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PAOLO RUZZA ANDREA CALDERAN BRUNO FILIPPI BARBARA BIONDI ARIANNA DONELLA DEANA LUCA CESARO LORENZO A. PINNA GIANFRANCO BORIN 《Chemical biology & drug design》1995,45(6):529-539
Tyrosine protein kinases (TPKs) of the src family contain two major phosphoacceptor sites which are homologous to the Tyr 416 and Tyr 527 of pp60c-src. The former represents the main autophosphorylation sites of these enzymes, and its phosphorylation correlates with increased kinase activity. It has previously been demonstrated that the Src-like tyrosine kinase expressed by the oncogene lyn displays a high affinity toward the heptapeptide H-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-OH, which reproduces the main autophosphorylation site of the Src family enzymes [Donella-Deana, A., Marin, O., Brunati, A.M. & Pinna, L.A. (1992) Eur. J. Biochem. 204 , 1159–1163]. Our study was addressed to the synthesis of some derivatives of this sequence in order to obtain both peptide substrates suitable for the detection of the Src-like tyrosine kinase activity and active site-directed inhibitors specific for this class of enzymes. For this purpose we synthesized by classical solution methods the heptapeptide and its dimeric form. Moreover, in order to improve the proteolytic resistance of these peptides we also synthesized their cyclic derivatives and their N-terminal acetylated and C-terminal amidated analogs. The correlation between the different structural properties induced by the modifications of the native sequence and the propensity of the peptides to act as Lyn substrates was examined. The kinetic data obtained indicate that the extent of the peptide phosphorylation varies considerably depending on the flexibility and length of the analogs. While the cyclization and the C-terminal amidation of the heptapeptide are detrimental for the Lyn activity, dimeric derivatives display very favourable kinetic constants. In particular the cyclic dimer is an especially suitable substrate for the tyrosine kinase and a powerful inhibitor of both the phosphorylation activity of Lyn and the enzyme autophosphorylation. © Munksgaard 1995. 相似文献
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PAOLO RUZZA ARIANNA DONELLA DEANA ANDREA CALDERAN MICHELA PAVANETTO LUCA CESARO LORENZO A. PINNA GIANFRANCO BORIN 《Chemical biology & drug design》1995,46(6):535-546
Tyrosine-specific protein kinases and phosphatases are important signal transducing enzymes in normal cellular growth and differentiation and have been implicated in the etiology of a number of human neoplastic processes. In order to develop agents which inhibit the function of these two classes of enzymes by interfering with the binding of their substrates, we synthesized analogs derived from the peptide EDNEYTA. This sequence reproduces the main autophosphorylation site of Src tyrosine kinases. In this work we report the synthesis, by classical solution methods, of the phosphotyrosyl peptide ED-NEYpTA as well as of three analogs in which the phosphotyrosine is replaced by a phosphinotyrosine and by two unnatural, non-hydrolyzable amino acids 4-phosphonomethyl-l -phenylalanine and 4-phosphono-l -phenylalanine. The Src peptide and its derivatives were tested as inhibitors of three non-receptor tyrosine kinases (Lyn, belonging to the Src family, CSK and PTK-IIB) and a non-receptor protein tyrosine phosphatase obtained from human T-cell (TC-PTP). The biomimetic analogues, which do not significantly affect the activity of CSK, PTK-IIB and TC-PTP, act:is efficient inhibitors on Lyn, influencing both the exogenous phosphorylation and, especially, its autophosphorylation. In particular, the Pphe derivative may provide a basis for the design of a class of inhibitors specific for Lyn and possibly Src tyrosine kinases, capable of being used in vivo and in vitro conditions. © Munksgaard 1995. 相似文献
45.
FABIO DELL'AVVOCATA M.D. RAMESH DAGGUBATI M.D. HO THUONG DUNG M.D. NGUYEN THUONG NGHIA M.D. Ph.D. ARAVINDA NANJIUNDAPPA M.D. MASSIMO GIORDAN M.D. PAOLO CARDAIOLI M.D. 《Journal of interventional cardiology》2013,26(4):392-398
Backgrounds
We reported the short‐ and long‐term results of our institutional single center registry Interatrial Septum Interventions Study (ISIS) about the impact of different anatomic characteristics and related device selection in patent foramen ovale (PFO) closure.Methods
Over a 9 year period (September 2003–September 2012) we prospectively enrolled 340 consecutive patients (mean age 44 ± 15. 5 years, 198 females) who had been referred to our center for PFO catheter‐based closure. The first 105 patients received a single type of device independently from the anatomy (single device strategy). The remaining 235 patients received a different device based on intracardiac echocardiographic study of interatrial septum anatomy (anatomic strategy).Results
Immediate success rate was 100% in both groups, whereas the rate of immediate complications was 10.4% and 2.5% (P < 0.01) in the single strategy group and anatomic strategy group, respectively. During a mean follow‐up of 59.3 ± 28.9 months, the occlusion rate was 86.6% and 94%, whereas the incidence of recurrences was 1.8% and 0% in the single device strategy group and anatomic strategy group, respectively.Conclusion
The results from ISIS registry showed that anatomy of interatrial septum associated with PFO is quite complex leading to an increased rate of complications and a slightly lower closure rate if treated with a single device strategy.46.
PAOLO ALBONI SALVATORE SCARFÒ GIUSEPPE FUCÀ NELLY PAPARELLA DONATO MELE 《Pacing and clinical electrophysiology : PACE》1999,22(4):600-604
The hemodynamic effects of atrial flutter (AF) are unknown. The purpose of the present study was to investigate the changes in atrial and ventricular pressures after induction of AF. In 23 patients with paroxysmal AF (age 59 ± 9 years), a hemodynamic study was performed both during sinus rhythm and after induction of the tachyarrhythmia. During AF, 13 patients showed a fixed 2:1 AV conduction and 10 patients showed variable conduction. Mean right and left atrial pressures increased (P < 0.001) and right and left ventricular end-diastolic pressures decreased (P < 0.001) after induction of AF. Roth the increase in mean atrial pressures and the decrease in ventricular end-diastolic pressures were present either in the patients with fixed 2:1 AV (heart rate: 133 ± 15 beats/min) or in those with variable conduction (heart rate 96 ± 15 beats/min), but were more marked in the former. AF produces an impairment of atrial function, as evidenced by the increase in mean atrial pressures and reduction in ventricular end-diastolic pressures in the absence of an elevated heart rate. The mechanisms responsible for the increase in mean atrial pressures are unknown; however, atrial contractions against closed AV valves seem to play an important role. 相似文献
47.
LAURA VIZZOTTO MAURIZIO VERTEMATI CARLO TOMMASINI DEGNA PAOLO ASENI 《Journal of anatomy》2000,198(5):603-610
Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients. 相似文献
48.
CLAUDIO PRATOLA M.D. ELISA BALDO M.D. TIZIANO TOSELLI M.D. PASQUALE NOTARSTEFANO M.D. ARTALE PAOLO M.D. ROBERTO FERRARI M.D. Ph .D.† 《Pacing and clinical electrophysiology : PACE》2009,32(7):842-850
Introduction: The aim of this study was to compare contact versus noncontact mapping for radiofrequency (RF) ablation of any sustained post-myocardial infarction (MI) ventricular tachycardia (VT).
Methods: Forty patients with tolerated VT post-MI were randomized to RF ablation with contact (group 1) or noncontact (group 2) mapping systems. In both groups ablation of tolerated VT was guided by VT activation map confirmed by concealed entrainment. When untolerated VTs were induced, ablation was performed in group 1 according to pace mapping starting from the scar border zone and in group 2 according to the VT activation map confirmed by pace mapping.
Results: No differences were seen between the groups in terms of acute success rate of clinical VT ablation (95% vs 100%, respectively; P = ns) and in the noninducibility of any VT at the end of the procedure (55% vs 85%, respectively; P = 0.08). Moreover, untolerated VTs were eliminated in 30% of group 1 versus 83.3% of group 2 patients (P < 0.05). The mean total procedural and fluoroscopy times were 236.4 ± 42.7 and 29.0 ± 7.8 minutes in group 1 and 144.5 ± 50.8 and 23.4 ± 5.8 minutes in group 2 (P < 0.001 and < 0.05, respectively). At a mean follow-up of 15.2 ± 6.7 months no differences were seen in VT recurrences between groups, but noninducibility at the end of the procedure was predictive of freedom from recurrences (P < 0.001).
Conclusion: Both systems are useful for ablation of tolerated VT. Noncontact mapping is more effective for ablation of untolerated VT and allows the reduction of procedural and fluoroscopy times. Noninducibility at the end of the procedure seems predictive of freedom from recurrences during follow-up. 相似文献
Methods: Forty patients with tolerated VT post-MI were randomized to RF ablation with contact (group 1) or noncontact (group 2) mapping systems. In both groups ablation of tolerated VT was guided by VT activation map confirmed by concealed entrainment. When untolerated VTs were induced, ablation was performed in group 1 according to pace mapping starting from the scar border zone and in group 2 according to the VT activation map confirmed by pace mapping.
Results: No differences were seen between the groups in terms of acute success rate of clinical VT ablation (95% vs 100%, respectively; P = ns) and in the noninducibility of any VT at the end of the procedure (55% vs 85%, respectively; P = 0.08). Moreover, untolerated VTs were eliminated in 30% of group 1 versus 83.3% of group 2 patients (P < 0.05). The mean total procedural and fluoroscopy times were 236.4 ± 42.7 and 29.0 ± 7.8 minutes in group 1 and 144.5 ± 50.8 and 23.4 ± 5.8 minutes in group 2 (P < 0.001 and < 0.05, respectively). At a mean follow-up of 15.2 ± 6.7 months no differences were seen in VT recurrences between groups, but noninducibility at the end of the procedure was predictive of freedom from recurrences (P < 0.001).
Conclusion: Both systems are useful for ablation of tolerated VT. Noncontact mapping is more effective for ablation of untolerated VT and allows the reduction of procedural and fluoroscopy times. Noninducibility at the end of the procedure seems predictive of freedom from recurrences during follow-up. 相似文献
49.
MARGHERITA PADELETTI M.D. SIMONE VIGNINI M.D. GIUSEPPE RICCIARDI M.D. PAOLO PIERAGNOLI M.D. VALERIO ZACÀ M.D. MICHELE EMDIN M.D. STEFANO FUMAGALLI M.D. SANJA JELIC M.D. 《Pacing and clinical electrophysiology : PACE》2010,33(12):1462-1466
Background: Sleep disordered breathing (SDB), a common condition among patients with permanent pacemaker (PM), is associated with greater incidence of cardiac arrhythmias. Scarce availability of sleep laboratories and the high costs of nocturnal‐attended polysomnography limit the routine screening of patients with PM for SDB. We investigated whether a novel PM that utilizes variations in transthoracic impedance to record the fluctuations in breathing pattern and minute ventilation could be used to screen patients for SDB. Methods: Twenty patients who underwent dual‐chamber PM implantation were studied. The Talent 3 DR PM (SORIN Group Italy S.r.l., Milan, Italy) calculates apnea‐hypopnea index (AHI) by computing minute ventilation signal derived from transthoracic impedance measurements. Within a month after PM implantation, an in‐home respiratory monitoring was performed to evaluate the accuracy of PM‐derived AHI. Patients were followed for mean ± standard deviation, 487 ± 166 days. The PM was checked at each follow‐up visit to retrieve the information about recurrent arrhythmias. Results: Eleven patients were diagnosed with SDB by an in‐home respiratory monitoring. An AHI derived from an in‐home respiratory monitoring was similar to pacemaker‐derived AHI (27 ± 14 vs 16 ± 13 events/hour, P = 0.15). The cumulative incidence of cardiac arrhythmias, including atrial fibrillation, extrasystolic beats, sustained and nonsustained ventricular tachycardia, and supraventricular tachycardia was similar in patients with and without SDB. Conclusion: SDB is highly prevalent in patients with permanent pacemaker. Screening for SDB with Talent 3 DR PM may facilitate diagnosis and treatment of SDB. (PACE 2010; 33:1462–1466) 相似文献
50.
DANIEL B. SIMS M.D. LUIS I. GARCIA M.D. ANDREA MIGNATTI M.D. PAOLO C. COLOMBO M.D. MARGARET JONES N.P. NIR URIEL M.D. DONNA M. MANCINI M.D. ULRICH P. JORDE M.D. 《Pacing and clinical electrophysiology : PACE》2010,33(8):988-993
Background: Internal cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) reduce mortality, but are underutilized in routine clinical practice. The use of these devices in patients at the time of an initial evaluation at an advanced heart failure and cardiac transplantation center is unknown. Methods: We retrospectively analyzed consecutive patients who were enrolled in a database examining parameters of cardiopulmonary exercise testing in chronic heart failure (CHF) patients at the time of an initial outpatient evaluation at a tertiary care center. Rates of ICD and CRT use in eligible patients were determined. Results: Two hundred two patients had an average age of 54 ± 13 years and an average peak oxygen consumption (pVO2) of 12.5 ± 4.5 mL/kg/min. Of 97 patients eligible for an ICD only, 57% had an ICD at the time of evaluation. Sixty‐four percent of ICD‐eligible male patients had an ICD compared to 36% of ICD‐eligible female patients (P = 0.015). Of 105 patients meeting criteria for CRT, 54% had a CRT device. There was no difference between CRT use in eligible male and female patients. Conclusions: ICDs and CRT are underutilized in patients with severe CHF at the time of evaluation at a tertiary care center despite young age, objective functional limitation, and active consideration for advanced CHF therapies. Female patients have lower rates of ICD use than male patients. (PACE 2010; 988–993) 相似文献