Search PubMed⌕ Search

Biomedical subjects

F Mollica

Publications and source records attributed to F Mollica.

At least 19 recordsLinked to original sources
PubMed2005

An experimental and theoretical composite model of the human mandible.

The purpose is to design and manufacture a composite mandible replicate suitable for testing the influence of prosthetic materials on the stress distribution of bone. Composite mandibles made of a poly(methylmethacrylate) core and a glass reinforced outer shell are manufactured and characterised through mechanical tests assisted by the finite element analysis. The mandible replicate has been conveniently equipped with strain gauges, moreover a video extensometer has also been used in order to measure the arch width change during loading. A close agreement is found between the experimental data and the theoretical predictions. By laterally loading the mandibles the maximum values of stress and strain take place in the premolar-incisal region. By varying technological parameters such as the fiber volume fraction and orientation, it is easy to replicate the behaviour of mandibles having different stiffnesses. The results obtained by laterally loading the composite mandibles through the condyles or through the gonion regions are consistent with literature data relative to the arch width decrease of natural jaws during opening and closing. This novel synthetic system coupled with the Finite Element model constitutes an experimental-theoretical model suitable to investigate the biomechanical effects of oral rehabilitations on mandibular bone.

Humans↗
PubMed2003

The role of stress in the growth of a multicell spheroid.

Rather recent experimental results demonstrate the non-negligible role of mechanical stress in the growth of a multicell spheroid. In this paper we discuss a theoretical framework for volumetric growth suitable for modeling the growth of soft tissues exhibiting the properties of a solid. After a proper kinematic decomposition, balance equations for mass, momentum and energy are discussed together with constitutive relationships. The mathematical model is then applied to avascular tumor growth. We show by numerical simulation that, under assumption of spherical symmetry, the mathematical model is able to reproduce the experimental data with a satisfying qualitative agreement.

Algorithms↗
PubMed2003

Dynamic mechanical behavior of PMMA based bone cements in wet environment.

The mechanical properties of three wet commercial bone cements, namely Braxel (from Bioland), Simplex-P (from Howmedica) and CMW1-G (from DePuy) are investigated by means of stress relaxation and dynamic mechanical analysis (DMA). The geometry of loading that was used is the three point bending method (ASTM D790); all the tests were performed in a water chamber by means of temperature sweeps between 17 and 57 degrees C and spanning four frequency decades. The results show that viscoelastic properties are strongly dependent on specimen conditioning (i.e. water uptake and heat treatment). The results also show that all the cements that were analyzed show mechanical properties which are intermediate between the ones of the cancellous bone and of the metals of which prostheses are normally made. As a consequence, the cement is able to reduce the stress concentrations due to the interfacing of materials which have very different stiffnesses. Moreover, the results of the DMA, particularly the ones concerning the damping factor (tan delta), indicate that at body temperature the bone cements tested show an increased capacity of dissipation, the higher is the loading frequency, thus displaying shock absorbing properties.

Journal Article↗
PubMed2001

Genetic, andrological and clinical characteristics of patients with congenital bilateral absence of the vas deferens.

The possibility of retrieving spermatozoa from the epididymis allows patients with congenital bilateral absence of the vas deferens (CBAVD) to father a child by means of assisted reproduction techniques. This has, however, increased the chance of transmitting a mutated allele of the cystic fibrosis transmembrane conductance regulator (CFTR) gene which increases the risk of generating offspring with cystic fibrosis (CF). Because of the increased heterogeneity of the CFTR locus, the study of a discrete number of mutations, as usually carried out in a diagnostic work-up, is unable to ascertain the presence of a mutation in a relatively high proportion of the patients screened. In an attempt to increase the chance of detecting the presence of CFTR gene abnormalities, 37 patients with CBAVD and one patient with congenital unilateral agenesis of the vas deferens (CUAVD) underwent an enlarged diagnostic protocol, which included screening for the most expected mutations of the CFTR gene in our population, evaluation of the five thymidine (5T) allelic variant, sweat test, respiratory function tests, evaluation of steatocrit, and an accurate evaluation of the history of the patient to search for symptoms commonly found in patients with CF. A single CFTR gene mutation was found in 18 patients (48.6%) with CBAVD and in the patient with CUAVD. The most frequent mutation observed was the Delta F508. Eleven patients (45.8%) had the 5T variant and in five of them it was not associated with any detectable mutation of the CFTR gene. Two female partners were found to be carriers of a mutation, whereas 5 (18.5%) had the 5T variant. As many as 71% of CBVAD patients had the simultaneous presence of at least two signs and/or symptoms suggestive of CF, albeit they were of mild intensity and the patients felt fit and healthy. In conclusion, these results suggested that some patients with CBAVD without CFTR gene mutation or 5T variant, even when their sweat test is negative, may show clinical suspicion of carrying a CFTR gene mutation and therefore are at risk of generating children affected by CF if the partner carries a mutation as well. The screening for mutations and a careful clinical examination may contribute to better identification of patients with CFTR-related CBAVD.

Adult↗
PubMed1999

Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn.

OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood.

Adolescent↗
PubMed1999

Deletions in the mitochondrial DNA and decrease in the oxidative phosphorylation activity of children with Fanconi syndrome secondary to antiblastic therapy.

The aim of this study is to verify whether there are deletions in mitochondrial DNA (mtDNA) and disorders in oxidative phosphorylation (Ox-phos) complexes in the pathogenesis of secondary Fanconi syndrome (FS). We studied 18 children with tumors who were previously treated with chemotherapy and were off therapy for at least 1 year. All the children had normal renal function at diagnosis. Only 4 children received ifosfamide (IFO) and platinum compounds. We evaluated renal function, Ox-phos activity measured on platelets, and mtDNA extracted from platelets for all patients. Only 2 patients, both treated with IFO and carboplatinum (CARBO) for Wilms' tumor and germ-cell tumor, respectively, developed FS 1 and 3 years after termination of therapy. They had decreased activities of Ox-phos that were statistically significant only for nicotinamide adenine dinucleotide (NAD)-reduced cytochrome-c reductase and cytochrome-c oxidase and specific and unidentified deletions in mtDNA that were not maternally inherited. Our data suggest that treatment with IFO and CARBO might be responsible for deletions in mtDNA, decreased activity of Ox-phos, and impaired rates of transport of D-glucose, phosphate, and amino acids.

Antineoplastic Agents↗
PubMed1998

Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia.

This report identifies eight new mutations of the phenylalanine hydroxylase gene detected in Italian patients with hyperphenylalaninemia. The trivial name of the mutations, predicted phenotypic effect, and population of origin (Italian region) are as follows: F55L (nonconservative change: classic, moderate, mild PKU ?; Sicily), IVS2nt-13 (splicing defect, classic PKU; Tuscany), I65N (nonconservative change classic, moderate, mild PKU ?; Sicily), H201Y (non-PKU HPA; Sicily), I269L (non-PKU HPA, or polymorphism; Sicily), IVS7nt3 (splicing defect or polymorphism; Sicily), I283N (classic PKU; Sicily), IVS12nt2 (splicing defect, classic PKU; Sicily and Apulia). In Sicily, the relative frequency of mutations F55L, I65N, H201Y, I269L, IVS7nt3, I283N, IVS12nt2 is < 1%. The seven new mutations identified in the Sicilian population increase the remarkable genetic heterogeneity typical of this population with an estimated homozygosity value at the PAH locus of 0.041.

Adolescent↗
PubMed1998

Mutations in the EXT1 and EXT2 genes in hereditary multiple exostoses.

Hereditary multiple exostoses (EXT; MIM 133700) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors (exostoses). Besides suffering complications caused by the pressure of these exostoses on the surrounding tissues, EXT patients are at an increased risk for malignant chondrosarcoma, which may develop from an exostosis. EXT is genetically heterogeneous, and three loci have been identified so far: EXT1, on chromosome 8q23-q24; EXT2, on 11p11-p12; and EXT3, on the short arm of chromosome 19. The EXT1 and EXT2 genes were cloned recently, and they were shown to be homologous. We have now analyzed the EXT1 and EXT2 genes, in 26 EXT families originating from nine countries, to identify the underlying disease-causing mutation. Of the 26 families, 10 families had an EXT1 mutation, and 10 had an EXT2 mutation. Twelve of these mutations have never been described before. In addition, we have reviewed all EXT1 and EXT2 mutations reported so far, to determine the nature, frequency, and distribution of mutations that cause EXT. From this analysis, we conclude that mutations in either the EXT1 or the EXT2 gene are responsible for the majority of EXT cases. Most of the mutations in EXT1 and EXT2 cause premature termination of the EXT proteins, whereas missense mutations are rare. The development is thus mainly due to loss of function of the EXT genes, consistent with the hypothesis that the EXT genes have a tumor- suppressor function.

Chromosome Mapping↗
PubMed1998

Hyporesponsiveness to intradermal administration of hepatitis B vaccine in insulin dependent diabetes mellitus.

The immune response to intradermal or intramuscular hepatitis B vaccine in 18 children with insulin dependent diabetes mellitus (IDDM) compared with 24 healthy children was studied. Patients were divided into responders, hyporesponders, and non-responders according to their antihepatitis B serum concentrations after hepatitis B vaccination. We also studied HLA class II antigen distribution and did delayed type hypersensitivity (DTH) tests on children with IDDM and controls. No difference in the immune response (antihepatitis B surface antigen antibody titres) was found with intramuscular administration, whereas with intradermal administration a statistically lower immune response (p < 0.001) was observed in children with IDDM v controls. This hyporesponsiveness cannot be attributed to HLA class II antigen distribution because their frequency was the same in both groups of children with IDDM. It is suggested that the poor immune response to intradermal hepatitis B vaccine may be due to impaired macrophage activity resulting in failure of antigen presentation, which may be of importance in the immune dysfunction in children with IDDM. This hypothesis is suggested by a significantly lower score on a DTH test to a battery of antigens in the IDDM group when compared with controls. It is therefore suggested that when the hepatitis B vaccination is offered to children with IDDM it may be preferable to give it intramuscularly.

Adolescent↗
PubMed1997

Double partial trisomy 9q34.1-->qter and 21pter-->q22.11: FISH and clinical findings.

We describe a patient with double trisomy 9q34.1-->qter and 21pter-->q22.1 resulting from 3:1 segregation of a maternal balanced translocation. The patient shows a clinical syndrome similar to that observed in patients with duplication of the chromosome 9q distal region, while no signs of trisomy 21 were observed. The use of high resolution banding and FISH were of fundamental importance for the cytogenetic diagnosis and for definition of the breakpoints on both chromosomes 9 and 21.

Abnormalities, Multiple↗
PubMed1996

Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura.

Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient.

Adult↗
PubMed1996

Safety and effectiveness of an acellular pertussis vaccine in subjects with Down's syndrome.

We evaluated the reactogenicity and immunogenicity of an acellular pertussis vaccine in 24 subjects affected by Down's syndrome and in 10 normal infants. Neither general nor local adverse reactions were observed in either group of subjects. The new acellular vaccine administration elicited protective levels of antibodies in all the subjects with Down's syndrome, although the geometric mean titres of IgG antibodies against Bordetella pertussis in these subjects were significantly lower than in normal controls.

Antibody Formation↗
PubMed1996

PAH deficiency in Italy: correlation of genotype with phenotype in the Sicilian population.

The results of the neonatal screening for phenylalanine hydroxylase (PAH) deficiency in Sicily show that its incidence is higher than previously reported for mainland Italians and that non-PKU HPA is in excess of classical and mild PKU. The latter finding suggests that a high number of non-PKU HPA mutations would occur in the Sicilian population compared to populations with an inverted PKU/non-PKU HPA ratio. Previous studies have identified 40 mutations accounting for the majority (98%) of mutant alleles underlying PAH deficiency in Sicily. In order to study the molecular basis of the distribution of PAH deficiency phenotypes in the Sicilian population, we have correlated 31 of those mutations with clinical and metabolic phenotypes in 12 mentally retarded patients, 14 treated patients with classic or mild PKU, and 13 subjects presenting the non-PKU HPA phenotype. The present study proposes a tentative classification for a large number (26) of PAH gene mutations which may represent an additional tool for establishing a differential diagnosis for PAH deficiency in the Sicilian population.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Two novel partial deletions of LDL-receptor gene in Italian patients with familial hypercholesterolemia (FH Siracusa and FH Reggio Emilia).

In the present study we report two novel partial deletions of the LDL-R gene. The first (FH Siracusa), found in an FH-heterozygote, consists of a 20 kb deletion spanning from the 5' flanking region to the intron 2 of the LDL-receptor gene. The elimination of the promoter and the first two exons prevents the transcription of the deleted allele, as shown by Northern blot analysis of LDL-R mRNA isolated from the proband's fibroblasts. The second deletion (FH Reggio Emilia), which eliminates 11 nucleotides of exon 10, was also found in an FH heterozygote. The characterization of this deletion was made possible by a combination of techniques such as single strand conformation polymorphism (SSCP) analysis, direct sequence of exon 10 and cloning of the normal and deleted exon 10 from the proband's DNA. The 11 nt deletion occurs in a region of exon 10 which contains three triplets (CTG) and two four-nucleotides (CTGG) direct repeats. This structural feature might render this region more susceptible to a slipped mispairing during DNA duplication. Since this deletion causes a shift of the BamHI site at the 5' end of exon 10, a method has been devised for its rapid screening which is based on the PCR amplification of exon 10 followed by BamHI digestion. FH Reggio Emilia deletion produces a shift in the reading frame downstream from Lys458, leading to a sequence of 51 novel amino acids before the occurrence of a premature stop codon (truncated receptor). However, since RT-PCR failed to demonstrate the presence of the mutant LDL-R mRNA in proband fibroblasts, it is likely that the amount of truncated receptor produced in these cells is negligible.

Adult↗
PubMed1996

Routine clinical application of the FRAXA Pfu PCR assay: limits and utility.

Fragile X genotype is characterized by the excessive amplification of an unstable region of DNA: a trinucleotide repeat CGG of variable copy number present in the FRAXA locus. Methods based on polymerase chain reaction (PCR) amplification of the CGG repeat region could facilitate the development of a rapid screening assay. Unfortunately, amplification across CGG repeats can be inefficient and unreliable due to their 100% G + C base composition. The utility of the exonuclease-deficient Pfu polymerase for amplification and detection of the CGG repeats at the FRAXA locus has been reported. In the present study we analysed the utility of a Pfu PCR assay as a rapid initial screening method to rule out a diagnosis of fragile X syndrome in males with mental retardation. Affected males did not show any amplification products or a smear of amplification products between 350 and 550 bp. Only 10% of affected male samples did not show any amplification products, while the vast majority showed the amplification smear. The amplification smears represent a serious drawback of the method, since they cannot be distinguished from the amplification products of normal samples after separation in 1% agarose gel. Several modifications of the PCR conditions were attempted to eliminate this problem, but none was appropriate for clinical applications. However, the problem was easily solved by using a higher resolution electrophoretic system that allows a clear distinction of normal bands from pathological smears. We tested the specificity of the Pfu PCR assay, followed by an improved MetaPhor gel electrophoretic separation of PCR products, on 50 samples from normal males and 24 samples form affected males. The results showed that this method is a rapid, sensitive and specific assay for the exclusion of fragile X syndrome diagnosis in mentally retarded males.

DNA-Directed DNA Polymerase↗