PubMed Health⌕ Search

Biomedical subjects

G Bosco

Publications and source records attributed to G Bosco.

At least 19 recordsLinked to original sources
PubMed2006

Spatial anisotropy in the encoding of three-dimensional passive limb position by the spinocerebellum.

In an earlier study, we found that the encoding of limb position in the sagittal plane across the population of spinocerebellar Purkinje cells was anisotropic with a preferential gradient along horizontal direction. The aim of this study was to extend to a three-dimensional (3D) workspace the analysis of the relationships between Purkinje cells activity and rat's forelimb spatial position. In anesthetized animals, the extracellular activity of 121 neurons was recorded while a robot passively placed the limb in 18 positions within a cubic workspace (3x3x3 cm). In order to characterize the relationship between spatial locations and Purkinje cell activity we performed a backward stepwise regression starting from a model with three independent variables representing the antero-posterior, the medial-lateral and the vertical axes of workspace. Regression analysis showed that the firing of most cells was modulated exclusively along the antero-posterior (25%) or the medial-lateral (38%) axis, while a small portion was related only to the vertical axis (8%), indicating a generalized nonuniform sensitivity of Purkinje cells to limb displacement in 3D space.

Action Potentials↗
PubMed2006

Hyperbaric oxygenation ameliorates indomethacin-induced enteropathy in rats by modulating TNF-alpha and IL-1beta production.

The effect of hyperbaric oxygenation (HBO2) was investigated in a rat model of indomethacin-induced enteropathy. Enteropathy was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) 24 hr apart. Six groups of rats (n=8) were treated with and without HBO2 (100% oxygen at 2.3 atm absolute) for 1 hr once or twice a day for 2 or 5 days. Disease activity index (DAI) and total ulcer length were measured. Other rats were randomized into two groups (n=16) with and without HBO2 (1 hr once a day) and four rats were killed in each group at 12, 24, 48, and 72 hr after the final injection of indomethacin. Serum and intestinal mucosal TNF-alpha, IL-1beta, myeloperoxidase (MPO), and iNOS expression was measured. HBO2 treatment significantly attenuated indomethacin -induced intestinal ulceration and improved DAI. Indomethacin increased MPO activity and iNOS expression, and these were reduced by HBO2 treatment, with a concomitant reduction in TNF-alpha and IL-1beta. Our data suggest that HBO2 treatment has a beneficial effect on indomethacin-induced enteropathy and this effect is possibly mediated by decreased production of TNF-alpha and IL-1beta.

Animals↗
PubMed2006

Phase-specific sensory representations in spinocerebellar activity during stepping: evidence for a hybrid kinematic/kinetic framework.

The dorsal spinocerebellar tract (DSCT) provides a major mossy fiber input to the spinocerebellum, which plays a significant role in the control of posture and locomotion. Recent work from our laboratory has provided evidence that DSCT neurons encode a global representation of hindlimb mechanics during passive limb movements. The framework that most successfully accounts for passive DSCT behavior is kinematics-based having the coordinates of the limb axis, limb-axis length and orientation. Here we examined the responses of DSCT neurons in decerebrate cats as they walked on a moving treadmill and compared them with the responses passive step-like movements of the hindlimb produced manually. We found that DSCT responses to active locomotion were quantitatively different from the responses to kinematically similar passive limb movements on the treadmill. The differences could not be simply accounted for by the difference in limb-axis kinematics in the two conditions, nor could they be accounted for by new or different response components. Instead, differences could be attributed to an increased relative prominence of specific response components occurring during the stance phase of active stepping, which may reflect a difference in the behavior of the sensory receptors and/or of the DSCT circuitry during active stepping. We propose from these results that DSCT neurons encode two global aspects of limb mechanics that are also important in controlling locomotion at the spinal level, namely the orientation angle of the limb axis and limb loading. Although limb-axis length seemed to be an independent predictor of DSCT activity during passive limb movements, we argue that it is not independent of limb loading, which is likely to be proportional to limb length under passive conditions.

Action Potentials↗
PubMed2006

Recurrent cerebrovascular ischaemic events in patients with interatrial septal abnormalities: a follow-up study.

The aim of this study was to evaluate the risk of recurrent ischaemic cerebrovascular events (stroke or transient ischaemic attack (TIA)) in patients with patent foramen ovale (PFO) or atrial septal aneurysm (ASA) treated with different therapeutic regimens. We enrolled 86 patients aged 18-60 years with an unexplained ischaemic stroke or TIA referred to our inpatient department in the period May 1994-December 1999. Follow-up lasted until April 2003. Patients were excluded if the stroke or TIA was related to large-artery atherosclerosis, small artery occlusion, major cardiac sources of embolism or other uncommon causes. During a follow-up (mean+/-SD) of 64.1+/-28.8 months (range 8.1-105.6) a recurrent ischaemic cerebrovascular event occurred in 11/86 patients (12.8%) (5 TIA and 6 strokes). Eight events (4 TIA, 4 strokes) occurred in the 59 patients with PFO alone, three (1 TIA, 2 strokes) in the 21 with PFO plus ASA and none in the 6 patients with ASA alone. In the overall population the cumulative risk of recurrent stroke/TIA was 1.2% at 2 years, 5.5% at 4 years, 7.6% at 6 years and 23.6% at 8 years, and was similar in patients with PFO alone vs. patients with PFO plus ASA (9.0% vs. 6.1% at 6 years, 26.0% vs. 23.1% at 8 years; p>0.05). Nine cerebral ischaemic events (4 TIA, 5 strokes) occurred in the 48 patients treated with antiplatelet drugs (7 in patients with PFO, 2 in patients with PFO plus ASA), and two (1 TIA, 1 stroke) in the 17 patients treated with oral anticoagulants (1 with PFO, 1 with PFO plus ASA). No events occurred in patients submitted to transcatheteral closure.

Adolescent↗
PubMed2005

Kinematic and non-kinematic signals transmitted to the cat cerebellum during passive treadmill stepping.

Previous work from this laboratory has shown that activity in the dorsal spinocerebellar tract (DSCT) relates strongly to global hindlimb kinematics variables during passive displacements of the hindlimb. A linear relationship to limb axis orientation and length variables accounts for most of the response variance for passive limb positioning and movement. Here we extend those observations to more natural movements by examining the information carried by the DSCT during passive stepping movements on a treadmill, and we compare it to information transmitted during passive robot-driven hindlimb movements. Using a principal component analysis approach, we found that a linear relationship between the responses and hindlimb kinematics was comparable across experimental conditions. We also observed systematic non-linearities in this relationship for both types of movement that could be attributed to events corresponding to the touch-down and lift-off phases of the movement. We concluded that proprioceptive information transmitted to the cerebellum by the DSCT during locomotion has at least two major components. One component is associated with limb kinematics (limb orientation) and may be more or less related to the metrics of the step (stride length, for example) or its velocity. The other component is associated with limb length and/or limb loading, and it may signal some aspect of limb stiffness.

Animals↗
PubMed2005

Apolipoprotein E polymorphism and stroke subtypes in an Italian cohort.

BACKGROUND: Studies have indicated that apolipoprotein E (ApoE)-epsilon4 is a risk factor for ischemic cerebrovascular diseases (ICVD), but the existence of this association is still controversial. The aims of this study were: (1) to compare ApoE genotype and allele frequencies in Italian cases with ICVD and in healthy control subjects and (2) to compare ApoE allele frequencies among ischemic stroke subtypes. METHODS: A hospital-based cohort of 302 Italian subjects with ICVD and 228 healthy subjects have been recruited to investigate the role of ApoE polymorphisms as risk factors for ICVD. TOAST criteria were employed to stratify ICVD cases by subtypes. RESULTS: No significant differences in ApoE genotype and allele frequencies were found between cases and control subjects. The frequency of ApoE-epsilon4 was lower in cases than in control subjects (6% vs. 10.1%), although not significantly. No differences in ApoE genotype and allele frequencies were evident among ICVD subtypes. However, out of 36 ApoE-epsilon4 alleles 23 (3.7%) were found in subjects with ICVD related to primary degenerative arterial disease related to large vessel disease and small vessel disease, and 13 (2.1%) in remaining subjects. Using logistic regression analysis we assessed whether ApoE-epsilon4 allele was independently associated with risk of ICVD related to a primary degenerative arterial disease compared to other ICVD subtypes. While classical risk factors were significantly associated with higher risk for ICVD due to large vessel disease and small vessel disease than other ICVD subtypes, the role of ApoE-epsilon4 allele was not significant (OR 1.25, 95% CI 0.57-2.74). CONCLUSION: Our study shows similar ApoE-epsilon4 genotype and allele frequencies in patients with ICVD and in control subjects. No differences were found among different ICVD subtypes either.

Adult↗
PubMed2003

Modulation of dorsal spinocerebellar responses to limb movement. I. Effect of serotonin.

Spinocerebellar neurons (DSCT) receive converging sensory information from various sensory receptors in the hindlimbs and lower trunk. Previous studies have shown that sensory processing by DSCT neurons results in a representation of global hindlimb kinematic parameters such as the length and the orientation of the limb axis. In addition to the sensory input, the DSCT circuitry also receives a descending input from the raphe nuclei in the brain stem. Recent studies have demonstrated that the raphe serotonergic terminals synapse directly on DSCT neurons and exert a differential modulatory influence on their sensory inputs. We examined the role of serotonergic modulation on the DSCT representation of hindlimb kinematic parameters by recording DSCT activity during passive hindlimb movements before and after perturbing serotonergic transmission. We used two types of perturbation: electrical stimulation of the raphe areas in the brain stem to release serotonin in the spinal cord (42 neurons) and intravenous administration of serotonergic agonists or antagonists, mostly the 5HTP2 antagonist ketanserin (30 neurons). We found that movement responses were altered in approximately 70% of the DSCT units studied with each protocol. Changes could include shifts in mean firing rate, increases or decreases in response amplitude, and changes in response waveform. We used a principal component analysis (PCA) to examine waveform components and to determine how they contributed to the response waveform changes caused by serotonin perturbation. Such changes could be explained by new or different response components that might indicate a modification in the data processing or by a different weighting of existing components that might indicate a modification of synaptic weighting. The results were consistent with the second alternative. We found that the same underlying response components could account for both control responses and those altered by serotonin perturbations. The observed changes in waveform could be entirely accounted for by a re-weighting of response components. In particular, the changes observed after raphe stimulation could be accounted for by selective changes in the weighting of the first principal component (PC) with only minor changes of the weighting of the second PC. Because these response components were shown previously to correlate with the limb axis orientation and length trajectories respectively, the finding is consistent with the idea that limb axis length and orientation information are processed separately within the spinal circuitry.

Animals↗
PubMed2003

Modulation of dorsal spinocerebellar responses to limb movement. II. Effect of sensory input.

Dorsal spinocerebellar tract (DSCT) neurons receive converging sensory inputs from muscle, skin, and joint receptors and their cerebellar projection is a product of the spinal sensory processing of movement-related information. We concluded earlier that DSCT activity relates to global rather than to local parameters of hindlimb postures and movement, specifically to a kinematic representation of the limb endpoint. The waveforms of principal components (PCs) derived from an ensemble of DSCT movement responses were found to correlate with either the waveform of the limb axis length or orientation trajectories. It was not clear, however, whether these global representations resulted from neural processing or from biomechanical factors. In this study, we perturbed the limb biomechanical factors by decoupling limb geometry from endpoint position during passively applied limb trajectories patterned after a step cycle. We used two types of perturbations: mechanical constraints that limited joint rotations and electrical stimulation of hindlimb muscles. We found that about half of the 89 cells studied showed statistically different response patterns during the perturbations. We compared the PCs of the altered responses with the PCs of the control responses, and found two basic results. With the joint constraints, >85% of the total variance in both control and changed responses was accounted for by the same five PCs that were also observed in the earlier study. The differences between altered and control responses could be fully accounted for by changes in the PC weighting, suggesting a modulation of global response components rather than an explicit representation of local parameters. With the muscle stimulation, only the first and third PCs were the same for the control and altered responses. The second PC was modified, and additional PCs were also required to account for the altered responses. This suggests that the stimulus parameters were specifically represented in the responses. The changes induced by both types of perturbation affected primarily the weighting or waveform of the second PC, which relates to the limb axis length trajectory. The results are consistent with the suggestion that information about limb orientation and length may be separately modulated.

Animals↗
PubMed2002

Independent representations of limb axis length and orientation in spinocerebellar response components.

Dorsal spinocerebellar tract (DSCT) neurons transmit sensory signals to the cerebellum that encode global hindlimb parameters, such as the hindlimb end-point position and its direction of movement. Here we use a population analysis approach to examine further the characteristics of DSCT neuronal responses during continuous movements of the hind foot. We used a robot to move the hind paw of anesthetized cats through the trajectories of a step or a figure-8 footpath in a parasagittal plane. Extracellular recordings from 82 cells converted to cycle histograms provided the basis for a principal-component analysis to determine the common features of the DSCT movement responses. Five principal components (PCs) accounted for about 80% of the total variance in the waveforms across units. The first two PCs accounted for about 60% of the variance and they were highly robust across samples. We examined the relationship between the responses and limb kinematic parameters by correlating the PC waveforms with waveforms of the joint angle and limb axis trajectories using multivariate linear regression models. Each PC waveform could be at least partly explained by a linear relationship to joint-angle trajectories, but except for the first PC, they required multiple angles. However, the limb axis parameters more closely related to both the first and second PC waveforms. In fact, linear regression models with limb axis length and orientation trajectories as predictors explained 94% of the variance in both PCs, and each was related to a particular linear combination of position and velocity. The first PC correlated with the limb axis orientation and orientation velocity trajectories, whereas second PC with the length and length velocity trajectories. These combinations were found to correspond to the dynamics of muscle spindle responses. The first two PCs were also most representative of the data set since about half the DSCT responses could be at least 85% accounted for by weighted linear combinations of these two PCs. Higher-order PCs were unrelated to limb axis trajectories and accounted instead for different dynamic components of the responses. The findings imply that an explicit and independent representation of the limb axis length and orientation may be present at the lowest levels of sensory processing in the spinal cord.

Anesthesia↗
PubMed2002

Encoding of hindlimb kinematics by spinocerebellar circuitry.

Earlier work from our laboratory showed that principal component waveforms (PCs) from an ensemble of DSCT movement responses correlated with either the waveform of the limb axis length or orientation trajectories, suggesting that DSCT circuitry might elaborate an explicit representation of limb endpoint kinematics independent from limb geometry. In this study, we tested this idea by decoupling limb geometry from endpoint position with mechanical constraints that blocked the motion of the knee joint during step-like movements applied passively to the hindlimb of anesthetized cats. Only about half of the 50 cells studied showed statistically different response patterns when the limb was constrained compared to the unconstrained condition (control). However, the PC waveforms extracted from responses that showed significant changes with the knee constrained were found to be identical to those extracted from control responses. Instead, the differences between constrained and control responses could be accounted for by changes in the weighting of PCs suggesting a modulation of global response components rather than an explicit representation of local parameters.

Action Potentials↗
PubMed2002

The stiff-person syndrome. Case report.

The stiff-person syndrome is a rare and disabling disorder, characterized by muscle rigidity with superimposed painful spasms involving axial and limb musculature. The clinical symptoms are continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest and the spasms that are precipitated by tactile stimuli, passive strach, volitional movement of affected or unaffected muscles, startling noises and emotional stimuli. Both the rigidity and the spasms are relieved by sleep, general anaesthesia, myoneural blockade and peripheral nerve blockade. The cause of the stiff-person syndrome is unknown but an autoimmune pathogenesis is suspected because 1) the presence in the cerebrospinal fluid (CSF) of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotrasmitter gamma-aminobutyric acid (GABA), 2) the association of the disease with other autoimmune disorders, 3) the presence of various autoantibodies and 4) a strong immunogenetic association. The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin and baclofen, provide modest relief of clinical symptoms. Immunomodulatory agents such as steroids, plasmapheresis and intravenous immunoglobulin, seem to offer substantial improvement.

Aged↗
PubMed2001

Hyperbaric O2 reduces intestinal ischemia-reperfusion-induced TNF-alpha production and lung neutrophil sequestration.

Treatment with hyperbaric O2 (HBO) ameliorates ischemia-reperfusion (I/R) injury. Since tumor necrosis factor-alpha (TNF-alpha) plays an important role in I/R injury, we hypothesized that the effect of HBO in I/R injury may be due to its ability to inhibit TNF-alpha production. In this study, one group of rats received HBO during 60 min of ischemia (HBO group, n = 9), while control rats endured the same procedure but did not receive HBO (non-HBO, n = 9). A group of sham-operated control rats (SHAM, n = 6) underwent laparotomy without occlusion of the artery and HBO treatment. Intestinal I/R led to an increase in serum TNF-alpha concentration to [mean (SEM)] 165 (32) pg/ml (P < 0.01 vs SHAM rats). HBO attenuated this increase [34 (9) pg/ml; P<0.05 vs non-HBO group]. Intestinal I/R also resulted in a marked increase in lung myeloperoxidase content [0.62 (0.04) U/g vs 0.17 (0.02) U/g of SHAM rats, P<0.01]. HBO suppressed this increase [0.40 (0.04) U/g, P<0.05 vs non-HBO rats]. HBO ameliorated the injury to the intestine and lung. The number of neutrophils sequestered in the lung was reduced in HBO rats compared to non-HBO rats [6.4 (0.9) neutrophils/per oil field and 10.9 (2) neutrophils/per oil field, respectively; P < 0.05]. These findings demonstrate that HBO inhibits TNF-alpha production during intestinal I/R, and this reduced TNF-alpha production may be attributed to the beneficial effects of HBO.

Acute Disease↗
PubMed2001

Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation.

Cdc42 and WASP are critical regulators of actin polymerization whose function during T cell signaling is poorly understood. Using a novel reagent that specifically detects Cdc42-GTP in fixed cells, we found that activated Cdc42 localizes to the T cell:APC contact site in an antigen-dependent manner. TCR signaling alone was sufficient to induce localization of Cdc42-GTP, and functional Lck and Zap-70 kinases were required. WASP also localized to the T cell:APC contact site in an antigen-dependent manner. Surprisingly, WASP localization was independent of the Cdc42 binding domain but required the proline-rich domain. Our results indicate that localized WASP activation requires the integration of multiple signals: WASP is recruited via interaction with SH3 domain-containing proteins and is activated by Cdc42-GTP concentrated at the same site.

Antigen-Presenting Cells↗
PubMed2001

DNA replication control through interaction of E2F-RB and the origin recognition complex.

The E2F transcription factor and retinoblastoma protein control cell-cycle progression and DNA replication during S phase. Mutations in the Drosophila dE2F1 and dDP genes affect the origin recognition complex (DmORC) and initiation of replication at the chorion gene replication origin. Here we show that mutants of Rbf (an retinoblastoma protein homologue) fail to limit DNA replication. We also show that the dDP, dE2F1 and Rbf proteins are located in a complex with DmORC, and that dE2F1 and DmORC are bound to the chorion origin of replication in vivo. Our results indicate that dE2F1 and Rbf function together at replication origins to limit DNA replication through interactions with DmORC.

Animals↗
PubMed2001

Low-density lipoprotein apheresis in a patient aged 3.5 years.

UNLABELLED: A 3.5 y-old girl carrying a severe mutation of the LDL-receptor gene known as "FH Pavia", affected by homozygous familial hypercholesterolaemia (FH), and at high risk of developing coronary artery atherosclerosis was treated with selective dextran sulphate cellulose (DSC) column low-density lipoprotein apheresis (LDL-a). This is the youngest patient ever treated with LDL-a. Plasma total cholesterol (982 mg/dl) and LDL-cholesterol (939 mg/dl) (T-Chol, LDL-Chol) levels at baseline showed a transient decrease: -13.4%, and -16.8%, respectively, after 9 mo of combined treatment with a diet, cholestyramine (max. 12 g/d) and atorvastatin (max. 30 mg/d). However, the drugs were discontinued because of intolerance and an increase in aminotransferases and creatine phosphokinase in the plasma. Moreover, after 9 mo of this therapy, the mean plasma T-Chol and LDL-Chol levels were still high (930 mg/dl and 869.5 mg/dl, respectively). Therefore, 9 consecutive treatments with LDL-a were carried out every 15 d (plasma volumes treated: 1000-1700 ml). Mean plasma T-Chol, LDL-Chol, triglycerides (TG), and Lp(a) decreased significantly: -75.5%, -77.2%, -67.5% and -50.8%, respectively. HDL-cholesterol (HDL-Chol) concentration was considerably decreased immediately after apheresis because of haemodilution (X: -45.1%). CONCLUSION: LDL-a treatment improved the plasma apo B 100-containing lipoproteins--LDL, Lp(a)--profile in a homozygote with a severe inherited disorder in which coronary artery atherosclerosis frequently has its clinical onset before 10 y of age. At the time of this report, no significant side effects had been observed.

Blood Component Removal↗