 memory cells (CD45RO+) and CD8+ lymphocytes expressing activation molecules. IL-7 was also able to support the growth of CD4+ lymphocytes, while having no effect on natural killer (NK)/K lymphocytes. Taken together, these data suggest that IL-7 acts cooperatively with the antigen supporting in vitro maturation of CTLp into functional cytotoxic effectors. Thus IL-7 may be an important biologic entity to consider as part of future immune-based therapies in which ex vivo expansion of antigen-driven CTL is an important determinant.

Animals↗
PubMed1995

A nonproducer, interfering human immunodeficiency virus (HIV) type 1 provirus can be transduced through a murine leukemia virus-based retroviral vector: recovery of an anti-HIV mouse/human pseudotype retrovirus.

The expression of a human immunodeficiency virus (HIV) type 1 provirus (F12-HIV) cloned from a nonproducer, chronically infected CD4 down-regulated Hut-78 cell clone (F12) does not lead to the formation of viral particles and, upon transfection in HeLa CD4+ cells, confers resistance to HIV superinfection without affecting the CD4 receptor exposure. In an attempt to transfer the anti-HIV properties of F12-HIV into human primary cell, we constructed a Moloney murine leukemia virus-based retroviral vector containing an F12-HIV genome lacking the 3' long terminal repeat and part of the nef gene, which was expressed under the control of its 5' long terminal repeat. The F12-HIV genome was inserted in the orientation opposite to that of the murine leukemia virus transcriptional unit and was designated the N2/F12-HIV nef-antisense vector. Lymphoblastoid CEMss cells, as well as human peripheral blood lymphocytes, were successfully transduced by the recombinant retrovirus emerging from the producer PA317 clones. CEMss clones expressing the F12-HIV nef-antisense vector became resistant to HIV superinfection even at the highest utilized multiplicity of infection (10(5) 50% tissue culture infective doses per 10(6) cells). In transduced CEMss cells the viral interference induced by the F12-HIV expression is not due to CD4 HIV receptor down-regulation. Nonproducer, interfering HIV proviruses transduced into retroviral vectors may, therefore, provide an alternative strategy for the protection of CD4+ human primary cells from HIV infection, which strategy may be used in designating a safe and efficient gene therapy protocol for patients with AIDS.

3T3 Cells↗
PubMed1995

Myogenic conversion of mammalian fibroblasts induced by differentiating muscle cells.

Somite-derived skeletal myoblasts are supposed to be the sole source of muscle fibre nuclei during pre- and postnatal development, but evidence is accumulating for unorthodox contributions to muscle fibre nuclei from other cell types. For example, in tissue culture, fibroblasts can fuse with dysgenic myoblasts and restore correct membrane function. We report here the results of a series of experiments investigating this phenomenon and its possible mechanism. 10T1/2 cells, infected with a replication defective retrovirus encoding the bacterial enzyme beta-galactosidase, fused to form beta-galactosidase positive, differentiated myotubes when cocultured with differentiating uninfected C2C12 or primary myogenic cells, but this did not occur when they were cocultured with other cells such as 3T3 fibroblasts or PC12 pheochromocytoma cells. Myogenic conversion ranged from 1 to 10% of the 10T1/2 cell population and required close cell interaction between the different cells types: it was not induced by conditioned medium or extracellular matrix deposited by C2C12 cells. Myogenic conversion was also observed in vivo, after injection of similarly infected 10T1/2 cells into regenerating muscle. Conversion was seen also after coculture of uninfected 10T1/2 cells with primary chick myoblasts, thus demonstrating that it was not dependent upon viral infection and that there is no species or class barrier in this phenomenon. Primary fibroblasts, isolated from different organs of transgenic mice carrying a Lac Z marker under the control of a muscle-specific promoter, restricting beta-galactosidase expression to striated muscle cells, also underwent myogenic conversion, when cocultured with C2C12 myoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗