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Biomedical subjects

G Luzzi

Publications and source records attributed to G Luzzi.

At least 19 recordsLinked to original sources
PubMed2004

HIV evolution: CTL escape mutation and reversion after transmission.

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Adult↗
PubMed2001

Usefulness of handgrip to improve ibutilide efficacy in organizing atrial electrical activity during atrial fibrillation.

We analyzed the effect of handgrip on atrial electrical activity during atrial fibrillation (AF) by recording right and left atrial activity in 15 patients with persistent AF under baseline conditions and after saline and ibutilide infusions. The handgrip test for 15 seconds, which was always associated with a significant increase in mean atrial cycle length, was recorded in both atria (right atrium: saline vs saline + handgrip 141 +/- 29 vs 171 +/- 24 ms, p <0.001; ibutilide vs ibutilide + handgrip: 197 +/- 43 vs 221 +/- 39 ms, p <0.005). Handgrip favorably modifies atrial electrophysiologic properties during AF.

Anti-Arrhythmia Agents↗
PubMed1999

Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.

Adoptive Transfer↗
PubMed1999

[Radiofrequency transcatheter ablation of a bidirectional decremental accessory atrioventricular pathway in the coronary sinus].

We report the case of a 63-year-old patient who underwent radiofrequency catheter ablation of an atrioventricular accessory pathway with bidirectional decremental conduction properties. The successful ablation site was the distal end of a wedge-shaped dilation of the first tract of the coronary sinus. Atrioventricular accessory pathways with anterograde decremental conduction properties was thought to belong to fibers with Mahaim type electrophysiological properties. They rarely show decremental retrograde conduction properties. Most Mahaim type atrioventricular pathways are right-sided with atrial insertion points at various sites along the tricuspid ring. On the other hand, left-sided decrementally conducting accessory pathways are very rare. Mahaim type atrioventricular pathways were never found in the coronary sinus. The bidirectional decremental conduction properties and in particular the anatomic site of the atrioventricular accessory pathway we describe in the present report are both very interesting findings.

Atrioventricular Node↗
PubMed1999

Automatic activity of a decremental long atrioventricular accessory pathway: an unusual feature.

The electrophysiological properties of decremental atrioventricular and atriofascicular pathways are not completely understood. We report the case of a patient with fast reentrant tachycardia due to a decremental long atrioventricular pathway, who showed a slow automatic tachycardia arising from the same pathway that was successfully eliminated by radiofrequency catheter ablation.

Adult↗
PubMed1998

Different trends of changes in heart rate variability in patients with anterior and inferior acute myocardial infarction.

Modifications in heart rate variability (HRV) parameters occur after acute myocardial infarction. The aim of this study was to evaluate the trend of HRV change during the acute phase and the first month after myocardial infarction, and establish whether they were affected by the anterior or inferior location of the infarction. The time-domain HRV measures of 59 patients with a first uncomplicated acute myocardial infarction were computed from 24-hour ECG recordings made on days 1, 2, 10, and 28 after hospital admission. At day 1, the mean RR cycle length (NN), the standard deviation of the NN intervals (SDNN), and the root mean square successive difference of NN intervals (RMSSD) were lower in the patients with anterior myocardial infarction. Although the parameters were similar in all of the patients at day 28, their behavior over time was different (P = 0.01): the SDNN in the patients with inferior myocardial infarction had decreased to the values found in anterior myocardial infarction patients by day 2 but, at day 10, both NN and SDNN tended to recover in both groups; RMSSD had diminished in both groups by day 2, but at day 10, had increased in the patients with anterior, but not in those with inferior myocardial infarction. These findings suggest that (1) in the very early phase of myocardial infarction, HRV is different in the two locations, (2) during the first hours of myocardial infarction patients with inferior location showed a greater vagal activity than patients with anterior location that became lower at day 10, and (3) the recovery of HRV is an early phenomenon in both groups, being already evident by the second week after myocardial infarction.

Case-Control Studies↗
PubMed1998

Radiofrequency catheter ablation of atrio-ventricular accessory pathways.

Radiofrequency catheter ablation of accessory pathways may represent the treatment of choice for patients with symptomatic atrio-ventricular reentrant tachycardia or atrial fibrillation and a high ventricular response through the accessory pathways with short antegrade refractory period. Moreover, catheter ablation has contributed towards understanding anatomical and electrophysiological characteristics of accessory pathways. As far as anatomical characteristics accessory pathways may be classified into fibers with proximal insertion in right or left atrium and fibers with proximal insertion in the atrio-ventricular nodal junction. As far as electrophysiological properties are concerned, accessory pathways may be differentiated into non-decremental and decremental. In non-decremental by-pass tracts (the so-called Kent bundles) the impulse can be conducted antegradely, retrogradely and in both directions. Decremental accessory pathways generally show only antegrade conduction properties (the so-called Mahaim fibers) and can be classified in long and short pathways; in particular, catheter ablation has given considerable evidence that the vast majority (but not all) of them has a proximal insertion on the tricuspid anulus (atrio-ventricular pathways) or on the atrio-ventricular node (nodo-ventricular pathways). Decremental accessory pathways with only retrograde conduction properties are involved in the so called "Permanent Junctional Reciprocating Reentrant Tachycardia".

Atrial Fibrillation↗
PubMed1997

Patterns of immunodominance in HIV-1-specific cytotoxic T lymphocyte responses in two human histocompatibility leukocyte antigens (HLA)-identical siblings with HLA-A*0201 are influenced by epitope mutation.

Primary human immunodeficiency virus (HIV) infection is controlled principally by HIV-specific cytotoxic T lymphocytes (CTL) to a steady-state level of virus load, which strongly influences the ultimate rate of progression to disease. Epitope selection by CTL may be an important determinant of the degree of immune control over the virus. This report describes the CTL responses of two HLA-identical hemophiliac brothers who were exposed to identical batches of Factor VIII and became seropositive within 10 wk of one another. Both have HLA-A*0201. The CTL responses of the two siblings were very dissimilar, one donor making strong responses to two epitopes within p17 Gag (HLA-A*0201-restricted SLYNTVATL and HLA-A3-restricted RLRPGGKKK). The sibling responded to neither epitope, but made strong responses to two epitopes presented by HLA-B7. This was not the result of differences in presentation of the epitopes. However, mutations in both immunodominant epitopes of the p17 Gag responder were seen in proviral sequences of the nonresponder. We then documented the CTL responses to two HLA-A*0201-restricted epitopes, in Gag (SLYNTVATL) and Pol (ILKEPVHGV) in 22 other HIV-infected donors with HLA-A*0201. The majority (71%) generated responses to the Gag epitope. In the 29% of donors failing to respond to the Gag epitope in standard assays, there was evidence of low frequency memory CTL responses using peptide stimulation of PBMC, and most of these donors also showed mutations in or around the Gag epitope. We concluded that HLA class I genotype determines epitope selection initially but that mutation in immunodominant epitopes can profoundly alter the pattern of CTL response.

Amino Acid Sequence↗
PubMed1997

Dependency of premature ventricular contractions on heart rate.

To identify a method for characterizing the dynamic behavior of ventricular arrhythmias at different heart rates, 201 consecutive patients with frequent premature ventricular contractions (PVCs) underwent two 24-hour electrocardiographic monitoring periods. The percentage of PVCs for each cycle length was calculated and then analyzed by linear regression analysis. On the basis of the significance of the p value, and the positive or negative value of the slope, we identified three trends: a tachycardia-enhanced pattern (p < 0.01, slope negative), a bradycardia-enhanced pattern (p < 0.01, slope positive), and an indifferent pattern (p > 0.01). During the first monitoring period, a tachycardia-enhanced pattern was present in 56 patients (28%), a bradycardia-enhanced pattern was present in 49 patients (24%), and an indifferent pattern was present in 96 patients (48%). This relationship was reproducible in 41 of the patients with a tachycardia-enhanced pattern (73%), in 29 of the patients with a bradycardia-enhanced pattern (59%), and in 70 patients with an indifferent pattern (72%). In conclusion, it is possible to identify a spontaneous trend between the incidence of ventricular arrhythmias and the length of the preceding cardiac cycle that seems to remain stable over time.

Adult↗
PubMed1997

Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS.

The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

A study of clinical and aetiological factors and possible associations of lichen sclerosus in males.

Lichen sclerosus is a chronic skin condition with a predilection for the genital area. In the present study, 35 male patients with lichen sclerosus were interviewed and examined. Blood screens were performed and histology was requested if not already performed. The findings indicate that lichen sclerosus in males exists as a spectrum of disease, ranging from a mild form with white plaques and few symptoms to a severe form with inflammation, atrophy and scarring with possible urological consequences. In many areas it differs from the condition in females; the association with autoimmune disease is weaker and there is less perianal and extragenital involvement. The association with malignancy in males is of lesser significance than initially believed.

Adolescent↗