Biomedical subjects
Publications and source records attributed to M Scarpa.
F- added to an erythrocyte suspension shows two separated resonances arisen from intra and extracellular compartments. Cu, Zn superoxide dismutase dominates the longitudinal relaxation rate of the intracellular F- resonance, while diamagnetic interactions with hemoglobin contribute mainly to the transversal relaxation rate.
The main aim of the present study was to clarify whether different types of grasping may affect the transport component of prehension movements. To this purpose two experiments were carried out. In the first experiment the kinematics of arm movements (transport and manipulation components) were studied in eight normal subjects instructed to reach and grasp different objects located either 20 or 30 cm from their hand. The objects employed required two different types of grip: prehension with the whole hand and prehension with the index finger and the thumb (precision grip). In the second experiment subjects were instructed to point to the same objects employed in the first experiment. This experiment served as a control for the precision requirements related to the object size. The results showed that, once the precision requirements were taken into account, the transport component remained unmodified with the different types of grip. The time course of the manipulation component and its temporal relations with the transport component changed with the type of grasping. The maximal hand aperture was reached earlier in the precision grip than in the whole hand prehension and the temporal coupling with the transport component was weaker in the former condition than in the latter. The data are interpreted as further evidence in favour of independence between the transport and the manipulation "channels".
We have characterized the recombinant replication-competent retrovirus (RCV) arising from p delta N2-derived vectors in the packaging cell lines psi 2 (ecotropic) and PA317 (amphotropic). Detailed restriction patterns and sequence of the envelope region of these RCVs has indicated that they arose from recombination events between the virus plasmids used to create the packaging cell line and the vectors. There was no evidence of recombination involving endogenous murine retroviral sequences in the packaging cell line or in transduced hematopoietic cells. In addition, we have confirmed that the mutation of the start codon of the pXM5(N2) derivatives gag+ sequence drastically decreased the occurrence of RCV production. These results offer encouragement that the risk of RCV production can be adequately decreased in gene therapy applications of defective retrovirus vectors.
The inherited deficiency in adenosine deaminase (ADA), which results in severe combined immunodeficiency, is generally regarded as an optimal model for the development of human somatic gene therapy. The ideal target for the correction of ADA deficiency and other lympho-hematopoietic disorders would be the hematopoietic stem cell. We have used a combination of recombinant human interleukins-3 and -6 to stimulate the proliferation of primitive human hematopoietic progenitor cells during a period of co-cultivation with irradiated cells producing high titers of an ADA-transducing retroviral vector packaged in amphotropic particles. In a series of nine experiments, an average of 83% of the clonogenic progenitors (CFU-E and CFU-GM) were found to have acquired the transferred sequence as determined by polymerase chain reaction analysis. In addition, in two experiments, 24-44% of the clonogenic progenitors derived from long-term myeloid cultures 9 weeks post-transduction were found to contain vector sequence. The latter cells are derived from so-called "long-term culture-initiating cells" (LTC-IC), which are primitive cells probably related to hematopoietic stem cells. Moreover, the transduced ADA enzyme was found to be expressed in both normal and ADA-deficient erythroid colonies, and in the nonadherent cells of long-term bone marrow culture for at least 2 weeks at levels that approximate the endogenous ADA levels of normal erythroid cells. These results indicate that the ADA coding sequence can efficiently be introduced by retroviral gene transfer into both committed and primitive human hematopoietic progenitor cells, and that this will result in adequate expression of the transduced enzyme in the progeny of committed hematopoietic progenitors.
Two novel retroviral vectors bearing lymphoid-specific enhancers were tested for improved expression of human adenosine deaminase (hADA) in tissue culture cells and in mouse bone marrow transplant recipients. These vectors carried either an added human T-cell receptor alpha-chain enhancer (delta N2TADA) or a substitution of the Moloney long terminal repeat (LTR) enhancer with the murine immunoglobulin mu heavy-chain first intron enhancer (delta N2 mu ADA). Each vector was produced at a titer of approximately 10(6) infectious units/ml and efficiently transduced hADA into murine fibroblast and myeloma cells in culture. No quantitative difference in expression was observed between the enhancer modified vectors and the basic retrovirus vector (delta N2ADA). In addition, each vector efficiently conferred hADA expression in lymphoid, myeloid, and erythroid cells of long-term transplanted mice. The majority of the transduced-marrow recipients demonstrated expression of the human enzyme for 4-8 months with each of the three vectors.
This paper outlines the clinical and CT scan features of a subtype of global aphasia, characterized by an extreme loss of communicative abilities, verbal as well as nonverbal. Three to four weeks after a left hemisphere stroke, 17 patients were completely unable to communicate with people addressing them. Though there were differences in their willingness to interact with the environment, they were characterized by complete loss of speech output and by inaccessibility to any kind of message, whether given verbally or through gestures. Patients who survived were reassessed 6 and 12 mos later and half of them were still found in a state of complete communicative isolation. The remainder had somewhat improved, but remained globally aphasic. The attempt to find a CT scan basis for this picture was disappointing. Only 35% of patients had a lesional pattern in agreement with the traditional view that ascribes global aphasia to the involvement of Broca's and Wernicke's areas. The location of lesion in the other cases spanned from anterior cortical damage, to posterior cortical damage, to deep nuclei damage and none of the lesions that have been proposed to account for subcortical global aphasia was consistently observed.
The activity of the superoxide dismutase was measured by the polarographic method of catalytic currents in the cerebrospinal fluid of patients with age-related neurologic degenerative diseases, namely, amyotrophic lateral sclerosis and Alzheimer's disease, and of a reference group of normal subjects. The superoxide dismutase activity was found to increase with age in reference subjects (r = 0.81) while no significant correlation was found in amyotrophic lateral sclerosis and Alzheimer's disease patients. The activity mean values were significantly lower (P less than 0.01) in patients with neurologic degenerative diseases than in the reference subjects. The changes of superoxide dismutase activity in the aging brain and in age-related neurologic degenerative diseases are discussed.
In this study the temporal coupling between transport and manipulation components of prehension movements was tested. For this purpose two experiments were carried out. In Experiment 1 six normal subjects were required to reach and grasp one of three spheres located at three different distances (Blocked trials). In Experiment 2 a visual perturbation paradigm was used in which the location of the object to be reached and grasped could change at onset of arm movement (Perturbed trials). The results of this study exclude a temporal coupling between events of transport and manipulation components. On the contrary they suggest that manipulation component organizes its time course having information about the time required to reach the object.
A case of spinal epidural haematoma diagnosed by means of Gadolinium-DTPA-enhanced MR imaging is described. The sensitivity of this recent technique is underlined.
We report the entire course of a case of thrombosis of the venous sinuses, very probably caused by contraceptive pill use, documented by MR imaging. MRI appears to be the examination of choice in such cases.
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Repressor of primer (Rop) is a small dimeric protein that participates in the mechanism that controls the copy number of plasmid of the ColE1 family by increasing the affinity between two complementary RNAs. The Rop dimer is a bundle of four tightly packed alpha-helices that are held together by hydrophobic interactions. We have systematically altered, by site directed mutagenesis, most of the solvent exposed amino acids of the Rop bundle and we have identified the alterations that cause a decrease of the activity of the regulatory molecule. We conclude that Rop folding is rather insensitive to amino acid substitutions and to other mutations as drastic as deletions and insertions. Looking along the 2-fold symmetry axis the amino acid side chains whose alterations affect the function of Rop are all located on one side of the molecule. Furthermore they are clustered at the extremities of the alpha-helix bundle, the only exception being the aromatic ring of Phe-14.
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This study aimed at assessing whether there was a relation between presence or absence of apraxia following a parietal and/or frontal left hemisphere lesion and "typical" skull asymmetries, evidenced by CT scan (prevalence of the left over the right occipital length and width and of the right over the left frontal length and width). Skull asymmetries were measured in a sample of 160 brain-damaged patients and their prevalence was found to agree with those reported by the literature in normal subjects. A subgroup of 72 patients with lesions restricted to the parietal and/or frontal lobe were given a movement imitation test and diagnosed as apraxic, borderline or normal making reference to the performance of 150 control subjects. The incidence in these three groups of typical or atypical occipital and frontal asymmetries was assessed and found not to differ significantly. It is concluded that no consistent relation between hemisphere dominance for praxis and skull asymmetry can be asserted. The study also investigated the relation of idemotor apraxia to the locus of left hemisphere damage and confirmed that both the incidence and the severity of the disorder are much greater following parietal than frontal lesions.
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.
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.
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.