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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 91 records · Page 5Linked to original sources
PubMed1998

gag, vif, and nef genes contribute to the homologous viral interference induced by a nonproducer human immunodeficiency virus type 1 (HIV-1) variant: identification of novel HIV-1-inhibiting viral protein mutants.

We previously demonstrated that expression of the nonproducer F12-human immunodeficiency virus type 1 (HIV-1) variant induces a block in the replication of superinfecting HIV that does not depend on the down-regulation of CD4 HIV receptors. In order to individuate the gene(s) involved in F12-HIV-induced interference, vectors expressing each of the nine F12-HIV proteins were transfected in HIV-susceptible HeLa CD4 cells. Pools of cell clones stably producing each viral protein were infected with HIV-1, and virus release was measured in terms of reverse transcriptase activity in supernatants. We hereby demonstrate that HeLa CD4 cells expressing the F12-HIV gag, vif, or nef gene were resistant, to different degrees, to infection with T-cell-line-adapted HIV-1 strains. Conversely, expression of either the tat, rev, or vpu F12-HIV gene increased the rate of HIV release, and no apparent effects on HIV replication were observed in cells expressing either the F12-HIV vpr, pol, or env gene. No variation of CD4 exposure was detected in any of the uninfected HeLa CD4 pools. These data indicate that F12-HIV homologous viral interference is the consequence of the synergistic anti-HIV effects of Gag, Vif, and Nef proteins. Retrovirus vectors expressing F12-HIV vif or nef allowed us to further establish that the expression of each mutated protein (i) inhibits the replication of clinical HIV-1 isolates as well, (ii) impairs the infectivity of the virus released by cells chronically infected with HIV-1, and (iii) limitedly to F12-HIV Vif protein, induces HIV resistance in both vif-permissive and vif-nonpermissive cells. The levels of action of F12-HIV vif and nef anti-HIV effects were also determined. We observed that HIV virions emerging from the first viral cycle on F12-HIV vif-expressing cells, although released in unaltered amounts, had a strongly reduced ability to initiate the retrotranscription process when they reinfected parental HeLa CD4 cells. Differently, we observed that expression of F12-HIV Nef protein affects the HIV life cycle at the level of viral assembling and/or release. For the first time, an inhibitory effect on the HIV life cycle in both acutely and chronically infected cells induced by mutated Vif and Nef HIV-1 proteins is described. These genes could thus be proposed as new useful reagents for anti-HIV gene therapy.

Amino Acid Sequence↗
PubMed1998

Body weight estimation in the Italian elderly.

We have developed two different equations, for each sex of the elderly italian population to predict weight from selected measures of recumbent anthropometry, using data of 172 females (72.8 +/- 8 years old) and 113 males (73.4 +/- 8 years old). The independent variables for both sexes were knee stature. subscapular skinfold, arm and calf circumferences. Cross validation was conducted on a free-living sample of 54 females and 30 males. The recommended equations have a 95% probability of predicting the weight of an elderly man or woman to be within plus or minus 4.9 or 6.1 Kg respectively.

Aged↗
PubMed1998

A computer controlled mock circulatory system for mono- and biventricular assist device testing.

The clinical use of heart assist devices for heart recovery, implies the problem of their in vitro testing and training to use. In a mock circulatory system developed to this aim, the main problem is reproducing interaction among the device, the ventricle and the circulatory network. This can be analysed by the position, on the p-v plane, of the working point defined by the intersection between end systolic ventricular (ESPVR) and arterial elastance lines. The system developed on this basis, connectable to mono- and biventricular parallel assist devices, was a closed loop model including systemic and pulmonary circulation. The arterial trees were reproduced by two windkessels with adjustable peripheral resistance, and the Starling's law of the heart by a variable elastance model. The software controls and monitors circulatory parameters and variables. Results showed the behavior of the system with preload or afterload changes. Further, the reproduction of physiological, pathological (obtained by modifying slope and volume intercept of the ESPVR line) and LVAD assisted circulatory conditions was shown. The assistance effect was underlined by the changes in the ventricular work cycle and in hemodynamics variables. The evaluation of the effect of device control strategy on the ventricle and its energetics (on p-v plane) were among the main characteristics of this system, which ought to be further improved to test devices such as the IABP, which requires a different aortic model.

Blood Pressure↗
PubMed1998

[Non-cardiac transcatheter intervention: operative possibilities in a hemodynamics laboratory].

INTRODUCTION: New possibilities for transcatheter treatment of the cardiovascular system are guaranteed with the improvement of materials and the availability of new devices. Nevertheless, a rationalization of the potential activity in this sector seems to be necessary, and it could arise through the presence of Catheterization Laboratories "open" to diagnostic procedures and therapy that are not confined to the coronary system. This clinical study reports the experiences and results of our work in this field. MATERIALS AND METHODS: During the period from May 1995 to May 1997, our laboratory performed 205 diagnostic procedures that did not involve the coronary system. Based on this diagnostic work, there emerged 91 cases with an indication for transcatheter intervention, which was subsequently performed at our laboratory. There were 68 peripheral angioplasty procedures on the iliofemoral axis, 2 angioplasties of the subclavian artery, 8 of the renal artery, 2 procedures involving the treatment of A-V fistulas, one case of femoral pseudoaneurysm treatment and 10 cases of transcutaneous pericardiotomy performed with a balloon catheter. All the procedures were performed by our laboratory staff using materials that are normally at our disposal. RESULTS: Successful results were obtained in 65 out of the 68 peripheral angioplasty procedures and in all of the 8 renal and 2 subclavian angioplasties. The positioning of the endoprosthesis for the closure of the A/V fistula was effective in one of the two cases. The transcatheter treatment of the femoral pseudoaneurysm was successful. In all cases where a pericardiotomy was performed with a balloon catheter, there was no reoccurrence of cardiac tamponade during the follow-up period. No complications were noted as a result of any of the procedures. CONCLUSIONS: Our experience documents how it is possible to increase the diagnostic and therapeutic options in a Catheterization Laboratory. However, willingness on the part of the staff to update their skills continually and collaborate with other specialists is necessary in order to maintain optimal operative standards.

Adult↗
PubMed1998

[Massive pulmonary embolism after blunt chest trauma: considerations on pathogenesis and therapy].

A blunt chest trauma may provoke many different kinds of cardiac injury, particularly myocardial contusion, sometimes causing subsequent acute myocardial infarction or cardiac arrest by ventricular tachyarrhythmia in the absence of structural lesions. We describe a case of acute massive pulmonary embolism after a blunt chest impact caused when the patient was kicked by a horse. The patient showed progressive dyspnea three days after the trauma. The diagnosis was reached by non-invasive means and finally confirmed by pulmonary angiography. Because of the contraindication to thrombolytic therapy, we performed percutaneous catheter and guide-wire clot fragmentation with at least partial immediate success and subsequent favorable course. We discuss possible pathophysiological mechanisms to explain this case, which has no precedents in the literature.

Angiography↗
PubMed1998

[Clinical anatomy of the human mental foramen].

BACKGROUND: The great diffusion of the surgical technics in oral implantology and the progress of the radiological imaging produces some interest for the clinical anatomy of the mental foramen (MF). The study, in addition to the measurements that define it, considers others anatomical features of practical utility and the variableness of them. METHODS: In the Anatomic Institute of the Bologna University, it has been made a morphometric revision of the MF on 100 dried mandibles of normal young adults (78 males, 32 females) random chosen with the complete integrity of the dental apparatus and of the mandibular bone criteria. The measurements have been made by anthropometric methods on the two sides of the same mandible (n = 200) and for everyone has been reported in the tables the medium, the maximum and the minimum values with their specific variation interval. The results are applicable to the common work conditions because they take in consideration among the specific characteristics of the MF in addition to the seat, the course of the mandibular canal, the thickness and the height of the mandibular bone. RESULTS: To the clinical and diagnostic imaging object the medium values of the anatomical measurements can be considered sufficent. To anthropometric, anesthesiologic and surgical aims it is also necessary the knowledge of the maximum and the minimum values and the variation interval. In the living man the anatomicomedical study of the MF is made by the diagnostic imaging, especially by computed tomography with specific algorithm, because it makes possible absolutely exact measurements. CONCLUSIONS: Finally, the specifications on the MF provided by the present study are important not only for an anatomical but also for a practical point of view because they are a datum point value in the patient clinical management.

Adult↗
PubMed1998

Transradial approach for coronary procedures: initial experience and results.

BACKGROUND: Due to the recent miniaturization of angioplasty equipment, the transradial approach has gained favor as an alternative catheterization method for coronary procedures. The purpose of this study was to assess the practical clinical application of this method. METHODS: Between June 1997 and February 1998, one operator (MG) attempted the percutaneous transradial approach in 185 consecutive unselected patients with functional radial arch attested using Allen's test. In this series of patients, 102 interventional procedures, balloon angioplasty including stent implantation, were performed with 6F or 7F guiding catheters. RESULTS: Radial arterial punctures for diagnostic procedures were performed in 179 patients with a success rate of 97%. In the six failed transradial accesses, the procedure was performed via the transfemoral route. Balloon angioplasty was performed in 29 patients, 28% (33 lesions), PTCA and stent implantation were performed in 73 patients, 72% (80 lesions). Procedural success was achieved in 100 (98.2%). Two PTCA failed due to the impossibility of crossing a total occlusion. During hospitalization, one patient died of unstable angina and poor left ventricular function 7 days after stenting without stent occlusion at angiography. No major complications related to entry site were observed, and no patients required vascular surgery or blood transfusions. CONCLUSION: This preliminary experience suggests that coronary procedures can be performed safely using the transradial approach. Access-site complications are virtually eliminated and early ambulation may result in a shortened hospital stay and lower hospital costs.

Adult↗
PubMed1997

Distinct intracellular compartments involved in invariant chain degradation and antigenic peptide loading of major histocompatibility complex (MHC) class II molecules.

Major histocompatibility complex (MHC) class II molecules are transported to intracellular MHC class II compartments via a transient association with the invariant chain (Ii). After removal of the invariant chain, peptides can be loaded onto class II molecules, a process catalyzed by human leukocyte antigen-DM (HLA-DM) molecules. Here we show that MHC class II compartments consist of two physically and functionally distinct organelles. Newly synthesized MHC class II/Ii complexes were targeted to endocytic organelles lacking HLA-DM molecules, where Ii degradation occurred. From these organelles, class II molecules were transported to a distinct organelle containing HLA-DM, in which peptides were loaded onto class II molecules. This latter organelle was not directly accessible via fluid phase endocytosis, suggesting that it is not part of the endosomal pathway. Uptake via antigen-specific membrane immunoglobulin resulted however in small amounts of antigen in the HLA-DM positive organelles. From this peptide-loading compartment, class II-peptide complexes were transported to the plasma membrane, in part after transit through endocytic organelles. The existence of two separate compartments, one involved in Ii removal and the other functioning in HLA-DM-dependent peptide loading of class II molecules, may contribute to the efficiency of antigen presentation by the selective recruitment of peptide-receptive MHC class II molecules and HLA-DM to the same subcellular location.

Antibodies, Bacterial↗
PubMed1997

Cyclin dependent kinase inhibitors and dominant negative cyclin dependent kinase 4 and 6 promote survival of NGF-deprived sympathetic neurons.

Neuronal apoptosis plays a critical role in both normal development and disease. However, the precise molecular events controlling neuronal apoptosis are not well understood. Previously, we hypothesized that cell cycle regulatory molecules function in controlling the apoptotic pathways of trophic factor-deprived neurons. To test this hypothesis, we used the RNA alphavirus Sindbis to express three known cyclin dependent kinase inhibitors (CKIs), p16(ink4), p21(waf/cip), and p27(kip1), and dominant negative mutant forms of four known G1 cyclin dependent kinases (CDKs), Cdk2, Cdk3, Cdk4, and Cdk6, in primary cultured rat superior cervical ganglion sympathetic neurons. We demonstrate that expression of each of the CKIs protects the postmitotic cultured neurons from apoptotic death evoked by withdrawal of NGF. In addition, we show that expression of dominant negative forms of Cdk4 or Cdk6, but not Cdk2 or Cdk3, protects NGF-deprived sympathetic neurons from death. Such findings suggest the participation of several CDKs and their cognate cyclins in a neuronal apoptotic pathway.

Animals↗
PubMed1997

Replication-defective canarypox (ALVAC) vectors effectively activate anti-human immunodeficiency virus-1 cytotoxic T lymphocytes present in infected patients: implications for antigen-specific immunotherapy.

In the attempt to develop immunotherapeutic strategies for acquired immunodeficiency syndrome capable of activating effector cells in an antigen-specific manner while maintaining the broadest possible T-cell repertoire, we evaluated two canarypox (ALVAC)-based vectors for their capacity to induce ex vivo activation/expansion of human immunodeficiency virus (HIV)-specific CD8+ cytotoxic lymphocyte precursors (CTLp) obtained from HIV-1-infected donors. These two vectors, vCP205 encoding HIV-1 gp120 + TM (28 amino acid transmembrane anchor sequence) in addition to Gag/protease and vCP300 encoding gp120 + Gag/protease as well as Nef and Pol CTL determinants, are pancytotropic but replication incompetent in mammalian cells. Bulk peripheral blood mononuclear cells (PBMCs) or enriched CD8+ T cells were stimulated for 10 days with autologous ALVAC-infected PBMCs in the presence of different cytokine combinations (interleukin-2 [IL-2], IL-4, IL-7, and IL-12). Activation by ALVAC constructs was highly antigen-specific, because vCP205 elicited only Env and Gag CTL, whereas vCP300 elicited broader reactivities against Env, Gag, Pol, and Nef determinants. The ALVAC activation of CTLp was IL-2 dependent and enhanced by the addition of IL-7, whereas IL-4 and IL-12 failed to augment cytotoxic reactivities elicited by these constructs. The expansion of enriched CD8+ T cells after activation with vCP300 was higher in patients with CD4 counts greater than 400 cells/microL. Two rounds of in vitro stimulation (IVS) with vCP300 resulted in nearly an eightfold expansion of CD8+ lymphocytes over a 25-day period. After the second IVS, an average 3.2-fold increase among the different antigen-specific CTL frequencies was achieved. These studies clearly show that HIV-recombinant ALVAC vectors represent powerful polyvalent antigenic stimuli for activation and expansion of the CD8 lymphocyte response that occurs as a result of HIV infection.

Adult↗
PubMed1997

Cell-surface marking of CD(34+)-restricted phenotypes of human hematopoietic progenitor cells by retrovirus-mediated gene transfer.

Human CD34+ cells lacking detectable levels of HLA-DR antigens (CD34+ DR-) are highly enriched in hematopoietic pluripotent progenitors with long-term marrow repopulating ability. We investigated the feasibility of transducing and marking CD34+ DR- progenitor cells from bone marrow (BM) or mobilized peripheral blood samples (MPB) of 13 patients undergoing BM transplantation with the purpose of developing a protocol for a large-scale clinical application. A new retroviral vector coding for the truncated form (delta) of the low-affinity nerve growth factor receptor (LNGFR) was used to quantitate the level of gene transfer into CD34+ cells and their progeny by multiparameter cytofluorimetry and immunocytochemistry. Light-density mononuclear cells as well as purified CD34+ cells were transduced either by direct incubation with retroviral supernatants or prestimulated in vitro with various combinations of growth factors prior to transduction. Transduction efficiency, assessed as G418-resistant growth of granulocyte-macrophage colony-forming units (CFU-GM) progenitors from MPB, was 1.7-fold higher (14.9% +/- 4.5%) than those from BM (8.5% +/- 3.9%) and it was further improved (26.9% +/- 3.1%) using a purified CD34+ population as target cells. Three-color fluorescence-activated cell sorting (FACS) analysis demonstrated the presence of transduced delta LNGFR+ cells within the CD34+ DR- subpopulation. In the absence of growth factors, gene transfer into BM or MPB CD34+ DR- cells was generally poor, but following a 72-hr prestimulation it peaked at 38% of total CD34+ DR- bone marrow (BM) cells in the presence of the c-kit ligand (KL) and at 31% in the presence of IL-3. Furthermore, KL gave, compared to the other cytokines, the highest absolute yield of BM delta LNGFR+ CD34+ DR- cells recovered after transduction (p = 0.05 compared to 24 hr). Gene transfer into in vitro primitive progenitor cells was further confirmed by expression of the delta LNGFR marker on CD34+ cells and CFU-GM derived from 5-week long-term culture on stroma.

Adult↗
PubMed1997

HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.

In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus-induced lymphoma after T cell-depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.

Bone Marrow Transplantation↗
PubMed1997

Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers.

A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable of destroying virally infected targets. Recent application of recombinant canarypox ALVAC/HIV-1 vectors as vaccine immunogens in HIV-1,-noninfected volunteers has produced CTL responses in a significant number of vaccinees. Using a newly developed targeting strategy, we examined the capacity of vaccine-induced CTL to lyse autologous targets infected with a diverse group of viral isolates. CTL derived from recipients of a canarypox ALVAC/HIV-1 gp160 (MN) vaccine were found capable of lysing autologous CD4+ lymphoblasts infected with the prototypic LAI strain of HIV-1. When tested against autologous targets infected with primary HIV-1 isolates representing genetically diverse viral clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis in which viruses from all clades tested were recognized as well as a highly restricted pattern in which no primary isolates, including clade B, were lysed. Differences in the HLA haplotypes of the volunteers immunized with the envelope vector might be a major determinant of the relative breadth of their CTL response. In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV-1 immunogen containing envelope as well as gag and protease genes consistently had CTL reactivities effective against a spectrum of primary isolate-infected targets. These studies demonstrate for the first time that clade B-based canarypox vaccines can elicit broad CTL reactivities capable of recognizing viruses belonging to genetically diverse HIV-1 clades. The results also reinforce the impact of viral core elements in the vaccine as well as the pattern of major histocompatibility complex class I allelic expression by the vaccine recipient in determining the relative breadth of the cellular response.

AIDS Vaccines↗
PubMed1997

Conversion of recent onset atrial fibrillation to sinus rhythm using a single oral loading dose of propafenone: comparison of two regimens.

A population of 105 patients with recent onset (< 72 h) atrial fibrillation was randomly treated with propafenone as a single oral loading dose of 450 mg (Regimen A) or 600 mg (Regimen B) or with placebo. A 24-h Holter was performed. Criteria of efficacy were conversion to sinus rhythm at 2, 4 and 8 h compared to placebo and also significant reduction of mean ventricular rate in persistent atrial fibrillation. After 2 h, regimen B was more effective than either regimen A (43% vs. 8%; p = 0.001) or placebo (11%; p = 0.004). At 4 h, both the active treatments were more effective than placebo (17% vs. 46% regimen A and 57% vs. regimen B; p < 0.04 and p < 0.001, respectively). Sinus rhythm resumed within 24 h in 71%, 80% and 69% of the patients with regimen A, B and placebo, respectively (p = not significant). The mean ventricular rate reduction after 1 h was 8%, 11% and 4% for regimen A, B and placebo, respectively (p < 0.005 vs. regimen B), and 17%, 25% and 6% respectively (p < 0.001 placebo vs. regimen A and B, p < 0.05 regimen B vs. A) at 2 h. No major adverse effect occurred. Atrial flutter with 1:1 atrioventricular conduction only in one case who received placebo. Propafenone acute oral administration is more effective than placebo in rapidly converting recent-onset atrial fibrillation to sinus rhythm and may be the treatment of choice in this setting limiting hospitalization and contributing to improved quality of life.

Administration, Oral↗
PubMed1997

Does p53 immunostaining improve diagnostic accuracy in urine cytology?

The frequent change of the transitional cell carcinoma of the urinary tract accounts for the fact that cytological abnormalities in urinary specimens are often not sufficient to enable a definitive diagnosis of malignancy. The purpose of this work was to evaluate the possible use of p53 protein in increasing the diagnostic accuracy of urinary cytology. The expression of p53 was investigated by immunocytochemistry in two groups of urinary specimens, one cytologically positive and the other cytologically negative for cancer. Immunostaining was carried out using a monoclonal antibody to p53. In the positive group, in which bladder cancer was confirmed by cystoscopy and biopsy (31 cases), positive reaction for p53 was found in 55% of the cases (17 cases). In the negative group (92 cases), presence of cancer was histologically ascertained in 64 cases and in this group 15 cases (23.4%) showed positive p53 staining. In the remaining 28 cases of this group, where TCC was not present, 7 cases showed p53 positivity in non-neoplastic urothelial cells. This result shows that, while immunocytochemical detection of p53 in urinary specimens may be used for prognostic evaluation of patients with bladder cancer, it does not contribute to the diagnostic accuracy in cases with morphologically inconclusive or negative cytology. The sensitivity and specificity of the method in detecting bladder carcinoma were 23.5 and 75%, respectively.

Biomarkers↗
PubMed1997

Identification of psychiatric distress by primary care physicians.

The aims of the present study were to evaluate the extent to which primary care physicians' (PCPs) identification of psychiatric distress is related to a number of nonpsychopathological factors, such as patient sociodemographic and health-related characteristics, and to assess the impact of depression on PCP identification of psychiatric distress, controlling for patient sociodemographic and health-related characteristics. Two patient samples were chosen to explore these issues: 1) patients not fulfilling any ICD-10-defined or subthreshold psychiatric diagnosis and, 2) patients with an ICD-10 diagnosis of current depression. Patients attending 46 primary care clinics during an index period were screened by the General Health Questionnaire (GHQ)-12 and selected for a second stage interview according to GHQ score. Among the 559 interviewed patients, 123 had no mental disorder and 66 had an ICD-10 current depressive disorder. Identification of psychiatric distress by the PCP was associated with retirement among subjects without mental disorders but not among depressed patients. Patient's negative overall health self-perception and severity of physical illness were significantly related to identification of psychiatric distress in the two groups, whereas neither disability nor reason for medical consultation had a significant effect. Patients with current depression, compared with those without, were 4.3 times more likely to be identified by PCPs as having psychiatric distress when adjusting for all the above nonpsychopathological variables. Patients with depression and comorbid anxiety disorders were more likely to be recognized by the PCP as compared with those with pure depression. Finally, among depressive symptoms, diurnal variation and symptoms related to suicidal tendencies were predictive of identification of psychiatric distress, whereas increase of appetite was negatively associated with PCP recognition.

Adult↗
PubMed1997

Long-term treatment of geropsychiatric depressed patients with venlafaxine.

Twenty-eight psychiatric patients older than 65 years with major depression with high probability of recurrence were enrolled in a 24-month open label clinical trial aimed at evaluating the long-term efficacy and safety of venlafaxine. All patients completed the acute phase of the study; 21 were responders and entered the follow-up period. During the continuation phase no relapse was observed. During the maintenance period, 20% of the patients had a single new recurrence. No significant side effects were observed. The results demonstrate that venlafaxine is both effective and safe in the long-term treatment of major depression in geropsychiatric patients.

Adrenergic Uptake Inhibitors↗