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Biomedical subjects

A Cavalli

Publications and source records attributed to A Cavalli.

At least 91 records · Page 5Linked to original sources

Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens.

In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B.

Ammonium Chloride↗

Autopresentation of hepatitis B virus envelope antigens by T cells.

Processing and presentation by T cells appear to be limited to antigens that can directly interact with the T-cell surface, thereby overcoming the T-cell inefficiency in antigen capture and internalization. Our study provides evidence that the hepatitis B virus (HBV) envelope proteins can also be efficiently processed and presented by CD4+ and CD8+ T cells to other T cells in a human leukocyte antigen class II-restricted fashion. This phenomenon suggests a receptor-mediated interaction between T cells and the HBV envelope and defines a system that can, we hope, be exploited for the identification of the receptor binding site within the HBV envelope and for the characterization of the putative cellular HBV receptor.

Antigen-Presenting Cells↗

[The frequency of early coronary reperfusion assessed by electrocardiographic criteria in relation to the timing of thrombolytic therapy in acute myocardial infarct].

This study was aimed at assessing coronary reperfusion in patients with acute myocardial infarction (AMI) undergoing systemic thrombolysis with SK and rtPA. The occurrence of reperfusion was related to the time of treatment. The evaluation of reperfusion was performed by monitoring ST segment changes. 56 patients with AMI were studied. 22 out of these (39.2%) showed a significant decrease (greater than 50%) in ST segment sum (sigma ST) at 100 minutes from the beginning of the treatment. Analysis of the relationship between reperfusion and elapsed time between the onset of symptoms and the treatment, reveals that the reperfusion is less frequent (p less than 0.05) in patients treated at 180 minutes or later. The standard electrocardiogram appears as the most useful method to evaluate indirectly coronary reperfusion in acute myocardial infarction. A further refinement of this method is desirable to recommend its widespread clinical use. The assessment of reperfusion by means of ECG in large series of patients will permit the evaluation of the benefits of reperfusion, in terms of survival, complications and incidence of ventricular dysfunction.

Adult↗

Release of acetylcholine by Xenopus oocytes injected with mRNAs from cholinergic neurons.

Xenopus laevis oocytes were injected with poly(A)+ mRNAs extracted from the electric lobes of Torpedo marmorata. The electric lobes contain the perikarya of approximately 120,000 cholinergic neurons that innervate the electric organs and are homologous to motor neurons. The injected oocytes accumulated acetylcholine and were able to synthesize [14C]acetylcholine from 1-[14C]acetate. With KCl depolarization and upon treatment with a Ca2+ ionophore, they released their endogenous as well as the radiolabelled neurotransmitter in a Ca(2+)-dependent manner. No synthesis or release were obtained from control oocytes. With respect to their dependency upon Ca2+ concentration, the oocytes injected with Torpedo electric lobe mRNAs released acetylcholine in a manner which closely resembled that found in the native synapses. In contrast to the controls, primed oocytes were also able to release [14C]acetylcholine that was injected a few hours prior to the release trial. Immunoblot analysis demonstrated that the 15 kd proteolipid antigen of the purified mediatophore, a 200 kd presynaptic protein able to translocate acetylcholine, was expressed in the ACh-releasing oocytes but not in the controls. The present observation may provide a useful approach for investigating the proteins involved in the release of acetylcholine and of other neurotransmitter substances.

Acetates↗

Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen.

Several lines of experimental evidence suggest that inclusion of core sequences in the hepatitis B vaccine may represent a feasible strategy to increase the efficacy of the vaccination. In order to identify immunodominant core epitopes, peripheral blood T cells purified from 23 patients with acute hepatitis B and different HLA haplotypes were tested with a panel of 18 short synthetic peptides (15 to 20 amino acids [AA]) covering the entire core region. All patients except one showed a strong T cell proliferative response to a single immunodominant 20 amino acid sequence located within the aminoterminal half of the core molecule. Two additional important sequences were also identified at the aminoterminal end and within the carboxyterminal half of the core molecule. These sequences were able to induce significant levels of T cell proliferation in 69 and 73% of the patients studied, respectively. T cell response to these epitopes was HLA class II restricted. The observations that (a) polyclonal T cell lines produced by PBMC stimulation with native HBcAg were specifically reactive with the relevant peptides and that (b) polyclonal T cell lines produced with synthetic peptides could be restimulated with native HBcAg, provide evidence that AA sequences contained within the synthetic peptides represent real products of the intracellular processing of the native core molecule. In conclusion, the identification of immunodominant T cell epitopes within the core molecule provides the molecular basis for the design of alternative and hopefully more immunogenic vaccines.

Amino Acid Sequence↗

[Evaluation of the kinetics of MB creatine kinase in patients undergoing systemic thrombolytic therapy].

This study was aimed to evaluate if the time-course of creatinkinase MB in acute myocardial infarction (AMI) is influenced by therapy and which index, derived from the enzymatic curve, is the most reliable marker of successful coronary artery recanalization. We studied the enzymatic curves in 38 patients with transmural myocardial infarction, 19 treated with streptokinase (SK) and 19 with tissue plasminogen activator (rtPA). Blood samples were obtained every 2 hours for the first 12 hours and every 6 hours until the level of serum CK returned to baseline. Three indexes were calculated: peak serum enzyme level, time to peak enzyme level and maximal enzyme rise velocity. Time to peak did not differ significantly between SK and rtPA groups. Peak levels were significantly higher (414 +/- 40 vs 249 +/- 33; p = 0.004) in rtPA groups, as well as maximal enzyme rise velocity (1.7 +/- 0.4 vs 0.8 +/- 0.1; p = 0.02). However, infarct size evaluated by the total release of CK-MB in 28 patients was greater in rtPA group (10949 +/- 1097 vs 6346 +/- 869; p = 0.002). These findings suggest that differences in peak level and in maximal velocity of rise observed between SK and rtPA are due to differences in infarct size and not to a different recanalization rate. Thus, enzymatic estimate of infarct size significantly correlates to peak enzyme (r = 0.894, p less than 0.001), and to maximal rise velocity (r = 0.518, p = 0.007) but not to time to peak (r = 0.208, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗

[Electrocardiographic diagnosis of ventricular tachycardia in patients with previous myocardial infarct: frequency and significance of diverse diagnostic criteria].

Electrocardiographic tracings of ventricular tachycardia were recorded from 34 patients with old myocardial infarction. The diagnostic criteria of ventricular tachycardia were carefully assessed in each tracing. The most commonly observed signs were: 1) QRS duration greater than 140 msec; 2) a prevalent negative deflection in Lead V6; 3) an interval from the beginning of the QRS complex to the S wave nadir greater than 100 msec in at least one precordial lead. The cases were subdivided into two groups on the basis of a predominant positive or negative deflection in Lead V1 (Group 1 and 2, respectively). The most common signs in Group 1 were a monophasic R wave configuration of the QRS complex in Lead V1, and a QS configuration in Lead V6. On the other hand, the most frequent criteria in Group 2 were an interval between the beginning of the QRS complex and the S wave nadir greater than 60 msec in Lead V1, and a QS configuration in Lead V6. Furthermore, none of the cases reflected a normal frontal plane QRS axis, but an axis deviation was evident in all 29 cases where axis could be calculated.

Diagnosis, Differential↗

Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection.

The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance.

Adult↗

Incidence and prognosis of secondary ventricular fibrillation in acute myocardial infarction. Evidence for a protective effect of thrombolytic therapy. GISSI Investigators.

The multicenter randomized study of the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico has provided the opportunity to analyze the impact of thrombolytic treatment on secondary ventricular fibrillation incidence in a large population of patients (11,712) with acute myocardial infarction. A reduction of about 20% in the frequency of secondary ventricular fibrillation was observed among patients allocated to thrombolytic treatment (streptokinase, 2.4% versus control, 2.9%; relative risk, 0.80; 95% confidence interval, 0.64-1.00). Streptokinase appeared to exert its protective effect specifically in patients treated within 3 hours of onset of symptoms (streptokinase, 2.6% versus control, 3.7%; relative risk, 0.71; 95% confidence interval, 0.53-0.95). This protection was essentially due to a reduced incidence of late ventricular fibrillation occurring after the first day of hospitalization. The 311 patients with secondary ventricular fibrillation represented an overall incidence of 2.7%. Such incidence was not related to infarct location or sex but was significantly more common in patients older than 65 years (3.3% versus 2.3% in younger patients). A significant excess of in-hospital deaths was found in patients with secondary ventricular fibrillation compared with those in the reference group (38% versus 24%; relative risk, 1.98; 95% confidence interval, 1.56-2.52). Conversely, secondary ventricular fibrillation was not a predictor of 1-year mortality for hospital survivors. Thrombolytic treatment with intravenous streptokinase affords protection against secondary ventricular fibrillation most probably by a limitation of infarct size. When the arrhythmia complicates the course of infarction, it is associated with an adverse short-term outcome, whereas the long-term prognosis is not influenced.

Aged↗

One-year prognosis of primary ventricular fibrillation complicating acute myocardial infarction. The GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico) investigators.

The 1-year prognosis of 293 patients discharged alive from the hospital after acute myocardial infarction (AMI), who experienced primary ventricular fibrillation (VF) in the acute phase, was compared with that of a reference group of 6,337 patients identified from the same population included in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico (GISSI) trial. There was no difference in the 6- and 12-month mortality between the patients with primary VF and the reference group (3.7 vs 2.7% and 4.1 vs 4.2%, respectively). Survival of the 2 groups was also similar when patients were stratified according to infarct site (anterior and posterior), and whether or not they received treatment with streptokinase during AMI. Thus, long-term mortality of patients discharged alive after AMI complicated by primary VF is low and is not influenced by previous fibrinolytic therapy or by infarct site. The excess mortality of patients with primary VF is confined to the hospital phase, after which survivors represent a low-risk subgroup.

Adrenergic beta-Antagonists↗

Evaluation of Western immunoblotting technique in the serological diagnosis of human syphilitic infections.

Purified human syphilitic antibodies against both 15.5 Kd and 45 Kd treponemal antigens appear T. pallidum specific and do not cross react with antigens possessed by other treponemes (T. phagedenis, T. hyodysenteriae and a human intestinal treponeme). By using Western immunoblotting technique, 107 out of 110 syphilitic patients and 291 out of 294 subjects with serologically positive diagnostic tests for syphilis were found to have in their sera antibodies against a 15.5 Kd specific antigen of T. pallidum. These antibodies were present in 100% of the patient with secondary or early latent syphilis, both untreated and treated, in 98.24% of those with late latent treated syphilis and in 100% of patients with neurosyphilis. On the contrary, they were absent in 47 patients with false positive reactions for syphilis and in 121 healthy blood donors. For these reasons, the demonstration of these kind of antibodies in a patient's serum can be considered of high value in differentiating syphilitic patients from non infected individuals.

Antibodies, Bacterial↗

Ibopamine as a substitute for digitalis in patients with congestive heart failure on chronic digoxin therapy. Smith Kline and French Ibopamine Group.

The substitution of digoxin with ibopamine, a new inotropic and vasodilating agent, was evaluated in a multicenter study in 58 patients with mild-to-moderate congestive heart failure, stabilized on diuretics, and digoxin therapy. The study was a parallel, double-blind, randomized trial of four weeks duration in which half of the group continued the pre-study medication (diuretics and digoxin) and half of the group was treated with diuretics and ibopamine (100 mg, three times a day). At baseline evaluation, the two groups were similar for age, sex, underlying cardiac disease, duration of congestive heart failure, symptom score, cardiothoracic ratio, echocardiographic parameters of left ventricular function and exercise tolerance as measured by bicycle ergometry. After four weeks, no clinical deterioration was found in the patients treated with ibopamine in any measured parameter. There were two deaths during the study: a sudden death and one following an acute myocardial infarction. Both patients were on digoxin. This study suggests that in patients with mild-to-moderate congestive heart failure, ibopamine therapy may effectively and safely substitute digoxin therapy for up to four weeks, representing an option for patients requiring inotropic support but are at risk for potential digoxin toxicity.

Adult↗

The preS1 antigen of hepatitis B virus is highly immunogenic at the T cell level in man.

14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man.

Chromobox Protein Homolog 5↗

Ibopamine: long-term safety study in patients with congestive heart failure. The Italian Ibopamine Working Group.

Ibopamine is a new orally active dopamine analogue with positive inotropic and vasodilating activity. The tolerability of the drug administered at the dose of 100 mg thrice daily for 12 months was studied in 302 patients with congestive heart failure, New York Heart Association (NYHA) class II and III. Of the 302 patients, 198 completed the study (65%); 59 patients (19%) were withdrawn for clinical events; 27 of them died (9%); 35 patients (12%) did not complete the study for non-compliance and 10 (3%) for protocol violations. Clinical events were generally related to the cardiovascular system and 85% of deaths were from cardiovascular causes. None of the deaths was considered related to treatment by the investigators. Clinically significant laboratory abnormalities were observed during the study in four patients only. This trial suggests that ibopamine is well tolerated in patients with congestive heart failure, NYHA class II and III, at the dose of 100 mg thrice daily for up to one year.

Adolescent↗