Cloning of 5' and 3' flanking regions of the Schistosoma mansoni calcineurin A gene and their characterization in transiently transformed parasites.
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3' Flanking Region↗
Biomedical subjects
Alessandro Rossi
Publications and source records attributed to Alessandro Rossi.
Pharmacologically induced enhancement of recurrent inhibition in humans: effects on motoneurone discharge patterns.
The aim of the present study was to investigate the effects of spinal recurrent inhibition on human motoneurone discharge patterns. The tonic discharge activity of motor unit pairs was recorded in the extensor carpi radialis (ECR) and abductor digiti minimi (ADM) muscles during voluntary isometric contraction. While undergoing continuous intravenous saline (NaCl 0.9 %) perfusion, the subjects were given a short lasting injection of L-acetylcarnitine (L-Ac), which has been found to potentiate recurrent inhibition in humans. The variability, synchronization and coherence of the motor unit discharges were analysed during four successive test periods (lasting 2-3 min each). A significant decrease in the inter-spike interval (ISI) coefficient of variation was observed in the discharge patterns of the motor units tested in the ECR and not in the ADM, which were not accompanied by any consistent changes in the mean ISIs of the motor unit activity in either muscle. The L-Ac injection also led to a significant increase in the synchronization in half of the motor unit pairs tested in the ECR muscle (n = 29), whereas no consistent changes were observed with the ADM motor units (n = 25). However, coherence analysis failed to reveal any consistent differences in the incidence of significant values of coherence spectrum between the pre-injection and injection periods among the motor unit pairs tested with either saline or L-Ac injections, in either the ECR or ADM muscles. The contrasting effects on the variability and the synchronization of the motor unit discharges observed with ECR motoneurones known to undergo recurrent inhibition and with ADM motoneurones known to lack recurrent inhibition suggest that the drug may have specific effects which are mediated by an enhancement of the Renshaw cell activity. The decrease in the ISI variability is in line with the hypothesis that recurrent inhibition may contribute along with the post-spike after-hyperpolarization to limiting the influence of the synaptic noise on the firing times of steadily discharging motoneurones. The present data, which suggest that recurrent inhibition plays a synchronizing rather than a desynchronizing role, are in keeping with the fact that the Renshaw cells may provide an important source of common inhibitory inputs.
Acetylcarnitine↗
Early somatosensory processing during tonic muscle pain in humans: relation to loss of proprioception and motor 'defensive' strategies.
OBJECTIVE: It is known that tonic muscle pain induced by a Levo-Ascorbic (L-AS) solution injected in a foot muscle can transiently modify both regional proprioception and stimulus perception. These findings are paralleled by changes of middle-latency lower-limb somatosensory evoked potentials (SEPs). However, little is known on the behaviourally relevant aspect whether eventual SEP pain-induced changes could be partly due to a sort of 'motor strategy' of subjects in the frame of a self-protective reaction towards the noxious stimulus. Movement and imagery of movements are in fact known to reduce mainly pre-central SEP amplitude (i.e. gating effect). METHODS: Low-threshold afferents ulnar SEPs, psychophysical pain ratings and fingers' position sense were monitored in the time-course during L-AS injection in the right first dorsal interosseous muscle. Control experiments included SEPs (either following prevalent ulnar nerve low-threshold afferent stimulation or more conventional mixed nerve stimulation) during actual movements execution and imagery of movements of the right hand. RESULTS: Tonic pain induced a significant reduction of the post-central N(20)-P(25)-N(33) complex and a significant increase of the N(18) wave. These changes, that were paralleled by distortion of the finger position sense, were delayed 2-5 min with respect to the maximal subjective pain sensation. Conversely, movement imagery tasks lead to a significant, selective, reduction of the pre-central N(30) complex. This wave was even more reduced during actual movements, in combination with a reduction of those post-central components peaking after the first activation of the primary sensory cortex. CONCLUSIONS: Early sensory processing at cortical level is changed during tonic muscle pain, mainly for those components which may be theoretically involved in proprioceptive afferent elaboration. These changes are likely not due to subconscious or voluntary motor strategies of the subjects in the frame of a self-protective aversive reaction towards the noxious stimulus.
Adult↗
Insight and neuropsychological function in patients with schizophrenia and bipolar disorder with psychotic features.
OBJECTIVES: This study investigates the pattern of association between patient unawareness of illness and neuropsychological tests of frontal lobe function in subjects with schizophrenia and bipolar disorder (BD) with psychotic features. METHOD: We administered the Wisconsin Card Sort Test (WCST) and a shortened version of the Scale to Assess Unawareness of Mental Disorder (SUMD) to a sample of 64 patients with psychosis (42 with schizophrenia and 22 with BD). RESULTS: None of the correlations between WCST scores and insight scores were statistically significant, either in the total group or in each group analyzed separately. Further, no differences were seen in insight scores between sexes and between the diagnostic groups. CONCLUSIONS: The 3 insight dimensions (that is, awareness of mental disorder, awareness of social consequences of mental disorder, and awareness of the benefits of medication) do not appear to be associated with frontal impairment, as measured by the WCST.
Adult↗
Schizotypal dimensions in normals and schizophrenic patients: a comparison with other clinical samples.
Schizotypy is usually referred to as a "liability" to schizophrenia, but it could also be more generally referred to as nonspecific "psychosis-proneness". This study examined the structure of schizotypy in a normal sample and in a sample of schizophrenics through the administration of the Schizotypal Personality Questionnaire (SPQ). Within a "fully dimensional" approach to psychiatric disorders, this study also compared SPQ scores in clinical samples of subjects with bipolar, unipolar and obsessive-compulsive (OCD) disorders. The results suggested that the disorganized three-factor model, Cognitive-Perceptual, Interpersonal Deficits and Disorganization, underlies individual differences across samples of normal and schizophrenic patients. Furthermore, the SPQ measures discriminated schizophrenia and bipolars from major depression but not from OCD.
Adult↗
Subjective experiences in schizophrenia and bipolar disorders.
Studies comparing 'subjective experiences' in schizophrenic and affective disorders have reached inconclusive results. We investigated the pattern of 'subjective perceived cognitive disturbances' in a group of 55 schizophrenic patients and 39 bipolar patients hospitalized for an index psychotic episode. The assessment of the subjective experiences was made using the Frankfurter Beschwerde-Fragebogen (FBF). Comparing the two groups on the four FBF factors, schizophrenic patients showed significantly higher scores in the areas of 'central cognitive disturbances', 'perception and motility' other than a significantly higher FBF total score. Our results suggest that cognitive, perception and motility disturbances are the most characteristic subjective experiences of schizophrenic patients in comparison with bipolar patients. This finding need to be further explored in light of the issue of cognitive dysfunction in schizophrenia.
Adult↗
Wisconsin Card-Sorting Test performance does not discriminate different patterns of premorbid behavioral abnormalities in schizophrenic patients.
It is well documented that premorbid behavior abnormalities precede the onset of schizophrenia in a large number of patients. The research findings suggest that there are differences in the type and severity of these premorbid dysfunctions. Another research field has shown impairment of preschizophrenic patients in several cognitive domains. The present study reports retrospective childhood and adolescence neurobehavioral assessment in 31 patients with schizophrenia by the Child Behavior Checklist (CBCL) and current Wisconsin Card-Sorting Test (WCST) evaluation in order to investigate whether specific behavioral abnormality (BA) patterns are related to executive function as evaluated by the WCST. Cluster analysis was conducted on the childhood premorbid behavior ratings for the schizophrenic patients and two subgroups emerged: (i) Cluster I with an initial low level of BA that increased over the years; and (ii) Cluster II with a high level of BA that remained relatively stable until early adulthood. Furthermore, Cluster II showed more severe current negative and total symptoms, but the two groups did not differ in WCST performance. Our results show that the patterns and severity of CBCL upon retrospective evaluation are not related to WCST performance, which seems to be a feature inherent to the disease process. Different factors could be responsible for cognitive and behavioral disturbances in schizophrenia.
Adolescent↗
Case of mania induced by withdrawal of interferon-alpha in a patient affected by bipolar disorder.
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Antiviral Agents↗
Historical, psychopathological, neurological, and neuropsychological aspects of deficit schizophrenia: a multicenter study.
OBJECTIVE: This multicenter study aimed to verify whether the historical and psychopathological characteristics of a large group of patients with deficit schizophrenia were consistent with those reported in previous studies. The authors also tested the hypothesis that neurological and neuropsychological indices sensitive to frontoparietal dysfunction, but not those sensitive to temporal lobe dysfunction, are more impaired in patients with deficit schizophrenia than in those with non-deficit schizophrenia. METHOD: For each patient with deficit schizophrenia enrolled in the study, a matched subject with non-deficit schizophrenia was recruited. Historical, psychopathological, neurological, and neuropsychological evaluations were carried out for all patients. RESULTS: Patients with deficit schizophrenia, compared with patients with non-deficit schizophrenia, had a similar severity of positive symptoms and disorganization and less hostility. They had poorer premorbid adjustment during childhood and early adolescence and exhibited more impairment in general cognitive abilities. The deficit state was associated with impairment in sequencing of complex motor acts, which suggests frontoparietal dysfunction. CONCLUSIONS: Previous reports of differences in historical, psychopathological, and neuropsychological characteristics between patients with deficit schizophrenia and those with non-deficit schizophrenia were mostly supported by the present findings. Neurological findings suggest that frontoparietal functioning is more impaired in patients with deficit schizophrenia. Deficit schizophrenia might represent a neurodevelopmental subtype of schizophrenia in which significant behavioral and cognitive impairment since childhood compromises the development of basic capacities relevant to subsequent cognitive and social functioning.
Adolescent↗
Electroencephalographic Seizure Duration in Electroconvulsive Therapy: A Clinical Study.
Electroencephalographic estimates of electroconvulsive therapy (ECT)-induced seizure duration were obtained in 141 patients with major depression (n = 41) or schizophrenia (n = 100). A slight reduction in seizure duration across a course of ECT failed to reach statistical significance and was unrelated to clinical improvement.
Journal Article↗
Rapamycin insensitivity in Schistosoma mansoni is not due to FKBP12 functionality.
Rapamycin (RAPA) is a well-known immunosuppressant, the action of which is mediated by the immunophilin FKBP12. Upon RAPA binding, FKBP12 forms ternary complexes with phosphatidyl inositol related kinases known as the target of RAPA (TOR), which can lead to a mitotic block at the G1-S phase transition. Such an antiproliferative effect makes RAPA an attractive anticancer, antifungal or antiparasitic compound. In this study, we found the helminth parasite Schistosoma mansoni to be insensitive to the drug. In order to elucidate the mechanism underlying RAPA resistance, the S. mansoni drug receptor FKBP12 (SmFKBP12) was cloned for functional analysis. Western blot experiments showed that the protein is constitutively expressed in all life cycle stages and in both male and female parasites. The Escherichia coli-synthesised recombinant protein possessed enzymatic activity, which was inhibitable by RAPA. Moreover, SmFKBP12 was able to complement mutant Saccharomyces cerevisiae cells lacking FKBP12 in their RAPA sensitivity phenotype, leading us to conclude that SmFKBP12 is expressed in yeast in a functional form and capable of interacting with the drug and yeast TOR kinase. Even though the wild type SmFKBP12 appeared to restore a large part of RAPA sensitivity, a mutation of Asp(89)-Lys(90) to Pro(89)-Gly(90) in the schistosome protein was found to be more effective and restored drug sensitivity to the same level as the endogenous yeast protein. Despite ternary complex formation, our results suggest that additional unknown factors other than a functional drug receptor are implicated in drug resistance mechanisms.
Amino Acid Sequence↗