Biomedical subjects

M Mantelli

Publications and source records attributed to M Mantelli.

8 recordsLinked to original sources

PubMed2005

Protein-surface interactions: an energy-based mathematical model.

This article describes an energy-based approach to protein adsorption, focusing on the energies involved in the interactions between a protein and a surface. Mathematical modeling and simulation based on this approach allow an improved understanding of the conditions that favor or prevent adsorption of a protein onto a surface and that can play a significant role in the design of material surfaces that interact with biological tissues according to specific needs. Biocompatibility with respect to fluids in motion, such as blood, is the main foreseeable application of our work. The considered energies are the van der Waals energy, the electrostatic energy, and the hydrophobic or hydrophilic energy. Moreover, the motion of the medium in which particles are immersed is also taken into account, considering the drag effect of the motion of the fluid on the particle, leading to a kinetic contribution to the total energy. It is shown that the adsorption behavior is not mainly determined by the van der Waals energy and by the double layer energy, but that a significant role is also played by the hydrophobic or hydrophilic energy. These results support the findings of experimental studies.

Adsorption↗

PubMed2000

A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families.

Germline mutations within the coding region of CDKN2A have been observed in affected members of melanoma-prone families. G101W is the most common CDKN2A missense mutation identified to date. It has been reported in several families from around the world, with a particularly high occurrence in France and Italy. Given the frequency of this mutation, we were interested in determining whether the mutation resulted from a single origin or represented a mutational hotspot in the CDKN2A gene. In addition, given the geographical distribution of the mutation, we examined the date of origination of the mutation and its migratory spread. We examined 10 families from Italy, 4 families from the United States, and 6 families from France with the G101W mutation. The following eight markers were employed for the haplotype analysis: IFNA, D9S736, D9S1749, D9S942, D9S1748, D9S1604, D9S171, and D9S126. Our findings showed no significant evidence for mutational heterogeneity, suggesting that all studied families derived from a single ancestral haplotype on which the mutation arose. Using maximum-likelihood methods, we estimated the mutation to have arisen 97 generations ago (1-LOD-unit support interval 70-133 generations) providing some explanation for the wide geographical spread of this common mutation, particularly in southwestern Europe. The presence of a founder mutation in a defined geographic area can facilitate carrier detection and genetic counseling and can provide an opportunity to study disease penetrance and the effect of environmental factors on the background of a common genetic susceptibility.

Amino Acid Substitution↗

PubMed2000

Mutation screening of the CDKN2A promoter in melanoma families.

Germline mutations of CDKN2A, at 9p21, are responsible for predisposition to melanoma in some families. However, evidence of linkage to 9p21 has been demonstrated in a significant proportion of kindreds with no detectable mutations in CDKN2A. It is possible that mutations in noncoding regions may be responsible for predisposition to melanoma in these families. We have analyzed approximately 1 kb of the CDKN2A promoter upstream of the start codon in an attempt to identify causal mutations in 107 melanoma families. Four sequence variants were detected. Two of these (A-191G and A-493T) did not segregate with disease and were present in a control population at a comparable frequency, indicating that they are unlikely to predispose to melanoma. The A-493T variant appeared to be in linkage disequilibrium with the previously described CDKN2A polymorphism Ala148Thr. The variant G-735A was detected in the control population, but segregation of this variant with melanoma within families could not be discounted. The fourth variant (G-34T), located in the 5' UTR, creates an aberrant initiation codon. This variant appeared to segregate with melanoma and was not detected in a control population. G-34T has recently been identified in a subset of Canadian melanoma families and was concluded to be associated with predisposition to melanoma. The creation of an aberrant initiation site in the 5' UTR may have an important role in carcinogenesis in a small percentage of families; however, mutations in the CDKN2A promoter appear to have a limited role in predisposition to melanoma.

Adolescent↗

PubMed1999

Characterization of ligurian melanoma families and risk of occurrence of other neoplasia.

Germline mutations impairing the p16(INK4)-function have previously been demonstrated to be responsible for genetic predisposition in at least one half of melanoma-prone kindreds of North European origin. Familial melanoma kindreds have also been found to present an increased risk of pancreatic cancer and other cancers, but results relative to more common neoplasias incidence, in particular, are heterogeneous. We report here a clinical-epidemiological study, including the presence of additional neoplasias, in 14 apparently unrelated kindreds coming from a small geographic region of Northern Italy (Liguria), having therefore lived for generations in similar environmental conditions. We identified the common p16 missense mutation (Gly101Trp) reported in several previously studied kindreds, in 7 of 14 families, whereas the remaining 7 families had no detectable mutations in the coding region of p16 gene. Median age at diagnosis and other melanoma features were studied. When compared with the expected figures, based on regional incidence rates, a significant excess of pancreatic cancer, with 4 cases diagnosed, and of breast cancer, with 7 cases, was observed. The 7 families without apparent CDKN2A involvement were also negative for hot-spot exon 2 mutation of CDK4. Environmental factors do not appear to play a role in the excess of non-melanoma neoplasia in our families, as somewhat substantiated by the control group, composed of spouses and members of non-affected branches; they do not reveal any increased cancer incidence compared with the general population. Furthermore, given the proven significance of interaction between the melanoma susceptibility gene and the propensity to sunburns and other environmental risk factors, our results, obtained from a small but homogeneous sample, may have important implications for further risk assessment studies.

Adolescent↗

PubMed1999

Computer modelling of the adsorption of proteins on solid surfaces under the influence of double layer and van der Waals energy.

The study of protein interactions with surfaces is important in many branches of biomedical engineering. A computer model has been set up in order to aid the understanding and prediction of the likelihood of protein adsorption at a surface and of coagulation between two proteins. In this model, a protein is represented as a hard sphere, neglecting conformation changes which may occur during the adsorption process. The sphere is assumed to be in a medium whose properties are described by the ionic strength, the pH and the dielectric permittivity. It is considered to interact both with an infinite plane, representing the surface, and with another sphere, representing another protein. The model focuses on the total interaction energy between a protein and a surface and between two proteins. The energy is expressed according to the DLVO theory of colloidal stability, which assumes that the adsorption behaviour of proteins at a surface depends, first, on the van der Waals interactions energy and, second, on the electrostatic double layer interaction energy. The conditions under which adhesion is prevented correspond to the presence of local extremes of the energy function, whereas the conditions under which adhesion is likely to take place correspond to absence of local extremes.

Adsorption↗

PubMed1997

c-Rel and p65 subunits bind to an upstream NF-kappaB site in human granulocyte macrophage-colony stimulating factor promoter involved in phorbol ester response in 5637 cells.

To further clarify the complex transcriptional regulation of the human GM-CSF gene, which was extensively investigated in activated T cells, we have studied the role of an upstream NF-kappaB like site in the 5637 non-lymphoid cell line, which derives from a bladder carcinoma and constitutively produces GM-CSF. This sequence, named the A element, has an active role on GM-CSF transcription and is responsive to the tumor promoter PMA in transient transfection experiments. We describe here a heterodimeric binding complex of NF-kappaB subunits (c-Rel and p65) which is identical to the one obtained using the HIV-LTR-kappaB site as recognition sequence and different from the one (c-Rel and p50) observed with nuclear extracts from Mo T-lymphoid HTLV-II infected cells.

Cell Nucleus↗

PubMed1993

[Validity of transrectal ultrasonography and echo-guided biopsy in the early diagnosis of prostatic neoplasms. Our experience on 100 cases].

100 patients from age 50 to 80 that presented urinary obstructive symptoms were studied with digital examination and with TR ultrasound; only 10 were palpably suspicious for prostatic carcinoma, the rest had a BPH. These 10 patients and 32 of the remaining revealed an abnormal area with ultrasound. 6 of the 10 palpably suspicious patients had prostatic carcinoma (60%). 8 of the 32 remaining patients had prostatic carcinoma (25%). Therefore of the 14 prostatic carcinoma 6 were of palpably positive patients, and 8 were of palpably negative patients. We suggest with this work that transrectal ultrasound is a useful technique in the early diagnosis and in the follow-up of prostatic nodules, and it is a necessary support in the decision for effecting echo-guided biopsy.

Aged↗

PubMed1991

Effect and pharmacokinetics of netilmicin given as bolus intramuscular administration: an open comparative trial versus amikacin and fosfomycin in elderly patients affected by urinary tract infections.

A randomized comparative open clinical trial was performed on 96 hospitalized patients of both sexes, most of whom (84.4%) over 60 years of age, affected by simple and complicated urinary tract infections. Patients were divided in three unequal sized groups and treated with a single administration of netilmicin (5 mg/kg intramuscularly), of amikacin (15 mg/kg i.m.) or of fosfomycin (3 g per os). Patients were evaluated clinically and microbiologically before the beginning of the therapy, 1, 7, 15, 30 days thereafter and at monthly intervals, up to the 18th month, after the drug administration. The pharmacokinetic study was performed in six elderly patients of both sexes, apparently in good general health, except for their urinary tract infections. Symptoms of urinary tract infection disappeared in 50 out of 53 (94.3%) patients treated with netilmicin 14.48 +/- 9.6 hours after the drug administration, in 22 out of 23 (95.6%) of those treated with amikacin after 31.9 +/- 14.3 hours and in 16 (84.2%) out of 19 of symptomatic patients treated with fosfomycin after 37.5 +/- 10.6 hours. The disappearance of symptoms in netilmicin-treated patients is significantly (p less than 0.01) faster than in the other two groups. Twenty-four hours after the administration, netilmicin and amikacin produced sterilization of the cultures in more than 95% of cases, fosfomycin in 90%. Of those patients in which sterilization of cultures was achieved about 70%, in the netilmicin group, and 50% in the other two treatment groups had sterile urine cultures after one month. At the end of the study, 18 months later, more than 60% of the patients treated with netilmicin, the infection had not recurred in comparison with 39.1% and 50% in the amikacin and fosfomycin groups respectively. If only the patients with uncomplicated infections were considered, 88.9% and 83.3% had sterile cultures after 1 and 18 months respectively in the netilmicin group. The corresponding figures in other two groups were: 66.7% for both time intervals in the case of amikacin and 60% both for 1 and 18 months in the case of fosfomycin. The pharmacokinetic results indicate that netilmicin is rapidly absorbed and distributed from the injection site, possesses a beta half-life of about two hours and is mainly excreted by the kidneys. The single dose administration produces very high urinary concentrations of the drug in the first 24 hours and concentrations above 4 micrograms/ml, the 90% minimum inhibitory concentration cut-off point for netilmicin sensitive strains, for four days(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗