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Biomedical subjects

P Turconi

Publications and source records attributed to P Turconi.

12 recordsLinked to original sources

Chromosomal alterations in atherosclerotic plaques.

Alterations of chromosomes 7 and 11 have been involved in the progression of atherosclerosis. Twenty-three carotid endarterectomy specimens were studied for the presence of alterations in chromosomes 7 and 11, and fibroblastic growth factor-3 (FGF-3) gene amplification. Besides classic histological stainings, immunophenotyping of cellular and vascular components and fluorescence in situ hybridization (FISH) were performed. At the caps, unstable plaques (n=18) showed inflammatory infiltration of macrophages, smooth muscle cells, and T-lymphocytes. Specifically in these regions, the FISH showed varying percentages of trisomy (15/18) and tetrasomy (8/15) of chromosome 7. In four cases polisomy 7 was noted in some nuclei. Monosomy of chromosome 11 and gene amplification of FGF-3 gene was observed. The FISH of the five stable plaques and normal arterial walls showed no chromosome alterations; furthermore, chromosome 3, which is not involved in atherosclerotic progression, presented a normal ploidy of smooth muscle cells in stable and unstable plaques and normal arterial walls. In conclusion, chromosome 7 and 11 alterations and FGF-3 gene amplification are components of unstable plaques, and might contribute to the evolution of stable plaques into complicated plaques.

Adult↗

Expression of apoptosis and proliferating cell nuclear antigen (PCNA) in the cardiac conduction system of crib death (SIDS).

Aim of this study is to determine the expression of apoptosis and Proliferating Cell Nuclear Antigen (PCNA) in the cardiac conduction system in crib death and explained death (ED) cases. Postnatal morphogenesis of the conducting tissue is an important part of its normal development. In the atrio-ventricular node (AVN) and His bundle (HB) it consists of degeneration, cell death and replacing in an orderly programmed way. However, its nature and its relation to crib death is not yet fully explained. Apoptosis and PCNA were investigated in 8 heart conduction systems of infants dying of crib death and in 3 conduction systems of infants dying of ED as controls. The cardiac conduction system was removed in two blocks: the first included the sino-atrial node (SAN) and the crista terminalis, the second contained the atrio-ventricular node (AVN), His bundle (HB), bifurcation, and bundle branches. In the conduction systems as well as in the common myocardium the PCNA Labeling Index (PCNA-LI) was found to be negative in all cases. The apoptotic indices (AI) in SIDS and in ED were found to have no statistically significant differences (p>0.05). The SAN, in both groups, showed an AI similar to the one detected in common myocardium. In almost all cases, TUNEL labeling was detected in peripheral region of the AVN, close to the atrial myocardium. The AI was higher in the AVN, HB and the initial tract of bundle branches than in the common myocardium (p<0.05; Student's t test).

Apoptosis↗

Inflammatory cells, apoptosis and Chlamydia pneumoniae infection in atherosclerosis.

Chlamydia pneumoniae (CP), chromosomal alterations and apoptosis were suggested as contributing factors in the pathogenesis of atherosclerosis. Early (EP) and unstable plaques (UP) were studied in order to assess infiltrate composition, the apoptotic index, chromosome 7 stability and to investigate the concurrent presence of CP in EP and UP. Paraffin embedded sections of three iliac arteries and four aortas from young donors (EP), and four coronaries and nine carotid arteries (UP) were used. Aside from histological techniques, immunophenotypification for macrophages, T and B cells, smooth muscle and endothelial cells; FISH and DNA nick end labeling were performed. The amplifications with PCR for CP infection were negative in all specimens. In the EP, a focal myointimal thickening with foam cells and scarce smooth muscle cells was observed. Macrophages were most frequent in the intima (10.8%) while T and B cells were found in 2.3 and 1.5%. In the UP a thin cap covering a lipid-rich core with widespread vascularization and with severe luminal obstruction was observed. Macrophages were increased (21%), and T (1.5%) and B cells (3.5%) in the caps and inner areas of the lipid cores. At these sites, the FISH showed trisomy and tetrasomy of chromosome 7 and apoptosis was very frequent (10-30%). Macrophages in intimal lesions is one of the most prominent, consistent and permanent features in EP, and an elevated apoptotic index and chromosome 7 instability might contribute to evolution from stable to complicated plaques, while CP seems to play no role. However, further studies are needed with more cases to confirm this last observation.

Adult↗

[Proliferative activity and chromosomal alterations of smooth muscle cells in atherosclerosis].

Atherosclerosis is the most frequent cause of death in industrialized countries. Lesions are characterized by lipid deposits, focal thickening of the arterial wall with proliferation of smooth muscle cells (SMC), mononuclear infiltrates and neoformed vessels. In this paper, we studied the proliferative characteristics and cytogenetic alterations of SMC. These cells, expressing specific muscular actin, were diploid with an increased proliferative index for PCNA. A high percentage of SMC showed intense expression of p53. There were signs of chromosomal instability, being the most frequent findings chromosome 7 trisomy and chromosome 11 monosomy. Additionally, the gene for FGF-3 showed a marked amplification. These findings strongly suggest that SMC proliferation is active, and is related to the accumulation or mutation of the p53 oncoprotein. It also presents specific chromosomal alterations in close relation with growth factors. According to these findings SMC hyperplasia in the atherosclerosis plaque may be considered as a cellular clonal expansion.

Arteriosclerosis↗

p53 over-expression and its correlation with PCNA index in nasal polyps.

Our knowledge about the etiopathogenesis of nasal polyps (Nps) is still limited. In this study, in order to define the biological features of these neoformations, we investigated with immunohistochemistry the p53 over-expression and the proliferating cell nuclear antigen (PCNA) in 32 cases of Nps and in normal mucosa of 11 control cases. The evaluation of PCNA showed a wide range of indices (0.5-18.2%) with a mean value (6.8%) significantly higher than in normal mucosa (2.9%). Over-expression of the p53 oncoprotein, observed in 50% of Nps, was statistically related to a high PCNA-index (> 6.8%). Our results suggest that Nps can behave, in a high percentage of cases, like tumours.

Female↗

Detection of trisomy 7 with fluorescence in situ hybridization and its correlation with DNA content and proliferating cell nuclear antigen-positivity in prostate cancer.

The authors applied fluorescence in situ hybridization (FISH), using specific DNA probes for chromosome 7, to routine paraffin-embedded tissue sections obtained from 35 radical-prostatectomy specimens. Proliferative activity was also evaluated using static cytometry to assess DNA content and immunohistochemistry for proliferating cell nuclear antigen (PCNA) positivity. These results were correlated with each other and with the morphologic parameters. The presence of three or more of chromosome 7 was observed in 71% of the cases, as was a high S phase, with a triploid prevalent DNA content and a PCNA index above mean value in 66% of the cases. No correlation was detected between these findings and histologic grade; conversely, there was a significant correlation with stage (chi-square = 5.33; p = 0.021). From these results, the authors maintain that the presence of an extra chromosome 7-correlated in most cases with an increase in cell kinetics and an advanced stage-may be an additional prognostic marker of aggressive behavior.

Adenocarcinoma↗

Cytogenetic aspects of cell proliferation in atherosclerotic plaques.

Fluorescence in situ hybridization (FISH) using chromosome specific alpha-satellite DNA probes for chromosome 7, was performed on paraffin-embedded sections of 21 cases of human "unstable" atherosclerotic plaques, in order to determine whether trisomy 7, found by some Authors with conventional cytogenetics, is a biological characteristic of the atherosclerotic plaque. In 15 cases (71%) the FISH method showed smooth muscle cells with three or more spots. In particular the trisomy 7 was the most significant and constant result. The presence of an extra chromosome 7 is strictly correlated with an overexpression of the gene for chain A of the platelet-derived growth factor (PDGF), which was mapped at pter-7q22 region. Therefore trisomy 7 seems to correspond to an increase in PDGF synthesis and consequently to an increase in proliferative activity of smooth muscle cells.

Arteriosclerosis↗

Stimulation of Cl- secretion by the mucoactive drug S-carboxymethylcysteine-lysine salt in the isolated rabbit trachea.

Ion transport by the airway epithelium contributes to the regulation of the quantity and composition of respiratory tract fluid, thereby affecting mucociliary clearance. We have investigated the effect of the mucoactive drug S-carboxymethylcysteine-lysine salt (S-CMC-Lys) on the transepithelial bioelectric properties of isolated rabbit trachea. Transepithelial potential difference (Vms), short-circuit current (Isc) and resistance (R) were measured in the isolated rabbit trachea mounted between flux half-chambers, in the presence and in the absence of S-CMC-Lys (100 microM), added to the mucosal or submucosal chamber. In some experiments, tissues were also exposed to ion channel-inhibitors, in order to evaluate the contribution of Na+ and Cl- active transport to Isc. The excised rabbit trachea expressed transepithelial bioelectric properties based on an active ion transport supported by the Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, since ouabain (500 microM) completely abolished the transepithelial potential difference. In control preparations, Vms and Isc declined significantly during 300 min recording, whereas R remained constant. The Isc decline was essentially attributable to a decrease in Cl- transport. Bumetanide (100 microM) almost completely abolished the Isc fraction related to Cl- transport. Treatment of the tissues with S-CMC-Lys reduced the progressive fall in Isc, with the most clear-cut and significant effect observed for the mucosal treatment. In parallel, S-CMC-Lys significantly lowered R, without affecting Vms. Either mucosal or submucosal exposure to S-CMC-Lys significantly increased Cl- secretion to normal values, whilst Na+ absorption was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Liquid drainage through the peritoneal diaphragmatic surface.

In 14 spontaneously breathing anesthetized rabbits, we used cyanoacrylate to glue a hollow capsule, at end expiration or at end inspiration, to the peritoneal surface of the tendinous portion of the diaphragm. The capsule was connected to a pressure transducer and a pipette calibrated in microliters. We filled the system with fluid and measured flow into the diaphragmatic surface facing the capsule (Fcap, microliter/cm2), from liquid displacement in the pipette at different hydraulic pressures in the system (Pcap). Pleural liquid pressure was simultaneously measured in the supraphrenic region (Psup). Fcap was positively correlated to transdiaphragmatic pressure gradient (Psup-Pcap) and breathing frequency but was unaffected by protein concentration of capsular fluid. For a breathing frequency of 30 cycles/min and a Psup - Pcap = -2 cmH2O, Fcap was 0.54 microliter.min-1.cm-2 for capsules applied at end expiration and 10-fold greater for capsules applied at end inspiration. Data indicate that the diaphragmatic tendinous portion in rabbits is a draining site for peritoneal fluid and that the conductance of the draining pathways (lymphatic stomata) is related to diaphragmatic tension. In the intact rabbit the average peritoneal fluid drainage through the tendinous portion of the diaphragm (approximately 16 cm2) was estimated at 43 microliters/min.

Absorption↗

Significance of trisomy 7 related to PCNA index in cholesteatoma.

PURPOSE: To define the biological features of the variable aggressiveness of cholesteatoma, we performed a retrospective cytogenetic and kinetic study. MATERIALS AND METHODS: We studied 44 cases of cholesteatoma by using fluorescence in situ hybridization with specific alpha-satellite DNA probes for chromosome 7 and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) with PC10 monoclonal antibody. RESULTS: We observed the presence of three or four chromosome 7 in elevated percentages of cells of 23 cases, and a high PCNA index (above mean value) in 22 cases. CONCLUSION: Based on our results, we maintain that the presence of an extra chromosome 7 is correlated with an increase of proliferative activity. Therefore, trisomy 7 can be considered a prognostic marker and an indicator of aggressive behavior in cholesteatoma.

Adolescent↗

The role of different biomarkers (DNA, PCNA, apoptosis and karyotype) in prognostic evaluation of superficial transitional cell bladder carcinoma.

BACKGROUND: In order to clarify the variable behaviour of transitional cell bladder carcinomas (TCBC) with same clinico-pathologic pattern, we investigated the prognostic significance of various biomarkers (PCNA, DNA, apoptosis, karyotype). MATERIALS AND METHODS: We studied 177 superficial TCBC (stage T1) undergoing transurethral resection (TUR). Analysis of biological indicators was performed on serial paraffin sections: DNA by static cytometry, karyotype by fluorescence in situ hybridisation (FISH), PCNA and apoptosis by immunohistochemistry. RESULTS: The most salient results are represented by prevalence of diploidy (56%), a mean PCNA labeling index (PCNA-LI) of 8.2%, nonrandom trisomies and tetrasomies of chromosome 7, and a high presence of apoptosis (in 72% of cases). These data were not related to histological grading. Multivariate analysis showed that only PCNA-LI is a an independent prognostic marker for patient survival (p = 0.01). Besides, we observed a worse prognosis in the presence of both very high PCNA indices and low or absent apoptosis. CONCLUSIONS: The results of this study suggest that tumor prognostic potential in TCBC should be evaluated on the basis of the association between PCNA cell kinetics and cell apoptosis information.

Aged↗

Prognostic significance of different biological markers (DNA index, PCNA index, apoptosis, p53, karyotype) in 126 adenocarcinoma gastric biopsies.

BACKGROUND: The different clinical evolution of gastric adenocarcinomas with the same clinico-pathologic characteristics prompted the authors to investigate the prognostic significance of different biological markers. METHODS: One hundred twenty-six preoperative cancer gastric biopsies, selected according the stage evaluated after following gastrectomy, were examined for DNA content by means the static cytometry, proliferating cell nuclear antigen (PCNA), p53 mutation, apoptosis by immunohistochemistry and karyotype using fluorescence in situ hybridization (FISH) techniques. RESULTS: The gastric cancers, ail belonging at stage III, were adenocarcinomas histologically typed as: 26 well differentiated (G1), 45 moderately differentiated (G2), 43 poorly differentiated (G3) and 12 of undifferentiated type with signet-ring cells. The tumours showed a prevalence of diploidy (68%), a mean PCNA-LI of 4.8%, trisomy of chromosome 7 in 40% of the cases, low presence of apoptosis (30%) and p53 mutation (17%). Only apoptosis was significantly correlated to histological diagnosis (p = 0.009). A multivariate analysis showed that the DNA content and PCNA-LI were the only independent prognostic markers for survival (p = 0.005 and p = 0.0002 respectively). CONCLUSIONS: The evaluation of these two biological variables, especially of the PCNA index, on gastric cancer biopsies may be useful in predicting the aggressiveness of each tumor and in identifying patients in need of additional perioperative therapies.

Adenocarcinoma↗