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M Gentile

Publications and source records attributed to M Gentile.

At least 55 records · Page 3Linked to original sources
PubMed2003

Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases.

OBJECTIVE: To assess the accuracy of prenatal diagnosis, the incidence of extracardiac and chromosomal anomalies, and the perinatal outcome in a population of fetuses with common arterial trunk (CAT). DESIGN: Observational study of 23 fetuses from three referral centres with a confirmed diagnosis of CAT. All underwent fetal echocardiography, detailed anatomical scanning, and karyotyping. In 19 cases, FISH analysis was done to detect 22q11 microdeletion. The following variables were evaluated: gestational age at diagnosis, anatomical variants of the CAT, presence of extracardiac and chromosomal anomalies, pregnancy, and fetal-neonatal outcome. Necropsy reports and postnatal files were available for confirmation of the prenatal diagnosis in all cases. RESULTS: The prenatal diagnosis proved correct in 23 of 24 cases, the last being pulmonary atresia with ventricular septal defect (PAVSD). A second cardiovascular anomaly was present in eight cases (34.8%); extracardiac anomalies were found in 10 (43.4%). FISH analysis showed 22q11 microdeletion in six of 19 cases (31.6%). Outcomes were as follows: eight terminations of pregnancy (34.8%), two intrauterine deaths (8.7%), five postnatal deaths (before or after surgery) (21.7%); the remaining eight neonates (34.8%) are alive and thriving after surgery (six) or awaiting surgery (two). CONCLUSIONS: CAT can be reliably diagnosed and characterised in prenatal life, although differentiation from PAVSD may be challenging. The association with chromosomal anomalies is consistent (8.7%), but there is a higher risk of 22q11 microdeletion (31.6%), in agreement with postnatal studies. The relatively poor survival rate (34.8%) reflects the high rate of terminations and the unfavourable cardiac anatomy in some cases.

Aorta, Thoracic↗
PubMed2003

[So-called benign broncho-esophageal fistula].

Broncho-oesophageal fistulae are rare lesions and may be benign or malignant. The articles in medical literature generally concern one case of BEF, and rarely more cases. The term "benign" is debatable, considering the severity of this disease in view of the aetiology and the bronchopulmonary complications. The aetiology in the past was connected to tuberculosis or toxoplasmosis, now to bacterial, viral or fungal infections. The Authors report three acquired cases and one congenital. They confirm the importance of anamnesis, symptomatology and oesophagography for diagnosis and CT scan for detection of pulmonary lesions. The treatment is surgical with resection of fistula and suture of the oesophagus and bronchus, interposing pleura or pericardium or intercostal muscle.

Bronchial Fistula↗
PubMed2002

Pulmonary alveolar microlithiasis: clinical features, evolution of the phenotype, and review of the literature.

Pulmonary alveolar microlithiasis (PAM) (MIM 265100) is a rare, autosomal recessive pneumopathy characterized by intra-alveolar formation and accumulation of tiny, roundish corpuscles called "microliths". The name "alveolar microlithiasis" was first used by Puhr in 1933; since then, several reports have appeared, and over 300 individuals with this condition have been reported. We have reviewed the PAM cases in the literature in light of personal experience, focusing on medical implications, disease diagnosis and progression over time, familial predisposition, and geographical and sex distribution. This study confirms autosomal recessive inheritance and does not support the role of other, non-genetic, factors in the pathogenesis of PAM.

Adolescent↗
PubMed2002

Interrupted aortic arch type A with 22q11 deletion: prenatal detection of an unusual association.

Interrupted aortic arch is a rare, severe congenital heart defect subdivided into three types, A, B and C, according to the site of interruption. Type C is by far the least common form of interrupted aortic arch (less than 5% of cases), type A is commonly an isolated defect whereas type B is frequently associated with 22q11 deletion. Differentiation of interrupted aortic arch type A from type B by prenatal echocardiography is possible but difficult; it needs to be done on the basis of observation of reliable morphological indicators which point to the correct diagnosis. Here we report the first case of prenatal diagnosis of interrupted aortic arch type A associated with 22q11 deletion. The significance of this association is not yet clear, since 22q11 genes mainly affect embryonic cardiovascular morphogenesis of those regions whose development is critically dependent on neural crest cell migration and function, affected in type B defect but not in type A.

Adult↗
PubMed2002

Evaluation of risk of Parkinson's disease in a cohort of licensed pesticide users.

In the last two years, the environmental theory on the aetiology of Parkinson disease has acquired new data. From an experimental point of view, a new model of parkinsonism induced by rotenone, a diffuse insecticide, has been proposed, and in vitro studies have provided proof that several pesticides stimulate the formation of alpha-synuclein fibrils (one of the principal constituents of Lewy bodies). Moreover, a meta-analysis of all case-control studies so far performed showed a positive, statistically significant association between pesticide exposure and PD. In this context, we are performing a cohort study on 5575 licensed pesticide users in the province of Viterbo. After 27 years of follow-up, 4788 subjects are still alive. The aim of this study is to measure the prevalence of Parkinson's disease in a large group of workers with theoretically increased risk.

Cohort Studies↗
PubMed2002

Prenatal diagnosis of interruption of the aortic arch and its association with deletion of chromosome 22q11.

OBJECTIVES: Differentiation of interruption of the aortic arch (IAA) type A from type B by prenatal echocardiography is possible but difficult. We report nine consecutive cases of the prenatal detection of IAA and evaluate the feasibility of making a correct prenatal diagnosis with fetal echocardiography. The incidence of 22q11 microdeletion in our series, detected using fluorescent in situ hybridization (FISH) analysis, was determined. METHODS: Echocardiography and FISH for the DiGeorge critical region (22q11) were performed in all cases. The findings were confirmed by autopsy (three cases) or at postnatal surgery (six cases). RESULTS: On fetal echocardiography we identified six type B cases and three type A. FISH detected microdeletions in 22q11 in five of nine fetuses (four type B cases and an unusual association with type A in one case). CONCLUSIONS: Our report confirms the feasibility of making a correct prenatal diagnosis of IAA and its different types, based on echocardiographic examination. Furthermore our data are consistent with previous reports indicating that type A and type B are distinct entities. In more than 50% of fetuses with IAA type B, 22q11 microdeletion and DiGeorge or velo-cardio-facial syndromes may be expected. IAA type A is not commonly associated with 22q11 hemizygosity.

Aorta, Thoracic↗
PubMed2002

Prevalence of the E1317Q variant of the APC gene in Italian patients with colorectal adenomas.

Loss of APC is an initial, rate-limiting event in inherited and sporadic colorectal tumorigenesis. Rare germline APC mutations have been identified in patients with multiple colorectal adenomas. Recently, the E1317Q APC variant has been associated with a predisposition to the development of multiple colorectal adenomas. In this study, the prevalence of the E1317Q variant was examined in 182 patients with single or multiple colorectal adenomas, and in 235 controls. In all, E1317Q was identified in two of 182 patients with adenomatous polyps (1.1%) and in two of 235 controls (0.8%) (p = 0.59). The risk of harboring adenoma(s) among subjects bearing the E1317Q variant was 1.29 (95% CI 0.09-18.0). No difference in the prevalence of E1317Q between cases with single (2.0%) or multiple colorectal adenomas (0.7%) and controls (0.8%) was found. None of the subjects with a family history of colorectal cancer carried the E1317Q variant. In conclusion, our results confirm that only a very small fraction of colorectal adenomas may be associated with the presence of E1317Q.

Adenoma↗
PubMed2002

Molecular and cytogenetic characterization of an azoospermic male with a de-novo Y;14 translocation and alternate centromere inactivation.

BACKGROUND: Y-autosome (Y/A) translocations have been reported in association with male infertility. Different hypotheses have been made as to correlations between Y/A translocations and spermatogenetic disturbances. We describe an azoospermic patient with a de-novo Y;14 translocation: 45,X,dic(Y;14)(q12;p11). METHODS AND RESULTS: Cytogenetic, fluorescent in-situ hybridization (FISH) and molecular studies have been performed. A 14/22 (D14Z1/D22Z1) centromere and a Y centromere (DYZ1) probe both showed a signal on the translocation chromosome, confirming its dicentricity. Each copy of the translocation chromosome had only one primary constriction, with inactivation of the Y centromere in most (90%) of the cells. The 14 centromere was inactive in the remaining cells (10%). FISH and molecular deletion mapping analysis allowed acute assignment of the Yq breakpoint to the junction of euchromatin and heterochromatin (Yq12), distal to the AZF gene location (Yq11). CONCLUSIONS: This study supports the hypothesis that in Y/A translocations infertility might be related to meiotic disturbances with spermatogenetic arrest. In addition, sex chromosome molecular investigations, performed on single spermatids, suggest a highly increased risk of producing chromosomally abnormal embryos.

Adult↗
PubMed2001

Candidate tumour suppressor genes at 11q23-q24 in breast cancer: evidence of alterations in PIG8, a gene involved in p53-induced apoptosis.

One of the most consistently deleted chromosomal regions in solid tumours is 11q23-q25, which consequently has been postulated to harbour one or more tumour suppressor loci. Despite large efforts to identify the responsible genes, the goal remains elusive, but as knowledge accumulates new candidates are emerging. The present study was undertaken in an attempt to assess the possible implication of four genes residing at 11q23-q24, in a population of early onset breast cancer (n=41). The coding sequence of PIG8, CHK1, LOH11CR2A and PPP2R1B were screened for mutations using the protein truncation test or single-strand conformational polymorphism, in combination with direct DNA sequencing. Varying proportions of alterations were detected, ranging from 6% in PPP2R1B to 39% in PIG8. Many of these changes were deletions, in some cases corresponding to complete exons, thus likely to represent splice variants, while others were presumed to arise from aberrant splicing, since they occurred at sites with resemblance to exon/intron borders. Considering only bona fide mutations, the highest alteration frequency (17%) was again found in PIG8. Most of these alterations were likely to have an adverse impact on the translated protein as they either altered the reading frame or affected phylogenetically conserved residues. Our data represent the first evidence of alterations in the PIG8 gene in human malignancies, a finding that substantiates its role as a potential tumour suppressor gene as suggested by its involvement in p53-induced apoptosis.

Adult↗
PubMed2001

Sex chromosome loss, micronuclei, sister chromatid exchange and aging: a study including 16 centenarians.

In the present study we analysed the possible effect of age, sex and smoking on the mean values of micronucleus (MN) and sister chromatid exchange (SCE) frequencies on peripheral blood obtained from 38 subjects ranging in age from 16 to 63 years and 16 centenarians. The mean number of binucleated cells with micronuclei varied in function of age and sex (as demonstrated by the analysis of covariance (F=13.13; P<0.001), particularly evident was the increment observed in women with increasing age (interaction age/sex: F=5.53; P<0.05). Smoking habits had no effects on MN frequency (F=0.36; P>0.05). Sex (F=4.18; P<0.05) and smoking habits (F=14.64; P<0.001) influenced significantly SCE per cell frequencies, but age had no effects on them (F=2.45; P>0.05). The age-associated increase of sex chromosome loss was studied using fluorescence in situ hybridisation (FISH) on interphase nuclei. The loss of Y signals was observed in approximately 10% of interphase cells from the centenarians males, that is six times more often than in the younger control men (approximately 1.6%). The frequency of X signal loss (approximately 1.7%) in young women was similar to that observed in male controls of the same age but the incidence of the X chromosome aneuploidy in centenarian females was appreciably higher (approximately 22%) than that found for the Y chromosome in males. These results were correlated with the data on MN formation and a positive correlation between the percentage of aneuploid cells (FISH) and MN values was observed (r=0.50; P<0.05).

Adolescent↗
PubMed2001

Oestrogen receptors and microsatellite instability in colorectal carcinoma patients.

About 10-15% of sporadic colorectal cancers show microsatellite instability (MIN), a mutator phenotype of mismatch repair genes. It seems that oestrogens may inhibit the pathway to colorectal carcinoma which involves a mismatch repair deficiency. Oestrogen receptorial status was evaluated in the neoplastic tissue and uninvolved surrounding mucosa of 17 MIN-positive and 33 MIN-negative tumours using an immunoenzymatic assay. MIN status was examined using the polymerase chain reaction and specific microsatellite markers. MIN was significantly associated with very low levels of oestrogen receptor in tumour tissue. Our findings suggest that MIN-positive tumours might lose a possible oestrogenic modulation mechanism.

Adult↗
PubMed2001

p53 Mutations are present in colorectal cancer with cytoplasmic p53 accumulation.

Previous studies have shown that nuclear p53 over-expression is an indicator of p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be an independent prognostic factor in colorectal adenocarcinomas. The purpose was to examine whether mutations occur in cases with p53 accumulated in the cytoplasm and whether there are any differences in the frequency and characteristics of p53 mutations in different staining patterns. In the present study, we identified p53 mutations using PCR single-strand conformation polymorphism (SSCP) and DNA sequencing in 75 primary colorectal adenocarcinomas with different staining patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show that the frequency and nature of mutations in tumors with cytoplasmic p53 accumulation were similar to those with nuclear p53 expression. However, the tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher mutation rate. We suppose that the role of cytoplasmic p53 accumulation in predicting prognosis in patients with colorectal cancer may be dependent on both mutational and non-mutational mechanisms.

Biomarkers, Tumor↗
PubMed2001

Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer.

Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes.

Adult↗
PubMed2001

Histamine induces exocytosis and IL-6 production from human lung macrophages through interaction with H1 receptors.

Increasing evidence suggests that a continuous release of histamine from mast cells occurs in the airways of asthmatic patients and that histamine may modulate functions of other inflammatory cells such as macrophages. In the present study histamine (10(-9)-10(-6) M) increased in a concentration-dependent fashion the basal release of beta-glucuronidase (EC(50) = 8.2 +/- 3.5 x 10(-9) M) and IL-6 (EC(50) = 9.3 +/- 2.9 x 10(-8) M) from human lung macrophages. Enhancement of beta-glucuronidase release induced by histamine was evident after 30 min and peaked at 90 min, whereas that of IL-6 required 2-6 h of incubation. These effects were reproduced by the H(1) agonist (6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane carboxamide but not by the H(2) agonist dimaprit. Furthermore, histamine induced a concentration-dependent increase of intracellular Ca(2+) concentrations ([Ca(2+)](i)) that followed three types of response, one characterized by a rapid increase, a second in which [Ca(2+)](i) displays a slow but progressive increase, and a third characterized by an oscillatory pattern. Histamine-induced beta-glucuronidase and IL-6 release and [Ca(2+)](i) elevation were inhibited by the selective H(1) antagonist fexofenadine (10(-7)-10(-4) M), but not by the H(2) antagonist ranitidine. Inhibition of histamine-induced beta-glucuronidase and IL-6 release by fexofenadine was concentration dependent and displayed the characteristics of a competitive antagonism (K(d) = 89 nM). These data demonstrate that histamine induces exocytosis and IL-6 production from human macrophages by activating H(1) receptor and by increasing [Ca(2+)](i) and they suggest that histamine may play a relevant role in the long-term sustainment of allergic inflammation in the airways.

Calcium↗
PubMed2001

Nine novel APC mutations in Italian FAP patients.

Familial adenomatous polyposis (FAP) is a common hereditary syndrome characterized by early development of colorectal cancer consequent to extensive adenomatous polyps of the colon. In addition to the colonic manifestations the syndrome presents several extracolonic features including polyps of the upper gastrointestinal tract, congenital hypertrophy of the retinal pigment, jaw cysts, osteomata and desmoid tumors. In this study the entire APC coding region has been analysed for mutation in a panel of one Turcot and 33 unrelated Italian FAP patients using SSCP analysis, PTT and DNA sequencing. We detected APC mutations in 23 of them and identified nine which, to our knowledge were not previously reported. All of these novel mutations are in exon 15, including two nonsense mutations, 6 deletions or insertions leading to premature termination of the protein and one missense mutation (7697G>A). This last mutation occurs in the EB1-binding domain of the APC protein and segregates in four relatives of the patient with three of them presenting 2-3 adenomatous polyps.

Adenoma↗
PubMed2001

Nucleotide sequence variation of the VP7 gene of two G3-type rotaviruses isolated from dogs.

The sequence of the VP7 gene of two rotaviruses isolated from dogs in southern Italy was determined and the inferred amino acid sequence was compared with that of other rotavirus strains. There was very high nucleotide and amino acid identity between canine strain RV198/95 and other canine strains, and to the human strain HCR3A. Strain RV52/96, however, was found to have about 95% identity to the G3 serotype canine strains K9, A79-10 and CU-1 and 96% identity to strain RV198/95 and to the simian strain RRV. Therefore both of the canine strains belong to the G3 serotype. Nevertheless, detailed analysis of the VP7 variable regions revealed that RV52/96 possesses amino acid substitutions uncommon to the other canine isolates. In addition, strain RV52/96 exhibited a nucleotide divergence greater than 16% from all the other canine strains studied; however, it revealed the closest identity (90.4%) to the simian strain RRV. With only a few exceptions, phylogenetic analysis allowed clear differentiation of the G3 rotaviruses on the basis of the species of origin. The nucleotide and amino acid variations observed in strain RV52/96 could account for the existence of a canine rotavirus G3 sub-type.

Amino Acid Sequence↗