Search PubMed⌕ Search

Biomedical subjects

L Bianchi

Publications and source records attributed to L Bianchi.

At least 109 records · Page 6Linked to original sources
PubMed2000

Linear classification of low-resolution EEG patterns produced by imagined hand movements.

Electroencephalograph (EEG)-based brain-computer interfaces (BCI's) require on-line detection of mental states from spontaneous EEG signals. In this framework, surface Laplacian (SL) transformation of EEG signals has proved to improve the recognition scores of imagined motor activity. The results we obtained in the first year of an European project named adaptive brain interfaces (ABI) suggest that: 1) the detection of mental imagined activity can be obtained by using the signal space projection (SSP) method as a classifier and 2) a particular type of electrodes can be used in such a BCI device, reconciling the benefits of SL waveforms and the need for the use of few electrodes. Recognition of mental activity was attempted on both raw and SL-transformed EEG data from five healthy people performing two mental tasks, namely imagined right and left hand movements.

Adult↗
PubMed2000

Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias.

The aim of this study was to test the hypothesis that some cases of drug-induced arrhythmias depend on genetic predisposition. Excessive prolongation of the QT interval and life-threatening arrhythmias (torsades de pointes or ventricular fibrillation) may occur in response to a variety of cardiac and noncardiac drugs, with detrimental effects on patient safety and the investments made by the pharmaceutical industry. Moss and Schwartz hypothesized that some drug-induced arrhythmias might represent cases of "forme fruste" of the congenital long QT syndrome (LQTS). The availability of molecular screening techniques for LQTS genes allowed us to test this hypothesis. An elderly female patient with documented cardiac arrest related to cisapride, a prokynetic drug that blocks I(Kr), and transiently prolonged QT interval underwent mutational analysis of the known LQTS-related genes performed by single-strand conformational polymorphism and DNA sequencing. Double-electrode voltage clamp in Xenopus oocytes as the expression system was used to study the in vitro cellular phenotype caused by the genetic defect in coexpression with the wild-type (WT) gene. Molecular analysis revealed a heterozygous mutation leading to substitution of a highly conserved amino acid in the pore region of KvLQT1. This mutation was present not only in the patient with ventricular fibrillation but also in her two adult asymptomatic sons who have a normal QT interval. In vitro expression of the mutated KvLQT1 protein showed a severe loss of current with a dominant negative effect on the WT-KvLQT1 channel. Our findings demonstrate that some cases of drug-induced QT prolongation may depend on a genetic substrate. Molecular screening may allow identification among family members of gene carriers potentially at risk if treated with I(Kr) blockers. Evolving technology may lead to rapid screening for mutations of candidate genes that cause drug-induced life-threatening arrhythmias and allow early identification of individuals at risk.

Aged↗
PubMed2000

Decreased levels of CD54 (ICAM-1)-positive lymphocytes in the peripheral blood in untreated patients with active juvenile dermatomyositis.

Significant abnormalities are observed in the peripheral blood of juvenile dermatomyositis (JDM) patients with active disease. In this study, we confirm that there is a significant increase in the relative percentage of B lymphocytes in the peripheral blood of a group of untreated children with newly diagnosed active JDM compared to healthy children (P < 0.0001). In order to investigate if properties intrinsic to B cells contributed to their relative increase in JDM, the percentage of B cells expressing activation markers (CD23, CD25, CD54, and CD69) was measured and compared to pediatric controls. Compared to healthy children less than 10 years of age (not significantly different from the JDM group), the JDM patients had an increase in the proportion of lymphocytes expressing CD19 (B cells; P = 0.0017) and decreases in the percentage of lymphocytes that were CD3(-) CD16(+) and/or CD56(+) (NK cells; P = 0. 01) and CD3(+) CD8(+) (T suppressor/cytotoxic cells; P = 0.02). There were no significant differences in any of the B-cell activation markers assessed. Of note, the percentage of CD54(+) non-B lymphocytes (i.e., T cells and NK cells expressing CD54) was significantly lower in the JDM patients (25% +/- 5%) than in the "age-related" healthy control group (43% +/- 4%; P = 0.013). These results suggest the following for untreated children with active JDM: (i) the increase in the percentage of peripheral blood B cells is not due to intrinsic B-cell activation, and (ii) CD54/ICAM-1(+) non-B cells, CD8(+) T cells, and NK cells are being removed from circulation and may be participating in the pathophysiology of the disease.

Dermatomyositis↗
PubMed2000

Mechanisms of I(Ks) suppression in LQT1 mutants.

Mutations in the cardiac potassium ion channel gene KCNQ1 (voltage-gated K(+) channel subtype KvLQT1) cause LQT1, the most common type of hereditary long Q-T syndrome. KvLQT1 mutations prolong Q-T by reducing the repolarizing cardiac current [slow delayed rectifier K(+) current (I(Ks) )], but, for reasons that are not well understood, the clinical phenotypes may vary considerably even for carriers of the same mutation, perhaps explaining the mode of inheritance. At present, only currents expressed by LQT1 mutants have been studied, and it is unknown whether abnormal subunits are transported to the cell surface. Here, we have examined for the first time trafficking of KvLQT1 mutations and correlated the results with the I(Ks) currents that were expressed. Two missense mutations, S225L and A300T, produced abnormal currents, and two others, Y281C and Y315C, produced no currents. However, all four KvLQT1 mutations were detected at the cell surface. S225L, Y281C, and Y315C produced dominant negative effects on wild-type I(Ks) current, whereas the mutant with the mildest dysfunction, A300T, did not. We examined trafficking of a severe insertion deletion mutant Delta544 and detected this protein at the cell surface as well. We compared the cellular and clinical phenotypes and found a poor correlation for the severely dysfunctional mutations.

Animals↗
PubMed2000

Heat-stress-induced hyperthermia alters CSF osmolality and composition in conscious rabbits.

Amino acids have received increased attention with regard to their thermoregulatory effects and possible role as neurotransmitters within the thermoregulatory system. The purpose of the present work was to evaluate in conscious rabbits the changes in cerebrospinal fluid (CSF) concentration of taurine, GABA, aspartate, and glutamate during exposure to high ambient temperature (50 min, 40 degrees C) to investigate their involvement in heat stress (HS). CSF and plasma osmolality and CSF concentrations of some cations and proteins were also determined. HS animals underwent transient hyperthermia and thereafter fully recovered. This was accompanied by a significant rise in CSF and plasma osmolality, CSF protein, calcium, taurine, and GABA. Artificial CSF osmolality measurements after addition of CaCl(2) or taurine demonstrated that the increased CSF osmolality after HS is accounted for, only in part, by the increased concentrations of either calcium and taurine. It is suggested that, during HS, taurine and GABA are released in the extracellular space of brain tissues in higher amounts, possibly to counteract the resulting hyperthermia.

Amino Acids↗
PubMed2000

Production of endogenous nitric oxide in chronic obstructive pulmonary disease and patients with cor pulmonale. Correlates with echo-Doppler assessment.

Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary disease (COPD) has been loosely related to the severity of illness, being significantly reduced in the most severe cases. Pulmonary hypertension is associated with lower NO output from the lung. In this study expired NO was measured in patients with severe stable COPD with or without cor pulmonale (CP). Echocardiographic estimates of right heart function, lung function, diffusion capacity, respiratory muscle strength, and arterial blood gases were obtained in 34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was measured by chemiluminiscence to obtain fractional exhaled concentrations at peak (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO showed a negative correlation with both systolic pulmonary artery pressure (Pspa) (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but not with any measurement of lung function. When the patients were divided according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7 +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6 +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO production from the airways was significantly lower and inversely related to development of CP in patients with severe COPD. Impaired endothelial release may account for the reduced levels of expired NO.

Aged↗
PubMed2000

A spectrum of histopathologic findings in autoimmune liver disease.

We retrospectively studied 42 liver biopsy specimens from 39 patients who met serologic and histologic criteria of autoimmune liver diseases. We found 10 cases of overlap syndrome (OLS), 10 autoimmune cholangitis (AIC), 10 primary biliary cirrhosis (PBC), and 9 autoimmune hepatitis (AIH) type 1. The following results were obtained: (1) Granulomas and biliary duct lesions were more prominent in PBC and AIC than in OLS and AIH. (2) Bile duct loss was not observed in AIH cases. (3) Features of hepatocellular damage such as piecemeal necrosis, spotty lobular necrosis, and confluent necrosis, were much more prevalent in OLS and AIH than in PBC and AIC. (4) HLA-DR antigen expression by hepatocytes was more frequent in AIH and OLS, whereas the expression of the same antigen by the bile duct epithelium was more frequent in PBC and AIC. We conclude there is a morphologic spectrum in autoimmune liver diseases, in which PBC forms one end of the spectrum, AIH the other, OLS the middle but closer clinically and histologically to AIH than to PBC, and AIC, which seems to be an antimitochondrial antibody-negative subtype of PBC.

Adult↗
PubMed2000

Exhaled nitric oxide and exercise in stable COPD patients.

STUDY OBJECTIVE: To evaluate exhaled nitric oxide (eNO) during exercise in patients with stable COPD. SETTING: Outpatient evaluation in a rehabilitation center. PATIENTS: Eleven consecutive male patients with stable COPD (age, 65 +/- 6 years; FEV(1), 56 +/- 10% predicted). Eight healthy (six men; age, 51 +/- 16 years) nonsmoking, nonatopic volunteers served as control subjects. METHODS: In each subject, a symptom-limited cycle ergometry test was performed by monitoring eNO with the tidal-breath method to assess eNO concentration (FENO) and output (VNO) at rest, peak exercise, and recovery time. RESULTS: Resting FENO (9.8 +/- 5.1 and 14.1 +/- 6.3 parts per billion, respectively) and VNO (4.2 +/- 2.0 and 5.9 +/- 3.4 nmol/min, respectively) were lower, although not significantly, in COPD patients than in control subjects. In both groups, FENO significantly decreased whereas VNO significantly increased during exercise. Both variables returned to baseline during the recovery time. Peak exercise VNO, but not FENO, was significantly lower in COPD patients than in control subjects (7.9 +/- 5.4 and 12.7 +/- 6.0 nmol/min, respectively, p < 0.05). The rise in VNO was weakly correlated to oxygen consumption VO(2)) both in control subjects (r = 0.31, p = 0. 002) and in COPD patients (r = 0.22, p = 0.03). FENO showed an inverse correlation to VO(2) in both groups (r = -0.53, p = 0.000; r = -0.31, p = 0.003 in control subjects and COPD patients, respectively). CONCLUSIONS: In patients with mild and moderate COPD, eNO during exercise parallels that observed in normal control subjects. VNO, but not FENO, is significantly reduced at peak exercise in COPD patients as compared with control subjects. The long-term effects of exercise training on eNO has to be evaluated by further studies.

Adult↗
PubMed2000

The appropriate setting of noninvasive pressure support ventilation in stable COPD patients.

STUDY OBJECTIVE: To evaluate the short-term physiologic effects of two settings of nasal pressure-support ventilation (NPSV) in stable COPD patients with chronic hypercapnia. DESIGN: Randomized controlled physiologic study. SETTING: Lung function units and outpatient clinic of two affiliated pulmonary rehabilitation centers. PATIENTS: Twenty-three patients receiving domiciliary nocturnal NPSV for a mean (+/- SD) duration of 31 +/- 20 months. METHODS: Evaluation of arterial blood gases, breathing pattern, respiratory muscles, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) during both unassisted and assisted ventilation. Two settings of NPSV were randomly applied for 30 min each: (1) usual setting (U), the setting of NPSV actually used by the individual patient at home; and (2) physiologic setting (PHY), the level of inspiratory pressure support (IPS) and external positive end-expiratory pressure (PEEPe) tailored to patient according to invasive evaluation of respiratory muscular function and mechanics. RESULTS: All patients tolerated NPSV well throughout the procedure. Mean U was IPS, 16 +/- 3 cm H(2)O and PEEPe, 3.6 +/- 1.4 cm H(2)O; mean PHY was IPS, 15 +/- 3 cm H(2)O and PEEPe, 3.1 +/- 1.6 cm H(2)O. NPSV was able to significantly (p < 0.01) improve arterial blood gases independent of the setting applied. When compared with spontaneous breathing, both settings induced a significant increase in minute ventilation (p < 0.01). Both settings were able to reduce the diaphragmatic pressure-time product, but the reduction was significantly greater with PHY (by 64%; p < 0.01) than with U (56%; p < 0.05). Eleven of 23 patients (48%) with U and 7 of 23 patients (30%) with PHY showed ineffective efforts (IE); the prevalence of IE (20 +/- 39% vs 6 +/- 11% of their respiratory rate with U and PHY, respectively) was statistically different (p < 0.05). CONCLUSION: In COPD patients with chronic hypercapnia, NPSV is effective in improving arterial blood gases and in unloading inspiratory muscles independent of whether it is set on the basis of patient comfort and improvement in arterial blood gases or tailored to a patient's respiratory muscle effort and mechanics. However, setting of inspiratory assistance and PEEPe by the invasive evaluation of lung mechanics and respiratory muscle function may result in reduction in ineffective inspiratory efforts. These short-term results must be confirmed in the long-term clinical setting.

Aged↗
PubMed1999

Effect of adenosine A2A receptor stimulation on GABA release from the striatum of young and aged rats in vivo.

The effect of the adenosine A2A receptor agonist CGS 21680 on GABA release from the striatum was investigated in vivo in young and old rats by microdialysis experiments. CGS 21680 at 10 microM significantly increased GABA spontaneous outflow in young but not in old rats. Conversely, CGS 21680 significantly increased potassium-evoked GABA release in old but not in young rats. The stimulating effect of CGS 21680 on spontaneous GABA release may be both secondary to an increased outflow of excitatory amino acids and to the removal, brought about by A2A receptor stimulation, of the inhibitory influence exerted by dopamine through D2 receptors on GABA-enkephalinergic neurones. The stimulating effect of CGS 21680 on potassium-evoked GABA release in old rats may be ascribed to an age-dependent imbalance in favour of adenosine vs. dopamine, recently described in the striatum of old rats.

Adenosine↗
PubMed1999

HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation.

Treatment with iron chelators mimics hypoxic induction of the hypoxia inducible factor (HIF-1) which activates transcription by binding to hypoxia responsive elements (HRE). We investigated whether HIF-1 is involved in transcriptional activation of the transferrin receptor (TfR), a membrane protein which mediates cellular iron uptake, in response to iron deprivation. The transcription rate of the TfR gene in isolated nuclei was up-regulated by treatment of Hep3B human hepatoma cells with the iron chelator desferrioxamine (DFO). The role of HIF-1 in the activation of TfR was indicated by the following observations: (i) DFO-dependent activation of a luciferase reporter gene in transfected Hep3B cells was mediated by a fragment of the human TfR promoter containing a putative HRE sequence; (ii) mutation of this sequence prevented stimulation of luciferase activity; (iii) binding to this sequence of HIF-1alpha, identified by competition experiments and supershift assays, was induced by DFO. Furthermore, in mouse hepatoma cells unable to assemble functional HIF-1, inducibility of TfR transcription by DFO was lost and TfR mRNA up-regulation was reduced. These results, which show the role of HIF-1 in the control of TfR gene expression in conditions of iron depletion, give insights into the mechanisms of transcriptional regulation which concur with the well-characterized post-transcriptional control of TfR expression to expand the extent of response to iron deficiency.

Animals↗
PubMed1999

Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation.

The tight relationship between oxygen and iron prompted us to investigate whether the expression of transferrin receptor (TfR), which mediates cellular iron uptake, is regulated by hypoxia. In Hep3B human hepatoma cells incubated in 1% O(2) or treated with CoCl(2), which mimics hypoxia, we detected a 3-fold increase of TfR mRNA despite a decrease of iron regulatory proteins activity. Increased expression resulted from a 4-fold stimulation of the nuclear transcription rate of the TfR gene by both hypoxia and CoCl(2). A role for hypoxia-inducible factor (HIF-1), which activates transcription by binding to hypoxia-responsive elements in the activation of TfR, stems from the following observations. (a) Hypoxia and CoCl(2)-dependent expression of luciferase reporter gene in transiently transfected Hep3B cells was mediated by a fragment of the human TfR promoter containing a putative hypoxia-responsive element sequence, (b) mutation of this sequence prevented hypoxic stimulation of luciferase activity, (c) binding to this sequence of HIF-1alpha, identified by competition experiments and supershift assays, was induced in Hep3B cells by hypoxia and CoCl(2). In erythroid K562 cells, the same treatments did not affect iron regulatory proteins activity, thus resulting in a stimulation of TfR gene expression higher than in hepatoma cells.

Cell Hypoxia↗
PubMed1999

Zidovudine-induced experimental myopathy: dual mechanism of mitochondrial damage.

Myopathy often complicates Zidovudine (AZT) treatment in patients with acquired immunodeficiency syndrome (AIDS). The pathogenesis of the myopathy is controversial, since clinical phenomena intrinsic to AIDS may interfere per se with the onset of the myopathy. In the present work we investigated the in vivo effect of AZT in an animal model species (rat) not susceptible to HIV infection. Histochemical and electron microscopic analyses demonstrated that, under the experimental conditions used, the in vivo treatment with AZT does not cause in skeletal muscle true dystrophic lesions, but rather mitochondrial alterations confined to the fast fibers. In the same animal models, the biochemical analysis confirmed that mitochondria are the target of AZT toxicity in muscles. The effects of AZT on mitochondria energy transducing mechanisms were investigated in isolated mitochondria both in vivo and in vitro. Membrane potential abnormalities, due to a partial impairment of the respiratory chain capability observed in muscle mitochondria from AZT-treated rats, closely resemble those of control mitochondria in the presence of externally added AZT. mtDNA deletion analysis by PCR amplification and Southern blot analysis did not show any relevant deletion, while mtDNA depletion analysis demonstrated a significant decrease in mtDNA in AZT-treated rats. The present findings show that AZT causes damage to mitochondria by two mechanisms: a short-term mechanism that affects directly the respiratory chain, and a long-term mechanism that alters the mitochondrial DNA thus impairing the mitochondrial protein synthesis. In addition, the ultrastructural observations indicate that the fiber types are differently affected upon AZT treatment, which poses a number of questions as to the pathogenesis of this myopathy.

Animals↗
PubMed1999

Beta(1-40) amyloid peptide injection into the nucleus basalis of rats induces microglia reaction and enhances cortical gamma-aminobutyric acid release in vivo.

The nucleus basalis of adult rats was injected with beta(1-40) amyloid peptide. A marked increase in basal and K(+)-evoked GABA release in the ipsilateral cortex and a significant decrease in GAD activity in the injected NB were found 30 days after injection. An intense activation of microglial cells that surrounded and infiltrated the deposit was observed. These data demonstrate that a local injection of beta(1-40) peptide into the NB induces glia activation and affects GABAergic neurons.

Amyloid beta-Peptides↗
PubMed1999

Striatal A2A adenosine receptors differentially regulate spontaneous and K+-evoked glutamate release in vivo in young and aged rats.

The effect of the adenosine A2A receptor agonist CGS 21680 on glutamate and aspartate release was investigated in the striatum of young and old rats by microdialysis experiments. CGS 21680 (10 microM) significantly increased glutamate and aspartate spontaneous outflow in young but not in old rats. On the contrary, CGS 21680 induced the same decrease in K+-evoked glutamate outflow in both young and aged rats. A lower dose of CGS 21680 (1 microM) failed to modify either spontaneous or K+-evoked outflow. It is suggested that the opposite effects of the A2A agonist on excitatory amino acid outflow may be respectively mediated by striatal A2A adenosine receptors located on glutamatergic terminals and on the striatal indirect output pathway.

Adenosine↗
PubMed1999

Simultaneous determination of basal and evoked output levels of aspartate, glutamate, taurine and 4-aminobutyric acid during microdialysis and from superfused brain slices.

A HPLC method, involving pre-column derivatisation with o-phthalaldehyde and fluorescence detection, is described. It allows the resolution of aspartate, glutamate, taurine and GABA, in a single run with detection limits of 3.2, 1.7, 1.4 and 2 fmol/microl of perfusate, respectively. It is sufficiently sensitive and rapid (15 min) for the determination "on line" of the four amino acids in perfusates obtained during in vivo microdialysis experiments. The procedure has been used to determine basal, K+ - or veratridine-stimulated release of these amino acids in different brain areas during microdialysis and from perfused tissue slices.

Animals↗