Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 55 records · Page 3Linked to original sources

PubMed2000

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.

Adult↗

PubMed2000

Recombinant bacillus Calmette-Guérin as a potential vector for preventive HIV type 1 vaccines.

In August 1997, the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) convened an expert working group to discuss current strategies for the development of HIV type 1 vaccines. Based on the recent findings of investigators from Japan's National Institute of Infectious Diseases (NIID) in Tokyo using recombinant bacillus Calmette-Guérin (rBCG) as a potential vectored vaccine for HIV, a recommendation was made that further work in this area is a priority. As a result, the working group reconvened in September 1998 to discuss the progress to date with this vaccine approach, as well as areas of related research to assess the feasibility of a BCG-vectored HIV vaccine. This report summarizes the discussions addressing the available scientific data on the potential use of rBCG as a vector for preventive HIV vaccines, the work necessary to move such candidate vaccines into Phase 1 clinical trials, and recommendations targeted at facilitating the long-term development of rBCG-vectored HIV vaccines.

AIDS Vaccines↗

PubMed2000

Computer simulation of haemodynamic parameters changes with left ventricle assist device and mechanical ventilation.

Left Ventricular Assist Device is used for recovery in patients with heart failure and is supposed to increase total cardiac output, systemic arterial pressure and to decrease left atrial pressure. Aim of our computer simulation was to assess the influence of Left Ventricular Assist Device (LVAD) on chosen haemodynamic parameters in the presence of ventilatory support. The software package used for this simulation reproduces, in stationary conditions, the heart and the circulatory system in terms of pressure and volume relationships. Different circulatory sections (left and right heart, systemic and pulmonary arterial circulation, systemic and pulmonary venous circulation) are described by lumped parameter models. Mechanical properties of each section are modelled by RLC elements. The model chosen for the representation of the Starling's law of the heart for each ventricle is based on the variable elastance model. The LVAD model is inserted between the left atrium and the aorta. The contractility of the heart and systemic arterial resistance were adjusted to model pathological states. Our simulation showed that positive thoracic pressure generated by mechanical ventilation of the lungs dramatically changes left atrial and pulmonary arterial pressures and should be considered when assessing LVAD effectiveness. Pathological changes of systemic arterial resistance may have a considerable effect on these parameters, especially when LVAD is applied simultaneously with mechanical ventilation. Cardiac output, systemic arterial and right atrial pressures are less affected by changes of thoracic pressure in cases of heart pathology.

Animals↗

PubMed2000

Transcript imaging of the development of human T helper cells using oligonucleotide arrays.

Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.

Apoptosis↗

PubMed2000

Epithelioid sarcoma of the penis: a case report and review of the literature.

A rare case of epithelioid sarcoma (ES) of the penis is presented. The patient, a 35-year-old man, was initially treated as having Peyronie's disease, but the subsequent appearance of a subcutaneous nodule displayed a 'distal-type' ES. At immunohistochemical phenotypification, the tumor was positive for vimentin, cytokeratins and epithelial membrane antigen (EMA), as well as for some other multidirectional antibodies, including a membranous reaction for CD99. The review of 11 similar cases so far reported in the literature led to the conclusion that the clinicopathological characteristics of penile ES are basically the same as those of tumors in more classical locations: the age at diagnosis ranged from 23 to 43 years, the interval between first manifestations and diagnosis averaged 37 months (delayed diagnosis being common because of the slow growth rate and the harmless appearance of the lesion), the typical sign was a superficial nodule or mass, usually accompanied (better preceded) by urethral stenosis, dysuria and erectile disturbances. Total or partial penectomy was the treatment of choice in most patients, but lack of adequate follow up did not permit any definitive conclusion to be reached regarding its efficacy.

Adult↗

PubMed2000

Riboflavin phosphorylation is the crucial event in riboflavin transport by isolated rat enterocytes.

In isolated rat enterocytes, both normoenergized (normal) and de-energized with rotenone, riboflavin intracellular metabolic processes, operating in association with a membrane-specific transport mechanism, were investigated. The contents of unlabeled (endogenous) and labeled (exogenous) flavins [riboflavin (RF), flavin mononucleotide (FMN), flavin adenindinucleotide (FAD)] were determined by HPLC before and after incubation with tritiated RF. In normoenergized enterocytes, total labeled RF content (i.e., total uptake, the sum of RF membrane transport and intracellular metabolism) increased steadily to a plateau after 20 min incubation; FMN and FAD contents reached a plateau between 3 and 20 min, whereas free RF content increased constantly. The phosphorylated forms prevailed over the free form ( approximately 60% of total flavins). In de-energized enterocytes, RF total uptake was significantly lower than in normoenergized enterocytes and reached a plateau after only 3 min incubation. FMN and FAD contents were significantly lower than in normoenergized enterocytes, and free RF represented the prevailing form of flavins (70% of total RF ). In both normoenergized and de-energized enterocytes, the contents of unlabeled total RF, FMN and FAD decreased significantly after 20 min incubation, whereas free RF increased significantly only in normoenergized enterocytes. After 20 min incubation, the RF structural analog 8-dimethyl-amino-8-demethyl-RF caused a significant decrease of all flavin contents, whereas 5'-deoxy-RF decreased only the total and free RF contents. Results directly confirmed the leading role of metabolic processes such as phosphorylation in RF transport by isolated small intestinal enterocytes.

Animals↗

PubMed2000

Expression of p53 and bcl-2 in clinically localized prostate cancer before and after neo-adjuvant hormonal therapy.

The prognostic significance of p53 and bcl-2 expression in prostate carcinoma is currently under investigation. The aim of the present study was to analyze their expression in diagnostic biopsies and in prostatectomies performed after neo-adjuvant hormonal therapy to investigate their role in hormone resistance. One hundred and six patients with advanced prostate carcinoma were treated for 3 months with LHRH analogues before radical surgery. The expression of p53 and bcl-2 was analyzed by immunohistochemistry in all cases of prostatectomy and in available biopsies obtained before treatment, and was correlated with clinicopathologic parameters and follow-up. A significant increase in p53 expression was found following hormonal therapy, whereas no changes were observed in the expression of bcl-2. The increase in p53 did not correlate with the presence of therapy-induced morphological changes in prostate cancers, but it did correlate significantly with histologic grade and pathologic stage, biochemical progression of the disease, and short overall survival. At multivariate analysis, only grade and stage proved to be independent predictors of shorter survival. There were no correlations between bcl-2 and clinicopathologic variables whether in biopsies or in prostatectomies. The unfavorable clinical course associated with p53-positive carcinomas suggests that neo-adjuvant hormonal therapy may cause the selection of minor p53 mutated clones, rather than the induction of wild-type p53. In any case, the enhanced expression of p53 could label hormone-resistant cancers for further adjuvant therapy.

Aged↗

PubMed2000

Prediction of stature in the Italian elderly.

Adequate quantification of weight and stature is essential in order to determine levels of nutritional support and to monitor the effects of nutritional intervention. Traditional anthropometric techniques are difficult to apply in elderly or handicapped patients chair or bed-bound. The purpose of the present study is to elaborate regression equations for the estimation of stature in the italian elderly population from other anthropometric measures that can be more easily determined. We have found a single model valid for both sexes (in which the value of the variable "sex" equals 0 if woman and 1 if man) to predict stature in italian elderly: Stature = 94.87 + 1.58 knee-height - 0.23 age + 4.8 sex. Cross validation on a control sample of 30 males and 54 females yielded pure errors of 3.1 cm for men and 2.74 cm for women.

Aged↗

PubMed2000

A physical model of the human systemic arterial tree.

A physical model of the human arterial tree has been developed to be used in a computer controlled mock circulatory system (MCS). Its aim is to represent systemic arterial tree properties and extend the capacity of the MCS to intraortic balloon pump (IABP) testing. The main problem was to model the aorta simply and to accurately reproduce aortic impedance and related flow and pressure waveforms at different sections. The model is composed of eight segments; lumped parameter models are used for its peripheral loads. After the numerical simulation, the physical model was reproduced as a silicon rubber tapered tube. This rubber was chosen for its stability over time and the acceptable behaviour of its Young's modulus (Ey = 22.23 gf x mm(-2)) with different loads and in comparison with data from the literature (Ey approximately 20.4 gf x mm(-2)). The properties of each segment of the aorta were defined in terms of compliance, resistance and inertance as a function of length, radius and thickness. The variable thickness was obtained using positive and negative molds. Total static compliance of the aorta model is about 1.125 x 10(-3) g(-1) x cm4 x sec2 (1.5 cm3 x mmHg(-1)). Measurements were performed both on numerical and physical models (in open and closed loop configuration). Data reported show pressure and flow waveforms along with input impedance modulus and phase. The results are in good agreement with data from the literature.

Aorta↗

PubMed2000

Computer simulation of hemodynamic parameter changes by mechanical ventilation and biventricular circulatory support.

When a Bi-Ventricular Assist Device (BVAD) is used in conjunction with mechanical ventilation (MV) of the lungs with positive intrathoracic pressure (Pt), the latter influences hemodynamics. The aim of our study was to assess the simultaneous influence of BVAD and MV on hemodynamics. We assumed ventricular pathological conditions as reduced elastances and increased rest volumes. Peripheral systemic arterial resistance was assumed to have different values. Data were obtained by computer simulation. Trends in main hemodynamic variables were compared with clinical data from literature. Simulation showed that systemic venous, pulmonary arterial and left atrial pressures are very sensitive to Pt (-2 to 5 mmHg).

Computer Simulation↗

PubMed2000

[Equilibrium and orthognathodontic surgery: correlations in a group of patients undergoing treatment].

BACKGROUND: The aim of this study was to evaluate the main parameters provided by the static stabilometric test (mean X, mean Y, mean velocity, length of tracing, standard deviation of velocity, ellipse area) in the follow-up of patients suffering from skeletal occlusive pathology undergoing orthognathodontic surgery to confirm the re-establishment of postural equilibrium. METHODS: Fifteen patients with skeletal dysgnathia were correlated with a group of 10 healthy subjects. The same parameters were analysed in the dysgnathic subjects at 6 and 12 months after surgical correction. The patients enrolled in this study underwent surgery at the Division of Maxillofacial surgery of Turin University. Student's "t"-test and multivariate statistical analysis (Cox regression) were used for the statistical analysis of results. RESULTS: A significant variability was noted in some of the main parameters analysed (mean X, mean Y, tracing length) between the two populations (healthy and dysgnathic) compared to visual signs (eyes opened-closed). The change in stabilometric values within the group of dysgnathic patients was highly significant 6 and 12 months after surgery, not only in terms of visual signs but also the cervical component (retroflexion of the head), above all the value of mean Y (p = 0.001). CONCLUSIONS: An analysis of these results shows that static stabilometry can be a valuable aid both during the preoperative evaluation and during the follow-up in patients undergoing jaw surgery since it can quantify the improvement of body balance.

Adolescent↗

PubMed1999

Reversible immortalization of human myogenic cells by site-specific excision of a retrovirally transferred oncogene.

Myogenic cells have a limited life span in culture, which prevents expansion at clinically relevant levels, and seriously limits any potential use in cell replacement or ex vivo gene therapy. We developed a strategy for reversibly immortalizing human primary myogenic cells, based on retrovirus-mediated integration of a wild-type SV40 large-T antigen (Tag), excisable by means of the Cre-Lox recombination system. Myogenic cells were transduced with a vector (LTTN-LoxP) expressing the SV40 Tag under the control of an LTR modified by the insertion of a LoxP site in the U3 region. Clonal isolates of Tag-positive cells showed modified growth characteristics and a significantly extended life span, while maintaining a full myogenic potential. Transient expression of Cre recombinase, delivered by transfection or adenoviral vector transduction, allowed excision of the entire provirus with up to >90% efficiency. Cultures of Cre-treated (Tag-) or untreated (Tag+) myogenic cells were genetically labeled with a lacZ retroviral vector, and injected into the regenerating muscle of SCID/bg immunodeficient mice. Tag- cells underwent terminal differentiation in vivo, giving rise to clusters of beta-Gal+ hybrid fibers with an efficiency comparable to that of control untransduced cells. Tag+ cells could not be detected after injection. Neither Tag+ nor Tag- cells formed tumor in this xenotransplantation model. Reversible immortalization by Tag therefore allows the expansion of primary myogenic cells in culture without compromising their ability to differentiate in vivo, and could represent a safe method by which to increase the availability of these cells for clinical application.

3T3 Cells↗

PubMed1999

Transcriptional targeting of retroviral vectors to the erythroblastic progeny of transduced hematopoietic stem cells.

Targeted expression to specific tissues or cell lineages is a necessary feature of a gene therapy vector for many clinical applications, such as correction of hemoglobinopathies or thalassemias by transplantation of genetically modified hematopoietic stem cells. We developed retroviral vectors in which the constitutive viral enhancer in the U3 region of the 3' LTR is replaced by an autoregulatory enhancer of the erythroid-specific GATA-1 transcription factor gene. The replaced enhancer is propagated to the 5' LTR upon integration into the target cell genome. The modified vectors were used to transduce human hematopoietic cell lines, cord blood-derived CD34(+) stem/progenitor cells, and murine bone marrow repopulating stem cells. The expression of appropriate reporter genes (triangle upLNGFR, EGFP) was analyzed in the differentiated progeny of transduced stem cells in vitro, in liquid culture as well as in clonogenic assay, and in vivo, after bone marrow transplantation in lethally irradiated mice. The GATA-1 autoregulatory enhancer effectively restricts the expression of the LTR-driven proviral transcription unit to the erythroblastic progeny of both human progenitors and mouse-repopulating stem cells. Packaging of viral particles, integration into the target genome, and stability of the integrated provirus are not affected by the LTR modification. Enhancer replacement is therefore an effective strategy to target expression of a retroviral transgene to a specific progeny of transduced hematopoietic stem cells.

Animals↗

PubMed1999

A coat protein on phagosomes involved in the intracellular survival of mycobacteria.

Mycobacteria are intracellular pathogens that can survive within macrophage phagosomes, thereby evading host defense strategies by largely unknown mechanisms. We have identified a WD repeat host protein that was recruited to and actively retained on phagosomes by living, but not dead, mycobacteria. This protein, termed TACO, represents a component of the phagosome coat that is normally released prior to phagosome fusion with or maturation into lysosomes. In macrophages lacking TACO, mycobacteria were readily transported to lysosomes followed by their degradation. Expression of TACO in nonmacrophages prevented lysosomal delivery of mycobacteria and prolonged their intracellular survival. Active retention of TACO on phagosomes by living mycobacteria thus represents a mechanism preventing cargo delivery to lysosomes, allowing mycobacteria to survive within macrophages.

Animals↗

PubMed1999

Lack of infection in HIV-exposed individuals is associated with a strong CD8(+) cell noncytotoxic anti-HIV response.

Individuals repeatedly exposed to HIV, but who remain uninfected, form a population enriched for persons likely to have either natural or acquired resistance to the virus. We have studied four such exposed uninfected cohorts, representing 60 individuals, for evidence of protective immunity. This population included participants exposed to HIV through anal or vaginal receptive intercourse on multiple occasions over many years. We observed CD8(+)-cell noncytotoxic inhibition of HIV replication in acutely infected CD4(+) cells in the vast majority of individuals most recently exposed to the virus (within 1 year). The levels of this CD8(+)-cell response were sufficient to inhibit the in vitro infection of the exposed subjects' peripheral blood mononuclear cells. We found no evidence of a significant role for CCR5 Delta32 mutation in this population, nor did CD4(+) cell susceptibility to infection or HIV-specific cytotoxic T-lymphocytes correlate with resistance to infection in the individuals tested. Therefore, the observed strong noncytotoxic CD8(+)-cell anti-HIV responses may be an antiviral immune activity contributing to the apparent protection from infection in these exposed uninfected individuals.

Adult↗

PubMed1999

Plasma levels of apolipoprotein E and genetic markers in elderly patients with Alzheimer's disease.

Besides apolipoprotein E (APOE) polymorphism, whose association with Alzheimer's disease (AD) has been confirmed in most of the numerous population samples studied, other markers have been investigated. In most cases the association firstly described was not confirmed in subsequent works. Since it is important to examine these associations in as many populations as possible, we investigated APOE, APOC1, APOC2, alpha-1 antichymotrypsin (ACT) and presenilin-1 (PS-1) polymorphisms in a series of elderly patients with late-onset sporadic AD from Northern Italy and in a sex and age-matched control group. We could not confirm the significantly higher frequency of the ACT*A allele among carriers of APOE e*4 allele described elsewhere, although a similar trend was observed. The APOC2 and the PS-1 distributions were similar between patients and controls. However, we observed a significant difference in the genotype and allele frequencies of APOE and APOC1: patients had higher e*4 and C1*2 allele frequencies. This finding confirms the important role for APOE in AD occurrence. In addition, APOC1 seems to be an interesting marker because, though in strict linkage disequilibrium with APOE, it seems to play an independent role in AD risk. In contrast to previously reported data, plasma apoE concentrations were similar in patients and in controls. An interaction between APOE and APOC1 polymorphisms and apoE levels was observed in patients: subjects carrying the APOE E3/E2 or the APOC1 2-2 genotype have higher apoE concentrations than those who do not.

Aged↗

PubMed1999

Evidence for an abnormal cortical sensory processing in dystonia: selective enhancement of lower limb P37-N50 somatosensory evoked potential.

We evaluated brain stem P30, contralateral frontal N37, and the vertex-ipsilateral central P37, N50 somatosensory evoked potentials (SEPs) obtained in response to stimulation of the tibial nerve in 10 patients with idiopathic dystonia. Results were compared with those obtained in 10 healthy subjects matched for age and sex. The amplitude of the brain stem P30 potential and of the contralateral frontal N37 response in dystonic patients was not significantly different from that recorded in normal subjects. The vertex- ipsilateral central P37-N50 complex, which is thought to originate in the pre-rolandic cortex, was significantly enhanced in patients compared with the control group. These results suggest the enhancement of the vertex-ipsilateral central P37-N50 complex might reflect an abnormal response to somatosensory inputs of a precentral cortex which is excessively activated because of a disorder of the basal ganglia. Such inefficient sensory processing in motor areas might contribute to motor impairment in dystonia.

Adult↗

PubMed1999

Bovine virus diarrhoea (BVD) control programme in an area in the Rome province (Italy).

A BVD control programme based on the identification and removal of persistently infected (PI) animals is being undertaken in an area in the Rome province, where BVD outbreaks had been previously detected. It involves 174 mainly dairy herds, from which blood samples of all bovines older than 1 year are obtained through the national brucellosis and leukosis eradication programme. Samples sufficient to detect the presence of seropositive animals at a prevalence of 5% or more are initially screened for antibodies against BVD virus (BVDV) using an immunoenzymatic assay. Upon identification of seroreagents additional blood samples are tested from the 6-12-month age category not included in the initial samples. Animals are considered immunotolerant if BVDV is demonstrated twice at a minimum 30-day interval. When no seropositive animals are detected during the first serological screening the herd is declared BVD-free if a second testing, preferably carried on the same animals previously tested, confirms the seronegative status of the herd. At present 147 farms have been tested, of which 63 (42.9%) are negative with respect to antibodies against BVDV. Of the 84 remaining herds in which one or more seropositives are detected, 13 are classified as recently infected. In eight of these recently infected herds, 22 PI animals have been identified.

Animals↗