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Biomedical subjects

G Greco

Publications and source records attributed to G Greco.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Prognostic value of echo-dobutamine test in patients with ischemic heart disease: comparison with exercise test].

BACKGROUNDS: The aim of the study was to assess the relative prognostic accuracy of dobutamine echocardiography (TED) vs maximal bicycle exercise electrocardiography (TE) in patients with proven coronary artery disease. METHODS: One hundred and thirty consecutive patients (70 patients with uncomplicated recent myocardial infarction, 19 asymptomatic patients with previous myocardial infarction and 41 patients with stable angina pectoris and previous myocardial infarction or previous myocardial revascularization procedure) underwent TED (incremental dobutamine infusion: 5 to 40 ncg/kg/min, continued with atropine 0.25 to 1 mg iv if necessary) and TE on different days and in random order. Criteria for positivity were: new or worsening regional dyssynergy for TED; ST segment shift > or = 1 mm from baseline for TE. End points were defined as spontaneous events (cardiac death, myocardial infarction and unstable angina) and total events (spontaneous events plus myocardial revascularization procedures). RESULTS: During 15.4 +/- 7.9 (range 1-33) months of follow-up, 33 events occurred: cardiac death (1), myocardial infarction (4) unstable angina (21) myocardial revascularization (7). Sensitivity, specificity, positive and negative predictive value, prognostic accuracy were similar for TED and TE (P = NS). Cumulative event-free survival curves as a function of TED and TE results were both statistically significant. A Cox stepwise regression analysis identified TED positivity obtained without atropine administration as the best predictor of spontaneous and total events (Odds ratio 5.33 and 4.38, respectively). Cumulative survival curves obtained by the combination of TED and TE results were statistically different (P < 0.05 and P < 0.001 for spontaneous and total events, respectively) and showed a poor clinical outcome in patients with both tests or only TED positive. TED correctly predicted clinical outcome in 24/39 patients in whom there was disagreement between the two tests. CONCLUSIONS: In patients with proven coronary artery disease, TED and TE have a similar accuracy for predicting clinical outcome. Where a discrepancy is seen between the two tests, TED appears to have a slightly higher prognostic value.

Aged↗
PubMed1996

Modification of the potent peptide FK888 with unusual aminoacids: effects on activity on neurokinin receptors.

We report on the synthesis and the pharmacological properties of a new series of tachykinin antagonists based on the peptide N2-[(4R)-4-hydroxy-1-[(1-methyl-1H-indol-3-yl) carbonyl]-L-prolyl]-N-methyl-N-(phe-nylmethyl)-3-(2-naphthyl)-L-al aninamide (FK888) modified on the (2-naphthyl)-L-alanine and the [(1-methyl-1H-indol-3-yl)carbonyl] moieties. The compounds were tested on guinea pig ileum for NK-1, rat colon for NK-2 and rat portal vein for NK-3 receptors. The two most potent peptides of this series, 1b and 2b, were selective for the NK-2 receptor (pA2 = 7.5 and 7.3, respectively).

Amino Acid Sequence↗
PubMed1996

[Percutaneous mitral valvuloplasty in patients who have undergone surgical commissurotomy].

Percutaneous mitral valvuloplasty (PMV) was performed with Inoue's catheter, by anterograde approach, in 19 patients (2 males and 17 females, mean age of 56 +/- 13 years) with restenosis after surgical commissurotomy. Mean valvular area increased from 1.2 +/- 0.2 to 1.9 +/- 0.2 cm2 while mean transvalvular gradient decreased from 13 +/- 6 to 7 +/- 4 mmHg. All but 2 patients reached optimal results; one had a suboptimal result (final valvular area > 1.5 cm2, percentage of increase less than 25%), and 1 was sent to the surgeon for a significant increase in mitral regurgitation ( ). At 1 year follow-up, (available for 11 patients), mean valvular area was 1.7 +/- 0.3 cm2 and transmitral gradient was of 5.4 +/- 2 mmHg. Four patients showed a restenosis; 1 of them underwent surgical mitral valve replacement after a second unsuccessful PMV; 2 showed good clinical conditions, while the fourth patient was sent to the surgeon for the high echocardiographic score. At 2-year follow-up, available for 4 patients, the mean gradient was of 5.5 +/- 2.5 mmHg and the mitral valve area was 1.8 +/- 0.2 cm2. NYHA functional class progressively improved after the procedure in all patients but those undergoing mitral valve replacement. In conclusion, despite the occurrence of restenosis, PMV seems to be feasible in patients who already underwent surgical commissurotomy; this procedure can avoid the risks of a second surgery, and should be considered the first choice treatment in these patients.

Adult↗
PubMed1995

The peptide-binding motif for the human transporter associated with antigen processing.

Presentation of antigenic peptides by human leukocyte antigen class I molecules is dependent on peptide transport into the endoplasmic reticulum by the transporters associated with antigen processing (TAP) (Germain, R. N. 1994. Cell. 76:287-299). This translocation step is currently regarded as permissive for all peptides with COOH-terminal residues capable of binding to HLA class I molecules (Momburg, F., J. Roelse, J. C. Howard, G. W. Butcher, G.J. Hämmerling, and J.J. Neefjes. 1994. Nature (Lond.). 367:648-651). In this report, we show that the human transporter selects peptides according to a binding motif based on the strong effects on peptide affinity of the three NH2-terminal positions and the COOH-terminal residues. TAP favors strongly hydrophobic residues in position 3 (P3) and hydrophobic or charged residues in P2, whereas aromatic or acidic residues in P1, as well as Pro in P1 and P2, have strong deleterious effects. Selection of naturally presented peptides by the transporter is suggested by their higher average affinity for TAP, as compared to nonselected peptides. The TAP preferences in the three NH2-terminal positions correspond to those of the vast majority of human leukocyte antigen class I alleles, but they represent an obstacle for peptide supply to some alleles, e.g., the B7-like group. We propose that peptides binding to these alleles, and in general, peptides with TAP affinities below a certain threshold, may be transported as extended precursors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The essential role of endogenous IFN alpha/beta in the anti-metastatic action of sensitized T lymphocytes in mice injected with Friend erythroleukemia cells.

Adoptive transfer of splenic T lymphocytes from DBA/2 mice immunized against Friend erythroleukemia cells (FLC) inhibited the development of visceral metastases and increased the survival time of DBA/2 mice challenged i.v. with parental FLC 24 hr to 2 months later. Immune spleen cells were ineffective in mice pre-treated with potent neutralizing antibody to mouse IFN alpha/beta (but not to IFN gamma), demonstrating the essential participation of endogenous IFN alpha/beta in the inhibitory action of immune T lymphocytes against FLC metastases. These findings suggest that the reported inability of immune T lymphocytes to exert an anti-FLC effect in immunodeficient DBA/2 mutant beige (bg/bg) mice (unless these mice had also been treated with IFN alpha/beta), may have been due to lower levels of endogenous IFN alpha/beta in DBA/2 bg/bg mice than in normal DBA/2+/bg mice. Experimental results in support of this hypothesis are presented.

Animals↗
PubMed1995

A concerted study using binding measurements, X-ray structural data, and molecular modeling on the stereochemical features responsible for the affinity of 6-arylpyrrolo[2,1-d][1,5]benzothiazepines toward mitochondrial benzodiazepine receptors.

The 7-(acyloxy)-6-arylpyrrolo[2,1-d][1,5]benzothiazepine derivatives have been recently proposed as a new class of ligands specific for the mitochondrial benzodiazepine receptor (Fiorini et al. J. Med. Chem. 1994, 37, 1427-1438) (Greco et al. J. Med. Chem. 1994, 37, 4100-4108). In this paper we report the X-ray crystallographic structures of three potent (1-3) and two inactive (4 and 5) previously described benzothiazepines, as well as binding affinity constants for two newly assayed analogs in which the acyloxy side chain was replaced by a methoxy group (6) or removed (7). Structure-affinity relationships and molecular mechanics calculations performed using crystal structures as references have led to a revised 3D pharmacophore model accounting for all the data available up until now. Interestingly, the hypothetical receptor-bound conformations of 1-3 display a considerable degree of similarity with their crystal geometries. Additional calculations have confirmed that the poor affinities of benzothiazepines bearing an aroyloxy group (4 and 5) should be ascribed to the steric and/or electronic features of the side chain aryl moieties rather than to unfavorable conformational properties.

Animals↗
PubMed1995

Correlation between the sensitivity or resistance to IL-2 and the response to cyclophosphamide of 4 tumors transplantable in the same murine host.

We have studied the anti-tumor response to cyclophosphamide (CTX) in DBA/2 mice transplanted s.c. with 4 tumors exhibiting different responses to IL-2: ESb lymphoma and Friend leukemia cells (non-responsive or poorly responsive, respectively), p11-R-Eb and Eb lymphoma cells (both highly responsive to IL-2). CTX injections on days 7, 14 and 21 resulted in a significant anti-tumor response in mice transplanted s.c. with Friend leukemia cells or ESb cells, whereas no anti-tumor effect was observed in mice injected with Eb or p11-R-Eb cells. All 4 tumor cell lines were equally sensitive to the cytotoxic effects of mafosfamide, an in vitro active analogue of CTX. To define the host mechanisms responsible for the lack of an anti-tumor effect of CTX in mice transplanted with IL-2-responsive tumors, we studied several aspects of the spontaneous or IL-2-induced anti-tumor response in mice transplanted with p11-R-Eb cells. Injection of monoclonal antibodies (MAbs) to IFN-gamma completely abolished the anti-tumor effects of IL-2. Using a Winn assay, clear-cut anti-tumor activity was found in spleen cells from mice transplanted with the IL-2-responsive tumors. This activity was abolished by CTX, which also abrogated the anti-tumor response to IL-2 in mice injected with p11-R-Eb cells. Our results indicate an inverse correlation between sensitivity to IL-2 and response to CTX and emphasize the importance of initial host-tumor interaction in determining the type of response to IL-2 or CTX.

Animals↗
PubMed1995

Differences in peptide-binding specificity of two ankylosing spondylitis-associated HLA-B27 subtypes.

Two HLA-B27 subtypes, B*2702 and B*2705, both associated with ankylosing spondylitis, were tested for binding affinity with a panel of polyalanine model nonapeptides carrying Arg at position 2 (P2) and a series of different amino acids at position 9 (P9). The alpha chains were isolated from BTB(B*2705), C1R/B*2702 (a B*2702 transfectant cell line) and from the NW (B*2702) cell line that has a peculiar peptide presentation behavior. Peptide binding was measured by the HLA alpha chain refolding assay. The results obtained show that: 1) Peptides with basic residues (Arg and Lys) and also aliphatic (Leu) and aromatic (Phe and Tyr) peptides at P9 have a similar high affinity in the binding to B*2705; 2) B*2702 binds well to P9 aliphatic and aromatic peptides but only very weakly to P9 basic peptides. Since both B*2702 and B*2705 are associated with AS the presumed arthritogenic peptide is hypothesized to have an aromatic or aliphatic residue at position 9. Peptides with basic residues in this position would be excluded as candidates because of their low binding affinity with B*2702.

Amino Acid Sequence↗
PubMed1995

Prognostic value of high dose dipyridamole echocardiography in patients with chronic coronary artery disease and preserved left ventricular function.

OBJECTIVES: The prognostic value of dipyridamole echocardiography was assessed in patients with chronic coronary artery disease and preserved left ventricular function. BACKGROUND: Few data are available on the prognostic value of dipyridamole echocardiography in patients with a low risk of cardiac events. METHODS: Two hundred sixty-eight consecutive patients with stable, proven or suspected coronary artery disease and ejection fraction > or = 0.40 underwent high dose (up to 0.84 mg/kg body weight) dipyridamole echocardiography. In 204 patients definite exercise electrocardiographic (ECG) results were also available. RESULTS: During a mean (+/- SD) follow-up period of 16 +/- 8 months (range 6 to 36), 33 spontaneous events occurred: 15 "hard" events (cardiac death [n = 6], myocardial infarction [n = 9]) and 18 "soft" events (unstable angina). Events occurred more frequently in patients with positive findings on dipyridamole echocardiography (59% vs. 3%, p < 0.001; hard events 24% vs. 2%, p < 0.01). A positive response at the low dose (up to 0.56 mg/kg) identified patients with a high incidence of hard events (7 of 16 patients, sensitivity 50%, specificity 96%). In patients with an exercise ECG, a comparable sensitivity for cardiac events was found (89% vs. 93%, p = NS), but dipyridamole echocardiography was more specific (91% vs. 61%, p < 0.01). A positive response on the low work load exercise ECG (< 8 min) and a positive response to low dose dipyridamole echocardiography had similar accuracy (82% vs. 90%, p = NS). Cox analysis identified dipyridamole echocardiography as the best predictor of cardiac events (odds ratio [OR] 20.9, 95% confidence interval [CI] 10.8 to 37.9); the highest risk of hard events was found in patients with a positive response to low dose dipyridamole echocardiography (OR 25.4, 95% CI 12.2 to 54.1). CONCLUSIONS: In patients with chronic coronary artery disease and a low incidence of cardiac events, dipyridamole echocardiography was effective in prognostic stratification, and positive low work load exercise ECG results were a reliable predictor of subsequent events. Consequently, dipyridamole echocardiography should be considered a complementary tool in the presence of high work load positivity or ambiguous exercise ECG results.

Coronary Disease↗
PubMed1995

Synthesis of 3-(2'-furoyl)indole derivatives as potential new ligands at the benzodiazepine receptor, structurally more restrained analogues of indoleglyoxylylamides.

A number of furoylindoles were synthesized with the aim of obtaining structurally more restrained analogues of the previously described indoleglyoxylylamides, which are high affinity ligands at the benzodiazepine receptor. In these new compounds, the oxygen atom of the oxalyl CO(2) is inserted into the rigid furan ring. However, unlike the glyoxylylamides, they proved to be incapable of interacting with the benzodiazepine receptor. To rationalize these results, molecular electrostatic potentials were calculated; these indicated a positive electrostatic potential region for the furan oxygen, which thus prevents the formation of a hydrogen bond necessary for interaction with the receptor. Nevertheless, these findings confirmed that the CO(2) of the indoleglyoxylylamide derivatives represents one of the principal points of interaction with the receptor site for these kinds of ligands, as previously hypothesized by us.

Animals↗
PubMed1995

[A comparison between flecainide and sotalol in the prevention of recurrences of paroxysmal atrial fibrillation].

OBJECTIVES: Aim of the present study was to assess the efficacy and safety of flecainide (F) and sotalol (S) for the prevention of recurrences of paroxysmal atrial fibrillation (PAF). METHODS: Sixty-six patients with PAF (> or = 3 episodes of atrial fibrillation in the last year) in sinus rhythm, were randomized to pharmacological oral treatment with F (20 patients-Group A), with S (20 patients-Group B) and placebo (P) (26 patients-Group C). During the follow-up (one year duration) were evaluated on I, III, VI and XII months the number and tolerance of the atrial fibrillation recurrences, cardiac and/or noncardiac side effects. The patients with more than two recurrences in the same follow-up interval withdrew from the study. In each patient 14 clinical and laboratory variables were evaluated. RESULTS: After 12 months were arrhythmia-free respectively 70% of Group A patients, 60% of Group B patients, 27% of Group C patients. Univariate analysis showed that treatment with F was related to decrease of atrial fibrillation recurrences (one recurrence 67%, two recurrences 81%, three recurrences 81%), treatment with S was related to decrease of recurrences (two recurrences 59%); the variable most significantly related to the risk of arrhythmia recurrence is the higher value of basal cardiac rate (one recurrence t = 2.15, two t = 2.22, three t = 2.96, four t = 2.06). There was not statistically significant difference in maintenance of sinus rhythm at the end of the follow-up between the groups of patients on F and S (p = 0.163); treatment efficacy was significantly higher than P (p = 0.002). Multivariate analysis showed that treatment with F and S decreases the risk of arrhythmia recurrence respectively of 85% and 76% versus placebo at the end of the follow-up. The incidence of cardiac and/or noncardiac side effects was not clinically significant. CONCLUSION: F and S are both effective and safe for prevention of PAF, with 70% and 60% respectively of patients arrhythmia-free after 12 months of treatment. Side effects were common, but clinically significant adverse events were uncommon. A higher value of basal cardiac rate was predictive of atrial fibrillation recurrences in the patients during treatment.

Adult↗
PubMed1995

[Diagnostic accuracy of transesophageal echocardiography in the diagnosis of aortic dissection: comparison with computerized axial tomography].

This study was designed to assess the sensibility, specificity and diagnostic accuracy of transesophageal echocardiography (TEE) and X-ray contrast enhanced computed tomography (CT) in the diagnosis of aortic dissection and its complications. Fifty patients with clinically suspected aortic dissection were examined. Imaging results were validated in each case by intraoperative and/or autopsy findings and/or the results of cineangiography. The Stanford and DeBakey classifications were used to differentiate the dissection type; the patients were also subdivided by TEE according to a modified DeBakey classification. The sensibility of TEE to detect aortic dissection was 100%, significantly higher (p < 0.05) than that of CT for type A dissections (77.2%). The two imaging procedures did not statistically differ (NS) in the detection of type B dissection (CT sensibility 87.5%). The specificity of TEE for the detection of type A aortic dissection was 94%; it was not significantly higher (NS) than that of CT (CT specificity 86.6%). Both TEE and CT had no false negative findings in the diagnosis of type B aortic dissection (100%; TEE vs CT, NS). TEE was reliable in the correct identification of the primary entry site in the ascending aorta (80%), the arch (62.5%) and descending aorta (71.4%), and also in the involvement of coronary arteries (62.5%), and aortic arch branch vessels (71.4%); CT scanning was not effective in detecting any of these complications. Aortic regurgitation was accurately identified by TEE in each case. Both TEE and CT scanning correctly identified thrombosis of the false lumen and pericardial effusion. Intraoperative TEE documented in all patients postrepair persistence of the intimal flap in aortic segments that were not operated; flow in the false lumen was detected in 46.6% of the patients; in 26.6% of them secondary tears, not seen before surgical treatment, were detected. In conclusion, TEE allows a bedside, safe and accurate diagnosis and classification of aortic dissection. It also provides the diagnostic information necessary for the therapeutical decision making. Intraoperative TEE allows improvement in preoperatory diagnosis and gives important information for the management of the patient immediately after cardiopulmonary bypass and in the follow-up.

Adult↗
PubMed1995

Synthesis and in vitro activities of highly potent and selective tripeptide antagonists of the neurokinin NK-1 receptor.

We report on the synthesis and the pharmacological properties of a new series of tachykinin antagonists based on the tripeptide Ac-Thr-D-Trp(CHO)-Phe-N(Me)-Bzl (1, FR113680) partly modified on the C-terminal amide part. Stereochemistry around the benzilic carbon, as well as nitrogen substitution was investigated. Selected compounds were tested on guinea pig ileum for NK-1, rat colon and rat portal vein for NK-2 and NK-3 receptors, respectively. Two of these peptides were shown to have higher tachykinin antagonist activity (pA2 > 8.8) and selectivity for NK-1 receptors compared with compound 1 taken as reference (Table 2). In addition we investigated the stability of compounds 2 and 3 on guinea pig plasma and liver homogenate.

Amino Acid Sequence↗
PubMed1995

[Use of high doses of atropine during dipyridamole echocardiography: safety and efficacy of the combined test].

BACKGROUND: Recent reports demonstrated an increased accuracy of dipyridamole echocardiography test with the intravenous infusion of 0.25 to 1 mg of atropine in 1-4 consecutive administrations at the end of the test. The effect of higher doses of atropine during dipyridamole echocardiography, potentially able to further increase heart rate and myocardial oxygen consumption, has not been evaluated. The aim of the study was to evaluate the effect of high doses of atropine during dipyridamole echocardiography and to investigate the possible pharmacological interference between dipyridamole and atropine. METHODS: One-hundred consecutive patients (M = 81, F = 19; mean age 58 yrs) without inducible wall motion abnormalities at 14th minute of a high-dose (0.84 mg/Kg in 10') dipyridamole echocardiography test were studied. Seventy-five patients referred to the test in pharmacological wash-out were randomly divided in three groups: 25 patients (Group 1) received 10 mcg/Kg of atropine in 60"; 25 patients (Group 2) received 15 mcg/Kg of atropine in 120"; 25 patients (Group 3) received 20 mcg/Kg of atropine in 120"; moreover, 25 patients with a full-dose oral beta-blocker therapy (Group 4) received 20 mcg/Kg of atropine in 120". Atropine was infused during the 15th and 16th minute of the test. Heart rate (HR) changes and new wall motion abnormalities induced by atropine were considered and compared for each Group. In 60 patients (15 randomly selected from each Group) the effect on mean HR and R-R interval (msec) of the same dose of atropine infused during dipyridamole echocardiography was evaluated in resting conditions 24 hours apart. RESULTS: The dipyridamole-atropine test was well tolerated and accomplished in all patients. HR increased significantly in all Groups of patients in comparison with pre-atropine HR values (Group 1: +14 +/- 8 b/m', p < 0.0001; Group 2: +19 +/- 8 b/m', p < 0.0001; Group 3: +22 +/- 9 b/m', p < 0.0001; Group 4: +19 +/- 8 b/m', p < 0.0001; Groups 2, 4 vs Group 1: p = 0.03, Group 3 vs Group 1: p = 0.002). No patients in Group 1 (0%), 3 patients in Groups 2 and 3 (12%), and 5 patients in Group 4 (20%) showed new wall motion abnormalities after atropine infusion (Group 4 vs Group 1: p = 0.06). Effects of atropine on HR and mean R-R interval were significantly more pronounced in resting conditions than during dipyridamole test (HR: +25 +/- 11 vs +18 +/- 9 b/m', p < 0.001; R-R: -256 +/- 122 vs -127 +/- 68 msec, p < 0.0001). CONCLUSIONS: High doses of atropine during dipyridamole echocardiography test are safe and more effective for induction of new wall motion abnormalities than usual doses, particularly in patients tacking beta-blockers. The likelihood of an antagonistic mechanism between atropine and endogenous, dipyridamole-induced adenosine on sinus node is supported from our results.

Administration, Oral↗
PubMed1994

Combined interleukin-1 beta/interleukin-6 treatment in mice: synergistic myelostimulatory activity and myelorestorative effect after cyclophosphamide-induced myelosuppression.

We have studied the effects of single and combined treatment with recombinant human interleukin 1 beta (IL-1 beta) and recombinant human interleukin-6 (IL-6) on spleen and bone marrow hematopoiesis in normal and cyclophosphamide-treated mice. Injection of IL-1 beta alone resulted in a significant increase in the number of granulocytes and splenic progenitors [burst-forming units-erythroid (BFU-E) and colony-forming units-granulomonocytic (CFU-GM)] as compared with control mice but did not markedly enhance the number of bone marrow BFU-E and CFU-GM. IL-6 alone had little effect on the number of splenic progenitors but significantly increased the number of marrow BFU-E and CFU-GM, especially after a 6-day cytokine treatment. Combined daily administration of IL-1 beta and IL-6 for 3 days resulted in a synergistic stimulation of hematopoiesis as evaluated by the number of spleen and bone marrow CFU-GM and BFU-E colonies. Likewise, IL-1 beta/IL-6 markedly enhanced the number of circulating neutrophils, whereas each cytokine alone had little or no effect. When the numbers of spleen progenitors and peripheral granulocytes were determined 1 day after the last injection, a synergistic myelostimulatory effect of combined IL-1 beta/IL-6 treatment was observed at all doses (IL-1 beta, 0.25-0.5 microgram; IL-6, 1-20 micrograms). Furthermore, combined treatment with IL-1 beta/IL-6 accelerated and potentiated the recovery of myeloid cells after cyclophosphamide injection, whereas the single regimen treatment was not effective. Particularly, the rebound of WBC (especially neutrophilic granulocytes) after cyclophosphamide treatment was markedly enhanced by the combined treatment, whereas the single regimen was ineffective. Altogether these results may contribute to the development of combination therapies with cytokines and antiblastic agents in the treatment of cancer patients.

Animals↗