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Paola Francalanci

Publications and source records attributed to Paola Francalanci.

16 recordsLinked to original sources
PubMed2006

CD44-v6 expression in smooth muscle cells in the postnatal remodeling process of ductus arteriosus.

Closure of the ductus arteriosus (DA) is due to functional constriction followed by wall remodeling, with neointimal formation caused by proliferation and migration of smooth muscle cells (SMCs) from the media to subendothelium. CD44 is a surface cell proteoglycan family. Its isoform, CD44-v6, is only minimally expressed in SMCs in the media of normal arteries, but is highly expressed in SMCs in the intima and media of injured arteries (e.g., atherosclerosis). Twenty-two autopsy DA specimens, 11 from full-term babies (age range 2 days to 5 months) and 11 from premature babies (age range 3 days to 5 months), with varying degrees of ductal wall remodeling, were evaluated by immunohistochemistry using antiactin, antifibronectin-extradomain A, anti-leukocyte common antigen, anti-CD44, and anti-CD44-v6. In DA with wall remodeling, synthetic antifibronectin-extradomain A-positive SMCs were evident at the neointimal mounds, and the SMCs were highly positive for the CD44-v6 isoform, irrespective of gestational age at birth. Conversely, SMCs of either closed DAs or persistently patent DAs were CD44-v6 negative. In conclusion, the present data provide evidence that closure of DA involves synthetic SMCs highly positive for CD44-v6, and patent or closed DAs are populated by CD44-v6-negative SMCs.

Ductus Arteriosus↗
PubMed2006

A new ABCB11 mutation in two Italian children with familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) syndromes are characterized by defects in transporters of conjugated bile acids into the bile canaliculus. Three genes (ATP8B1, ABCB11, ABCB4) are associated with the different forms, but no easy genotype-phenotype correlations help in the prioritization for gene testing. We developed a denaturing high-performance liquid chromatography (DHPLC) method to screen patients with PFIC for mutations in ATP8B1 and ABCB11, and combined genetic analyses with immunolabeling in liver for the ABCB11 and ABCB4 gene products. Used in combination with commercially available antibodies on liver specimens, the DHPLC approach allowed us to confirm the clinical diagnosis in two Italian sisters and to identify a novel missesnse mutation in ABCB11. Our findings are expected to facilitate detection of the molecular cause of PFIC in affected families.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Cystitis glandularis in children.

OBJECTIVE: To assess the characteristics of cystitis glandularis in children. PATIENTS AND METHODS: Three cases of cystitis glandularis in children are described, occurring in boys aged 9-13 years. The presenting symptoms were gross haematuria in the first patient and frequency and urgency in the second. The third patient was asymptomatic and the lesion appeared as a wide thickening of the bladder wall on follow-up ultrasonography for previous surgery. In all patients, a polypoid bladder mass was found at cystoscopy and diagnosed at histology. The endoscopic resection, with long-term antibiotic prophylaxis, was the treatment of choice, with no recurrence at 12-30 months of follow-up. CONCLUSION: Cystitis glandularis has been rarely described in children, and is probably related to chronic or recurrent infections or an inflammatory reaction. Its potential premalignant significance is still the subject of debate.

Adolescent↗
PubMed2004

Cardiotropic viruses in the myocardium of children with end-stage heart disease.

BACKGROUND: Transplantation has become a lifesaving procedure for children with end-stage heart failure. The long-term outcome for children who undergo transplantation has been of considerable interest, but the causes of graft failure and death are largely unknown, and the role of pre-transplant viral infection is unclear. METHODS: Myocardial samples from 80 explanted hearts from children with end-stage heart disease caused by congenital heart disease (CHD), cardiomyopathy, or chronic rejection were analyzed using polymerase chain reaction and reverse-transcriptase polymerase chain reaction for cardiotropic viruses using virus-specific primers. We used immunohistochemical analysis of cytoskeletal proteins to evaluate myocyte architecture. RESULTS: We identified parvoviral genomes in 6 patients (3 with CHD and 3 with cardiomyopathy). We detected no other viruses. Immunohistochemistry showed normal staining for key components of the cytoskeleton/sarcolemma, sarcomere, and nuclear membrane in the 6 virus-positive samples. The clinical outcome of these children was worse (4 long-term survivors, but 2 deaths) than for individuals without the genome. CONCLUSIONS: Detecting viruses within the myocardium at the point of end-stage heart failure is not common, regardless of the primary pathology. However, the presence of viruses may result in poor outcome for the patient.

Child↗
PubMed2004

Microaspiration in infants with laryngomalacia.

OBJECTIVES/HYPOTHESIS: Laryngomalacia is the most common congenital laryngeal anomaly and the most frequent cause of stridor in infants. Infants with laryngomalacia may have associated respiratory symptoms other than stridor. In this study, we evaluated whether infants with laryngomalacia have episodes of microaspiration by calculating the amount of lipids present in the alveolar macrophages. STUDY DESIGN: We reviewed bronchoalveolar lavage (BAL) findings obtained in 14 infants with laryngomalacia and in 11 control children. METHODS: BAL was performed during flexible fiberoptic bronchoscopy (FFB) to diagnose persistent stridor. The presence of microaspiration was determined by evaluating the amount of lipid per single macrophage, assigning each cell a score from 0 to 4 according to the amount of lipid in the cytoplasm. RESULTS: The lipid-laden macrophage index was similar in patients and controls (31.5, range 12-177 vs. 45, range 35-106). In 5 of the 14 (36%) patients the index exceeded 100, and more than 25% of the cells were graded 3 and 4, indicating the presence of microaspiration. The lipid-laden macrophage index correlated significantly with the number and percentage of BAL neutrophils (Pearson correlation test, r = 0.83, P < .001 and r = 0.925, P < .001) as a marker of lung inflammation. CONCLUSIONS: Infants with laryngomalacia may have episodes of microaspiration. BAL performed during FFB to evaluate stridor may add helpful therapeutic information without increasing the risks of the procedure.

Bronchoalveolar Lavage Fluid↗
PubMed2003

Beta-catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts.

OBJECTIVE: To evaluate whether cardiomyocyte membrane structure and cell/extracellular matrix adhesion alterations perturb the cadherin/catenin complex in the hypertrophic cardiomyopathy (HCM). METHODS: Hypertrophic cardiomyopathic hamster (UM-X7.1 strain) and human hearts were studied by light and electron microscopy, Northern and Western blot analyses and immunohistochemistry. RESULTS: Intercalated disks are disorganized in both hamster and human cardiomyopathic hearts; beta-catenin is increased and accumulated in intercalated disks depriving cardiomyocyte nuclei of fundamental signals. The accumulation of beta-catenin is post-translationally regulated by an increased Wnt expression, a simultaneous decrease in glycogen synthase kinase 3beta (GSK3beta) expression and a different expression pattern of adenomatous polyposis coli (APC) isoforms. CONCLUSION: The reorganization of cell/cell adhesion in cardiomyopathic hearts is mainly contributed by the cadherin/catenin system, which is differently regulated to sustain cell structural rather than signalling needs causing considerable consequences in the determination of cardiomyocyte phenotype and clinical outcome. The accumulation of beta-catenin in intercalated disks could concur to increase myocardial wall stiffness and left ventricular end-diastolic pressure (LVEDP) in hypertrophic cardiomyopathic hamster and human hearts.

Animals↗
PubMed2003

Expression of the lipogenic enzyme fatty acid synthase (FAS) as a predictor of poor outcome in nephroblastoma: an interinstitutional study.

BACKGROUND: Treatment of nephroblastoma (Wilms tumor) has presently achieved a greater than 80% cure rate. Pathologic stage and grade are considered the most reliable prognostic parameters, but other biologic factors are under study in order to improve patient stratification into risk groups. Correlation of elevated levels of the lipogenic enzyme fatty acid synthase (FAS) with aggressiveness of some cancers has drawn attention to this enzyme as a possible marker of poor prognosis. PROCEDURE: To determine the predictive strength of FAS expression in Wilms tumor (with particular emphasis on intermediate risk, i.e., non anaplastic tumors, the vast majority of nephroblastomas), we evaluated immunostaining expression in archival specimens from 94 neoplasms. The degree of expression was correlated with stage, grade, clinical course and administration of prenephrectomy chemotherapy. RESULTS: Expression of FAS increased in anaplastic tumors (P = 0.043) and higher stages (P = 0.029). FAS expression correlated with OS and DFS at both univariate and multivariate analysis. Comparable results were obtained when analyzing the intermediate risk population separately. Pretreatment resulted in an increased FAS expression, without reaching significance level (P = 0.059). CONCLUSIONS: Expression of FAS might be an independent prognostic factor, particularly for intermediate-risk patients. The blockade of fatty acid synthesis by inhibition of FAS enzymatic function by means of metabolic analogues might prove a novel target pathway for the treatment of nephroblastoma.

Adolescent↗
PubMed2003

Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis.

Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.

Acid Phosphatase↗
PubMed2003

Malignant pancreatic endocrine tumor in a child with tuberous sclerosis.

Tuberous sclerosis complex (TSC) is an autosomal dominant condition whose signs and symptoms may vary from a few hypopigmented skin spots to epilepsy, severe mental retardation, and renal failure. The disease is caused by mutations in either TSC1 or TSC2 gene, at chromosome 9q34 and 16p13.3. Inactivation of both alleles at TSC1 or TSC2 loci is associated with the development of hamartomas in different organs, and only rarely with malignant neoplasms. In this study we present a 6-year-old boy with TSC and with a malignant islet cell tumor of the pancreas. Mutation analysis of DNA extracted from peripheral blood cells of the patient identified an R1459X de novo mutation in exon 33 of the TSC2 gene. Immunohistochemical analysis with anti-tuberin antibodies on paraffin-embedded tissue sections showed loss of tuberin immunostaining in tumor cells but normal expression in residual normal pancreas. DNA analysis of tumor and normal cells showed chromosome 16p13 loss of heterozygosity in malignant pancreatic islet cell tumor but not in normal pancreas. These findings suggest a role for tuberin, the TSC2 gene product, in the pathogenesis of malignant pancreatic endocrine tumor.

Carcinoma, Islet Cell↗
PubMed2002

Nephroblastoma: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells.

The development of chemoresistance in a variety of cancers seems related to overexpression of the P-glycoprotein (P-gp) drug pump. Nephroblastoma, the most common malignant renal tumor of childhood, usually is responsive to treatment, and prognosis is favorable in most cases. However, the disease in a subset of patients is refractory to treatment, and the disease follows an aggressive course. To study P-gp expression in this tumor and its correlation with outcome, tumor samples from 93 patients were examined by immunohistochemical analysis. P-gp expression was determined separately in both tumor cells and intratumoral capillary endothelium. The likelihood ratio test, the Kaplan-Meier method, and the log-rank test were used to evaluate its association with clinical course, grade, stage, and administration of preoperative chemotherapy. The results for the majority of nephroblastomas were variably positive; in 43 (46%) of them, newly formed capillary endothelial cells also stained positive. While no association of P-gp expression in tumor cells with clinical course, stage, and grade could be demonstrated, positivity in endothelial cells correlated significantly with unfavorable outcome, suggesting that chemoresistance depended on an active blood-tumor barrier. Previous chemotherapy induced P-gp overexpression in tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Cystic dysplasia of the rete testis: report of two cases and review of the literature.

Cystic dysplasia of the rete testis (CDT) is a rare congenital defect, characterized by multiple irregular cystic spaces in the mediastinum of the testis that may involve the whole gonad. A review of the literature has shown 32 reported cases, the majority of which were associated with ipsilateral renal malformations (agenesis/cystic dysplasia). Pathogenesis may be attributed to an early insult involving mesonephric duct development. Although treatment is surgical, when feasible, a conservative or nonoperative approach is suggested. Here we report two cases, one in a 3-year-old boy and one in a 10-day-old newborn. Concomitant cystic dysplasia of ipsilateral kidney was present in the former patient, while CDT was the solitary finding in the latter patient. Orchiectomy was performed in both patients, for extensive gonad involvement in the older boy and for suspected gonad torsion in the newborn patient.

Abnormalities, Multiple↗
PubMedDate not supplied

Pulmonary blastomas of childhood: histologic, immunohistochemical, ultrastructural aspects and therapeutic considerations.

Pulmonary blastomas are rare neoplasms typically occurring in patients of pediatric age, clinically characterized by fever, respiratory distress, and radiologic findings of a pulmonary cystic and/or solid mass with partial or complete obliteration of emithorax. Their behavior is aggressive and outcome is poor due to frequent relapses and metastases. The histological, immunohistochemical, and ultrastructural aspects of a personal series of 6 cases of pulmonary blastoma are described and the differences between childhood and adult types are stressed. Due to the aggressiveness of these rare tumors, therapeutic management is quite difficult. The expression of the transmembrane tyrosin kinase receptor c-kit in all the solid cases of this series leads the authors to hypothesize new possible therapeutic implications for these tumors.

Biomarkers, Tumor↗