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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 163 records · Page 9Linked to original sources
PubMed1992

Transfer of the ADA gene into human ADA-deficient T lymphocytes reconstitutes specific immune functions.

Peripheral blood lymphocytes obtained from a patient affected by adenosine deaminase (ADA) deficiency and severe combined immunodeficiency were infected with a retroviral vector containing two copies of a human ADA minigene, and injected into bg/nu/xid (BNX) immunodeficient mice. Six to 10 weeks after injection, human T cells were cloned from the spleens of recipient animals and analyzed for proliferative potential, T-cell surface markers, expression of ADA activity, integration of retroviral sequences, T-cell receptor (TCR) beta gene rearrangement, and specificity of antigen recognition. Efficient gene transfer and expression restored proliferative potential in vitro and long-term survival in vivo. All clonable human T lymphocytes obtained from the spleen of recipient animals had high levels of vector-derived ADA enzyme activity and showed predominantly the CD4+ phenotype. Retroviral integrations and TCR-beta gene rearrangements demonstrated the presence of a variety of different clones in the spleens of recipient mice. Furthermore, the combined analyses of vector integration and TCR rearrangement provided evidence that a circulating progenitor cell was transduced by the retroviral vector, giving rise to different and functional TCRs. Evaluation of antigen-specificity demonstrated both alloreactive and foreign antigen specific immune responses. These results suggest that restoration of enzyme activity in human ADA-deficient peripheral blood T cells by retroviral-mediated ADA gene transfer allows in vivo survival and reconstitution of specific immune functions. Therefore, retroviral vector-mediated gene transfer into circulating mononuclear cells could be successful not only in maintaining the metabolic homeostasis, but also for the development of a functional immune repertoire. This is a fundamental prerequisite for the usage of genetically engineered peripheral blood lymphocytes for somatic cell gene therapy of ADA deficiency.

Adenosine Deaminase↗
PubMed1992

Age-related thiamin transport by small intestinal microvillous vesicles of rat.

The effect of aging on the intestinal transport of thiamin was studied using small intestinal microvillous vesicles prepared from groups of rats aged 1, 2, 6, 12 and 24 months, respectively. The vesicles (enrichment 14.6-17.8-fold) were incubated with 0.125 to 12.5 microM tritiated thiamin and the radioactivity taken up was measured radiometrically after rapid filtration. The time course and cumulative uptake curves of thiamin and the inhibiting potency of the thiamin structural analogs pyrithiamin, amprolium and oxythiamin on the saturable component of thiamin transport were determined. The vesicle diameter was measured by using a computerized morphometric procedure, and found to be decreased in aged rats. The Km and Jmax values of the saturable component of transport increased with increasing age, the difference with younger groups being statistically significant at 24 and 12 months. The inhibitory potencies of pyrithiamin and amprolium gradually decreased with increasing age, while oxythiamin was devoid of significant inhibitory activity. Passive permeability coefficients decreased with increasing age, reaching their lowest value at 24 months. These results show that aging is associated with intrinsic alterations of the enterocytic plasma membrane resulting in a decrease of the affinity for thiamin, associated with a faster rate of the saturable component of thiamin transport, and with a significant depression of the non-saturable component.

Aging↗
PubMed1992

Gangliosides prevent the inhibition by K-252a of NGF responses in PC12 cells.

K-252a, a general kinase inhibitor, selectively blocks the actions of nerve growth factor (NGF) in PC12 cells. Since gangliosides have been reported to modulate neuronal cell responsiveness to NGF and to regulate several protein kinases, the ability of these compounds to reverse the inhibition by K-252a was tested. Parameters at both short- and long-term times following treatment of PC12 cells with NGF were analyzed which are known to be either transcription-dependent or -independent events. Gangliosides were found to completely prevent the inhibition by K-252a of NGF-induced neurite regeneration and c-fos induction, and partially also that of protein kinase N activation. The ganglioside protective effects were concentration-dependent and required the intact molecule. These findings raise the possibility that gangliosides might affect a specific pathway of NGF responses sensitive to inhibition by K-252a.

Animals↗
PubMed1992

Octreotide administration in the treatment of pancreatic fistulae after pancreas transplantation.

Among the surgical complications of pancreas transplantation are pancreatic fistulae, which arise rather frequently. Suppression of exocrine secretion with polymers has succeeded in reducing the rate of this complication. Nevertheless, in some instances, pancreatic fistulas may occur. Thirty pancreas transplantations were performed in 27 diabetic patients. In 5 cases a pancreatic fistula occurred and was drained after the insertion of a catheter for the collection of secretions. A serous liquid was collected with a high concentration of amylases (61604 +/- 19562 IU/24 h). Fistula output was 280 +/- 87 ml/24 h. Patients were treated with octreotide, administered subcutaneously in a dose of 300-750 micrograms/day. In all patients a progressive reduction in fistula output was observed after a mean of 16 + 2 days. Fistula flow rate dropped to 24 +/- 10 ml/24 h--a reduction of 95% +/- 5% and drainage was subsequently stopped. Sonographic follow-up did not show recurrence of peripancreatic collections in these patients. All patients were insulin-independent up to 12-44 months after surgery.

Adult↗
PubMed1992

A modular numerical model of the cardiovascular system for studying and training in the field of cardiovascular physiopathology.

A modular numerical model of the cardiovascular system has been developed to reproduce the most important circulatory phenomena in terms of pressure and volume relationships. It is an easy tool to use, designed to be used with a friendly approach on any IBM or compatible personal computer: it offers a wide selection of graphical and numerical outputs and can be rearranged easily for a particular experiment. A set of subroutines related to different circulatory phenomena has been developed; they can be assembled easily together and communicate with each other by two variables. A full description of the existing subroutines is presented in this paper with three different application examples resulting from the rearrangement of the existing software modules: the first concerns the behaviour of the natural ventricle model itself and can be regarded as a ventricle stand-alone characterization test in terms of preload and afterload sensitivities, the second is related to the use of a pneumatic ventricle instead of the model of the natural ventricle, and the third is a full model of the cardiocirculatory system.

Cardiology↗
PubMed1992

Chemoimmunotherapy for prophylaxis of recurrence in superficial bladder cancer: interferon-alpha 2b versus interferon-alpha 2b with epirubicin.

Eighty-five patients who had undergone transurethral resection (TUR) of superficial bladder cancer were randomized to one of two treatments. Patients in Group 1 received a 10-month course of intravesical therapy with interferon (IFN)-alpha 2b (50 MU dose), commencing 21 days after TUR once a week for 8 weeks, then once every 15 days for 4 months and then finally once a month for 4 months. Patients in Group 2 received epirubicin (80 mg) intravesically 0, 24 and 48 h after TUR, and then 21 days after TUR received IFN-alpha 2b as for Group 1. The results confirmed the efficacy of immunoprophylaxis with IFN-alpha 2b, and early treatment with epirubicin tended to further reduce the percentage of relapses and extended the disease-free interval.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

In vivo genetic variability of the human immunodeficiency virus type 2 V3 region.

The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cysteines of the V3 regions, but its functional similarity with the HIV-1 principal neutralizing epitope is uncertain. We studied the degree of genetic variation of the HIV-2 V3 region in fresh blood samples from 12 HIV-2-seropositive individuals from Guinea-Bissau. Polymerase chain reaction was used to amplify viral fragments of 465 bp containing the V3 region from cellular DNA. Nucleotide sequence analysis of the entire envelope fragment from each patient revealed that the degree of variation among field isolates of HIV-2 is comparable to that observed in the analogous region of HIV-1. Most of the HIV-2 isolates studied were highly related, suggesting the existence of a limited number of different viral strains in the cohort studied. Thus, the HIV-2 and HIV-1 V3 regions vary to a similar degree and may also have analogous functions.

Amino Acid Sequence↗
PubMed1992

Epidemiology of myasthenia gravis in the province of Trento (northern Italy).

The epidemiology of myasthenia gravis (MG) was studied in the province of Trento (northern Italy) among 444,879 inhabitants. On prevalence day (December 31, 1990) the crude rate was 82.9 per million population: 113 for females and 50.7 for males. The incidence rate was 7.4 per million per year: 10.8 for females and 4.6 for males. Over the same observation period (1981-1990), we calculated a death rate of 1.12 per million population per year. MG predominates in females. Nevertheless, we observed some differences related to age and to presence of thymoma, and our data supports the recognition of three types of MG: (1) predominating in females with a peak frequency at about 20-29 years; (2) affecting both males and females, with a frequency increasing with age, and (3) associated with thymoma.

Adolescent↗
PubMed1992

Lack of feedback inhibition of insulin secretion in denervated human pancreas.

In this study, pancreas transplantation is used as a clinical model of pancreas denervation in humans. To assess the role of innervation on the feedback autoinhibition of insulin secretion, we studied four groups of subjects--group 1: 16 patients with combined pancreas and kidney transplantation (plasma glucose = 5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The following means were used to study the groups: 1) a two-step hyperinsulinemic euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3 mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2, 3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/- 0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4, respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45, 20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

[Ultrasound and color Doppler in the diagnosis of vasculogenic impotence].

Echo-color-doppler is a non invasive diagnostic technique which can provide data about arterial and venous vascular circle of the penis with greater precision than Doppler CW. In the tumescent phase after a PGE1 injection the systolic velocity (SV) reaches a rate higher than 25 cm/sec and the diastolic velocity (DV) higher than 2 cm/sec, resistance index (RI) > to 0.70 with evident colour marked from 1 to 3 KHz. In erection arterial flow decrease and SV is lower than 25 cm/sec with DV lower than 2 cm/sec or with negative values; RI < to 0.70 or negative. The data are confirmed by clinical investigation and traditional diagnostic exams in normal and pathological patients. Echo-color-doppler reduces invasive exams and acquires a primary position on the diagnostic scale of impotence.

Erectile Dysfunction↗
PubMed1992

Effects of heparan-sulphate administration on clotting parameters and serum thromboxane B2 levels in cholesterol fed rabbits.

We evaluated the effects of heparan-sulphate administration on clotting times, thromboelastographic parameters and serum thromboxane B2 levels in hypercholesterolemic rabbits with aortic atherosclerotic lesions (sudanophilic areas). 24 New Zealand male rabbits were divided into three groups of 8 animals each. Group A and B were fed a rabbit chow diet containing 0.7% of cholesterol whereas Group C was fed a standard rabbit diet without cholesterol. Group A was treated by subcutaneous route with 6 mg/kg/day of heparan sulphate. At the beginning of the study and after 3 and 6 months of treatment, serum cholesterol and thromboxane B2 levels were tested. Furthermore, at the end of the experiment, we evaluated plasma fibrinogen, aPTT, PT and TT values. The administration of heparan-sulphate in cholesterol fed rabbits produced: a reduction of plasma fibrinogen levels, without modifying aPTT and TT; a protective effect vs the lengthening in PT values, likely induced by cholesterol rich diet; a reduction of plasma thrombophilic activities and of aortic atheromasic involvement induced by dietetic cholesterol intake. However, increased serum thromboxane B2 levels, likely through a proaggregant activity were observed. We suggest that heparan-sulphate administration, in cholesterol fed rabbits, has a favourable effect on clotting parameters, while contrasting effects were found on platelet activity.

Animals↗
PubMed1992

[Clinical implications of sensitization to inhalants in atopic dermatitis].

In 104 children with atopic dermatitis (AD) and RAST tests for 2 inhalant and 9 food allergen mixtures, RAST results, severity of skin involvement and presence of respiratory symptoms by history were analyzed in addition to total serum IgE values available in 66 children. Overall frequency of sensibilization was high (74%) with more positive RAST results for foods than inhalants, although of the latter the only two tested were among the more frequently positive. When the subjects positive for inhalants were considered alone, the frequency of respiratory symptoms was significantly higher in those sensitized to both inhalant mixtures tested (dermatophagoides and graminaceae) and the presence of more severe skin lesions was more common among those sensitized to graminaceae.

Allergens↗
PubMed1991

Tetanus toxin receptor. Specific cross-linking of tetanus toxin to a protein of NGF-differentiated PC 12 cells.

A subclone of rat pheochromocytoma cells expresses high affinity receptors for tetanus toxin on differentiation with NGF [Walton, K.M., Sandberg, K., Rogers, T.B. and Schnaar, R.L. (1988) J. Biol. Chem. 263, 2055-2063]. In the presence of protein cross-linking agents, [125I]tetanus toxin, bound to these cells at 0 degree C, forms a cross-linked product with apparent molecular weight of 120 kDa. The formation of [125I]tetanus toxin conjugate involves the heavy chain of the toxin, is prevented by cold toxin and it is largely reduced by pretreating cells with proteases. The cross-linked product is formed only upon incubation of the toxin with NGF-differentiated cells. These results suggest that a protein with apparent molecular weight of 20 kDa is involved in the neurospecific binding of tetanus toxin.

Animals↗
PubMed1991

[Vascular access for chronic hemodialysis in diabetic patients].

The aim of this study carried out on 33 uremic diabetic patients submitted to chronic hemodialytic treatment was to assess the kind of complications related to the vascular approach used as well as their short- and long-term incidences. Out of the 46 anastomoses prepared, 39 were arteriovenous fistulae according to Brescia-Cimino and 7 were PTFE grafts. The actuarial survival rate was 88%, 79%, and 63% after one, two and four years, respectively. The most frequent compliance was thrombosis. Our experience demonstrates that the distal arteriovenous fistula may be considered a valid vascular access for hemodialysis also in diabetic patients.

Adult↗
PubMed1991

Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo.

We have investigated the effect of granulocyte colony-stimulating factor (G-CSF) delivery at the site of tumor growth by transducing, via retroviral vector, the human (hu) G-CSF gene into the colon adenocarcinoma C-26 and assaying the ability of transduced cells to form tumors when injected into syngeneic mice. As a control, the same tumor cells were infected with retroviruses engineered to transduce an unrelated gene, the human nerve growth factor receptor, or carry the neomycin resistance gene only. Only cells transduced with the huG-CSF were unable to develop tumors, although huG-CSF was expressed and produced at low level as estimated by both RNA analysis and enzyme-linked immunosorbent assay, indicating that G-CSF can exert an antitumor effect at a physiological dose. Implication of G-CSF as mediator of tumor inhibition was proven by reversing the nontumorigenic phenotype of G-CSF-expressing cells with anti-huG-CSF monoclonal antibody injected at the tumor site. No tumors were formed by injecting C-26 infected cells into nu/nu mice, while neoplastic nodules appeared after injection into sublethally irradiated mice; such tumors, however, regressed when mice normalized their leukocyte counts after irradiation. Tumors were also formed after injection of a mixture of infected and uninfected C-26 cells, although critical delay in tumor formation occurred when infected cells were 10 times more represented in the mixture. Histological examination of tissues surrounding the site of injection showed infiltration of neutrophilic granulocytes, whose number correlated with that of G-CSF-expressing C-26 cells in the injected mixture. These results indicate that G-CSF may have a potent antitumoral activity when released, even at low doses, at the tumor site. The antitumoral effect is mediated by recruitment and targeting of neutrophilic granulocytes to G-CSF-releasing cells.

Adenocarcinoma↗
PubMed1991

An in vivo model of somatic cell gene therapy for human severe combined immunodeficiency.

Deficiency of adenosine deaminase (ADA) results in severe combined immunodeficiency (SCID), a candidate genetic disorder for somatic cell gene therapy. Peripheral blood lymphocytes from patients affected by ADA- SCID were transduced with a retroviral vector for human ADA and injected into immunodeficient mice. Long-term survival of vector-transduced human cells was demonstrated in recipient animals. Expression of vector-derived ADA restored immune functions, as indicated by the presence in reconstituted animals of human immunoglobulin and antigen-specific T cells. Retroviral vector gene transfer, therefore, is necessary and sufficient for development of specific immune functions in vivo and has therapeutic potential to correct this lethal immunodeficiency.

Adenosine Deaminase↗
PubMed1991

Efficiency of different criteria for selecting pharmacokinetic multiexponential equations.

Several statistical and empirical approaches have been proposed to select the multiexponential equation that best describes the time course of the plasma concentration of a drug. Recently, a new criterion (Ip) has been proposed according to which the model that best interprets a set of experimental data points is the one with the smallest area between the approximate confidence limits of estimated plasma concentration. We used large Montecarlo simulations to compare the ability of different selection criteria to select the correct model from data generated with an independent, normally distributed random error. The new criterion (Ip), Akaike's information criterion, the Schwartz test, and the F ratio test were studied. In this situation, the correct model was known and the performances of different selecting methods were assessed by examining their sensitivity to the number of exponential terms, the number of data points, and the size of the exponents in the true model. Mono-, bi-, and triexponential equations were studied. Overall mean percentages of right identification were 98.1 per cent for the new index, 82.8 per cent for Akaike's information criterion, 89.5 per cent for the Schwartz test, and 97.7 per cent for the F ratio test. The Akaike and Schwartz tests were not as efficient as the other tests with few (8-10) data points. The Ip and the F test raise the percentages of right identification of the model when the hybrid elimination rate macroconstants differ by at least a factor of four.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗