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Biomedical subjects

Andrea Pucci

Publications and source records attributed to Andrea Pucci.

7 recordsLinked to original sources

A study of the humoral immune response of breast cancer patients to a panel of human tumor antigens identified by phage display.

OBJECTIVE: In this article we provide evidence of a significant spontaneous humoral response in cancer patients. METHODS: A panel of tumor-associated antigens, previously identified through serological screening of phage-displayed cDNA libraries from solid human tumors, breast carcinoma cell lines and human testis by employing breast cancer patient sera, was used in this study to survey sera from 182 patients with known disease histories and clinical stages. RESULTS: This analysis reveals a statistically significant association between tumor disease and presence in peripheral blood of IgG antibodies against four autoantigens. One of these antigens (D7-1) is particularly interesting in that the antibody response against it grows with cancer progression from stages I through IV, with an incidence of 13.2, 13.5, 18.2 and 27%, respectively. The significance of this stage-dependent increase in the incidence is confirmed by the Mantel-Haenszel Chi-squared test (P=0.001). CONCLUSIONS: Our data confirm association between breast cancer diagnosis of patients and presence in their peripheral blood of antibodies against several autoantigens identified by phage display.

Adult↗

Dichroic properties of bis(benzoxazolyl)stilbene and bis(benzoxazolyl)thiophene dispersed into oriented polyethylene films: a combined experimental and density functional theory approach.

In this work, a combination of experimental and quantum mechanical investigations is performed for the study of dichroic absorption properties of melt-processed linear low-density polyethylene (LLDPE) oriented films containing < or =0.5 wt % of either 4,4'-bis(2-benzoxazolyl)stilbene (BBS) or 2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene (BTBBT). The data acquired reveal that the film optical anisotropy and the performances as linear polarizer are strongly dependent on the molecular structure of the chromophore. In particular, the rodlike structure of BBS favors the alignment of the dye along the drawing direction of the PE film, providing dichroic ratios as high as 100 and optical performances as linear polarizer close to the pseudo-affine deformation scheme. On the contrary BTBBT, although characterized by huge anisotropic potentialities, confers the oriented film very poor dichroism and is unsuitable for linear polarizer applications. This behavior is attributed to the more complex banana-shaped structure of BTBBT dye caused by the thiophene 2,5-functionalization that limits the molecule parallel orientation to the drawing direction.

Journal Article↗

Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study.

Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m(2.7)) than did control subjects (37 +/- 8 g/m(2.7), P < .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P < .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1 +/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.

Adult↗

Identification of a panel of tumor-associated antigens from breast carcinoma cell lines, solid tumors and testis cDNA libraries displayed on lambda phage.

BACKGROUND: Tumor-associated antigens recognized by humoral effectors of the immune system are a very attractive target for human cancer diagnostics and therapy. Recent advances in molecular techniques have led to molecular definition of immunogenic tumor proteins based on their reactivity with autologous patient sera (SEREX). METHODS: Several high complexity phage-displayed cDNA libraries from breast carcinomas, human testis and breast carcinoma cell lines MCF-7, MDA-MB-468 were constructed. The cDNAs were expressed in the libraries as fusion to bacteriophage lambda protein D. Lambda-displayed libraries were efficiently screened with sera from patients with breast cancer. RESULTS: A panel of 21 clones representing 18 different antigens, including eight proteins of unknown function, was identified. Three of these antigens (T7-1, T11-3 and T11-9) were found to be overexpressed in tumors as compared to normal breast. A serological analysis of the 21 different antigens revealed a strong cancer-related profile for at least five clones (T6-2, T6-7, T7-1, T9-21 and T9-27). CONCLUSIONS: Preliminary results indicate that patient serum reactivity against five of the antigens is associated with tumor disease. The novel T7-1 antigen, which is overexpressed in breast tumors and recognized specifically by breast cancer patient sera, is potentially useful in cancer diagnosis.

Amino Acid Sequence↗

Identification of tumor-associated antigens by screening phage-displayed human cDNA libraries with sera from tumor patients.

Screening cDNA libraries from solid human tumors with sera of autologous patients (SEREX) has proven to be a powerful approach to identifying tumor antigens recognized by the humoral arm of the immune system. In many cases, application of this methodology has led to the discovery of novel tumor antigens as unknown gene products. We tried to improve the potency of the SEREX approach by combining it with phage-display technology. We designed a new lambda vector to express protein fragments as N-terminal fusions to the D capsid protein and generated high-complexity cDNA libraries from human breast carcinoma cell lines and solid tumors. Screening these phage-displayed libraries required limited amounts of sera from patients and efficiently identified several tumor antigens specifically reacting with sera from breast cancer patients.

Adult↗

Molecular dissection of the human B-cell response against Toxoplasma gondii infection by lambda display of cDNA libraries.

The disorders generated by Toxoplasma gondii infection are closely associated with the competence of the host immune system and both humoral and cell mediated immunity are involved in response to parasite invasion. To identify antigens implicated in human B-cell responses, we screened a phage-display library of T. gondii cDNA fragments with sera of infected individuals. This approach identified a panel of recombinant phage clones carrying B-cell epitopes. All the peptide sequences selected by this procedure are regions of T. gondii gene products. These regions contain epitopes of the T. gondii antigens SAG1, GRA1, GRA7, GRA8 and MIC5, which are recognised by human immunoglobulins. Moreover, we report the isolation and characterisation of two additional immunodominant regions encoded by GRA3 and MIC3 genes, whose products have never been described as antigens of the human B-cell response against T. gondii infection. These results demonstrate potential of lambda-display technology for antigen discovery and for the study of the human antibody response against infectious agents.

Antigens, Protozoan↗

Nanoparticles from polylactide and polyether block copolymers: formation, properties, encapsulation, and release of pyrene--fluorescent model of hydrophobic drug.

Polylactide-b-polyglycidol-b-poly(ethylene oxide) terpolymers and their derivatives with carboxyl and 4-(phenylazo)phenyl labels in polyglycidol blocks were used for formation of nanoparticles. Nanoparticles were produced by self assembly of terpolymer macromolecules in water above the critical aggregation concentration and by dialysis of terpolymer solutions in 1,4-dioxane against water. For terpolymers with 4-(phenylazo)phenyl labels critical aggregation concentrations increased after irradiation with UV light (300 < lambda < 400 nm) inducing conformational change of the label from trans- to cis-conformation. Diameters of nanoparticles obtained by self-assembly of macromolecules ranged from 20 to 44 nm. Dialysis yielded nanoparticles with bimodal diameter distribution. One fraction had diameters below 35 nm and diameters of the second fraction were in a range from 350 to 2300 nm, depending on terpolymer structure. Mixtures of terpolymers with poly(L,L-lactide) and poly(D,D-lactide) blocks yielded nanoparticles with diameters from 350 to 440 nm. Pyrene was incorporated into nanoparticles by partition between solution and nanoparticles or directly during particle formation by dialysis. Monitoring of pyrene release from nanoparticles suggests that a fraction of this compound was entrapped into the polylactide core whereas the remaining one was located in the polyether rich shell. The release from shells is faster for nanoparticles made from copolymers with carboxyl labels in polyglycidol blocks.

Capsules↗