PubMed Health⌕ Search

Biomedical subjects

C Clementi

Publications and source records attributed to C Clementi.

18 recordsLinked to original sources
PubMed2005

In situ fluorimetry: a powerful non-invasive diagnostic technique for natural dyes used in artefacts Part I. Spectral characterization of orcein in solution, on silk and wool laboratory-standards and a fragment of Renaissance tapestry.

In this paper the potentialities of spectrophotometric and fluorimetric techniques for identifying the materials used in artistic textiles are investigated. A portable non-destructive instrument suitable to record fluorescence spectra on surfaces was set up and successfully experienced. A naturally occurring dye, orcein, which was widely used in antiquity for textile dyeing, has been spectrally characterized in both solution and powder. Laboratory samples of wool and silk orcein-dyed threads were analysed before and after ageing. An original fragment of Renaissance tapestry was also analysed. The textile (wool) and the colourant (orcein) were recognised by comparison with the data from the laboratory samples.

Animals↗
PubMed2001

Prediction of folding mechanism for circular-permuted proteins.

Recent theoretical and experimental studies have suggested that real proteins have sequences with sufficiently small energetic frustration that topological effects are central in determining the folding mechanism. A particularly interesting and challenging framework for exploring and testing the viability of these energetically unfrustrated models is the study of circular-permuted proteins. Here we present the results of the application of a topology-based model to the study of circular permuted SH3 and CI2, in comparison with the available experimental results. The folding mechanism of the permuted proteins emerging from our simulations is in very good agreement with the experimental observations. The differences between the folding mechanisms of the permuted and wild-type proteins seem then to be strongly related to the change in the native state topology.

Binding Sites↗
PubMed2000

How native-state topology affects the folding of dihydrofolate reductase and interleukin-1beta.

The overall structure of the transition-state and intermediate ensembles observed experimentally for dihydrofolate reductase and interleukin-1beta can be obtained by using simplified models that have almost no energetic frustration. The predictive power of these models suggests that, even for these very large proteins with completely different folding mechanisms and functions, real protein sequences are sufficiently well designed, and much of the structural heterogeneity observed in the intermediates and the transition-state ensembles is determined by topological effects.

Bacterial Proteins↗
PubMed2000

Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins.

Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small, fast-folding proteins. To investigate the extent of the topological control of the folding process, we studied the folding of simplified models of five small globular proteins constructed using a Go-like potential to retain the information about the native structures but drastically reduce the energetic frustration and energetic heterogeneity among residue-residue native interactions. By comparing the structure of the transition state ensemble (experimentally determined by Phi-values) and of the intermediates with those obtained using our models, we show that these energetically unfrustrated models can reproduce the global experimentally known features of the transition state ensembles and "en-route" intermediates, at least for the analyzed proteins. This result clearly indicates that, as long as the protein sequence is sufficiently minimally frustrated, topology plays a central role in determining the folding mechanism.

Bacterial Proteins↗
PubMed2000

Hamiltonian dynamics and geometry of phase transitions in classical XY models

The Hamiltonian dynamics associated with classical, planar, Heisenberg XY models is investigated for two- and three-dimensional lattices. In addition to the conventional signatures of phase transitions, here obtained through time averages of thermodynamical observables in place of ensemble averages, qualitatively different information is derived from the temperature dependence of Lyapunov exponents. A Riemannian geometrization of Newtonian dynamics suggests consideration of other observables of geometric meaning tightly related to the largest Lyapunov exponent. The numerical computation of these observables--unusual in the study of phase transitions--sheds light on the microscopic dynamical counterpart of thermodynamics, also pointing to the existence of some major change in the geometry of the mechanical manifolds at the thermodynamical transition. Through the microcanonical definition of the entropy, a relationship between thermodynamics and the extrinsic geometry of the constant energy surfaces sigma E of phase space can be naturally established. In this framework, an approximate formula is worked out determining a highly nontrivial relationship between temperature and topology of sigma E. From this it can be understood that the appearance of a phase transition must be tightly related to a suitable major topology change of sigma E. This contributes to the understanding of the origin of phase transitions in the microcanonical ensemble.

Journal Article↗
PubMed1999

Folding Lennard-Jones proteins by a contact potential.

We studied the possibility to approximate a Lennard-Jones interaction by a pairwise contact potential. First we used a Lennard-Jones potential to design off-lattice, protein-like heteropolymer sequences, whose lowest energy (native) conformations were then identified by molecular dynamics. Then we turned to investigate whether one can find a pairwise contact potential, whose ground states are the contact maps associated with these native conformations. We show that such a requirement cannot be satisfied exactly, i.e., no such contact parameters exist. Nevertheless, we found that one can find contact energy parameters for which an energy minimization procedure, acting in the space of contact maps, yields maps whose corresponding structures are close to the native ones. Finally, we show that when these structures are used as the initial point of a molecular dynamics energy minimization process, the correct native folds are recovered with high probability.

Drug Design↗
PubMed1999

Protein design is a key factor for subunit-subunit association.

Fundamental questions about role of the quaternary structures are addressed by using a statistical mechanics off-lattice model of a dimer protein. The model, in spite of its simplicity, captures key features of the monomer-monomer interactions revealed by atomic force experiments. Force curves during association and dissociation processes are characterized by sudden jumps followed by smooth behavior and form hysteresis loops. Furthermore, the process is reversible in a finite range of temperature stabilizing the dimer, and the width of the hysteresis loop increases as the design procedure improves: i.e., stabilizes the dimer more. It is shown that, in the interface between the two monomeric subunits, the design procedure naturally favors those amino acids whose mutual interaction is stronger.

Dimerization↗
PubMed1995

Hepatitis C virus RNA in peripheral blood mononuclear cells: relation with response to interferon treatment.

The polymerase chain reaction (PCR) was used to investigate the presence of positive and negative hepatitis C virus (HCV) RNA strands in serum and peripheral blood mononuclear cells (PBMC) of 20 patients with histologically proven HCV-related chronic liver disease. All patients completed a course of interferon (IFN) treatment (6 MU of IFN-alpha 2b three times a week for 24 weeks) and were followed-up for 12 months after treatment was discontinued. Pre-treatment, end-treatment and 6-month follow-up serum and PBMC samples were examined. At enrollment, the positive strand of HCV-RNA was detected in serum of 18 patients (90%), the negative strand in none. Positive-stranded HCV-RNA was detected in PBMC of 15 patients (75%), 13 of whom also had detectable levels of negative-stranded HCV-RNA in PBMC. By the end of the treatment, 12 patients (60%) were responders. The pre-treatment HCV infection of PBMC, indicated by the presence of both RNA strands, was found in 8 (66.7%) responders compared to 5 (62.5%) non-responders (P = n.s.). End-treatment loss of PBMC HCV-RNA correlated significantly with the response since it occurred in all responders compared to 2 non-responders (P = 0.02). However, end-treatment-negative serum and PBMC HCV-RNA did not predict the occurrence of a sustained response, which was observed at month 12 in 5 of 12 responders (P = n.s.). On the other hand, the persistent absence of HCV RNA in serum and PBMC at the end of the 6-month follow-up was significantly associated with the occurrence of a sustained response (P < 0.0001).

Adult↗
PubMed1995

High prevalence of hepatitis C virus infection in a small central Italian town: lack of evidence of parenteral exposure.

In the spring of 1994, anti-HCV prevalence and associated risk factors were evaluated in 681 subjects representing all age-groups in the general population of a small central Italian town. The overall anti-HCV prevalence was 8.4%, ranging from 3.7% in the 30-39 age-group to 18.2% (p < 0.01) in the 60-70 age-group; no subject below 30 years of age was positive. Multiple logistic regression analysis showed that the only variables independently associated with anti-HCV positivity were awareness of unspecified liver disease (O.R. 3.58), age > 45 years (O.R. 2.72), and lowest number of years of schooling (O.R. 11.0) while no association was found with any parenteral exposure such as blood transfusion, intravenous drug use, major or minor surgical intervention, use of glass syringes or dental therapy. The HBsAg prevalence in this population was 1.3%, which corresponds to the rate reported in central Italy. These findings show a high level of HCV endemicity, with no evidence of parenteral exposure.

Adolescent↗
PubMed1993

Isolate antibody to hepatitis C virus core antigen (C22) by RIBA-2: correlation with HCV-RNA and anti-NS5.

The presence of circulating hepatitis C virus genome (HCV-RNA), elevated ALT levels and antibodies to an NS5-derived synthetic peptide have been examined in 13 subjects with isolate positivity for antibodies to the HCV core antigen (C22) on RIBA-2 testing. All subjects were followed up for 8-18 months (mean 12.4 months). In seven subjects (54%), intermittent or persistent viremia was associated with abnormal ALT levels (6 subjects) and with positivity for antibodies to NS5-peptide (6 subjects). On the other hand, in 6 out of 13 subjects (46%) no viral replication, no liver cytonecrosis and no antibodies to NS5 were found. It is concluded that isolate reactivity to C22 by RIBA-2 is a heterogeneous condition that corresponds to two distinct categories of subjects: those with active HCV infection and those without evidence of virus replication. Although HCV-RNA determination is the most reliable means of identifying HCV carriers, antibodies to NS5 can be a useful marker of virus activity. In fact, antibodies to NS5 were detected in 6 out of 7 viremic patients, compared to 0 out of 6 non-viremic patients (P = 0.004). It remains to be elucidated whether the isolate reactivity to core antigen found in non-viremic subjects represents a specific, HCV-induced antibody response, or is an unrelated crossreactivity.

Adult↗
PubMed1993

Efficacy of different regimens of interferon alfa-2b treatment in chronic hepatitis C.

Four different dosage regimens of interferon (IFN) alfa-2b (3 million units (MU) three times weekly for three months, 3 MU three times weekly for six months, 6 MU two times weekly for six months, and 6 MU three times weekly for six months) were compared in patients with chronic hepatitis C. There was no significant difference measured by percentage of responders to treatment between the four groups, but the degree of response was inversely correlated with the severity of liver damage. Viraemia was undetectable in most (75%) of responders treated with interferon and also in 20% of those who did not respond to treatment.

Adolescent↗
PubMed1992

One course versus two courses of recombinant alpha interferon in chronic C hepatitis.

Fifty-five patients with antibodies to HCV and chronic liver disease have been enrolled in the study. Thirty-four patients were treated with recombinant alpha interferon (IFN, 3 MU daily for 10 days followed by 3 MU twice/week for 3 months), and were compared to 21 untreated controls. Alanine aminotransferase (ALT) normalization was observed in a significant proportion of treated patients (52.9%), but 66.6% of them experienced a relapse after discontinuation of the therapy. The evaluation of the early ALT behavior after the 10 days priming with daily IFN administration was useful in predicting the response. The administration of a second IFN course with the same schedule and duration as the first course did not increase the efficacy of the treatment. Increased dosage and/or prolonged administration are probably required.

Adult↗
PubMedDate not supplied

Liver cirrhosis: epidemiological aspects in Italy.

In order to improve our knowledge of the incidence of liver cirrhosis in Italy, we conducted two epidemiological studies. The first study showed that about 15% of asymptomatic subjects with persistent increase in alanine aminotransferase had histological evidence of cirrhosis. In this setting, cirrhosis was associated with viral aetiology in 91.4% of cases. In the second study, which enrolled cirrhosis patients from 13 centres from all regions of the country, viral infections were detected in 82.6% of patients, the large majority of whom, 71.2%, were positive for hepatitis C virus (HCV). Alcohol abuse was present in 8.7% of cases as exclusive aetiological factor. All the patients were classified according to Child-Pugh and were scored as class A in 62.4%, as class B in 23.8% and as class C in 13.8% of cases. The age distribution showed that about 55% of cirrhosis patients were under 60 years of age; 34.3% of them had a Child-Pugh score of class B or C. These data show that HCV infection represents the predominant aetiological factor of cirrhosis in Italy and that cirrhosis can be found frequently in asymptomatic subjects.

Alcoholism↗