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G Bardi

Publications and source records attributed to G Bardi.

At least 19 recordsLinked to original sources
PubMed2001

Assessments of clonal composition of colorectal adenomas by FISH analysis of chromosomes 1, 7, 13 and 20.

Chromosome banding analysis has shown that numerical aberrations, in particular gains of chromosomes 7, 13 and 20, are common in colorectal adenomas but cannot provide reliable information on the size of the abnormal clones in vivo. We examined interphase nuclei from 70 colorectal adenomas, of which 64 had been previously karyotyped, using fluorescence in situ hybridization (FISH) with probes for the pericentromeric regions of chromosomes 1, 7, 13 and 20. Gain of chromosome 7 was seen in 34% of the analyzed adenomas, +13 was seen in 44% and trisomy 20 was found in 32% of the adenomas, verifying that the trisomies are in vivo phenomena. The median proportion of cells with trisomy was larger than 50%. A comparison with the G-banding analysis showed a good correlation between the results yielded by the 2 methods. Based on the clonal size and karyotypic findings, a likely order of events during clonal evolution could be ascribed to each case. More than 1 numerical aberration was detected by FISH analysis in 16 adenomas. In 6 adenomas, a clone with only trisomy 7 was present alongside a clone with additional gain(s) of chromosomes 13 and/or 20. Seven cases had gain of chromosome 13 and/or gain of chromosome 20 in the largest clone, suggesting that a clone with either of these changes was present before the changes in chromosome 7 copy number took place. On the basis of the results of this combined meta- and interphase cytogenetic study, we conclude that gains of chromosomes 7, 13 and 20 are common in colorectal adenomas and that the trisomies usually are present in a large proportion of the cells. They seem to be primary chromosome aberrations in some adenomas, whereas in others they arise secondarily as part of the clonal evolution. Although the first gain usually is of chromosome 7, it is evident that it is the end result of the chromosomal aberrations, not the exact sequence in which they occur, that determines the pathogenetic consequences.

Adenoma↗
PubMed2001

Eotaxin is a natural antagonist for CCR2 and an agonist for CCR5.

Eotaxin is a potent inducer of eosinophil chemotaxis and was considered as a selective ligand of the CC chemokine receptor 3 (CCR3), which is expressed on eosinophils, basophils, and Th2 lymphocytes. This study shows that eotaxin also interacts with CCR2 and CCR5 and can, thus, affect the responses of monocytes, which express both receptors. In human monocytes pretreatment with eotaxin decreased responsiveness to MCP-1, a selective ligand for CCR2, as well as to RANTES and MIP-1 beta, which bind to CCR5. Similar effects were obtained with transfected cells expressing CCR2 or CCR5, but here a difference became apparent: Eotaxin triggered CCR5 at a concentration of 100 nM but not CCR2 even at 1 microM, suggesting an antagonistic effect on this receptor. In agreement with this observation, eotaxin induced internalization of CCR5 but not of CCR2 in human monocytes and transfected cells. Binding studies showed that eotaxin displaces (125) I-MCP-1 from monocytes in a concentration-dependent manner, and functional experiments showed that eotaxin inhibits MCP-1-induced chemotaxis and enzyme release. The results demonstrate that eotaxin is a CCR5 agonist and a CCR2 antagonist. The present findings suggest a role of eotaxin in the fine-tuning of cellular responses occurring at sites of allergic inflammation, in which both MCP-1 and eotaxin are produced. (Blood. 2001;97:1920-1924)

Calcium Signaling↗
PubMed2001

The T cell chemokine receptor CCR7 is internalized on stimulation with ELC, but not with SLC.

ELC and SLC are potent agonists for CCR7, a receptor of up-most importance for the regulation of the homing and traffic of lymphocytes into and within secondary lymphoid tissues. We have studied the effects of both chemokines on receptor re-distribution in T lymphocytes and other CCR7-bearing cells by flow cytometry and by assessing receptor mediated functions. In this paper we show that ELC and SLC differ fundamentally in the ability to induce the internalization of their receptor. ELC induced a rapid time- and concentration-dependent internalization of CCR7 and markedly decreased the ability of CCR7-bearing cells to respond to a second stimulation. No receptor internalization, by contrast, was observed on stimulation with SLC. Receptors that were internalized on stimulation with ELC were re-expressed when the cells were washed. Re-expression of receptors and consequent re-activation of the cells was prevented in the presence of ELC, but was not affected in the presence of SLC. These findings could explain how T lymphocytes that enter lymphoid tissues in response to SLC produced by high-endothelial venules can subsequently migrate in response to SLC and ELC expressed within the T cell areas.

Calcium↗
PubMed2000

The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3.

Th1 and Th2 lymphocytes express a different repertoire of chemokine receptors (CCRs). CXCR3, the receptor for I-TAC (interferon-inducible T cell alpha-chemoattractant), Mig (monokine induced by gamma-interferon), and IP10 (interferon-inducible protein 10), is expressed preferentially on Th1 cells, whereas CCR3, the receptor for eotaxin and several other CC chemokines, is characteristic of Th2 cells. While studying responses that are mediated by these two receptors, we found that the agonists for CXCR3 act as antagonists for CCR3. I-TAC, Mig, and IP10 compete for the binding of eotaxin to CCR3-bearing cells and inhibit migration and Ca(2+) changes induced in such cells by stimulation with eotaxin, eotaxin-2, MCP-2 (monocyte chemottractant protein-2), MCP-3, MCP-4, and RANTES (regulated on activation normal T cell expressed and secreted). A hybrid chemokine generated by substituting the first eight NH(2)-terminal residues of eotaxin with those of I-TAC bound CCR3 with higher affinity than eotaxin or I-TAC (3- and 10-fold, respectively). The hybrid was 5-fold more potent than I-TAC as an inhibitor of eotaxin activity and was effective at concentrations as low as 5 nm. None of the antagonists described induced the internalization of CCR3, indicating that they lack agonistic effects and thus qualify as pure antagonists. These results suggest that chemokines that attract Th1 cells via CXCR3 can concomitantly block the migration of Th2 cells in response to CCR3 ligands, thus enhancing the polarization of T cell recruitment.

Binding, Competitive↗
PubMed2000

Nasal ventilation in COPD exacerbations: early and late results of a prospective, controlled study.

Noninvasive positive pressure mechanical ventilation (NIPPV) in exacerbated chronic obstructive pulmonary disease (COPD) has been investigated early and after 1 yr of follow-up. To this end, 30 patients were enrolled in a prospective, controlled trial: 15 had early administration of NIPPV (Group A), 15 had medical therapy only (Group B); assignment was made on the basis of equipment availability only. In-hospital mortality, need for endotracheal intubation and mean length of hospitalization were lower in Group A, though the difference was not statistically significant. Arterial oxygen tension in arterial blood (Pa,O2), carbon dioxide tension in arterial blood (Pa,CO2) and HCO3- improved significantly in both groups from admission to discharge: 45.8+/-8.6 versus 64.9+/-10.0; 59.4+/-11.8 versus 48.6+/-7.3; 34.3+/-4.3 versus 30.1+/-3.4 in group A; 49.2+/-11.4 versus 60.9+/-8.2; 52.6+/-15.9 versus 44.4+/-8.7; 31.7+/-5.9 versus 28.0+/-3.6 in group B, respectively, p<0.05 for all comparisons; pH, percentage forced expiratory volume in one second (FEV1) and tidal volume (VT) improved significantly in patients of group A only: 7.36+/-0.04 versus 7.41+/-0.02; 39.8+/-13.6 versus 49.4+/-11.7; 0.71+/-0.3 versus 0.84+/-0.4, respectively, p<0.05. During follow-up, 3, 6, and 12 months survival rates were significantly higher in Group A than in Group B (p<0.02). Hospital new admissions over 1 yr were more frequent in Group B (n=6, incidence rate: 0.216%) than in Group A (n=4, incidence rate: 0.084%). Therefore, noninvasive positive pressure mechanical ventilation may be added to "conventional" medical therapy in exacerbated chronic obstructive pulmonary disease.

Aged↗
PubMed1999

Karyotypic evolution in breast carcinomas with i(1)(q10) and der(1;16)(q10;p10) as the primary chromosome abnormality.

The pattern of clonal karyotypic evolution in breast carcinomas carrying an i(1q) or a der(1;16)(q10;p10) as the primary chromosome abnormality was assessed in a series of 42 tumors, including 8 described here for the first time, with either or both (3 tumors) of them defining cytogenetic features. Evidence of clonal evolution was seen in somewhat more than half of all cases in both subgroups. The secondarily acquired aberrations appeared to be nonrandom in distribution. This was especially so for structural rearrangements of 11q leading to loss of material from this arm, which were clearly more common in both subgroups than in karyotypically abnormal breast carcinomas in general. Other deviations from random were less certain but seemed to include the frequent occurrence of +20 in tumors with i(1q) and +7 in tumors with der(1;16)(q10;p10). That differences were observed between i(1q) carcinomas and der(1;16)(q10;p10) carcinomas with regard to their patterns of clonal evolution hints that the pathogenetic effect of the primary change in these two situations may be more than the mere gain of an extra copy of 1q.

Breast Neoplasms↗
PubMed1999

Cytogenetic analyses of secondary liver tumors reveal significant differences in genomic imbalances between primary and metastatic colon carcinomas.

To investigate if karyotypic features of secondary liver tumors may provide diagnostic information and if the cytogenetic patterns of primary and metastatic colorectal carcinomas (CRC) are different, 33 liver metastases were analyzed: 25 CRC, 4 small intestine carcinoids, 1 ovarian carcinoid, 1 lobular breast cancer, 1 head-and-neck squamous cell carcinoma, and 1 uveal malignant melanoma. Chromosomal aberrations were detected in 24 cases, whereas 5 had normal karyotypes and 4 were uninformative due to lack of mitoses. Trisomy 12 was detected in 2 small intestine carcinoids, suggesting that +12 may be of pathogenetic importance in this tumor type. The breast and head-and-neck carcinomas and the uveal melanoma displayed aberrations previously reported as characteristic in primary tumors, e.g., der(1;16) and deletion of 3p in the breast cancer, losses of 3p and 8p and partial gain of 8q in the head-and-neck carcinoma, and monosomy 3 and i(8)(q10) in the uveal melanoma, indicating that cytogenetic investigations provide important diagnostic information in secondary liver tumors. In the 18 CRC metastases with chromosomal abnormalities, the cytogenetic findings agreed well with previously reported primary CRC. Common numerical abnormalities included gains of chromosomes 7, 11, 13, and 20, and losses of Y, 4, 18, 21, and 22. Structural rearrangements most often affected chromosome bands 1p13, 1q10, 3p21, 5q10, 5q11, 7q10, 8q10, 8q11, 12q13, 16p13, 17p11, 20p13, 20p11, and 20q10, and frequently resulted in losses of 1p, 8p, and 17p, and gains of 5p, 6p, 7p, 8q, and 20q. Comparing the present cases with primary CRC previously analyzed in our department revealed that additional gains of 6p, 6q, 7p, and 20q, and losses of 1p, 4p, 4q, 8p, 18p, 18q, and 22 were more common (P < 0.05) in the metastases, suggesting that these genomic sites harbor genes of importance in the metastatic process of CRC.

Adult↗
PubMed1999

Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig sertoli cells.

A large body of evidence suggests the existence of an intratesticular IGF system complete with ligands, receptors and binding proteins (IGFBPs); the aim of the present study was to evaluate tri-iodothyronine (T(3)) and retinoic acid (RA) effects on IGFBP production by Sertoli cells. A significant dose-dependent increase in IGFBP-4 mRNA levels was observed in Sertoli cells cultured in the presence of physiological concentrations of T(3) or RA. This response was inhibited by cycloheximide, indicating that de novo protein synthesis is required, as well as by actinomycin D, suggesting that the increase in mRNA levels requires transcriptional activation. As shown by ligand blot assays the stimulatory effects of both agents on IGFBP-4 mRNA expression appears to be consistent with an enhanced synthesis and secretion of IGFBP-4, thus suggesting that the transcriptional response is transduced to the protein level. Our data establish an important direct role for T(3) and RA in regulating IGFBP-4 expression and consequently IGF activity at the testis level.

Animals↗
PubMed1999

Bovine pericardial bioprosthesis in mitral position. A ten-year follow-up.

BACKGROUND: The pericardial bovine prosthesis Pericarbon should offer some advantages in comparison with the former generations, because its development is focused on solving previous problems and resulted in the variation of the pericardial fixation method, of valve structure and of stent coating. This hypothesis was evaluated through a retrospective follow-up. METHODS: Between 1985 and 1989, 78 Pericarbon prostheses O 29 were implanted in mitral position by the same surgeon. All patients received warfarin for the first three months to maintain an International Normalized Ratio between 2.5 and 3.5; after which they received antiaggregant therapy indefinitely. With an average follow-up period of 7.34 years for a total of 573 patient-years, we evaluated perioperative and late mortality, late morbidity (thromboembolic and haemorrhagic events, reoperations, primary tissue failures, endocarditic events) and patient clinical conditions. RESULTS: Perioperative mortality was 1.28% (1/78), late mortality was 11.6% (9/77) with 5 valve-related deaths. 5-year survival was 93% and 10-year survival 97%. Fifteen patients required reoperation for prosthetic replacement, fourteen for primary tissue failure. There were ten minor thromboembolic events, one major event, one haemorrhage and one prosthetic endocarditis (the last two with patient exitus). After 10 years (75% of patients were in New York Heart Association class I-II. CONCLUSIONS: Besides the known better haemodynamic performance, Pericarbon bioprosthesis seems to present a survival and redofreedom curve comparable to the best porcine prosthesis, with less incidence of endocarditis, thromboembolic events and prosthesis leakage.

Aged↗
PubMed1999

Presence and localization of molecules related to the cholinergic system in developing rat testis.

The presence of cholinergic molecules was recently found in male gametes of different animal species; very little is known from this point of view about the somatic component of the gonad. In the present study, a contribution is given to the localization of some cholinergic-like molecules, such as acetylcholinesterase (AChE), nicotinic acetylcholine and muscarinic acetylcoline (nAchR and mAChR, respectively) receptors during postnatal development of the testis. Maturation stages were checked by use of histochemical stainings, such as DAPI for nuclear shape changes, and PSA binding to reveal acrosomal maturation. The distribution of cholinergic-like molecules, revealed by immunocytochemical methods in both gametes and somatic cells, varied with development. Generally, during early stages, molecules immunologically related to AChE, and to mAChR's were mainly found in the interstitial and peritubular compartment, while, during maturation, they were found in Sertoli cells and in differentiating germ cells. nAChR's were not found in the somatic compartment, except in the blood vessel walls, and were distributed in mature germ cells, mainly in the flagella. The presence of cholinergic molecules in somatic as well as germ cells could play a role in cell-to-cell communications affecting testicular cell differentiation and function.

Acetylcholinesterase↗
PubMed1998

Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors.

The phenotypic progression of colorectal tumors is driven by their step-by-step acquisition of genomic alterations. These pathogenetically important mutations are at the same time markers of tumor clonality. The aim of this study was to describe the clonal relation among synchronous colorectal adenomas. Twenty-four colorectal adenomas from 11 patients were subjected to chromosome banding analysis. Clonal chromosome abnormalities were found in 20 tumors. Recurrent structural rearrangements involved chromosomes 1, 13, 17, and 18. The most common numerical changes were gain of chromosomes 7, 13, 20, and 3 and loss of chromosome 18. Eight adenomas had subclones as evidence of clonal evolution. Similar clones in separate polyps were seen in tumors from 6 patients; these adenomas were always located in the same part of the large bowel. In 2 patients, both with one rectal adenoma and one adenoma in the colon, no karyotypic similarity between the lesions was found. Our findings indicate that whereas close, but macroscopically distinct, synchronous colorectal adenomas usually have a common pathway of progression, perhaps even the same clonal origin, large bowel adenomas at a considerable distance from one another exhibit karyotypic differences, indicating that they arise independently.

Adenoma↗
PubMed1998

Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target region identified between DIS199 and DIS234.

Both cytogenetic and molecular genetic analyses have shown that many colorectal adenomas carry an acquired deletion distally in the short arm of one chromosome 1, but the two methods have never been brought to bear on the same tumors. The major part of this study was the analysis of 53 previously short-term cultured and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had cytogenetically visible abnormalities of chromosome 1, as well as in four adenomas that either had a normal karyotype (one case) or had clonal chromosome abnormalities that did not seem to involve chromosome 1 (three cases); i.e., 30% of the adenomas had abnormalities involving 1p by the combined approach. A minimal region of overlap seemed to map to between DIS199 and DIS234, suggesting that this is a relevant target region. This genomic area contains the human homologue of the tumor modifier gene Mom1 (1p35-36.1), which, in mice, modifies the number of intestinal tumors in multiple intestinal neoplasia (Min)-mutated animals. To evaluate whether the imbalances corresponded to interstitial deletions of 1p material, we performed fluorescence in situ hybridization with a pericentromeric probe (15 adenomas) and a telomeric probe (6 adenomas) on uncultured cells from the 16 adenomas with chromosome 1 abnormalities. Except for three adenomas that had already been shown by banding analysis to have a trisomic pattern, two centromere 1 signals were invariably found. In the cases hybridized with the 1p-telomeric probe, we found the same frequencies of telomeric and centromeric signals, in agreement with the interpretation that the deletions were interstitial. One of the 53 adenomas had genomic instability, seen as new alleles at five of eight microsatellite loci. A comparison of the genetic findings with clinicopathologic data indicated that adenomas in the rectum have 1p abnormalities more often than do adenomas of the sigmoid colon, and that adenomas with 1p changes are larger than adenomas without abnormalities of chromosome 1.

Adenoma↗
PubMed1998

Early and late risk factors in surgical treatment of acute type A aortic dissection.

BACKGROUND: Morbidity and mortality of emergency repair of type A dissecting aneurysms of the aorta are high. This is an attempt to investigate the risk determinants of early and late results. METHODS: A series of preoperative and operative variables were retrospectively collected from the clinical records of 291 patients operated on between January 1, 1979, and December 31, 1995. Risk factors for surgical death were investigated with univariate analysis and stepwise logistic regression. Follow-up was conducted between December 1995 and February 1996. Analysis of late results was conducted by means of actuarial survival curves (life method). After removing the surgical deaths, risk factors for late deaths were analyzed by a Cox model. RESULTS: The in-hospital mortality rate was 36.1%. Significant independent determinants of operative or early death were preoperative shock, preoperative neurologic impairment, operation before 1986, perioperative bleeding, and prolonged clamping time. The 10-year survival rate was 36.9% +/- 4.4%. Twenty-six patients required repeat operation. The long-term prognosis was significantly worse in patients who needed reoperation. CONCLUSIONS: Growing awareness of this disease and quicker diagnosis have increased the number of patients with acute dissection of the ascending aorta who are taken early to operation. This new challenge must be met by better preoperative support and intraoperative monitoring, and by surgical techniques that focus on lowering the rate of late complications, for which lifelong follow-up must be provided.

Adult↗
PubMed1998

Ornithine decarboxylase activity during development of cerebellar granule neurons.

Ornithine decarboxylase (ODC), the key enzyme for polyamine biosynthesis, dramatically decreases in activity during normal cerebellar development, in parallel with the progressive differentiation of granule neurons. We have studied whether a similar pattern is displayed by cerebellar granule neurons during survival and differentiation in culture. We report that when granule cells were kept in vitro under trophic conditions (high K+ concentration), ODC activity progressively decreased in parallel with neuronal differentiation. Under nontrophic conditions (cultures kept in low K+ concentration), the enzymatic activity dropped quickly in parallel with an increased apoptotic elimination of cells. Cultures kept in high K+ but chronically exposed to 10 mM lithium showed both an increased rate of apoptotic cell death at 2 and 4 days in vitro and a quicker drop of ODC activity and immunocytochemical staining. A short chronic treatment of rat pups with lithium also resulted in transient decrease of cerebellar ODC activity and increased programmed cell death, as revealed by in situ detection of apoptotic granule neurons. The present data indicate that a sustained ODC activity is associated with the phase of survival and differentiation of granule neurons and that, conversely, conditions that favor their apoptotic elimination are accompanied by a down-regulation of the enzymatic activity.

Animals↗
PubMed1998

Cytogenetic comparison of primary tumors and lymph node metastases in breast cancer patients.

Chromosome banding analysis of primary tumors and axillary lymph node metastases from 10 breast cancer patients revealed abnormal karyotypes in all samples with cytogenetic similarities between the primary tumor and the metastasis in all informative pairs. Although karyotypically unrelated clones were also found in the lymph node samples, they were less numerous than in the primary tumors, indicating that there was more genetic heterogeneity among the neoplastic cells in the primary than in the secondary tumors. On the other hand, some of the clones had become more complex in the metastases as a result of clonal evolution, and by and large these metastatic breast cancer cases had more karyotypic anomalies than do unselected primary breast carcinomas. Among the aberrations occurring more frequently, and that consequently may predispose to disease spread, were losses of chromosomes 17 and 22 and homogeneously staining regions, a cytogenetic sign of gene amplification.

Adult↗
PubMed1998

Direct stimulatory effects of insulin-like growth factor-I (IGF-I) on nuclear RNA polymerase II activity and overall protein synthesis in immature rat Sertoli cells.

A large body of evidence support the existence of an intratesticular Insulin-like Growth Factor I (IGF-I) system that can be viewed as a positive regulator of testicular functions. IGF-I may act at the testis level as a paracrine and autocrine differentiating factor. In the present study the role of IGF-I on Sertoli cell protein synthesis at transcriptional level has been investigated by evaluating the effect of IGF-I on nuclear RNA polymerase II activity as well as on total protein synthesis. Sertoli cells isolated from midpubertal rats and cultured in the presence of physiological doses of IGF-I showed a significant increase in nuclear RNA polymerase II activity (+80%) which appears to be correlated with a 50% increase in overall protein synthesis and a 40% increase in Androgen Binding Protein (ABP) production. These data provide the first evidence for a conceivable role of IGF-I in the modulation of Sertoli cell development through a direct action at the transcriptional level resulting in augmented protein synthesis.

Androgen-Binding Protein↗