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Biomedical subjects

A M Lavezzi

Publications and source records attributed to A M Lavezzi.

At least 19 recordsLinked to original sources
PubMed2006

Hypoplasia and neuronal immaturity of the hypoglossal nucleus in sudden infant death.

OBJECTIVE: To report the case of five month old female baby with a history of episodes of gastro-oesophageal reflux and pneumonia. Her sudden death offered a unique insight into the possible role of delayed neuronal maturation and hypoplasia of the hypoglossal nucleus in representing a likely morphological substrate of sudden death. METHODS: Morphometric analysis was carried out with an Image-Pro Plus Image analyser (Media Cybernetics) on both sides of the brain stem. RESULTS: Hypoplasia and neuronal immaturity of the hypoglossal nucleus were demonstrated, accompanied by hypoplasia of the arcuate nucleus. CONCLUSIONS: Much attention should be paid to the possible role of the hypoglossal nucleus in determining a lethal outcome in infancy through impairment of deglutition and subsequent recurrent episodes of pneumonia, and as a necropsy finding.

Adult↗
PubMed2005

Sudden infant death triggered by dive reflex.

The dive reflex is the reflex mechanism most frequently considered in the aetiopathogenesis of sudden infant death syndrome (SIDS). This seems to persist in human beings as an inheritance from diver birds and amphibians. It has been reported that washing the face with cold water or plunging into cold water can provoke cardiac deceleration through the intervention of the ambiguus and the vagal dorsal nuclei. This report describes a case of SIDS that offers a unique insight into the role of the dive reflex in determining a lethal outcome. Examination of the brainstem on serial sections revealed severe bilateral hypoplasia of the arcuate nucleus and gliosis of the other cardiorespiratory medullary nuclei. The coronary and cardiac conduction arteries presented early atherosclerotic lesions. The possible role of parental cigarette smoking in the pathogenesis of arcuate nucleus hypoplasia and early coronary atherosclerotic lesions is also discussed.

Brain Stem↗
PubMed2004

Autoptic examination in sudden infant death syndrome and sudden intrauterine unexpected death: proposal of a national law.

The autoptic procedures in sudden infant death syndrome (SIDS) and sudden intrauterine unexpected death (SIUD) victims requires an in-depth examination of the autonomic nervous system, central and peripheral, as well as of the cardiac conduction system. In these pathologies, our studies have identified frequent developmental abnormalities in the brain stem, particularly hypoplasia of the arcuate nucleus, and accessory atrioventricular pathways in the cardiac conduction system. The law 'Post-mortem Investigation on the SIDS and of Unexplained Late Fetal Death' designated the Institute of Pathology of Milan University as the National Reference Center. The objectives of this law include, in article 4, widespread informative and preventive campaigns and continuous formation of programs for medical personnel.

Autopsy↗
PubMed2003

Intimal preatherosclerotic thickening of the coronary arteries in human fetuses of smoker mothers.

BACKGROUND: Many studies have described the development of preatherosclerotic coronary artery lesions in infancy. The observations reported in the literature regarding the fetal origin of coronary artery lesions are rare and controversial. OBJECTIVES: To identify the features of preatherosclerotic coronary artery lesions in late fetal stillborns and the possible atherogenic role of maternal cigarette smoking. METHODS; We examined 22 stillborns (13 males and nine females), all of whom had died sine causa after the 32nd week of gestation. All underwent autopsy. Twelve of the mothers smoked over five cigarettes per day before and during the pregnancy. The four major epicardial coronary arteries were isolated along their whole length, embedded in paraffin and serially cut for histologic examination and immunohistochemical studies, particularly searching for the proliferating cell nuclear antigen and c-Fos expression. Alterations of chromosome 7 were also investigated by the fluorescence in situ hybridization technique. RESULTS: In over 50% of the fetuses, almost all from smoker mothers, multifocal structural alterations of coronary walls were evident. The smooth muscle cells (SMCs) presented loss of polarity, forming columns perpendicular to the axis of the media and infiltrating the subendothelial connective tissue. Increased amounts of mucoid ground substance were also observed in the subendothelial connective tissue. In all the cases with coronary alterations, study of the biological markers showed intense c-Fos positivity of the SMCs. CONCLUSIONS: Preatherosclerotic intimal alterations of the coronary arteries are already detectable in the prenatal period and are significantly associated with maternal cigarette smoking.

Actins↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

[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↗
PubMed1999

The prognostic value of cell proliferation in colorectal adenomas assessed with tritiated thymidine and anti-proliferating cell nuclear antigen.

We analyze the cell kinetics of colorectal adenomas by tritiated thymidine (3HTdR) autoradiographic method and anti-proliferating cell nuclear antigen (PCNA) antibodies. A total of 46 patients who underwent prior endoscopic polypectomy for colorectal adenomas were reevaluated by colonoscopy for 4 years. Thymidine labeling index (T-LI) in index adenomas ranged from 1.40 to 38.0% (median value: 10. 75%); PCNA labeling index (PCNA-LI) in index adenomas ranged from 0 to 27.0% (median value: 1.95%). Among the 46 patients studied, 16 developed recurrent adenomas (Group A) and 30 were free of recurrent adenomas (Group B). The T-LI and PCNA-LI comparisons between Groups A and B were statistically significant (p < 0.0001, chi2 test). These results demonstrate that T-LI and PCNA-LI in colorectal adenomas might be helpful to predict the development of metachronous adenomas and hence to plan the follow-up of patients with adenomatous polyps after polypectomy.

Adenomatous Polyps↗
PubMed1999

Proliferating cell nuclear antigen (PCNA) and apoptosis in hyperacute and acute myocardial infarction.

The aim of this study was to determine whether cell proliferation and/or apoptotic cell death occur in hyperacute and acute infarction. Proliferating cell nuclear antigen (PCNA) and apoptosis were investigated in ten autoptic hearts within a few hours of infarction and in three normal hearts as controls. The PCNA Labeling Index (PCNA-LI) ranged from 0 to 3.1 in hyperacute infarction (mean 1.38), from 0.3 to 4 in acute infarction (mean 2.04) and from 0 to 1.2 in controls (mean 0.7). Although the results were not statistically significant, PCNA-LI was higher in acute than in hyperacute myocardial infarctions; and it was higher in hyperacute infarctions than in controls. Regarding apoptosis, the Apoptotic Index (AI) in hyperacute infarctions ranged from 0.7 to 3 (mean 1.78), in acute infarctions from 0.9 to 5 (mean 3.24) and in controls from 0 to 0.4 (mean 0.1). The AI was significantly higher in hyperacute and acute infarctions than in controls (p < 0.05).

Aged↗
PubMed1999

Evidence for apoptosis in non-small cell lung carcinoma. Relationship with cell kinetics and prognosis.

OBJECTIVE: To investigate cell death via apoptosis in non-small cell lung carcinoma (NSCLC) and its correlation with proliferative indices and follow-up. STUDY DESIGN: In 38 cases of NSCLC (21 squamous cell carcinomas and 17 adenocarcinomas) we analyzed apoptosis by nuclear morphology and in situ DNA fragmentation end labeling and the cell kinetics by an autoradiographic method with tritiated thymidine and by immunohistochemistry with anti-proliferating cell nuclear antigen (anti-PCNA) antibodies. We also evaluated mitotic frequency. Apoptotic index (AI) was correlated with the thymidine and PCNA labeling indices (T-LI and PCNA-LI, respectively) and with the mitotic index. RESULTS: The percentage of proliferating cells (T-LI range, 0.1-20.1%; PCNA-LI range, 0-14.7%) was generally considerably higher than that of apoptotic cells (range, 0-8%) and of mitotic cells (range, 0.1-1%). Survival at six years was significantly higher in patients with high levels of apoptosis and low T-LI values. CONCLUSION: AI and T-LI are independent and very useful prognostic factors in NSCLC. A high percentage of proliferating cells in terms of T-LI correlates with poor prognosis, whereas a high AI indicates a favorable outcome.

Adenocarcinoma↗
PubMed1998

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↗
PubMed1997

Significance of the DNA synthesis in hypertrophic cardiomyopathies.

DNA content and proliferating cell nuclear antigen (PCNA) expression were investigated in normal hearts, in hypertrophic from hemodynamic overload hearts and in hypertrophic cardiomyopathy (HCM). The aim of this study was mainly to determine whether the hyperdiploid myocardial cells in all cases are in dynamic or static phase. The percentage of PCNA positive cells only in the HCM group was significantly higher (mean value = 25.4%) than the percentage of hyperdiploid cells (mean value = 9.3%). Therefore, the DNA replication occurs through a different process from that of normal cell cycle which lead to an increase in ploidy and eventually mitosis. These data should be interpreted not only as the result of a periodic amitotic DNA renewal and not even as the result of an increased apoptosis, but especially as a repair process of the DNA molecules affected by a various types of damages in HCMs.

Adult↗
PubMed1997

DNA content and thymidine labeling index correlate with prognosis in squamous cell carcinoma of the larynx.

The prognostic value of proliferative activity was determined in 48 cases of squamous cell carcinoma of the larynx. Tumor samples were obtained during surgery: DNA content was determined by static cytometry with an image analysis program, and cell kinetics were analyzed by the in vitro thymidine labeling index (T-LI). The DNA content analysis visualized a diploid cellular population in 32 cases and an aneuploid cellular population in 16 cases. The DNA content was not significantly related to the sex and the age of the patients or the TN stage of the tumors, but to histological grade (p = 0.03). Similarly significant correlation was found between T-LI and age of the patients, indeed the median value was higher in patients older than 59 (p = 0.024). T-LI was not related to the sex of the patients, or to the histological grade or the TN stage of the tumors. In multivariate analysis, using the Cox model, T-LI was the most important prognostic parameter (p = 0.015), superior to DNA content (p = 0.021) and to TN stage (p = 0.047; p = 0.043). From the data obtained in this study it can be concluded that evaluation of DNA content and thymidine labeling index in squamous cell carcinoma of the larynx may be new independent parameters of prognosis and may contribute to optimal and individualized therapy.

Adult↗
PubMed1997

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↗
PubMed1997

Thymidine labeling index in colorectal carcinoma: relation to clinicopathological parameters and to mitotic index.

Two cell-kinetic parameters, the thymidine labeling index (T-LI) and the mitotic index (MI) were determined for a prospective series of 74 primary colorectal cancers. Dukes' stages were used to define the extent of the tumor: 10 tumors were classified as Dukes' A, 36 as Dukes' B, and 22 as Dukes' C. Of these tumors, 14 were well-differentiated, 44 moderately differentiated, and 15 poorly differentiated adenocarcinomas. The H3dT-LI values obtained varied widely, from 2.5 to 38.9% (median value: 16.8%). The MI shows a range of from 0 to 13.2% with a median value of 3.2%. The T-LI values were independent of the sex and age of the patients and of the histological grading and Dukes' stage. Conversely, the MI was related to histological grading. This study indicates that the T-LI, whose application has reached the gold standard, still represents an independent parameter and the most sensible, objective, and specific complementary method for the analysis of the S phase.

Adult↗
PubMed1996

Cell kinetics of pleomorphic adenomas of the parotid gland.

The aim of the present study is to characterise the cell kinetics of pleomorphic adenoma of the parotid gland by assessing DNA content and proliferating cell nuclear antigen (PCNA) positivity. In 22 parotid adenomas, DNA content was measured by densitometry in histological serial sections stained with Feulgen's method and PCNA positivity was determined by immunohistochemistry with the monoclonal antibody PC10. To assess the proliferative activity, DNA index and PCNA index were evaluated. It was possible to distinguish two types of adenoma. In Group I there was a prevalence of diploid cells with a low PCNA index. Group II is represented by adenomas with a large percentage of triploid cells and a PCNA index significantly higher than that of Group I. Our findings suggest that the possibility of recurrence or malignant transformation depends on intrinsic biological properties of each adenoma.

Adenoma, Pleomorphic↗