Search PubMed⌕ Search

Biomedical subjects

M Scarpa

Publications and source records attributed to M Scarpa.

At least 91 records · Page 5Linked to original sources

Diagnostic investigations in MS: which is the most sensitive?

In an attempt to establish the efficacy of the different diagnostic tests, 41 multiple sclerosis (MS) patients at different stages of the disease were studied by means of visual evoked potential (VEP) recording, T-lymphocyte subset determination cerebrospinal fluid (CSF) analysis and magnetic resonance (MR) imaging. MR and CSF oligoclonal bands (OB) were the most sensitive techniques for the diagnosis of MS, being positive in 88% of patients, while VEP and helper/suppressor (H/S) T-cell ratio were altered in 54% and 46% of patients respectively. Low significant agreement coefficient were found among the 4 tests and the major value, even though "fairly" significant, was between MR and OB.

Adolescent↗

[Kinematic study of reaching-grasping movements].

The experiment was conducted to investigate, by using kinematic parameters, the influence of the type of prehension on the transportation component in reaching-grasping movements. The main question was whether the transportation component is influenced by the type of prehension besides the distance of the object. The experiment was carried out on eight subjects who performed reaching-grasping movements toward objects located at different distances. Two types of prehension were examined: whole hand prehension and precision grip. The following kinematic parameters of the transportation component (wrist movement) were studied: movement times, profiles of velocity and accelerations. Our results have shown that the transportation component is affected by the two factors. However the kinematic parameters were influenced differently by the distance and the type of prehension. Our conclusion is that, although distance and type of prehension affect the transportation component, they are computed separately in programming this component.

Adolescent↗

[Effects of age on orientation of attention].

The present experiment investigated the influence of age on the magnitude of attentional effects. Subjects were cued to attend to one of two possible stimulus locations horizontally arranged. The instructions were to respond as fast as possible to the occurrence of a visual stimulus, regardless of whether it occurred in a cued or in a non-cued location. When the stimulus occurred in a non-cued location, the subject had to reorient attention to the non-attended, but stimulated, location. Reorienting of attention was directed toward either the left or the right side. The results showed that for the elders, time for reorienting was longer than for younger subjects.

Adult↗

A kinetic study of the reactions between H2O2 and Cu,Zn superoxide dismutase; evidence for an electrostatic control of the reaction rate.

H2O2 was shown to reduce the copper ion of native bovine Cu,Zn superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) (ECu2+) and to oxidize the reduced enzyme (ECu+). The time-course of these processes was monitored by NMR measurement of the longitudinal relaxation rate of the water protons. A steady-state characterized by the same ratio [ECu2+]/[( EC2+] + [ECu+]) was obtained either by starting from the oxidized or the reduced enzyme. The kinetics of these processes appear to be quite complex, since different reactions between H2O2, or its reaction products, and the enzyme-bound copper control the reaction rate. The solution of the differential equations describing the kinetic processes showed that the oxidation and the reduction of the copper ion by H2O2 are first-order with respect to the copper ion itself only when these processes approach the steady-state. The rate constants of the reduction and oxidation reactions were calculated according to these equations and were found to have comparable values which are in the range 5-80 and 5-45 M-1.min-1, respectively, changing the pH from 5.6 to 7 at 0.21 M ionic strength. This result, together with the dependence of the reaction rates on pH and ionic strength, points to HO2- as the reactive species in both processes, and indicates that the electrostatic control of the access of the peroxide to the active site is the rate-determining step of the two redox reactions.

Animals↗

Epidemiology of amyotrophic lateral sclerosis in the province of Modena, Italy. Influence of environmental exposure to lead.

A retrospective study of all admissions to the University of Modena Neurological Department from 1976-1986; 51 cases of amyotrophic lateral sclerosis (ALS) were found. ALS mean annual incidence was 0.78/100,000 inhabitants, while prevalence was 2.35/100,000. Mean age at onset was 61.43 years, mean and median duration of illness were, respectively, 28.83 and 24.5 months, and survival at 5 years post-onset was 24.4%. A tendency to higher incidence and prevalence of ALS in the ceramic district, when compared with those of the rest of the province was found. However, the small number of cases did not allow any conclusive statistical correlation between environmental exposure to lead and frequency of ALS.

Adult↗

Transient global amnesia: pathogenesis and prognosis.

Fifty-five patients admitted to hospital for 'pure' transient global amnesia (TGA) were studied and followed up for a period ranging from 12 to 67 months. The major pathogenetic theories of TGA (epileptic, thrombotic and migrainous) were investigated through the study of clinical histories and risk factors and the recurrences of neurological disturbances during follow-up. Seventy-one percent of the sample had one or more thrombotic risk factors (TRF), 2 patients had both TRF and a history of migraine, and none ever experienced a seizure. A computerized tomography (CT) scan was performed in 40 out of 55 patients to detect focal lesions: 3 patients (7.5%) had a lacuna in the deep structures of the brain. Over the follow-up period, 1 patient died from hepatic cirrhosis, 1 patient died from cerebral haemorrhage, 2 patients experienced transient ischaemic attacks and 3 patients had a total of 4 TGA recurrences. Our conclusion is that TGA represents a benign form of transient ischaemic cerebral disease.

Adult↗

Antagonistic controls regulate copy number of the yeast 2 mu plasmid.

The endogenous 2 mu plasmid of yeast encodes a site-specific recombinase FLP that can cause an amplification of plasmid copy number. Using strains overexpressing 2 mu plasmid proteins from chromosomal constructs to disrupt the normal balance of gene products, we show here that copy number is controlled by regulating the transcript level of FLP. Expression of FLP is negatively regulated over a 100-fold range by the joint action of the plasmid-encoded REP1 and REP2 proteins, which also have a role in plasmid partition. We also show that the product of the fourth plasmid open reading frame D increases FLP expression by relieving the repression caused by REP1 and REP2. This is the first demonstration of a function for this gene, which we call RAF. The transcription of RAF is also repressed by REP1 and REP2 acting together, but requires a higher level for complete inhibition than that required to repress FLP. Copy number is therefore negatively regulated by REP1-REP2 concentration both by direct repression of FLP and indirectly, by control of the positive element, the anti-repressor RAF. We propose that these antagonistic regulatory mechanisms amplify the signal produced by a small fall in copy number.

DNA Nucleotidyltransferases↗

Electrostatic control of the rate-determining step of the copper, zinc superoxide dismutase catalytic reaction.

The dependence of the activity of bovine Cu,Zn superoxide dismutase on pH and ionic strength was extensively investigated in the ranges of pH 7.4-pH 12.3 and of ionic strength of 0.02-0.25 M. The results obtained indicate that two positively charged groups having pK values of approximately 10.1 and 10.8 are involved in the control of the activity. On the basis of previous work on the three-dimensional structure and on the chemically modified enzyme, these groups are likely to be lysine side chains, in particular Lys-120 and Lys-134. The oxidation state of the enzyme-bound copper ion at the steady state was found to be the same at either pH 7.4 or pH 11.5. The diffusion of superoxide ion into the active site, which is controlled by the positive charges around the active site itself, appears to be the rate-determining step of the dismutation reaction. NMR measurements of the relaxation rates of F- showed that this control also applies to the access of F- to the active site. Comparison of the nuclear relaxation rates of F- with the enzyme activity indicates that F- relaxation is controlled by the deprotonation of the group with pK approximately 10.8, which appears to be responsible for about 50% of the total activity measured at neutral pH.

Animals↗

The incidence of aphasia and global aphasia in left brain-damaged patients.

Two hundred and twenty three right-handed patients consecutively admitted to the wards in a 21-month period for a left-sided cerebrovascular disease were examined 15 to 30 days after the stroke for the presence of aphasia. Twenty-seven of them could not be assessed. Of the remaining 196, 108 (55.1%) were aphasic. The incidence of global aphasia (43%) in the latter group was higher than in previous studies. Based on CT-scan data it was associated in 32% of patients with a deep lesion and only in 53% with an antero-posterior cortical-subcortical lesion, contrary to what is traditionally assumed. There was no sex difference in the incidence and distribution of aphasia.

Acute Disease↗

Age dependence of the level of the enzymes involved in the protection against active oxygen species in the rat brain.

Levels of Cu, Zn superoxide dismutase (CuSOD), Mn superoxide dismutase (MnSOD), catalase, and glutathione peroxidase (GPx) were assessed in the rat brain cortex. The concentrations of Cu- and MnSOD were found to increase linearly with the logarithm of the age of the animal from 3 days before birth to 30 months, both in the whole cortex tissue and in its cytoplasmic fraction. Catalase and GPx levels showed different trends; in particular, GPx, which appears to play a key role in detoxification of hydrogen peroxide, after an initial fall increases steadily with age. The enhancement of the levels of SOD and GPx could be related to protection against an increased production of reactive oxygen species in the aging process.

Age Factors↗

Oxidation of reduced Cu,Zn superoxide dismutase by molecular oxygen. A kinetic study.

The rate of oxidation of reduced bovine Cu,Zn superoxide dismutase [ECu(I)] by molecular O2 was studied by magnetic-resonance techniques and was found to be low under physiological conditions. The analysis of the kinetic data and of the experiments carried out in the presence of tetranitromethane confirms that O2.- is a product of the oxidation process. At [ECu(I)]/([ECu(I)] + [ECu(II)]) greater than 0.5 the O2.- produced reacts mainly with ECu(I), increasing the oxidation rate of the enzyme, whereas at [ECu(I)]/([ECu(I)] + [ECu(II)]) less than 0.5 it reacts mainly with ECu(II), decreasing the oxidation rate, the kinetics, at constant O2 concentration, being an apparent second-order process. The oxidation rate increased linearly with both O2 and OH- concentration, indicating that only a deprotonated form of the ECu(I) reacts with O2.-.

Hydrogen-Ion Concentration↗

Limb apraxia in patients with damage confined to the left basal ganglia and thalamus.

Limb apraxia was investigated with standardised tests in 14 patients whose CT scan provided evidence of a vascular lesion confined to the left basal ganglia, or the thalamus, or both, and not involving the cortex or adjacent white matter. Five patients were severely impaired in imitating movements and pantomiming object use. Four of them also performed poorly when tested with real objects. In two patients the lesion was primarily thalamic and in three the lesion was primarily in the lenticular nucleus and the posterior limb of the internal capsule. Patients without apraxia generally had smaller injuries, but there were exceptions. Apraxia is currently conceived of as due to damage of cortical areas and their cortico-cortical connections, but the present data suggest that the model should be enlarged to include the deep nuclei and the pathways running through them.

Aged↗

Increased rate of superoxide ion generation in Fanconi anemia erythrocytes.

The rate of generation of superoxide ion, the concentration of Cu, Zn superoxide dismutase and the hematological parameters were measured in red blood cells obtained from Fanconi anemia patients and from healthy individuals. No significative difference in the superoxide dismutase concentration was found, while the rate of generation of the superoxide ion doubled in Fanconi anemia patients. The steady-state concentration of the superoxide ion was calculated from these data and was found to be 2.3 times higher in Fanconi anemia erythrocytes than in controls. The possible consequences with respect to the alterations in FA are discussed.

Anemia, Aplastic↗

Preparation of reduced bovine Cu,Zn superoxide dismutase.

N.m.r. and e.p.r. were used to measure the oxidation state of copper in Cu,Zn superoxide dismutase treated with reducing agents such as NaBH4, K4Fe(CN)6, Na2S2O4 and H2O2. The activity and the electrophoretic pattern of the treated enzyme were also studied. On the basis of the reducing ability and of the absence of inactivating effects, NaBH4 was the most suitable reducer of those tested. Some characteristics of the reduction of superoxide dismutase by NaBH4 were further investigated. The results obtained indicate that NaBH4 can be used to prepare, in a few minutes, solutions of completely reduced enzyme without any apparent change of the activity and of the structure.

Borohydrides↗

Coordinate expression of MnSOD and CuZnSOD in human fibroblasts.

The amount of manganese superoxide dismutase (MnSOD) and the activity of copper-zinc superoxide dismutase (CuZnSOD) have been studied in five karyotypically normal human fibroblast strains, using nuclear magnetic resonance (NMR) and polarographic methods. A significant correlation between the two enzyme activities, and a linear increase of MnSOD with the increase of CuZnSOD have been demonstrated. Both enzymes are present in nuclei, mitochondria, lysosome-microsome fraction and cytosol. These findings suggest that the two enzymes dismutate the O-2 cooperatively and that a common genetic control maintains the relative amounts of the two enzymes constant.

Adolescent↗

Coordinate expression of Mn-containing superoxide dismutase and Cu,Zn-containing superoxide dismutase in human fibroblasts with trisomy 21.

The amount of Mn superoxide dismutase (MnSOD) and the activity of Cu,Zn-superoxide dismutase (CuZnSOD) have been studied in human fibroblasts of five subjects with trisomy 21 and five subjects with normal karyotype, using nuclear magnetic relaxation and polarographic methods. In the trisomic fibroblasts we have found a mean molar amount of MnSOD 25.4% lower than in the control, and an amount of CuZnSOD 54.7% higher. A positive significant correlation between the activities of both enzymes has been observed indicating that the two enzymes dismute the O2- cooperatively. However, the increase of MnSOD per unit of CuZnSOD appears significantly lower in the trisomic fibroblasts, an effect that is not due to a diminished inducibility of MnSOD. These findings suggest that the MnSOD and CuZnSOD genes interact to preserve the normal level of total SOD activity.

Adolescent↗

Formation of alpha-tocopherol radical and recycling of alpha-tocopherol by ascorbate during peroxidation of phosphatidylcholine liposomes. An electron paramagnetic resonance study.

The events accompanying the inhibitory effect of alpha-tocopherol and/or ascorbate on the peroxidation of soybean L-alpha-phosphatidylcholine liposomes, which are an accepted model of biological membranes, were investigated by electron paramagnetic resonance, optical and polarographic methods. The presence of alpha-tocopherol radical in the concentration range 10(-8)-10(-7) M was detected from its EPR spectrum during the peroxidation of liposomes, catalysed by the Fe3+-triethylenetatramine complex. The alpha-tocopherol radical, generated in the phosphatidylcholine bilayer, is accessible to ascorbic acid, present in the aqueous phase at physiological concentrations. Ascorbic acid regenerates from it the alpha-tocopherol itself. A kinetic rate constant of about 2 X 10(5) M-1 X s-1 was estimated from the reaction as it occurs under the adopted experimental conditions. The scavenging effect of alpha-tocopherol on lipid peroxidation is maintained as long a ascorbic acid is present.

Ascorbic Acid↗

Generation of superoxide ion in human red blood cell lysates.

The generation of superoxide ion in human red blood cell lysates was investigated by an experimental method employing Cu,Zn superoxide dismutase as O2- scavenger and EPR to probe the oxidation state of the enzyme. The average value of the O2- flux in the erythrocytes of 8 normal individuals was (2.02 +/- 0.97) X 10(-8) M S-1. A progressive saturation of the rate of O2- production was found increasing PO2, KM = 1.04 X 10(-4) M, while the autoxidation of oxyhemoglobin did not contribute significantly to the measured O2- production.

Adult↗