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Biomedical subjects

C Basso

Publications and source records attributed to C Basso.

At least 19 recordsLinked to original sources
PubMed2005

Control of the CFTR channel's gates.

Unique among ABC (ATP-binding cassette) protein family members, CFTR (cystic fibrosis transmembrane conductance regulator), also termed ABCC7, encoded by the gene mutated in cystic fibrosis patients, functions as an ion channel. Opening and closing of its anion-selective pore are linked to ATP binding and hydrolysis at CFTR's two NBDs (nucleotide-binding domains), NBD1 and NBD2. Isolated NBDs of prokaryotic ABC proteins form homodimers upon binding ATP, but separate after hydrolysis of the ATP. By combining mutagenesis with single-channel recording and nucleotide photolabelling on intact CFTR molecules, we relate opening and closing of the channel gates to ATP-mediated events in the NBDs. In particular, we demonstrate that two CFTR residues, predicted to lie on opposite sides of its anticipated NBD1-NBD2 heterodimer interface, are energetically coupled when the channels open but are independent of each other in closed channels. This directly links ATP-driven tight dimerization of CFTR's cytoplasmic NBDs to opening of the ion channel in the transmembrane domains. Evolutionary conservation of the energetically coupled residues in a manner that preserves their ability to form a hydrogen bond argues that this molecular mechanism, involving dynamic restructuring of the NBD dimer interface, is shared by all members of the ABC protein superfamily.

ATP-Binding Cassette Transporters↗
PubMed2003

Comparison of the predation rate of freshwater cyclopoid copepod species on larvae of the mosquito Culex pipiens.

The predation rates of six copepod species: Acanthocyclops robustus G.O. Sars, Eucyclops neumani Pesta, Macrocyclops albidus Jurine, Mesocyclops longisetus Thibaud, Metacyclops grandis Kiefer and Metacyclops mendocinus Wierzejski (Copepoda: Cyclopidae) on mosquito larvae, Culex pipiens Linnaeus (Diptera: Culicidae) were assessed. Experiments consisted of 24-h incubations of one copepod and 10 larvae without extra food at 16 degrees C and 26 degrees C. Nine replicates were considered for each species and temperature. Predation rates (larvae per copepod per day) were: M. mendocinus (1.8), M. grandis (3.1), E. neumani (3.8), A. robustus (3.8), Ma. albidus (6.1) and Me. longisetus (7.0). There was a significant effect of both species and temperature on predation: all species experienced higher predation at 26 degrees C than at 16 degrees C, except for A. robustus whose predation rate was similar at both temperatures. These observations are consistent with previous results that point to Macrocyclops and Mesocyclops genera as important larval predators and suggest the need for field trials to evaluate the response of Ma. albidus and Me. longisetus under natural conditions in Uruguay.

Animals↗
PubMed2002

Unexpected mechanical bileaflet valve thrombosis in mitral position: what is better to do, re-replacement or thrombolysis.

BACKGROUND AND AIMS: The longevity of the mechanical heart valve prosthesis is an advantage when compared with its biological counterpart, although the former carries a risk of thrombosis depending on valve design, materials and host-related interface; therefore, a patient with a mechanical valve prosthesis, particularly in mitral position, is at risk for systemic thromboembolism even when properly anticoagulated. PATIENTS AND METHODS: We report a case of a 60-year-old woman who underwent a mitral valve replacement with a St. Jude Medical (SJM) standard bileaflet mechanical heart valve. RESULTS: On the twelfth post-operative day a primary thrombosis with blockage of the anterior valve leaflet occurred. CONCLUSIONS: Aware of the risk of recurrent thromboembolism in this special clinical framework and possible cerebral bleeding in case of thrombolysis, we replaced the prosthesis with a new biologic porcine valve, the SJM Biocor.

Acute Disease↗
PubMed2001

Dispersion of ventricular depolarization-repolarization: a noninvasive marker for risk stratification in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: We retrospectively investigated the value of clinical and ECG findings as well as QT-QRS dispersion in predicting the risk of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: Duration and interlead variability of the QT interval and QRS complex were measured manually from standard ECGs in 20 sudden death victims with ARVC diagnosed at autopsy (group I), in 20 living ARVC patients with sustained ventricular tachycardia (group II), in 20 living ARVC patients with </=3 consecutive premature ventricular beats (group III), and in 20 control subjects (group IV). QT and QRS dispersions were greater in group I (77.5+/-10.6 ms for QT and 45.7+/-8.1 ms for QRS) compared with group II (64.5+/-13.9 ms for QT [P=0.001] and 33.5+/-8.7 ms for QRS [P=0.0004]) and in group II compared with group III (48+/-8.9 ms for QT [P<0.0001] and 28+/-5.2 ms for QRS [P<0.0001]) and group IV (33.5+/-4.8 ms for QT [P<0.0001] and 18.5+/-3.6 ms for QRS [P<0.0001]). Negative T wave beyond V(1) and syncope were statistically more frequent in group I (P=0.02 and P=0.007, respectively). On multivariate analysis, QRS dispersion remained an independent predictor of sudden death (P<0.0001), followed by syncope (P=0.09). In assessing risk of sudden death, QRS dispersion >/=40 ms had a sensitivity and specificity of 90% and 77%, respectively; QT dispersion >65 ms, 85% and 75%, respectively; negative T wave beyond V(1), 85% and 42%, respectively; and syncope, 40% and 90%, respectively. CONCLUSIONS: QRS dispersion (>/=40 ms) was the strongest independent predictor of sudden death in ARVC. Syncope, QT dispersion >65 ms, and negative T wave beyond V(1) refined arrhythmic risk stratification in these patients.

Adolescent↗
PubMed2001

Right bundle branch block, right precordial st-segment elevation, and sudden death in young people.

BACKGROUND: Patients with the ECG pattern of right bundle branch block and right precordial ST-segment elevation may experience sudden death in the setting of either arrhythmogenic right ventricular cardiomyopathy (ARVC) or a functional electrical disorder such as Brugada syndrome. METHODS AND RESULTS: Among a series of 273 young (</=35 years) victims of cardiovascular sudden death who were prospectively studied from 1979 to 1998 in the Veneto Region of Italy, 12-lead ECG was available in 96 cases. Thirteen (14%; 12 males and 1 female aged 24+/-8 years) had right precordial ST-segment elevation, either isolated (9 cases) or associated with right bundle branch block (4 cases). At autopsy, all patients had ARVC (92%) except one, who had no evidence of structural heart disease. Compared with the 19 young sudden death victims with ARVC and no ST-segment abnormalities from the same series, those with AVRC and right precordial ST-segment elevation included fewer competitive athletes (17% versus 58%; P:=0.03), more often died suddenly at rest or during sleep (83% versus 26%; P:=0.003), and showed serial ECG changes over time (83% versus 0; P:=0.015), polymorphic ventricular tachycardia (33% versus 0; P:=0.016), and predominant fatty replacement of the right ventricular anterior wall (58% versus 21%; P:=0.05), CONCLUSIONS: Right precordial ST-segment elevation was found in 14% of young sudden death victims with available ECG. It mostly reflected underlying ARVC with predominant right ventricular anterior wall involvement and characterized a subgroup of patients who share with Brugada patients the propensity to die from non-exercise-related cardiac arrest and to exhibit dynamic ECG changes and polymorphic ventricular tachycardia.

Adult↗
PubMed2001

Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy type 2 (ARVD2).

Arrhythmogenic right ventricular dysplasia type 2 (ARVD2, OMIM 600996) is an autosomal dominant cardiomyopathy, characterized by partial degeneration of the myocardium of the right ventricle, electrical instability and sudden death. The disease locus was mapped to chromosome 1q42--q43. We report here on the physical mapping of the critical ARVD2 region, exclusion of two candidate genes (actinin 2 and nidogen), elucidation of the genomic structure of the cardiac ryanodine receptor gene (RYR2) and identification of RYR2 mutations in four independent families. In myocardial cells, the RyR2 protein, activated by Ca(2+), induces the release of calcium from the sarcoplasmic reticulum into the cytosol. RyR2 is the cardiac counterpart of RyR1, the skeletal muscle ryanodine receptor, involved in malignant hyperthermia (MH) susceptibility and in central core disease (CCD). The RyR2 mutations detected in the present study occurred in two highly conserved regions, strictly corresponding to those where mutations causing MH or CCD are clustered in the RYR1 gene. The detection of RyR2 mutations causing ARVD2, reported in this paper, opens the way to pre-symptomatic detection of carriers of the disease in childhood, thus enabling early monitoring and treatment.

Amino Acid Sequence↗
PubMed2001

Ventricular preexcitation in children and young adults: atrial myocarditis as a possible trigger of sudden death.

BACKGROUND: Sudden death (SD) in ventricular preexcitation (VP) syndrome is believed to be the result of atrial fibrillation with rapid ventricular response over the accessory pathway. Previous reports are anecdotal and often lack autopsy validation. METHODS AND RESULTS: Prevalence and clinicopathological features of VP were investigated in a series of 273 SDs in children and young adults (aged <or=35 years). Site of accessory atrioventricular (AV) connection was predicted by 12-lead ECG. Right and left AV ring together with the sinoatrial and AV septal junction were studied in serial histological sections. Ten patients (3.6%; male, mean age 24+/-7 years) had VP: 8 had Wolff-Parkinson-White (WPW) and 2 had Lown-Ganong-Levine (LGL) syndrome. Six patients had previous symptoms, and SD occurred at rest in all but 1. Pathological substrates of LGL consisted of AV-node hypoplasia and right-sided atrio-Hisian tract, respectively. In the 8 WPW patients, 10 total accessory AV pathways consisting of ordinary myocardium were found (7 left lateral, 2 right posterolateral, and 1 septal). These pathways were close to the endocardium (mean distance, 750+/-530 microm) and 310+/-190 microm thick. In 4 WPW patients (50%), isolated acute atrial myocarditis was found, which was polymorphous in 1 and lymphocytic in 3. CONCLUSIONS: VP accounted for 3.6% of SD in young people and was not preceded by warning symptoms in 40%. A left accessory pathway was the most frequent substrate, and its subendocardial location supports the feasibility of catheter ablation. Isolated atrial myocarditis may act as a trigger of paroxysmal atrial fibrillation that leads to SD.

Adult↗
PubMed2001

Sudden cardiac death in young people with apparently normal heart.

OBJECTIVE: The aim of the present study was to assess the prevalence of subtle morphologic substrates, clinically unrecognizable, underlying sudden cardiac death (SCD) in young people with apparently normal heart. METHODS: In the time interval 1979--1998, 273 consecutive cases of SCD in young people (< or =35 years) which occurred in the Veneto Region of Italy were prospectively studied. Following exclusion of extracardiac causes of sudden death, the heart was examined according to a detailed morphologic protocol consisting of macroscopic and histologic examination, including study of the specialized conduction system by serial sections. RESULTS: At macroscopic examination, 197 SCD victims (72%) had an overt underlying structural heart disease such as cardiomyopathy in 56, obstructive coronary atherosclerosis in 54, valve disease in 32, non-atherosclerotic coronary artery disease in 28, aortic rupture in 13, postoperative congenital heart disease in five, and other disease in nine. The remaining 76 cases (28%) (50 males and 26 females, aged 4-35 years, mean 23+/-5 years) had a macroscopically normal heart. A total of 28 of them (37%) had experienced one or more of the following prodroma: syncope, palpitations or both in 20, ECG abnormalities in 18 and arrhythmias in ten. In 79% of them, histologic examination disclosed concealed pathologic substrates consisting of focal myocarditis in 27 cases, regional arrhythmogenic right ventricular cardiomyopathy, mostly localized to RV outflow tract, in nine, and conduction system abnormalities in 24 (leading to ventricular preexcitation in 18 and heart block in six). In 16 hearts (6%) there was no evidence of structural heart disease even after histologic study. CONCLUSION: Macroscopic heart features were normal in nearly one-third of young SCD victims. In 79% of them, however, histologic study unmasked concealed pathologic substrates such as focal myocarditis or cardiomyopathy and conduction system diseases. A total of 16 victims (6%) had no evidence of structural heart disease and the mechanism of their SCD remained unexplained.

Adolescent↗
PubMed2001

Cardiogenic shock due to metastatic cardiac lymphoma: still a diagnostic and therapeutic challenge.

Myocardial involvement by metastatic lymphoma progressively leads to severe contractile impairment and fatal outcome. Correct diagnosis is often late due to misleading presentation signs. We report on a case of extensive cardiac involvement of a T-cell thymic lymphoma in a young woman, necessitating emergent extracorporeal membrane oxygenation (ECMO) circulatory support, with satisfactory hemodynamic recovery and subsequent ECMO weaning. Unfortunately, the following clinical course was rapidly fatal. This case seems to confirm that early aggressive instrumental diagnosis is crucial before severe myocardial impairment can prevent any therapeutic option. Extensive use of transesophageal echocardiographic examination and early endomyocardial biopsy are highly recommended.

Adult↗
PubMed2000

Spontaneously occurring arrhythmogenic right ventricular cardiomyopathy in the domestic cat: A new animal model similar to the human disease.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disease of incompletely resolved pathogenesis and is a largely unappreciated cause of sudden death in the young. METHODS AND RESULTS: Clinical features of 12 domestic cats with ARVC (7 male; 1 to 20 years old, mean 7.3+/-5.2 years) were right-sided congestive heart failure (n=8), supraventricular tachyarrhythmias (n=5), ventricular tachycardia (n=3), polymorphic ventricular arrhythmias (n=6), and right bundle-branch block (n=5). ARVC was suspected in all 8 cats examined with echocardiography by marked enlargement of the right ventricle (RV) and right atrium and tricuspid regurgitation. Eight died of cardiovascular disease and 4 died of noncardiac conditions. At autopsy, hearts of ARVC cats were characterized grossly by moderate-to-severe RV cavity enlargement and wall thinning (n=12) and apical aneurysm formation (n=6). Histology demonstrated pronounced RV lesions in all 12 ARVC cats, including marked myocardial injury (myocyte death and atrophy) and repair (fibrous and/or fatty replacement). Injury and repair were also evident in the left ventricle (LV) in 10 cats, and 2 had involvement of both atria. Myocarditis was present in 10 of the 12 ARVC cats. Apoptosis was detected in 9 ARVC cats (mean apoptotic index, 28+/-23% RV, 21+/-19% LV, and 17+/-15% ventricular septum) but not in controls. CONCLUSIONS: In the common domestic cat, we identified a clinically relevant cardiomyopathy that closely mimics ARVC in humans. This unique feline model of human disease will be relevant to defining pathogenesis and investigating mechanisms responsible for disease progression in ARVC.

Animals↗
PubMed2000

Familial effort polymorphic ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy map to chromosome 1q42-43.

In the present study we report on another cause of an arrhythmia associated with familial arrhythmogenic right ventricular cardiomyopathy (ARVC), which is linked to chromosome 1q42-43. Two families with 48 subjects were studied with 12-lead electrocardiography, 24-hour ambulatory electrocardiography, chest x-ray, M-mode and 2-dimensional echocardiography, signal-averaging electrocardiography, and exercise stress testing. Six subjects also underwent right and left ventricular angiography and electrophysiologic study. An endomyocardial biopsy was performed in 1 subject. The genetic study included pedigree reconstruction and linkage analysis with polymorphic DNA markers. Five young subjects died suddenly during exercise; autopsy was performed in 3 and showed segmental fibro-fatty replacement of the right ventricle, mostly at the apex. Two of them experienced syncopal attacks during effort. Sixteen living subjects, without arrhythmias at rest had polymorphic ventricular arrhythmias during effort; ARVC was diagnosed in 15, whereas 1 did not have any demonstrable cardiac abnormality. The remaining family members were healthy and did not have arrhythmias. The linkage study assigned the disease locus to chromosome 1q42-q43, in close proximity to the alpha-actinin 2 locus (maximal lod score was 5.754 at theta = 0) with a 95% penetrance. Thus, these data suggest that effort-induced polymorphic ventricular arrhythmias and juvenile sudden death can be due to adrenergic stimulation in a particular genetic group of ARVC patients. In these cases the pathology was segmental, mostly localized to the right ventricular apex. Ventricular arrhythmias that are present in these families differ from the monomorphic ones that are usually seen in patients with ARVC.

Adult↗