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Biomedical subjects

G Matteucci

Publications and source records attributed to G Matteucci.

At least 19 recordsLinked to original sources

Downward fluxes of particulate carbon, nitrogen and phosphorus in the north-western Adriatic sea.

Downward fluxes of particles, organic carbon, total nitrogen and total phosphorus and the composition of the settled particulate matter were determined in the north-western Adriatic Sea at two coastal sites influenced by the outflows of the Po and Adige rivers and one offshore site. Vertical fluxes were strongly influenced by resuspension processes in addition to the primary flux and advection. The resuspended material contributed on average 34-43% of the total matter sedimented in the near bottom traps in coastal waters. Net annual vertical fluxes (due to primary flux and advection) of organic carbon, total nitrogen and phosphorus in the coastal stations were: 71-97 g C m(-2) year(-1), 8-14 g N m(-2) year(-1) and 2.1-2.3 g P m(-2) year(-1), with the highest values recorded at the station off the Po river delta. The offshore site was characterised by net annual fluxes of particulates, C, N and P approximately one order of magnitude lower than the above. The carbon export to the bottom was limited in the warm seasons when it constituted only 2-9% of primary production, due to high recycling and utilisation in the upper layer of the water column, increasing up to 8-18% in winter because of the instability of the water column and low biological utilisation.

Carbon↗

Reported diagnosis of previous asthma in a sample of the Italian general population.

In this cross-sectional study we describe the prevalence and characteristics of subjects who self-reported a diagnosis of previous asthma in a sample of the Italian general population. We chose a wide age range (3-69 yrs) in order to obtain data over a large spectrum of the population. Interviews were conducted in 1,038 subjects by trained physicians using a modified version of the American Thoracic Society and National Heart & Lung Institute--Division of Lung Disease questionnaire proposed in 1978 (ATS-DLD-78). 791 subjects underwent skin prick tests for 7 common aeroallergens; 422 subjects underwent spirometry and 212 methacholine challenge tests. Cumulative prevalence of asthma was 7.9% (82/1038). Previous asthma (PA) was reported by 29 (35.4%) of the subjects, who said they had been but were no longer asthmatic; 65.5% of these claimed that PA had developed at or before the age of 14 yrs. No significant differences emerged in sex, age, family and personal history of atopy, and size of skin test reaction in subjects with PA compared to those with current asthma (CA). Although the difference was not statistically significant, the latter tended to be lifetime nonsmokers while subjects with PA were more often current smokers. Age at onset of asthma was significantly higher in subjects with CA than in subjects with PA (24.6 +/- 20 yrs vs. 12.0 +/- 15.0 yrs, p = 0.005). Bronchial hyperreactivity was present in 37.5% of subjects with PA, while forced expiratory volume in 1 sec (FEV1) was within normal limits in all. In conclusion, in this sample of the Italian population, PA was reported by about 1/3 of the asthmatic subjects, most of whom were atopic. Lung function was within normal limits in all, but bronchial hyperreactivity persisted in 1/3 subjects.

Adolescent↗

Respiration as the main determinant of carbon balance in European forests.

Carbon exchange between the terrestrial biosphere and the atmosphere is one of the key processes that need to be assessed in the context of the Kyoto Protocol. Several studies suggest that the terrestrial biosphere is gaining carbon, but these estimates are obtained primarily by indirect methods, and the factors that control terrestrial carbon exchange, its magnitude and primary locations, are under debate. Here we present data of net ecosystem carbon exchange, collected between 1996 and 1998 from 15 European forests, which confirm that many European forest ecosystems act as carbon sinks. The annual carbon balances range from an uptake of 6.6 tonnes of carbon per hectare per year to a release of nearly 1 t C ha(-1) yr(-1), with a large variability between forests. The data show a significant increase of carbon uptake with decreasing latitude, whereas the gross primary production seems to be largely independent of latitude. Our observations indicate that, in general, ecosystem respiration determines net ecosystem carbon exchange. Also, for an accurate assessment of the carbon balance in a particular forest ecosystem, remote sensing of the normalized difference vegetation index or estimates based on forest inventories may not be sufficient.

Atmosphere↗

Protection of intrinsic nerves of guinea-pig detrusor strips against anoxia/glucopenia and reperfusion injury by taurine.

There is ample evidence that ischaemia is associated with partial denervation of the detrusor muscle and that this is responsible for much of its abnormal contractile behaviour, resulting in bladder dysfunction (instability). In guinea-pig nerves are very susceptible to the ischaemic damage as compared to the muscle cells. The purpose of this study was to assess the neuroprotection afforded by taurine on guinea-pig detrusor under ischaemic-like conditions. Guinea-pig detrusor strips were subjected for 60 min to ischaemic-like conditions, followed by 150 min reperfusion. Intrinsic nerves underwent every 30 min electrical field stimulation (EFS) by 5-s trains of square voltage pulses of 0.05 ms duration (15 Hz, 50 V). Detrusor strips were perfused with 0.1, 1, 3 or 10 mM taurine during the ischaemia-like exposure and the first 30 min of reperfusion. Taurine (1 and 3 mM) significantly improved the response of the strips to EFS both at the end of ischaemia and reperfusion. On the contrary, neither 0.1 nor 10 mM taurine had significant effects. It is concluded that taurine can partially counteract the ischaemia-reperfusion injury in the guinea-pig urinary bladder.

Aminoethylphosphonic Acid↗

Reduction pneumoplasty versus respiratory rehabilitation in severe emphysema: a randomized study. Pulmonary Emphysema Research Group.

BACKGROUND: The purpose of the study was to determine in a prospective randomized trial the independent short-term physiologic impact of reduction pneumoplasty (RP) on respiratory rehabilitation (RR). METHODS: Sixty patients eligible for RP were randomly selected by computer to receive either RP (n = 30) or comprehensive RR (n = 30). Pulmonary function tests, analysis of blood gas levels, measurement of respiratory muscle strength (maximal inspiratory and expiratory pressures), 6-minute walk test (6MWT), and incremental treadmill test (ITT), were performed at baseline and at 3 and 6 months. RESULTS: Two treatment-related deaths occurred after RP and one after RR. At 6 months dyspnea index, maximal inspiratory pressure, 6MWT, ITT, and PaO2 were significantly improved in both groups whereas forced expiratory volume in 1 second and residual volume were significantly improved only in the surgical arm. In addition at 6 months, dyspnea index, 6MWT, maximal ITT, and PaO2 improved significantly more after RP than after RR. CONCLUSIONS: In our study short-term improvements in dyspnea index, oxygenation, inspiratory muscle strength, and exercise capacity occurred after either RP and RR. However dyspnea index, PaO2, and exercise capacity improved more after RP than after RR whereas pulmonary function improved only after RP.

Aged↗

Sediment composition and normalisation procedures: an example from a QUASH project sediment exercise.

The QUASH UE-Project was designed to assess the reliability of normalisation approaches to compensate the influence of natural process affecting the distribution and concentration of contaminants in sediment. The focus of this paper was to test the influence on normalisation procedures of an inorganic matrix using a sample collected in the Venice Lagoon, Italy.

Environmental Monitoring↗

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from lubricating oil.

OBJECTIVES: Percutaneous penetration of polycyclic aromatic hydrocarbons (PAHs) is affected by various factors connected to exposure conditions. The nature of the matrix, such as that of oil, can strongly affect their percutaneous penetration. Risk assessment should consider these effects. We examined the effect of matrix on percutaneous penetration of PAHs, particularly that of lubricating oil. METHODS: The test apparatus consisted of an in vitro static diffusion cell system using full-thickness monkey (Cercopithecus aetiops) skin as the membrane and saline solution with gentamycin sulfate and 4% bovine serum albumin as receptor fluid. Chemical analysis of PAHs in the samples obtained from cells was carried out by inverse-phase HPCL, and the results were read by spectrofluorimetry. RESULTS: Comparing the penetration of 13 PAHs from a lubricating oil and from acetone solution with artificial sweat resulted in a significantly slower passage from the oil matrix for acenaphthene, anthracene, phenanthrene, fluoranthene, naphthalene, pyrene, fluorene (Mann-Whitney U test, P < 0.05). No significant differences in the passage were found for chrysene because, in the test with oil, its concentration was very often below the detection limit. For benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene it was possible to demonstrate a passage through the skin only when compounds were applied in acetone solution with artificial sweat. CONCLUSIONS: The results of the study suggest the necessity of dermal penetration data relevant for risk assessment, obtained under experimental conditions similar to the real exposure conditions.

Acetone↗

The structural basis for the regulation of tissue transglutaminase by calcium ions.

The role of calcium ions in the regulation of tissue transglutaminase is investigated by experimental approaches and computer modeling. A three-dimensional model of the transglutaminase is computed by homology building on crystallized human factor XIII and is used to interpret structural and functional results. The molecule is a prolate ellipsoid (6.2 x 4.2 x 11 nm) and comprises four domains, assembled pairwise into N-terminal and C-terminal regions. The active site is hidden in a cleft between these regions and is inaccessible to macromolecular substrates in the calcium-free form. Protein dynamics simulation indicates that these regions move apart upon addition of calcium ions, revealing the active site for catalysis. The protein dimensions are consistent with results obtained with small-angle neutron and X-ray scattering. The gyration radius of the protein (3 nm) increases in the presence of calcium ions (3.9 nm), but it is virtually unaffected in the presence of GTP, suggesting that only calcium ions can promote major structural changes in the native protein. Proteolysis of an exposed loop connecting the N-terminal and C-terminal regions is linearly correlated with enzyme inactivation and prevents the calcium-induced conformational changes.

Amino Acid Sequence↗

Conformational stability of human erythrocyte transglutaminase. Patterns of thermal unfolding at acid and alkaline pH.

Tissue-type transglutaminase is irreversibly inactivated during heat treatment. The rate of inactivation is low at pH 7.5; it increases slightly at acid pH (6.1) but much more at alkaline pH (9.0-9.5), suggesting that specific effects take place in the alkaline range, possibly in relation to decreased stability of the transition-state intermediate as pH is raised above 9.0. Differential scanning calorimetry experiments indicate that thermal unfolding of the protein occurs with two separate transitions, involving independent regions of the enzyme. They are assigned to domains 1 and 2 and domains 3 and 4, respectively, by a combination of calorimetric and spectroscopic techniques. When considering the effects of pH, we noted that transglutaminase was unfolded via different pathways at the different pH values considered. At acid pH, the whole structure of the protein was lost irreversibly, with massive aggregation. At neutral and, even more so, at alkaline pH, aggregation was absent (or very limited at high protein concentration) and the loss of secondary structure was dependent on the ionization state of crucial lysine residues. Unfolding at pH 9.5 apparently chiefly involved the N-terminal region, as testified by changes in protein intrinsic fluorescence. In addition, the C-terminal region was destabilized at each pH value tested during thermal unfolding, as shown by digestion with V8 proteinase, which is inactive on the native protein. Evidence was obtained that the N-terminal and C-terminal regions interact with each other in determining the structure of the native protein.

Calorimetry↗

Prediction of percutaneous absorption from physicochemical data: a model based on data of in vitro experiments.

Correlations between in vitro percutaneous absorption data and physicochemical properties of industrial chemicals are evaluated in order to develop predictive mathematical models based on said properties. Percutaneous diffusion of 16 pounds of occupational interest, eight of which were polycyclic aromatic hydrocarbons (acenaphthene, anthracene, benzo(a)anthracene, chrysene, phenanthrene, fluorene, naphthalene, pyrene), six organophosphorus insecticides (acephate, chlorpyrifos, dimethoate, fenitrothion, methamidophos, omethoate) and two phenoxycarboxylic herbicides (2,4-D, MCPA), were tested in vitro using monkey (Cercopithecus aetiops) skin. The test apparatus consisted of nine static diffusion cells with normal saline, gentamycin sulphate and 4% bovine serum albumin as receiving solution. Test compounds were applied at various concentrations in 30 microliters of acetone solution and determined, in the receiving phase, by chemical analysis. Values for ln Kow (octanol/water partition coefficient) were correlated with experimentally determined values of the permeability constant Kp (r = 0.90, P < 0.001) and lag time (r = 0.81, P < 0.01). Analysis of variance in a model of multiple linear regression between Kp, ln Kow and water solubility [water] of the compounds, showed that the data had a highly significant fit (P < 0.0001). A more general model which also included molecular weight (MW) and vapour pressure was evaluated as well, but the two variables made no substantial difference. Multiple regression analysis between lag time, ln Kow and [water] was significant (P < 0.0001), whereas introduction of vapour pressure and MW as independent variables did not significantly improve the predictive effect on lag time. Our experimental system, therefore, enables the values of Kp and lag time to be predicted with reasonable precision on the basis of ln Kow and [water] values, using the algorithm derived from the multiple linear regression equation.

Animals↗

Active site labeling of erythrocyte transglutaminase by o-phthalaldehyde.

Tissue-type transglutaminase is inactivated in a time-dependent way during incubation with submillimolar concentrations of o-phthalaldehyde, with affinity labeling kinetics. The rate of inactivation by the reagent is greatly enhanced in the presence of the essential enzyme cofactor calcium and is decreased by GTP, an allosteric inhibitor. A fluorescent isoindole derivative is formed during the modification apparently through crosslinkage of active site Cys 277 to a lysine residue. These data and the quenching of fluorescence by addition of calcium ions suggest that the enzyme active site is directly involved in the inactivation process.

Binding Sites↗

Preparation and immunogenicity of an inactivated hepatitis A vaccine.

A hepatitis A vaccine was prepared by formaldehyde inactivation of purified hepatitis A virus (HAV) LSH/S strain grown on human diploid MRC-5 cells. The vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. Infectious HAV particles were not detected in faeces and sera of the vaccinated primates by ELISA or after passages in MRC-5 cells. The immunogenicity of the vaccine was evaluated by injecting guinea-pigs with 0.8, 0.2 or 0.05 micrograms of HAV antigen adsorbed onto 0.5 and 1 mg of Al (OH)3 or 0.3 mg of AlPO4. The antibody response, measured by a competitive radioimmunoassay, was dose- and adjuvant-dependent. One injection of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced seroconversion in 100% of animals and high levels of specific and neutralizing serum antibodies. A further increase of antibody titres was observed after the second and third inoculations. These results show that this vaccine formulation is safe and immunogenic in animal models, and suggest that it should be evaluated further by human clinical studies.

Adjuvants, Immunologic↗

Differential activity of interleukin 1 alpha and interleukin 1 beta in the stimulation of the immune response in vivo.

The biological activities of human recombinant interleukin (IL) 1 alpha and IL 1 beta were compared in different biological systems. The two IL 1 forms were equally active in vitro in inducing proliferation of murine thymocytes and of the murine T helper clone D10.G4.1, and in triggering release of prostaglandin E2 from human skin fibroblasts. In vivo, IL 1 alpha and IL 1 beta were similarly pyrogenic both in rabbits and mice, and could equally increase the circulating levels of the acute phase protein serum amyloid A in mice. However, only IL 1 beta showed immunostimulatory activity in vivo, as it could enhance the number of specific antibody-producing cells in the spleen of mice immunized with either a T-dependent or a T-independent antigen. Although devoid of immunostimulatory activity, IL 1 alpha could efficiently compete immunostimulation induced by IL 1 beta, suggesting an effective interaction with the IL 1 receptor. Thus, IL 1 beta appears to have an important role in the positive regulation of immune responses, while IL 1 alpha may act as down-regulator of the IL 1 beta effect.

Animals↗

Characterization of genetically inactivated pertussis toxin mutants: candidates for a new vaccine against whooping cough.

the introduction of two amino acid substitutions within the enzymatically active subunit S1 of pertussis toxin (PT) abolishes its ADP-ribosyltransferase activity and toxicity on CHO cells (Pizza et al., Science 246:497-500, 1989). These genetically inactivated molecules are also devoid of other in vivo adverse reactions typical of PT, such as induction of leukocytosis, potentiation of anaphylaxis, stimulation of insulin secretion, and histamine sensitivity. However, the mutant PT molecules are indistinguishable from wild-type PT in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and maintain all the physical and chemical properties of PT, including affinity for toxin-neutralizing poly- and monoclonal antibodies. Either alone or stabilized with formaldehyde, PT mutants are able to induce high levels of neutralizing antibodies and to protect mice in a dose-dependent fashion against intracerebral challenge with virulent B. pertussis. These results clearly show that these genetically inactivated PT molecules are nontoxic but still immunogenic and justify their development as a component of a new, safer acellular vaccine against whooping cough.

Adjuvants, Immunologic↗

A monoclonal antibody to the IL-1 beta peptide 163-171 blocks adjuvanticity but not pyrogenicity of IL-1 beta in vivo.

The synthetic fragment VQGEESNDK, corresponding to the amino acid sequence in position 163-171 of human IL-1 beta, possesses the immunostimulatory but not the pyrogenic activity of the mature IL-1 beta polypeptide in vivo. To assess the relevance of this domain of IL-1 beta for its biologic activities, a mAb was raised against the synthetic peptide 163-171. The mAb Vhp20 could effectively recognize human rIL-1 beta in RIA and immunoblotting. In vivo, the mAb Vhp20 was able to selectively inhibit the immunostimulatory activity of IL-1 beta, but it could not affect the fever-inducing capacity of IL-1 beta. It is proposed that functional domains could be identified in the human IL-1 beta protein and that the fragment in position 163-171 is of major importance for the adjuvant capacity of the entire molecule, but irrelevant to its pyrogenic activity.

Adjuvants, Immunologic↗