Biomedical subjects

D Grasso

Publications and source records attributed to D Grasso.

At least 19 recordsLinked to original sources

PubMed2006

Substrate reduction therapy in the infantile form of Tay-Sachs disease.

Substrate reduction therapy (SRT) with miglustat has been proposed for treatment of some lysosomal storage disorders. Based on the positive experience in Gaucher disease and experimental data in Tay-Sachs (TSD) and Sandhoff animal models, the authors investigated the clinical efficacy of SRT in two patients with infantile TSD. SRT could not arrest the patients' neurologic deterioration. However, a significant drug concentration in CSF as well as macrocephaly prevention were observed.

1-Deoxynojirimycin↗

PubMed2005

Macro- and nanoscale observations of adhesive behavior for several E. coli strains (O157:H7 and environmental isolates) on mineral surfaces.

Subsurface biobarriers can be conceived to attenuate the migration of pathogens by adhesion to mineral surfaces. Candidate biobarrier materials of varied surface characteristics (dolomite, alpha-alumina, silica, pyrophyllite, and Pyrax (a composite form of pyrophyllite, mica, and silica)) were tested for Escherichia coli adhesive capacity in macroscale continuous-flow columns. Atomic force microscopy (AFM) was used to determine nanoscale interaction energies. Predicted attractive interaction energies correlated well with macroscale adhesive behavior for tested E. coli strains. AFM measurements confirmed ExDLVO model predictions of attachment in the primary minima for E. coli O157:H7 and two environmental isolates E. coli (UCFL339 and UCFL-348) with MOPS conditioned Pyrax. In macroscale column experiments, pyrophyllite and Pyrax demonstrated significantly higher bacterial retention, higher deposition coefficients and lower initial cell breakthrough values for E. coli O157:H7 than did alpha-alumina, silica, or dolomite (pyrophyllite, 0.93, 3.56 h(-1), 3.2% ODo; Pyrax, 0.95, 3.73 h(-1), 2.8% ODo; alpha-alumina, 0.74, 1.60 h(-1), 33% ODo; silica, 0.63, 0.43 h(-1), 73% ODo; and dolomite, 0.33, 0.17 h(-1), 89% ODo, respectively). Bacterial hydrophilicity impacted cell retention in Pyrax columns with the relatively hydrophobic E. coli isolate UCFL-339 (0.99, 6.13 h(-1), 0.4% ODo) retained better than the more hydrophilic E. coli isolate UCFL348 (0.94, 3.70 h(-1), 3.6% ODo). The strong adhesive behavior of Pyrax was attributed to the hydrophobic (deltaGiwi = -32.4 mJ/m2) pyrophyllite component of the mineral. Vicinal water appears poised between the bacterial and the mineral surface during initial attachment. Overall, observed behavior of the various E. coli strains and the selected mineral surfaces was consistent with surface analyses, conducted at both the macro- and nanoscale.

Aluminum Oxide↗

PubMed2005

Mutational analysis of the inhibin alpha gene in preeclamptic women.

BACKGROUND: Preeclampsia (PE) is a disorder that occurs in at least 5% of pregnancies and affects both the mother and the unborn baby. A dramatic increase of maternal serum inhibin A concentration in the second and third trimester of pregnancy is a common feature of PE and inhibin A measurement may add significant prognostic information for predicting PE in pregnant women. DESIGN: We evaluated the presence and prevalence of gene polymorphisms for inhibin alpha subunit (INHalpha) in patients affected by PE (no.=50; study group), and in the general population (control group composed of 103 women and 42 men). METHODS: DNA extraction, single strand conformation polymorphism analysis, DNA sequencing, restriction fragment length polymorphism analysis, and Fisher's exact test were used. RESULTS: A 769G-->A transition was found in INHalpha1, but not in INHalpha2 or INHalpha3 fragment. This variant was found in 10/145 normal controls (7,6%), and in 1/50 preeclamptic patients (2%), without significant difference between the two groups (p=0.29). CONCLUSIONS: The prevalence of INHalpha gene variants is not increased in PE. Due to its frequency, the 769G-->A transition may be considered a polymorphism present in the general Italian population.

Adult↗

PubMed2004

Multiple states of nonlinear drift-tearing islands.

Nonlinear drift-tearing magnetic islands are studied numerically with a four-field model that includes the parallel ion dynamics. In certain regions of the parameter space, multiple solutions are found. In particular, linearly stable drift-tearing perturbations can grow to finite size magnetic islands when the amplitude of the initial perturbation is sufficiently large.

Journal Article↗

PubMed2003

The effect of copper/zinc replacement on the folding free energy of wild type and Cys3Ala/Cys26Ala azurin.

The effect of copper/zinc metal ion replacement on the folding free energy of wild type (w.t.) and disulfide bridge depleted (C3A/C26A) azurin has been investigated by differential scanning calorimetry (DSC) and fluorescence techniques. The denaturation experiments have shown that, in both cases, the thermal transitions of the zinc derivative of azurins can be depicted in terms of the classical Lumry-Eyring model, N if U-->F, thus resembling the unfolding path of the two copper proteins. The thermally induced transition of Zn azurin, monitored by fluorescence occurs at lower temperature than the DSC scans indicating that a local conformational rearrangement of the Trp microenvironment, takes place before protein denaturation. For Zn C3A/C26A azurin, the two techniques reveal the same transition temperature. Comparison of the thermodynamic data shows that the presence of Zn in the active site stabilises the three-dimensional structure of azurin only when the disulfide bridge is present. Compared to the copper form of the protein, the unfolding temperature of Zn azurin has increased by 4 degrees C, while the unfolding free energy, deltaG, is 31 kJ/mol higher. Both enthalpic and entropic factors contribute to the observed DeltaG increase. However, the copper/zinc replacement has no effect on the unfolding free energy of C3A/C26A azurin. Taking Cu azurin w.t. as the reference state, for both Cu and Zn C3A/C26A azurin the unfolding free energy is decreased by about 28 kJ/mol, indicating that metal substitution is not able to compensate the destabilising effect induced by the disulfide bridge depletion. It is noteworthy that the thermal denaturation of the Zn derivative, which thermodynamically is the most stable form of azurin, is also characterized by the highest value of the activation energy, E(a), as derived from the kinetic stability analysis.

Alanine↗

PubMed2003

Response to first-line chemotherapy and long-term survival in patients with multiple myeloma: results of the MM87 prospective randomised protocol.

In this study we evaluated whether a good response to conventional chemotherapy, i.e. a significant tumour reduction, is a prerequisite for improved survival in multiple myeloma (MM). Between January 1987 and March 1990, 341 consecutive previously untreated patients with MM received chemotherapy within the prospective, multicentre, randomised Protocol MM87. Of these, 258 patients were evaluable for both response and long-term survival and 244 (94.6%) have died. The median survival of all patients was 40 months (6-162 months). The median survival did not differ between patients who had complete response (CR) (50 months (9-162 months)), partial response (PR) (46 months (8-147 months)) or stable disease (SD) (41 months (7-135 months)). The median survival was shorter (13.6 months (6-135 months)) (P<0.0001) in patients whose disease progressed while they were receiving first induction chemotherapy. Causes of death were more frequently (P=0.04) related to MM in patients who had progressive disease (PD) than in patients who had a CR or PR or SD. The main clinical and laboratory characteristics were similar in the four groups. These data indicate that patients who maintain SD during first-line chemotherapy have a prognosis similar to that of patients who attain a response. Only patients whose disease progresses have a distinctly worse outcome.

Analysis of Variance↗

PubMed2002

Induction and recovery phases of methacholine-induced bronchoconstriction using FEV1 according to the degree of bronchial hyperresponsiveness.

Forty-eight patients suffering from intermittent bronchial asthma underwent methacholine challenge test. Response was stronger in 29 patients and less pronounced in 19. The two groups had the same characteristics except for the cumulative methacholine dose which was lower in severe hyperresponsiveness. The patients were studied both in the phase of induced bronchospasm and in the subsequent phase of spontaneous recovery. Dose-response curves to methacholine were analyzed as FEV1% decline/methacholine dose for the induction phase of bronchoconstriction and as FEV1% increase*methacholine dose/time after PD20FEV1 for the recovery phase. The phase of induced bronchospasm as well as spontaneous recovery had a linear pattern in severe hyperresponsiveness; in patients with moderate response, induced bronchoconstriction had a curvilinear pattern whereas spontaneous recovery had a linear pattern. This latter group had to break down an amount of methacholine that was fivefold greater than the former, therefore the mechanism of local homeostasis recovery may be more efficient in moderate hyperresponsiveness. However, in both groups recovery after the bronchospasm was not complete after 60 min (p < 0.01 versus baseline). Furthermore, recovery was faster in the first 15 min than in the remaining time. In conclusion the behavior of methacholine-induced bronchospasm and its spontaneous recovery in both severe and moderate hyperresponsiveness seem to be different although several and not well-established mechanisms may be responsible for this phenomenon.

Administration, Inhalation↗

PubMed2002

Nitric oxide and apoptosis induced in Peyer's patches by attenuated strains of Salmonella enterica serovar Enteritidis.

Nitric oxide (NO) is a toxic molecule of the immune system which contributes to the control of microbial pathogens. Additional functions of NO in innate and adaptive immunity have recently been described; these functions include the modulation of the cytokine response of lymphocytes and the regulation of immune cell apoptosis. In addition to direct microbicidal actions, NO has immunoregulatory effects relevant to the control of infections. In turn, infected macrophages and macrophage-regulating lymphocytes may undergo apoptosis during infection by Salmonella spp. In this work we investigated the ability of attenuated strains of Salmonella enterica serovar Enteritidis with different protective capacities to induce intestinal inducible nitric oxide synthase (iNOS) and apoptosis in Peyer's patches (PP) in mice. Results showed that the intestinal iNOS activity correlated with increased apoptosis in PP. Furthermore, the ability to induce intestinal NO production and apoptosis within the first few hours after immunization seemed to correlate with the protective capacity of mutant E/1/3 of S. enterica serovar Enteritidis. It was found that nonprotective mutant C/2/2, which was unable to induce intestinal NO production, also failed to induce apoptosis in PP. Moreover, aminoguanidine treatment at the time of immunization resulted in inhibition of the NO production and apoptosis induced by protective mutant E/1/3 and completely abolished protection against challenge. These results suggest that the induction of iNOS in the intestinal mucosa by attenuated mutant E/1/3 of S. enterica serovar Enteritidis at the time of immunization is necessary to generate a protective immune response.

Animals↗

PubMed2001

A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01).

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III-IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n = 1), cardiac toxicity (n = 1), early death during FEC chemotherapy (n = 1), major protocol violations (n = 4), hypersensitivity reaction (n = 1) and early death during paclitaxel chemotherapy (n = 1). The overall response rate was 65% (95% CI = 53-76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect.

Adult↗

PubMed2001

Phase mixing and island saturation in Hamiltonian reconnection.

The nonlinear evolution of a Hamiltonian magnetic field line reconnection in a two-dimensional fluid plasma leads to a macroscopic equilibrium with a finite-size island and fine-scale spatial structures. The latter arise from the phase mixing of the Lagrangian invariant fields. This equilibrium is the analog of the Bernstein-Greene-Kruskal equilibrium solution for electrostatic Langmuir waves.

Journal Article↗

PubMed2001

Mobilization of soil organic matter by complexing agents and implications for polycyclic aromatic hydrocarbon desorption.

Complexing agents are frequently used in treatment technologies to remediate soils, sediments and wastes contaminated with toxic metals. The present study reports results that indicate that the rate and extent of soil organic matter (SOM) as represented by dissolved natural organic carbon (DNOC) and polycyclic aromatic hydrocarbon (PAH) desorption from a contaminated soil from a manufactured gas plant (MGP) site can be significantly enhanced with the aid of complexing agents. Desorption of DNOC and PAH compounds was pH dependent, with minimal release occurring at pH 2-3 and maximal release at pH 7-8. At pH-6, chelate solutions were shown to dissolve large amounts of humic substances from the soil compared to controls. The complexing agents mobilized polyvalent metal ions, particularly Fe and Al from the soil. Metal ion chelation may disrupt humic (metal ion)-mineral linkages, resulting in mobilization of SOM and accompanying PAH molecules into the aqueous phase; and/or reduce the degree of cross-linking in the soil organic matter phase, which could accelerate PAH diffusion.

Chelating Agents↗

PubMed2000

Pancreatic acinar cells submitted to stress activate TNF-alpha gene expression.

To elucidate whether pancreatic acinar cell submitted to stress is able to express TNF-alpha, we studied TNF-alpha mRNA expression by Northern blot and in situ hybridization in healthy pancreas, in tissue from caerulein-induced pancreatitis and after lipopolysaccharide (LPS) treatment. In specimens from normal pancreas, TNF-alpha mRNA expression, as judged by both Northern blot and in situ hybridization, was negative, whereas a strong but transient expression was observed in acinar cells from caerulein pancreatitis and LPS treatment. TNF-alpha mRNA appeared as rapidly as 30 min after treatment, and was maximal 6 h after. At this time, there was mild infiltration consisting mostly of polymorphonuclear leukocytes (PMNL) and no signal of TNF-alpha transcript was found in their cytoplasm. Our results strongly indicate that pancreatic acinar cell is the source of TNF-alpha early in the course of acute pancreatitis and LPS treatment, and suggest that the expression of this cytokine is a part of a general response of the acinar cell to aggression.

Animals↗

PubMed2000

Cloning and expression of the mouse PIP49 (Pancreatitis Induced Protein 49) mRNA which encodes a new putative transmembrane protein activated in the pancreas with acute pancreatitis.

We have used a microarray-based strategy to characterize, at the molecular level, the pancreatic emergency program set up by the pancreatic cells in response to pancreatitis. In this strategy, the phenotype of the pancreatitis-affected pancreas is established by characterization of a large number of its transcripts using a high-density mouse cDNA microarray. This method allows identification of transcripts differentially expressed during pancreatitis. We describe here the cloning, sequencing, and expression analysis of a new gene, named PIP49 (Pancreatitis Induced Protein 49). Its very strong expression is specific of acinar cells and occurs rapidly after initiation of the acute phase of pancreatitis. Analysis of its primary and secondary structures strongly suggests that PIP49 encodes a putative transmembrane protein.

Acute Disease↗

PubMed2000

Health, medicine, and food messages in television commercials during 1992 and 1998.

The potential effects of television advertisements on knowledge, attitudes, and behavior have generated considerable concern. Part of this concern arises from the overall exposure of children to this medium. By the time they graduate from high school, the time devoted to watching television will exceed the hours spent in school. Hence, health professionals should recognize the disproportionate role of television as an informational and attitudinal source for children. The potential impact of television advertisements, particularly those promoting health-related products such as medications and foods, coupled with the changing nature of television points to this medium as an important candidate for examination. The purpose of this study was to content analyze and compare advertisements broadcast in 1992 and 1998 to create a description of the health information conveyed in top-rated, prime time network television advertisements and to determine the congruence of this information with current health recommendations.

Adolescent↗

PubMed1999

A spectroscopic and calorimetric investigation on the thermal stability of the Cys3Ala/Cys26Ala azurin mutant.

The disulfide bond connecting Cys-3 and Cys-26 in wild type azurin has been removed to study the contribution of the -SS- bond to the high thermal resistance previously registered for this protein (. J. Phys. Chem. 99:14864-14870). Site-directed mutagenesis was used to replace both cysteines for alanines. The characterization of the Cys-3Ala/Cys-26Ala azurin mutant has been carried out by means of electron paramagnetic resonance spectroscopy at 77 K, UV-VIS optical absorption, fluorescence emission and circular dichroism at room temperature. The results show that the spectral features of the Cys-3Ala/Cys-26Ala azurin resemble those of the wild type azurin, indicating that the double mutation does not affect either the formation of the protein's overall structure or the assembly of the metal-binding site. The thermal unfolding of the Cys-3Ala/Cys-26Ala azurin has been followed by differential scanning calorimetry, optical absorption variation at lambda(max) = 625 nm, and fluorescence emission using 295 nm as excitation wavelength. The analysis of the data shows that the thermal transition from the native to the denaturated state of the modified azurin follows the same multistep unfolding pathway as observed in wild type azurin. However, the removal of the disulfide bridge results in a dramatic reduction of the thermodynamic stability of the protein. In fact, the transition temperatures registered by the different techniques are down-shifted by about 20 degrees C with respect to wild type azurin. Moreover, the Gibbs free energy value is about half of that found for the native azurin. These results suggest that the disulfide bridge is a structural element that significantly contributes to the high stability of wild type azurin.

Alanine↗

PubMed1998

Anomalous phase transition in dipalmitoylphosphatidylethanolamine/palmitoylphosphatidylcholine/water system.

An anomalous phase transition with a marked rise in specific heat, the isobaric thermal expansion coefficient, and the compressibility coefficient at 62.5 degrees C for an equimolar mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1-palmitoyl-sn-glycero-3-phosphocholine (PLPC), in water (34 wt.%) has been shown by differential scanning calorimetry, scanning dilatometry and isothermal compressibility measurements. This transition occurs 15 degrees C above a first-order transition observed in the same system. (31)P and (2)H nuclear magnetic resonance results are consistent with the occurrence of 'defects' in the bilayer in the temperature range between the first and the anomalous phase transitions. It is proposed that conically, PLPC molecules prefer regions with high curvature in the defective bilayer, while DPPE molecules are mostly confined to the flat regions of the bilayers.

Journal Article↗

PubMed1997

An alternative approach in the structure-based predictions of the thermodynamics of protein unfolding.

A new approach for a first-order prediction of the thermodynamic properties of small globular proteins has been developed. The method put forward here has been shown to be successful in predicting, within acceptable margins of uncertainty, the denaturational heat capacity changes of a given protein if its amino acid composition is known. If compared with other models this method has the following advantages: (1) no details about the three-dimensional structure of the protein are required; (2) comparison with the thermodynamic properties of small model compounds is not necessary; (3) the temperature dependence of the denaturational heat capacity change is taken into account. Moreover, the equations developed have allowed us to point out the errors that can be made if the temperature-dependence of the denaturational heat capacity change is not taken into account in the calculation of the unfolding thermodynamic functions.

Amino Acids↗

PubMed1996

Theoretical basis for differential scanning calorimetric analysis of multimeric proteins.

A new general equation simulating irreversible DSC transitions of multimeric proteins was developed. The equation put forward here is the result of an improved mathematical re-elaboration of the classical Lumry-Eyring models, where no restrictive a priori assumptions are made on the kinetic constraints of the denaturation process, or on the enthalpy of the final denatured state. In order to test the wide applicability of this new effective theoretical tool, a series of DSC transitions were simulated with the aim of determining the effects of all relevant thermodynamic, kinetic or experimental parameters on the shape of DSC profiles. Moreover, the classical equations used widely in DSC investigations for the calculus in both kinetic parameters and changes of molecularity, were studied in the light of the model developed here, highlighting, in each case, their rather limited applicability. The new approach proposed in this article was applied to study the thermal denaturation of an hexameric protein (Glucosamine-6-phosphate deaminase), putting in evidence the practical applicability of the theoretical equations developed.

Journal Article↗