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A Ferraris

Publications and source records attributed to A Ferraris.

At least 37 records · Page 2Linked to original sources
PubMed1995

Human CD4+ T cells can discriminate the molecular and structural context of T epitopes of HIV gp120 and HIV p66.

CD4+ T cell lines and clones specific for human immunodeficiency virus (HIV) antigens have been generated from peripheral lymphocytes of naive individuals by priming with the envelope protein gp120, the enzyme reverse transcriptase (p66), and their synthetic peptides. T cells were tested for proliferation to proteins, to peptides, and to HIV virions. Different patterns of reaction were identified. T cells primed in vitro with the whole antigen responded to the protein, but recognition of overlapping peptides occurred with a fraction of the lines or clones. The virus was recognized by some, but not all, of the gp120- and p66-specific T cells, with an efficiency 2 logs higher than the recombinant soluble proteins on a molar basis. One T cell line specific for gp120 responded to virions presented by B cells, but not by monocytes. In contrast, T cells induced with peptides did not always respond to the proteins. Generation of T cell lines from naive individuals may be an in vitro model for T cell immunization, and the response patterns may have implications for the design of vaccines aimed at inducing a T helper response. In fact our in vitro data suggest that (a) immunization with peptides does not always induce T cells recognizing the whole protein, (b) immunization with proteins does not always induce T cells recognizing the protein in the context of the HIV virus, and (c) recognition of gp120 in the context of HIV may be dictated by the type of presenting cells.

Amino Acid Sequence↗
PubMed1995

Recognition of human T-leukemia virus (HTLV-1) envelope by human CD4+ T-cell lines from HTLV-1 seronegative individuals: specificity and clonal heterogeneity.

Because T-helper cells are critical for immune responses in retroviral infections, CD4+ T-cell lines specific for the human T-leukemia virus type 1 (HTLV-1) envelope have been generated from peripheral T lymphocytes of nonimmune donors to study their naive repertoire. Recombinant fragments (RE1, amino acids [aa] 26-200; RE3, aa 165-307; RE5, aa 308-401; and RE6, aa 165-401) of HTLV-1 envelope, whole envelope glycoprotein, and synthetic peptides were used to induce T-cell lines. CD4+ T-cell lines specific for one or more fragments were obtained from seven of eight individuals tested. T-cell lines generated against envelope glycoprotein from five of five donors did not cross-react with the RE fragments and vice versa. The lines specific for RE and env were mapped with overlapping peptides. The lines with single peptide (narrow) specificity contained a variety of clones that used different T-cell receptor V beta genes. These data (1) suggest that most of the normal individuals carry T-helper precursors specific for epitopes on HTLV-1 envelope; (2) indicate that heterogeneity of HTLV-1 envelope-specific T cells can be detected in the naive repertoire; and (3) define optimal antigenic preparations to be used to assess cellular immunity in HTLV-1-infected individuals.

CD4-Positive T-Lymphocytes↗
PubMed1995

Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope-specific antibodies.

Cooperation between B cells specific for an antigen exposed on a viral structure and T helper (Th) cells specific for an internal antigen, as demonstrated with influenza, hepatitis B and rabies viruses, has been termed intrastructural help. Th cells specific for internal proteins of HIV, which are much less mutated than its exposed antigens, may be valuable in vaccine design against this virus. We investigated the human Th repertoire specific for the core HIV antigen reverse transcriptase (p66), and determined whether these cells could be candidate intrastructural T helpers. CD4+ T lines and clones were generated from non-immune individuals by stimulation with p66-pulsed antigen-presenting cells (APC). Specific lines were obtained with p66 from 19 out of 21 (90%) of these individuals, vs. 7 out of 29 (24%) with gp120. Diverse epitopes were recognized by different individuals, and various V beta genes were used by these clones. Clones using the same V beta genes were of diverse origin, according to VDJ region sequence. Of these lines 45% responded to p66 in the context of HIV virions. Moreover, p66-specific clones could respond to APC that had internalized HIV complexed with envelope-specific monoclonal antibodies, suggesting that p66-specific Th cells may participate in intrastructural help. These studies indicate that p66-specific Th cells are detectable in vitro in most naive individuals and exhibit clonal heterogeneity, and that the majority recognize an HIV conserved antigen. They respond to p66 following processing of whole virions and are clearly candidates for intrastructural help. If confirmed in vivo, p66 should be included among vaccine candidates investigated to optimize the anti-HIV Th response.

Amino Acid Sequence↗
PubMed1987

Mutagenicity of 4-hydroxynonenal in V79 Chinese hamster cells.

4-Hydroxynonenal (HNE), a major product of the peroxidation of liver microsomal lipids, was examined for mutagenic activity at the hypoxanthine-guanine phosphoribosyltransferase locus in V79 Chinese hamster lung cells. At concentrations ranging from 10 to 45 microM, HNE induced a dose-dependent increase in the number of mutations to 6-thioguanine resistance, which reached the level of 4.7X baseline at the highest concentration tested.

Aldehydes↗
PubMed1985

[Doppler ultrasound and strain gauge plethymography in the diagnosis of the post-phlebitic syndrome].

Certain non-invasive techniques like Doppler CW and strain gauge plethysmography are highly effective ways of evaluating the natural history of postphlebitic syndrome. 40 patients of both sexes, average age 51.5 +/- 6.9 with a history of deep venous thrombosis (28 documented phlebographically) were subjected to Doppler tests with assessment of venous blood pressure and bilateral strain gauge plethysmography. 34 of the 40 suspected PPS cases were confirmed, though not all cases were at the same stage. Persistent deep venous thrombosis was found in five of the extremities and the last one examined revealed a primary varicose syndrome. A comparison of the Doppler and phlebography results showed both to be highly sensitive techniques (100% accuracy). When the contralateral limbs were examined, the Doppler technique revealed 7 cases of PPS and 21 primary varices. In contrast strain gauge plethysmography identified all 28 cases of increased venous capacitance as primary varices, thus confirming the inability of this technique to distinguish between the various varicose conditions. Assuming the presence of a vascular diagnosis laboratory where both techniques are available, strain gauge plethysmography is recommended as the examination of choice. This technique is simple and fast to perform and can provide extensive information whether at rest (filling and emptying volumes and times; venous tone and distensibility, venous blood pressure at rest) or in movement (venous pressure when standing, muscular pumping index). Hence plethysmography can reveal any canalisation present even in the earliest stages though it cannot pinpoint the precise site of the deep obstruction. The longer, more complex Doppler CW procedure should be reserved for secondary investigations. This technique is preferable to plethysmography when a more accurate assessment of the degree, site and extension of the venous recanalisation is needed. Doppler CW also provides information on any valvar sequelae since it records the direction of the blood flow in the presence of a substitution syndrome (increased venous flow in the surface vessels). Finally if used in a rational manner the two techniques can be combined to eliminate contrast medium techniques, which would only be adopted as a preoperative measure.

Adult↗
PubMed1981

Urinary colony-stimulating factor in acute leukemia follow-up and correlation with various phases of the disease.

Urinary colony-stimulating factor (CSF) was assayed in 19 patients with various leukemias and was monitored in various phases of acute leukemia in 3 patients. Significantly higher CSF levels were found at the onset of leukemia with a monoblastic component. Continuous monitoring of CSF in a patient with acute myelomonocytic leukemia revealed a decrease in CSF level during the remission phase, followed by a rebound to high levels preceding the clinical and hematological relapse. Concomitantly, a colony-inhibitory factor (CIF) was detected. Both CSF and CIF of this patient were isolated and partially characterized.

Acute Disease↗
PubMed1980

Hyper- and hyposensitivity of central serotonin receptors:[3H]serotonin binding and functional studies in the rat.

The effect of repeated treatment with D-fenfluramine, a serotonin releaser, or methergoline, a serotonin antagonist, on [3H]5-HT binding was studied in various rat brain areas. In animals with the same pretreatments, the anorectic activity of m-chlorophenylpiperazine, a serotonin agonist, was investigated. A 14-day treatment with D-fenfluramine caused a significant decrease in the number of [3H]5-HT binding sites (Bmax) in the diencephalon. A reduction of binding sites was found in the cortex too when D-fenfluramine was administered for 28 days. Methergoline caused no changes of [3H)5-HT binding in any brain area examined when given for 14 days but 28-day treatment led to a significant increase in the striatum, hippocampus and cortex. D-Fenfluramine and methergoline caused, respectively, a decrease and increase in the effect of m-chlorophenylpiperazine on food intake. The data show that central 5-HT receptor numbers and sensitivity may change after repeated treatments with drugs acting on brain serotonin.

Animals↗
PubMed1980

Repeated treatment with d-fenfluramine or metergoline alters cortex binding of 3H-serotonin and serotenergic sensitivity in rats.

28-day treatment with d-fenfluramine, a serotonin (5HT) releaser and uptake inhibitor, caused significant reduction (23%) of 3H-5HT binding sites (Bmax) in the rat cortex. These sites were significantly increased (31%) in cortical membranes of rats which had received metergoline, a potent serotonin antagonist, for 28 days. Parallel changes were found in the anorectic activity of metachlorophenylpiperazine (m-CPP), a potent central 5HT agonist: chronic treatment with d-fenfluramine or metergoline caused respectively a decrease and in the effect of m-CPP on food intake. The data show that changes in 5HT central receptor number and sensitivity may occur after chronic treatment with drugs acting on brain serotonin.

Animals↗
PubMed1979

Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats.

Meta-chlorophenylpiperazine inhibited serotonin and noradrenaline uptake by synaptosomes to the same extent with IC50 of 1.3 x 10(-6) M and 5.8 x 10(-6) M respectively. Dopamine uptake was less affected by meta-chlorophenylpiperazine (IC50 of 2.2 x 10(-5) M). Unlike d-amphetamine and d-fenfluramine, the drug did not significantly increase monoamine release in synaptosomal preparations. On the other hand, metachlorophenylpiperazine showed an IC50 of 620 nM in displacing 3H-5HT binding to brain membranes. Meta-chlorophenylpiperazine produced a dose-dependent reduction of food intake and this effect was prevented by a pretreatment with methergoline, a serotonin antagonist. The effect of metachlorophenylpiperazine was not modified by an intraventricular injection of 6-hydroxydopamine, electrolytic lesions of nucleus medianus raphe or ventral noradrenergic bundle, nor by a pretreatment with penfluridol, propranolol or phentolamine. The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist is the brain. The specificity of the effects on serotonin suggests that this compound could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.

Animals↗
PubMedDate not supplied

Percutaneous removal of biliary stones.

Since 1983 we have performed percutaneous treatment of biliary lithiasis in 97 patients. Previous retrograde endoscopic procedures were incomplete or infeasible in all patients. Immediate results were excellent resulting in complete resolution of lithiasis in 89 of 97 patients (92%). In 4 patients (4%) partial success was obtained (symptoms subsided although there were nonobstructing residual stones). Percutaneous treatment failed in 1 patient (1%). Three patients died. Complications occurred in 14 of 97 patients (14%) and mortality at 30 days was 3%. Long-term results were evaluated in 71 patients who had a least a 6-month follow-up (mean 31 months and range 6-78 months). Eight of 71 patients (11%) had recurrence of stones and 7 of these were successfully retreated transhepatically. Percutaneous removal of biliary stones is efficacious because it has a high cure rate, a low complication rate, and a mortality rate that compares favorably to that of surgery even though the patients are usually older and in poorer general condition.

Adult↗
PubMedDate not supplied

Handling of retroviral antigens by human antigen-presenting cells.

Antigen-specific T helper cells play an important role in retroviral infections. Indeed, they provide help for B-cell activation and antibody production and for clonal expansion of cytolytic lymphocytes. Therefore, we used retrovirus-specific human T helper clones in order to define modes of antigen presentation, antigen-presenting cells and the molecular context of Th epitopes that could be exploited in the design of immunogens aimed at optimizing the Th cell response. In particular, we describe several mechanisms of receptor-mediated antigen uptake that enhance the stimulation of human T-cell clones specific for HIV and HTLV-1 antigens; we report on the differential recognition of Th epitopes depending on the molecular-viral context; we show that dendritic cells are the most efficient presenting cells and are essential for the induction of in vitro primary Th cell responses; and finally, we propose that Th cells specific for internal, conserved antigens of HIV such as reverse transcriptase, may be candidates for intrastructural help resulting in induction of envelope specific antibodies.

Antigen Presentation↗
PubMedDate not supplied

Immunoglobulin secretion by mouse myeloma cells; involvement of an energy-requiring step.

The process of Immunoglobulin secretion has been extensively studied but the cellular mechanisms underlying assembly and transport of these molecules are still poorly understood. Evicence is presented in this paper for the presence, in the secretory pathway of mouse myeloma cells, of an energy requiring step, as indicated by the strong inhibition of Immunoglobulin secretion by a variety of respiratory chain inhibitors and of oxidative phosphorylation uncouplers.

Antimycin A↗