Search PubMed⌕ Search

Biomedical subjects

P Gallo

Publications and source records attributed to P Gallo.

At least 19 recordsLinked to original sources
PubMed1998

Time-course of interleukin-2 receptor expression in interferon beta-treated multiple sclerosis patients.

The time-course of CD25 (the 55-kD/alpha subunit of the interleukin-2 (IL-2) receptor) expression on CD4+ T lymphocytes, and serum levels of soluble IL-2 receptors (sIL-2R) and IL-2 were evaluated in relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta-1b (IFNbeta1b). Peripheral blood samples were collected before therapy (T0), and 1 (T1), 2 (T2), 3 (T3), 6 (T4), and 12 (T5) months after therapy initiation. While at T1 and T2, half the patients showed an increased number of circulating CD4+ CD25+ lymphocytes and an up-regulation of CD25 expression, at T3 this T-cell subset was significantly reduced in all the patients. From T4 to T5, however, the progressive return to pretreatment values was observed. Serum sIL-2R levels were not significantly affected by IFNbeta1b at any time point. IL-2 was detected in only a few patients at T0, and never at T1 to T5. The transient up-regulation of CD25+ expression that occurred in about 50% of the patients may explain the unchanged relapse rate observed during the first 2 to 3 months after starting IFNbeta1b therapy. Our study demonstrates that IFNbeta1b down-regulates CD25 expression in vivo. This effect, however, was observed only after 3 months of therapy, and was followed by the return to pretreatment values after 6 to 12 months. Taken all together, our findings suggest that IFNbeta1b only transiently affects CD25 expression in vivo, and that this effect cannot account for the reported long-lasting beneficial action of IFNbeta1b on RRMS.

Adjuvants, Immunologic↗
PubMed1998

Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. IV. Differential activation of human Th1 and Th2 lymphocytes and influence of the atopic status on lymphoma development.

Intraperitoneal transfer of PBMC from EBV+ donors into SCID mice leads to high human Ig levels in mouse serum and B cell lymphoproliferative disease. As these events depend on the activation of coinjected human T cells, we addressed the behavior of the Th1 and Th2 subsets in this model. Production of IFN-gamma, but not of Th2 cytokines such as IL-4, was detected in culture supernatants of PBMC stimulated in vitro with mouse splenocytes. Moreover, anti-CD3 stimulation of the human cells recovered from mice brought about IFN-gamma, but not IL-4, synthesis; on the other hand, PCR and in situ hybridization analysis of ex vivo-recovered cells disclosed the presence of mRNA for both cytokines following in vitro restimulation, thus suggesting posttranscriptional regulation of IL-4 gene expression. When SCID mice were inoculated with PBMC from atopic donors, whose Th1/Th2 profile displays an imbalance toward Th2 cells, tumor development rates were lower, and tumor latency was higher, compared with those in mice injected with PBMC from normal donors. Isotypic analysis of human Ig in mouse serum showed the exclusive presence of IFN-gamma-driven IgG subclasses; in addition, human IgE were low or undetectable in most cases. These findings indicate that following transfer into SCID mice, human Th1 lymphocytes undergo preferential activation, whereas Th2 function is down-regulated. Th1 lymphocytes probably are a major component in promoting EBV+ B cell expansion and tumor development; the individual Th1/Th2 profile could in part account for the as yet unexplained donor variability in tumor generation in this experimental model.

Adult↗
PubMed1998

Neuromuscular relaxants in non-cardiac surgery after cardiomyoplasty.

PURPOSE: Dynamic cardiomyoplasty is a therapeutic alternative to heart transplantation in irreversible cardiac insufficiency. Little information exists about the use of muscle relaxants in patients with cardiomyoplasty. In particular, it is not clear if the muscle flap is responsive to neuromuscular blockers. The purpose of this report is to describe the safe use of vecuronium in a patient with cardiomyoplasty. CLINICAL FEATURES: A 59-yr-old man, after cardiomyoplasty for dilated cardiomyopathy two years earlier, underwent general anaesthesia with fentanyl, propofol and vecuronium during surgery for intestinal ischaemia. Intraoperative transthoracic echocardiography showed that vecuronium did not affect muscle flap motion. Two days after surgery he died in septic shock. Post-mortem histological and immunohistochemical examination showed nervous degeneration of the flap probably as a result of the chronic low frequency pacing. There was also an increase in extrajunctional receptors and an alteration in junctional receptors, as demonstrated by the negative reaction to anti-synaptophysin antibodies, used to identify the neuromuscular plate. CONCLUSION: In patients undergoing non-cardiac surgery after previous cardiomyoplasty, muscle relaxants, such as vecuronium, may be used safely. Depolarising agents, such as succinylcholine, should probably be avoided because of the possible exaggerated actions on extrajunctional receptors.

Cardiomyoplasty↗
PubMed1998

Specific interaction between bovine cyclophilin A and synthetic analogues of cyclolinopeptide A.

Like cyclosporin A, cyclolinopeptide A binds specifically bovine cyclophilin A, inhibiting its peptidyl-prolyl cis-trans isomerase activity. We describe here the protein interaction with several synthetic analogues of cyclolinopeptide A, which are either homodetic or disulphide bridged heterodetic cyclopeptides characterized by different ring dimensions, in terms of dissociation and inhibition constants evaluated by fluorescence and inhibition of the enzyme activity, respectively. Dissociation constants from fluorescence experiments are practically identical and about 20-fold lower than for cyclosporin A. On the other hand, inhibition constants differ from compound to compound and are higher than for cyclosporin A. This result is therefore difficult to rationalize, but we would suggest decoupling between binding and inhibitory ability of cyclopeptides. The Pro1 residue of cyclolinopeptide A seems to play a fundamental role in determining the inhibition of the rotamase activity of cyclophilin A, as the homodetic analogue lacking this residue does not show any inhibitory ability. Similarly, heterodetic analogues with a ring size smaller than 7 residues do not display inhibition. We presume that the sequence -Pro-Pro-Phe-Phe- and a ring size of 8 residues for homodetic cyclic peptides could be used as starting points in the targeted synthesis of cyclopeptides able to bind both cyclosporin A and calcineurin. The only peptide showing similar values of the dissociation and inhibition constant is cyclolinopeptide A. This compound can be considered a novel model for the molecular design of immunosuppressant drugs.

Amino Acid Sequence↗
PubMed1998

Multiple sclerosis: IL-2 and sIL-2R levels in cerebrospinal fluid and serum. Review of literature and critical analysis of ELISA pitfalls.

The presence of interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2R) in the serum and cerebrospinal fluid (CSF) of patients suffering from multiple sclerosis (MS) has been extensively investigated. These studies, however, have produced conflicting results. The only significant finding concerns the frequent detection of increased sIL-2R levels in the serum in patients with relapsing-remitting MS (RRMS), especially after a short interval of time from the last relapse. Whether this finding can be used for clinical purposes requires further investigation. A standardization of the ELISA methods used to detect cytokines in biological fluids is urgently needed. Increased serum and/or CSF levels of IL-2 and sIL-2R strongly confirm a CD4+ Th1 activation.

Enzyme-Linked Immunosorbent Assay↗
PubMed1998

Time-course analysis of CD25 and HLA-DR expression on lymphocytes in interferon-beta 1b-treated multiple sclerosis patients.

To identify immunological markers that could be used to monitor relapsing-remitting multiple sclerosis (RRMS) course/activity during interferon beta 1b (IFN beta 1b) therapy, we longitudinally studied HLA-DR and CD25 expression by T lymphocytes in 15 IFN beta 1b-treated RRMS patients. Peripheral blood T cell subsets were analysed before therapy (T0), and after 1 (T1), 2 (T2), 3 (T3), 6 (T4) and 12 (T5) months after therapy initiation. HLA-DR expression and the CD3+HLA-DR+ T cell number showed a peculiar trend in almost all (14/15) the patients: a significant decrease at T1 and T2 followed by a return to pre-treatment levels from T3 to T5. At T1 and T2, eight patients showed an up-regulation of CD25 on CD4, as well as an increase in the CD4+CD25+ cell number. However, a marked, significant reduction of this T cell subset was observed in all the patients at T3, followed by the progressive return to pre-treatment values from T4 to T5. All the patients developed anti-IFN beta 1b 'binding' antibodies within the first three months of therapy. Our findings demonstrate that: (1) the expression of HLA-DR and CD25 on T cells, as well as the number of circulating CD3+HLA-DR+ and CD4+CD25+ cells, are only transiently reduced in vivo in IFN beta 1b-treated RRMS patients, (2) the expression of HLA-DR and CD25 on T lymphocytes cannot be used to monitor MS course/activity during IFN beta 1b therapy, (3) the long-lasting beneficial effect of IFN beta 1b on RRMS reported in the literature cannot be explained by the down-regulation of MHC class II antigens and/or interleukin-2 receptor expression induced by this cytokine.

Adjuvants, Immunologic↗
PubMed1998

Trade-offs in prenatal detection of Down syndrome.

OBJECTIVES: This paper presents the results of different screening policies for prenatal detection of Down syndrome that would allow decision makers to make informed choices. METHODS: A decision analysis model was built to compare 8 screening policies with regard to a selected set of outcome measures. Probabilities used in the analysis were obtained from official administrative data reports in Spain and Catalonia and from data published in the medical literature. Sensitivity analyses were carried out to test the robustness of screening policies' results to changes in uptake rates, diagnostic accuracy, and resources consumed. RESULTS: Selected screening policies posed major trades-offs regarding detection rates, false-positive results, fetal loss, and costs of the programs. All outcome measures considered were found quite robust to changes in uptake rates. Sensitivity and specificity rates of screening tests were shown to be the most influential factors in the outcome measures considered. CONCLUSIONS: The disclosed trade-offs emphasize the need to comprehensively inform decision makers about both positive and negative consequences of adopting one screening policy or another.

Abortion, Spontaneous↗
PubMed1997

Felodipine protects human atrial muscle from hypoxia-reoxygenation dysfunction: a force-frequency relationship study in an in vitro model of stunning.

AIMS: We aimed at investigating contractile changes after hypoxia-reoxygenation and dobutamine challenge in superfused human atrial pectinate muscle to see whether high versus low stimulation rate during hypoxia might account for outcome differences compatible with the definition of an in vitro model of myocardial stunning and whether pretreatment with the dihydropyridine Ca2+ entry blocker felodipine might afford protection. METHODS: Human right atrial trabeculae obtained from adult patients were superfused in an organ bath with oxygenated (O2 content 16 ml/l) and modified (NaHCO3 25.7 mmol/l) Tyrode's solution at 37 degrees C. Dobutamine (1 nmol/l to 10 micromol/l) was superfused in 10 oxygenated preparations to select the optimal drug concentration to be used in another 22 which were randomized. Group (A) consisted of time-related controls (Tyrodes's solution for 225 min at cycle length (CL) 1600 ms and no dobutamine). There were two test groups, respectively: (B) low (1600 ms CL) and (C) high (400 ms CL) stimulation rate. After 60 min of stabilization, in groups B and C, hypoxic superfusion (O2 content 5 ml/l) lasted 60 min, then reoxygenation (60 min) and dobutamine challenge (1 micromol/l, 15 min) were performed. Analysis of variance for repeated measures with the Greenhouse-Geisser correction, and a repeated measures model with structured covariance (preparation mass, length, width and time-varying time to peak tension) matrices were used whereby grouping (G), time (T) and G x T interaction were weighted. Force-frequency relationship and post-pausal potentiation were studied after each phase. Electrophysiology, histomorphometry and electron microscopy were carried out (n=6). Felodipine (0.1 micromol/l, n=5) pretreatment (15 min before hypoxia) was given in parallel experiments. RESULTS: Time-related controls showed approximately 10% per hour decrease of developed tension and the Paradise test provided approximately 80% of control values. In test groups (as compared to baseline values) contractility was decreased approximately 65% after hypoxia-reoxygenation and it increased approximately 25% after dobutamine (G, 0.0065<P<0.0155; T, P=0.00005; G x T, P=0.00005). High stimulation rate during hypoxia worsened hypoxia-reoxygenation contractile changes, whereas reversibility after dobutamine was less. In both B and C groups during hypoxia, contractility decreased quite rapidly, although by 10 min or so a plateau (approximately 50%) was reached in group B, whereas in group C contractility decreased to <20%. None of the covariates contributed significantly to predict the dependent variables investigated. Force-frequency relationship and post-pausal potentiation were repeatable, paralleled overall changes due to hypoxia, reoxygenation and dobutamine challenge and were useful to discriminate Ca2+-related diastolic processes thus helping index myocardial contractile reserve. Force-frequency relationship was negative at high stimulation rates, concomitant to an abrupt change of shape and duration of action potential with little time for Ca2+-related Ca2+ release and ensuing systolic processes. Felodipine pretreatment enabled an unblunted response to dobutamine. Histomorphometry showed an unexpected 'fibrotic core'. At electron microscopy, subendocardial and deep part of the same pectinate muscles showed identical degrees of degenerative lesions. Superfused samples showed, unexpectedly, less anoxic lesions than preparations fixed within 15 min from surgical explant, although lesions were higher than in samples fixed immediately after explant. CONCLUSIONS: This might be a relevant model, whereby pharmacological or physical interventions are tested. Native human atrial trabeculae might be used without dissection and/or preservatives. If high stimulation rate during hypoxia is used the power of hypothesis testing is maximized. Future studies with this material will be easier and comparatively smaller series might be investigated. Felo

Adult↗
PubMed1997

Cytokine pattern in the cerebrospinal fluid from patients with GBS and CIDP.

Macrophage-colony stimulating factor (M-CSF) and, less frequently, IL-1 beta and IL-6 were detected in the cerebrospinal fluid (SF) from Guillain-Barré syndrome (GBS) patients. IL-1 alpha, IL-2, IL-10, TNF alpha, and IFN gamma were not found. Detectable cytokine levels were not observed in chronic inflammatory demyelinating polyneuropathy (CIDP) SF nor in any of the sera studied. These findings suggest a prominent intrathecal activation of cells of the monocyte/macrophage lineage (Mø) in GBS, and further support the hypothesis of a crucial role for Mø in GBS immunopathology.

Cytokines↗
PubMed1997

Valvular perforation in left-sided infective endocarditis: a prospective echocardiographic evaluation and clinical outcome.

We undertook this study to determine the use of transthoracic and transesophageal echocardiography in detecting valvular perforation and the clinical impact of the latter on the outcome of left-sided infective endocarditis. Transthoracic echocardiography was performed in 58 consecutive patients with infective endocarditis. According to the study protocol, a subgroup of 42 patients also underwent transesophageal echocardiogrophy. At referral, 20 (34%) of 58 patients had echocardiographic evidence of valvular perforation (group A). No valvular perforations were found in the remaining 38 patients (group B). During a follow-up period of 27 +/- 16 months, a major complication occurred in 18 of 20 patients in group A and in 11 of 38 patients in group B (p < 0.0001). Univariate analysis indicated previous infective endocarditis, aortic involvement, and New York Heart Association functional class had a predictive value for valvular perforation (p < 0.001). Stepwise regression analysis confirmed aortic valve perforation as the only independent predictive variable for surgery and death. Valvular perforation is a common complication of infective endocarditis and is associated with an adverse outcome. Transthoracic echocardiography can detect or suggest valvular perforation in infective endocarditis, but transesophageal echocardiography better defines this complication and predicts severe heart failure or the need for early surgical management.

Adult↗
PubMed1997

Protection from experimental autoimmune encephalomyelitis (EAE): non-depleting anti-CD4 mAb treatment induces peripheral T-cell tolerance to MBP in PL/J mice.

Following pre-treatment with a non-depleting anti-CD4 mAb (H129.19) that produces long-lasting receptor saturation, PL/J mice were fully protected from experimental auto-immune encephalomyelitis (EAE) induced by injection of myelin basic protein (MBP). These mice did not develop EAE following MBP re-challenge 5-10 weeks later when the CD4+ cells were no longer coated by the mAb and their lymph node cells were specifically unresponsive to MBP stimulation in vitro. Moreover, superantigen staphylococcal enterotoxin B (SEB) inoculation, which re-induces EAE in MBP immunized mice, failed to activate encephalitogenic T-cells in anti-CD4 + MBP treated mice, even after MBP re-challenge, indicating that tolerance in the peripheral T-cell compartment was achieved. However, MBP re-challenge 16 weeks later, but not SEB, produced an acute episode of EAE in these mice, while it failed to induce disease in a parallel group of adult thymectomized mice. These results indicate that no memory of the first priming exists at this time and that new MBP-specific T-cell precursors are peripheralized and produce EAE after MBP recognition.

Animals↗
PubMed1997

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma.

In neuroblastoma, high levels of mRNA for p140trkA and p75LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140trkA and ME20.4 anti-p75LNGFR mAbs. Although weak, positive immunostaining was found in 9 of 28 tumors for p140trkA and in 5 of 28 tumors for p75LNGFR. As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140trkA (p < 0.05) and 71% (20 of 28 cases) for p75LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.

Antibodies, Monoclonal↗
PubMed1997

An "ecological" constructional test.

We describe a simple, three-dimensional constructional test (the Box test), which reflects common daily-living activities, to be used for the assessment of constructional disability in elderly brain-lesioned patients. Subjects are required to put as may of 12 objects of varied shape and volume as they can into a box. To carry out the task successfully subjects have to arrange the items according to an efficient constructional strategy. We administered this test to 68 normal subjects and to 50 brain-damaged patients. Analysis indicated the Box test is easy and simple to administer and can be used without difficulty by elderly patients having focal brain damage. Performance correlated well with general intelligence and other bidimensional, conventional constructional tasks. Right or left brain lesions have a similar, significant detrimental effect on performance but probably through different mechanisms.

Activities of Daily Living↗
PubMed1997

Causes of late failure after heart transplantation: a ten-year survey.

BACKGROUND: Little is known about the causes of death of heart transplant recipients who survive long-term. METHODS: The pathologic and clinical records of 97 patients who underwent heart transplantation in Italy from 1985 to 1995 and died (85 of 97) or underwent retransplantation (12 of 97) at least 2 years after transplantation were surveyed. Graft failures were classified as late (occurring between 2 and 5 years after transplantation) and belated (more than 5 years). RESULTS: Graft vasculopathy was the single most common cause of death (40.0%) and the only cause of late retransplantation. Tumors ranked second (23.5% of deaths), but the expected non-Hodgkin's lymphomas and Kaposi's sarcoma were accompanied by a high number of lung cancers (especially metastasizing adenocarcinomas). They were followed by the emergence or recurrence of pretransplantation diseases (9.4%), fatal infections (exclusively bacterial) (4.7%), the development of transmissible diseases (viral hepatitis and acquired immunodeficiency syndrome, 4.7%), and late acute rejection (2.3%). The distribution of failures differed in the late and belated periods: death and organ loss proportions for graft vasculopathy, respectively, fell and rose from the late to the belated period; some types of malignancy and fatal acute rejection were never observed in the belated period, whereas the emergence of pretransplantation diseases prevailed in the belated period. Graft vasculopathy was more frequent and tumors were less frequent among patients undergoing transplantation for ischemic heart disease. CONCLUSIONS: The reasons why heart transplant recipients die or undergo retransplantation, respectively, in the late and belated periods slightly differ from one another and are widely different than in short-term survivors.

Bacterial Infections↗
PubMed1996

Distinct effects of recombinant desulfatohirudin (Revasc) and heparin on plasma levels of fibrinopeptide A and prothrombin fragment F1.2 in unstable angina. A multicenter trial.

BACKGROUND: Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina. METHODS AND RESULTS: Patients were randomized to one of two doses of heparin (n = 50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n = 113) (0.05, 0.10, 0.20, or 0.30 mg.kg-1.h-1 by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg.kg-1.h-1 r-hirudin regimens were significantly lower than with 0.05 mg.kg-1.h-1 r-hirudin; levels with 0.1- to 0.2-mg.kg-1.h-1 r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg.kg-1.h-1 hirudin. At 24 hours, they were higher with the 0.05-mg.kg-1.h-1 r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group. CONCLUSIONS: Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.

Angina, Unstable↗
PubMed1996

Electrode positioning for reliable telemetry ECG recordings during social stress in unrestrained rats.

We describe a surgical procedure for optimizing the location of telemetry ECG leads in rats. The new location was aimed at obtaining an accurate representation of ECG features throughout the cardiac cycle by limiting the voltage instability usually observed during intense somatomotor activity and improving the signal-to-noise ratio. The two electrodes (wire loops) were fixed on the dorsal surface of the xiphoid process and in the anterior mediastinum close to the right atrium. The implantation procedure was fast, little invasive, and allowed animals to completely recover from intervention. The performance of the "improved" location (IL, n = 10) with respect to two subcutaneous (SC) positionings ("conventional positioning" CSP, n = 5; "updated location," USL, n = 5) was evaluated by comparing ECGs obtained in baseline, stress and recovery conditions and during different behavioral activities (immobility and grooming). The resident-intruder test (emotional/physical challenge) was chosen as experimental stress paradigm. The noise level of ECGs obtained from IL rats was lower than in CSP and USL animals, in all recording conditions. Percentages of correctly recognized beats (CRBs) over the total number of beats (TBs) were significantly higher in IL rats than in CSP and USL animals, both in baseline conditions (99% vs. 11% and 40%) and situations involving high somatomotor activity (stress: 97%, 5% and 16% recovery; 97%, 7% and 15%) (p < 0.01). The performance of IL as compared to CSP and USL was also better when percentages during grooming and immobility were considered (grooming: 93% vs. 4% and 23%: immobility: 97%, 6%, and 33%; p < 0.01).

Animals↗