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R Pellegrini

Publications and source records attributed to R Pellegrini.

At least 37 records · Page 2Linked to original sources
PubMed1992

p185 HER2/neu epitope mapping with murine monoclonal antibodies.

In order to obtain further information on the biological role of the HER2/neu oncoprotein, 7 new monoclonal antibodies (MAbs) were produced against the p185HER2 extracellular domain. These MAbs, together with two others previously produced, were used to investigate the p185HER2 expression in breast carcinomas and compare the recognized antigenic determinants. The 7 reagents (MGR4,5,6,7,8,9 and 10), were shown to define five distinct epitopes. Three of these MAbs (MGR5,7,10), as well as one previously produced (MGR2), recognize the same epitope (Epitope-1) which seems, therefore, to be highly immunogenic for the murine immune system. Epitope-2 recognized by the MGR4 MAb, appears to be closely related to epitope-1 due to a cross inhibition between MGR4 and MGR10, but not MGR2. Epitope-2 is the only one of the 5 also present on the product of the neu oncogene, the rat analogue of the human HER2/neu gene. None of the reagents against epitope-1 and epitope-2 were found to mediate receptor internalization, whereas MGR6 as well as a previously produced MAb (MGR3), both of which define epitope-3 and MGR8 which defines epitope-4, were found to do so. Epitope-4 like the neu-specific peptide recognized by the reference c-neu Ab3 MAb, was detectable on all p185HER2 positive breast cancer, independently from the quantitative content of the oncoprotein, at variance with the other 4 epitopes whose availability on p185HER2 for the relevant MAbs varied with the degree of overexpression. Epitope-5, recognized by the MGR9 MAb, on the contrary to the other epitopes, was prevalently localized at the basal membrane level of the tumor nodule.

Animals↗
PubMed1991

Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification.

In order to obtain further information on the biological role of the HER2/neu oncoprotein monoclonal antibodies (MAbs) were produced against the p185 extracellular domain. To immunize the mice and screen the hybridoma supernatants we selected a lung adenocarcinoma cell line (Calu-3), which demonstrated an over-expression of p185HER2 measured as the reactivity with polyclonal rabbit serum to the 14-amino-acid carboxy-terminal-HER2/neu. Two MAbs, designated MGR2 (IgG1) and MGR3 (IgG2), selected for reactivity on Calu-3 and negativity on A43I live cells, the reference target cell for EGF receptor expression, were found to immunoprecipitate a 185-kDa molecule. Immunodepletion experiments with the polyclonal antiserum and cross-competition experiments indicated that the 2 reagents recognized 2 different epitopes located on the p185HER2 molecule. One of the 2 MAbs, MGR3, was found to internalize, induce p185HER2 phosphorylation and inhibit tumor cell growth in vitro. These results indicate that MGR3 is directed against a determinant located in the p185HER2 ligand binding site and may compete with the p185HER2 ligand, but is incapable of inducing a complete mitotic signal.

Animals↗
PubMed1991

Characterization of a monoclonal antibody directed against the epidermal growth factor receptor binding site.

In this work a new monoclonal antibody (mAb), designated MGR1, which recognizes the epidermal growth factor receptor (EGF-R) binding site, is described. The main characteristic of this mAb is its ability to discriminate between cells that express normal levels of EGF-R from cells with overexpression, the detectability threshold by immunocytochemical tests being 5 x 10(4) receptors/cell of 10 microns diameter. MGR1 was found to inhibit EGF binding on the relevant target cells, and vice versa its binding was inhibited by EGF, which indicated that MGR1 recognizes the EGF receptor binding site. MGR1 exerted an inhibitory effect on both the in vitro and in vivo growth of cells with EGF-R overexpression, but had no effect on cells with a normal expression of the receptor. Tumour growth inhibition in athymic mice was also obtained on already implanted tumours. MGR1 therefore seems to be an adequate reagent for the development of immunotherapeutical approaches suitable for the treatment of tumours with EGF-R overexpression.

Animals↗
PubMed1991

Laminin receptors on SCLC cells.

Several studies have suggested a correlation between the metastatic potential and the expression of adhesion molecules and/or their receptors on tumour cell surface membranes. In this study we investigated the expression of functional laminin receptors on small cell lung cancer (SCLC) cells. To this aim we set up an adherence assay to determine the in vitro binding capability of tumour cell lines to laminin. All of the three SCLC lines tested and cells from a short-term SCLC line adhered to laminin in cell culture plates, and the affinity of cell-matrix adhesion proved to be higher than the cell-cell adhesion. This effect was always laminin dose-dependent. On a laminin affinity chromatography column three major proteins could be eluted with EDTA from soluble extracts of SCLC lines. Their molecular weights of 120, 90 and 30 kDa suggested a possible relationship with the integrin family. This putative integrin laminin receptor expressed on SCLC does not react with fibronectin, vitronectin or collagen.

Carcinoma, Small Cell↗
PubMed1989

Studies on the degradative mechanism of phosphoenolpyruvate carboxykinase from yeast Saccharomyces cerevisiae.

Previous work carried out in our laboratory (Burlini, N., Lamponi S., Radrizzani, M., Monti, E. and Tortora P. (1987) Biochim. Biophys. Acta 930, 220-229) led to the immunological identification of a yeast 65-kDa phosphoprotein as a modified form of phosphoenolpyruvate carboxykinase; moreover the appearance of this phospho form was proven to be independent of cAMP, whereas the glucose-induced inactivation of the native enzyme is cAMP-dependent. Here, we report further investigations on the mechanism of the glucose-triggered degradation of the enzyme which led to the following results: (a) the aforementioned phospho form displayed a binding pattern to 5 AMP-Sepharose 4B quite similar to that of native enzyme, although it did not retain its oligomeric structure, nor was it catalytically active; (b) its phosphate content was of about two residues per monomer; (c) its isoelectric point was slightly higher than that of native enzyme, this shows that the enzyme undergoes additional modifications besides phosphorylation; (d) it represented about 4% of the native enzyme in glucose-depressed cells; (e) other forms immunologically cross-reactive with the native enzyme were also isolated, whose molecular mass was in the range of 60-62 kDa, and they are probable candidates as degradation products of the phospho form; (f) time courses of the native and phospho forms in the presence and the absence of glucose provided data consistent with a kinetic model involving a strong stimulation of the decay of both forms effected by the sugar; (g) in the mutant ABYS1 (Achstetter, T., Emter, O., Ehmann, C. and Wolf, D.H. (1984) J. Biol. Chem. 259, 13334-13343) which is devoid of the four major vacuolar proteinases, the decay pattern was essentially the same as in wild-type; (h) effectors lowering intracellular ATP also retarded the first step of enzyme degradation; this points to an ATP-dependence of this step. Based on these results we propose a degradation mechanism consisting of an initial cAMP- and ATP-dependent modification of the enzyme, followed by a cAMP-independent phosphorylation, which leads to the appearance of the aforementioned monomeric phospho form; this in turn seems to undergo limited proteolysis. These data strongly suggest the occurrence of an intermediate form arising from the native one and whose phosphorylation gives rise to the 65-kDa phosphoprotein described here.

Adenosine Triphosphate↗
PubMed1987

Diagnostic x-ray spectra measurements using a silicon surface barrier detector.

A silicon surface barrier detector is used to analyse diagnostic x-ray spectra. This detector, usually employed to detect charged particles, has a very low efficiency for x-ray. This characteristic is advantageous in overcoming experimental problems caused by the high fluence rates typical of diagnostic x-ray beams. The pulse height distribution obtained with silicon surface barrier detectors is very different from the true photon spectra because of the presence of escaped Compton photons and the fact that detection efficiency falls abruptly when photon energy increases. A detailed analysis of the spurious effects involved in detection is made by applying a Monte Carlo method. A stripping procedure is described for implementation on a personal computer. The validity of this method is finally tested by comparison with the experimental results obtained with a Ge detector. The spectra obtained with the Si detector are in fairly good agreement with the analogous spectra measured with a Ge detector. The advantages of using Si as opposed to Ge detectors in x-ray spectrometry can be summarised as: its simplicity of use, its greater economy for use in routine diagnostic x-ray spectroscopy and the possibility that the stripping procedure can be implemented on a personal computer.

Radiography↗
PubMed1986

The radiation dose to the lens in radiology of the orbit.

This paper describes research into measurement and reduction of the radiation dose to the lens during various examinations, namely skull and orbit, optic canal and optic strut, superior and inferior orbital fissure, localisation of foreign bodies in the eye, calcifications, orbital fractures, macrodacryography and orbital venography. Using rare-earth screens and high-sensitivity films, without an antiscattering grid, and with an added filtration of 0.5 mm Cu, it is possible to reduce the radiological risk during all investigations involving skull, orbit and eyeballs, while maintaining a good image quality. Particularly in those examinations with direct magnification (macrodacryography and venography, foreign bodies in the eye, orbital fractures), the dose to the lens is very low: less than 0.2 mGy/radiograph.

Eye Diseases↗
PubMed1984

The use of cadmium telluride detectors for the qualitative analysis of diagnostic x-ray spectra.

A method is introduced for the evaluation of x-ray spectra from x-ray machines operating in the range 50-100 kVp using a cadmium telluride (CdTe) detector with low detection efficiency. The pulse height distribution obtained with this kind of detector does not represent the true photon spectra owing to the presence of K-escape, Compton scattering, etc.; these effects were evaluated using a Monte Carlo method. A stripping procedure is described for implementation on a Univac 1100/82 computer. The validity of our method was finally tested by comparison with experimental results obtained with a Ge detector and with data from the literature; the results are in good agreement with published data.

Cadmium↗
PubMed1982

[Inhibition of fructose-induced hyperuricacidemia by pretreatment with phosphates].

To test the hypothesis that intravenous injections of fructose rapidly decreases liver ATP and Pi and results in the rapid degradation of adenine nucleotides and hyperuricemia, fructose was administered intravenously to a group of normal and gouty subjects; 4 gouty patients were treated with a phosphate solution prior fructose loading. The results obtained show that fructose administration plus phosphate solution prevents Pi depletion and inhibits fructose-induced hyperuricemia.

Acidosis↗
PubMed1982

[Drug-induced changes in chemotaxis under normal conditions and in rheumatoid arthritis].

The effects of agents used in RA treatment, various drugs, RF, rheumatoid nodule and synovial fluid was studied on chemotaxis of PMNs. NSAIDS, corticosteroids, theophylline, colchicine, SOD, RF, rheumatoid nodule and synovial fluid were found to inhibit the chemotactic responsiveness while AMPc, GMPc, PGEI and immunodulator drugs enhanced chemotaxis. The results support the hypothesis that drugs tested may modulate chemotactic function by affecting cellular microtubules assembly and/or GMPc accumulation.

Alprostadil↗
PubMed1982

[The production of superoxide anion (O2-) by polymorphonuclear cells in patients with rheumatoid arthritis].

Superoxide anion production has been determined in controls and RA patients PMNs stimulated with zymosan, rheumatoid synovial membrane, nodule and synovial fluid, rheumatoid factor, aggregated gamma-globulins, Mycoplasma and Epstein-Barr virus. Patients with RA showed an increased production of O2- after incubation with zymosan and rheumatoid tissue extracts or synovial fluid in comparison to normal controls. The findings indicate that rheumatoid PMNs become activated by different stimuli to produce an excess of O2- which can contribute to chronic inflammatory process.

Adult↗
PubMed1980

[Plasma lipoprotein levels in relation to dietary habits].

We carried out a nutritional and haematological survey on 130 pupils of a boarding school in Cagliari in order to determine the relationship between plasma lipoprotein and nutritional habits, particularly, we determined beta/alpha ratio of lipoprotein comparing it with plasma values in hospitalized patients, suffering from metabolic and cardiovascular disease. The results allowed us to observe that 92% of hospitalized patients and 17% of subjects, presumably in good health, showed beta/alpha ratio greater than 2,5. The latter, apparently insignificant, is very important because it was detected in young subjects; as their diet was high-fat and high-carbohydrate, a nutritional and haematological survey will be always necessary in order to prevent illnesses.

Adolescent↗
PubMed1979

Clinical effects of trithiozine, a newer gastric anti-secretory agent.

Trithiozine is a new product which in animal studies proved to have a marked anti-secretory and anti-ulcer effect, along with a very low acute and chronic toxicity and no ganglioplegic, anticholinergic and anti-H2 activity. Clinical trials with trithiozine have been performed in some European countries. The results of these trials, most of which were conducted on a double-blind basis, and including already several hundreds of patients, have shown that oral trithiozine: exerts a very significant action on both basal and stimulated gastric acid secretion, without a rebound hypersecretion; promotes, in most patients, a complete endoscopic healing of peptic ulcer, in addition to an early symptomatic relief; has a mild sedative action; does not affect the pancreatic secretion; is well tolerated even for long-term (up to 10 months) treatments.

Anti-Ulcer Agents↗