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Biomedical subjects

C Caserta

Publications and source records attributed to C Caserta.

7 recordsLinked to original sources

Sensory representation of passive movement kinematics by rat's spinocerebellar Purkinje cells.

In this paper we examined Purkinje cells' sensory representations of kinematic parameters of passive movements imposed to the forelimb of anesthetized rats. Simple spike Purkinje cell activity was recorded while the rat's ipsilateral forearm was moved passively along circular footpaths at two different speeds. We found that the activity of 35.33% (165/467) of the neurons was significantly modulated during movement cycles. A multivariate regression analysis indicated that movement direction was the predominant factor in determining Purkinje cell activity, whereas movement velocity (i.e. the combination of movement direction and speed) was represented to a much lesser degree. Based on this result, we might suggest that a cortical efferent copy is necessary to the cerebellum in order to elaborate a movement velocity signal.

Action Potentials↗

Distribution of spinocerebellar Purkinje cell responses to passive forelimb movements in the rat.

We recorded Purkinje cell activity throughout the spinocerebellum of anaesthetized rats while imposing circular passive movements to the unrestrained forelimb. The aim was to understand the type of processing of sensory information occurring at the level of the cerebellar cortex, on the basis that precerebellar sensory neurons have been shown to represent whole limb movement parameters better than single joint movements. We observed that neurons representing sensory aspects of arm movements were scattered throughout the spinocerebellar cortex without a distinct segregation from those that did not respond, albeit the relative density of responsive and unresponsive neurons was quite variable and depended on the area of the cortex. Furthermore, Purkinje cells that responded significantly to the arm movement cycles all showed the same response pattern consisting of a firing rate increase during the downward extension of the arm. These results are discussed as suggesting a coordinate framework for the representation of proprioceptive information in the cerebellum congruent to that observed for encoding motor parameters.

Animals↗

Electromyographic effects of serotonin application into the lateral vestibular nucleus.

Electromyographic responses (EMGs) of limb muscles were studied during microiontophoretic application of 5-hydroxytryptamine (5-HT) into the lateral vestibular nucleus (LVN) or the spinal vestibular nucleus (SpVe) of anaesthetized rats. The aim was to ascertain whether the level of 5-HT in these nuclei was able to modulate muscle responsiveness. Increased levels of 5-HT in LVN (and to a weaker extent in SpVe) enhanced the EMGs of proximal extensor muscles and depressed those of flexors. The 5-HT2A receptor antagonist ketanserin, applied into the LVN, prevented 5-HT effects on EMG-evoked responses. It is concluded that 5-HT can modulate the motor output via the vestibulospinal pathway, exerting a differential control over flexor and extensor muscles.

Animals↗

HIV protease substrate conformation: modulation by cyclophilin A.

Cyclophilin A (CyPA), a cytosolic peptidyl-prolyl trans-cis isomerase can accelerate the trans-cis isomerization of Xxx-Pro peptide bonds. One- and two-dimensional 1H-NMR spectroscopy were used to determine that the heptapeptide Ser-Gln-Asn-Tyr-Pro-Ile-Val, a model peptide of an HIV-1 protease cleavage site in the gag polyprotein of HIV-1, is a substrate for CyPA. Experiments revealed a slow exchange about the Tyr-Pro peptide bond with 30 +/- 5% in the cis conformation (pH 1-9). While the interconversion rate is too slow to measure by kinetic NMR methods in the absence of CyPA, these methods, saturation transfer and NOE experiments, established that CyPA enhanced the rate of trans-cis interconversion, a process inhibited by cyclosporin A (CsA). With a substrate:CyPA ratio of 40:1, an interconversion rate of 2.5 s(-1) at 25 degrees C was observed.

Amino Acid Isomerases↗

Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells.

BACKGROUND: Proximal tubular epithelial cells express a surface C3-convertase activity which induces C fixation and insertion of the C5b-9 membrane attack complex (MAC) into the cell plasma membrane. The physiopathological consequences of this phenomenon are unknown. METHODS: The effect of C fixation on the production of inflammatory mediators by human proximal tubular epithelial cells in culture was explored. RESULTS: Proximal tubular epithelial cells incubated with a sublytic amount of normal human serum as a source of C, but not with heat-inactivated human serum, showed a time-dependent calcium influx and a concomitant release of 14C-arachidonic acid (14C-AA). Eicosanoid synthesis following the arachidonic acid mobilization was studied as prostaglandin E2 release. Mg2+/EGTA, which did not prevent C activation by the C3-convertase, and p-bromodiphenacyl bromide a phospholipase A2-inhibitor, inhibited mobilization of 14C-AA. These results suggest the activation of an extracellular Ca(2+)-dependent, phospholipase A2. Complement fixation was associated with the synthesis of proinflammatory cytokines such as IL-6 and TNF-alpha. Experiments with C6-deficient sera indicated that the release of 14C-AA and the production of cytokines were dependent on the insertion of the terminal components of complement in the plasma membrane. Indeed, the reconstitution of normal haemolytic activity of C6-deficient sera with purified C6 restored also the release of 14C-AA and the production of cytokines. CONCLUSIONS: In vitro complement activation on the proximal tubular cell surface triggers the generation of proinflammatory mediators, which may potentially contribute to the pathogenesis of tubulointerstitial injury.

Arachidonic Acid↗

Interstitial deletion of 4(q21q25) in a liveborn male.

We describe a liveborn male with a de novo deletion of 4(q21q25). The findings in this infant are compared with those of other 4q interstitial deletion patients with similar break-points. Given the reproducible findings including skull asymmetry, cardiac defects, renal cysts, "butterfly" vertebrae, as well as a particular dysmorphic face with developmental delay, there is evidence for an interstitial 4q deletion syndrome.

Abnormalities, Multiple↗

Modeling of biological and medical systems: a systemic strategy.

A strategy in the frame of General System Theory is proposed for the study of biological systems for medical purposes. Its definition and use requires in each experiment the collaboration between physician and system scientists and hence the definition of a common language, by which the real system under study is described. The strategy is based on three intermingled steps: first an ingenuous model is proposed, gathering all the medical knowledge about the studied system, organized within an informal frame derived from the state space approach. Next, a functional model is derived, enlightening the organization of the relations in the medical model. Finally, this organization is formalized by the most suitable algebraic tools, which are thereafter translated into APL programs. This last version is used for simulation, which is exploited not only as a tool to describe and make provisions on the dynamics of the models, but also to deepen and improve the knowledge about the observed system.

Computer Simulation↗