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Biomedical subjects

C Fiorentini

Publications and source records attributed to C Fiorentini.

At least 73 records · Page 4Linked to original sources
PubMed1998

Time-course of dobutamine-induced wall motion abnormalities in the infarct area following thrombolytic therapy.

Stress-induced asynergies in the infarct area following thrombolytic therapy are considered to reflect incomplete recanalization of the culprit vessel. However, reperfusion is a dynamic process with successive pathophysiological phases, so that the timing of assessment of residual ischemia may have relevant clinical implications. We studied the time-course of dobutamine-induced homozonal asynergies in 61 (group B) survivors of uncomplicated infarction as compared to 54 (group A) control subjects showing normal response to dobutamine stress echocardiography within 10 days of acute myocardial infarction. The 79 (43 of group A and 36 of group B) patients not presenting new cardiac events underwent further dobutamine stress echo within 90 +/- 17 days, which was positive in 20 and negative in 59. Persistence of test positivity was observed in just 17/36 (47%) patients, who showed significantly more extensive dobutamine-induced asynergies as compared to pre-discharge evaluation and less frequent (p < 0.01) evidence of viable myocardium. These results arise question about the decisional impact of stress-induced wall motion abnormalities in the culprit vessel area early after thrombolysis in low-risk patients and emphasize the need to further clarify the time factor role in this setting.

Cardiotonic Agents↗
PubMed1998

Multicenter trial on prognostic value of inducible ischemia, assessed by dobutamine stress echocardiography and exercise electrocardiography test, in patients with uncomplicated myocardial infarction, treated with thrombolytic therapy.

BACKGROUND: Thrombolysis has reduced early and longterm mortality by about 20%; sometimes, however, there is a re-occlusion of the infarct related artery or an unsuccessful thrombolysis. In these situations, there is a possible increase in detrimental events in the follow-up. OBJECTIVES: The aim of the study was to compare the prognostic value of dobutamine echocardiography (DET) and ECG exercise test (EET) in pts submitted to thrombolysis. METHODS: One hundred and fifty-one pts, with acute uncomplicated myocardial infarction, were enrolled. The pts were able to perform EET and had a sufficient echocardiographic window; 58 had anterior myocardial infarction (38%), 79 had inferior (52%), 2 had lateral (1%), 12 had non-Q (8%). EET was performed with an initial load of 25 Watt, and thereafter, 25 W every two minutes. DET was performed with step-wise infusion every three minutes (5, 10, 20, 30 and 40 mcg/kg/min.). If the target heart rate was not reached, a further dose of 40 mcg/kg/min. together with atropine 0.25-1 mg was administered, in the absence of signs and symptoms of ischemia. RESULTS: During a mean (+/- SD) follow-up period of 8 +/- 4.5 months (range 1-23), 16 spontaneous events happened (4 deaths, 5 non-fatal re-infarctions, 7 unstable angina). One-hundred and three EET (68%) were negative for ongoing ischaemia, while 48 were positive, 79 DET (52%) were negative for ongoing ischaemia and 72 were positive (48%). Statistical results: DET and EET had a sensitivity of 41% and 54%, a specificity of 57% and 74%, a positive predictive value of 7% and 14%, a negative predictive value of 91% and 95%, an accuracy of 56% and 73%. Kaplan-Maier survival curves demonstrated that patients with Peak Wall motion > 1.8 and EET score > 3, had the higher risk of spontaneous events. CONCLUSION: A few spontaneous events happened in the follow-up. These data demonstrate that patients treated with thrombolysis are not at high risk of spontaneous events. DET and EET, therefore, have had a high negative predictive value. For this reason, we can conclude that pts with negative tests can be considered at low risk and do not need any further investigations.

Dobutamine↗
PubMed1998

Bacterial toxins and the Rho GTP-binding protein: what microbes teach us about cell regulation.

In the present review activities of two bacterial toxins, Clostridium botulinum exoenzyme C3 and Escherichia coli CNF1, both acting on the GTP-binding protein Rho are analyzed. Proteins belonging to the Rho family regulate the actin cytoskeleton and act as molecular switches in a number of signal transduction pathways. C3 and CNF1 have opposite effects on Rho thus representing useful tools for studies on cell division, cell differentiation and apoptosis.

ADP Ribose Transferases↗
PubMed1998

Rho-dependent cell spreading activated by E.coli cytotoxic necrotizing factor 1 hinders apoptosis in epithelial cells.

Cell-cell and cell-matrix interactions play a pivotal role in numerous cell functions including cell survival and death. In this work, we report evidence that the Rho-dependent cell spreading activated by a protein toxin from E. coli, the cytotoxic necrotizing factor 1 (CNF1), is capable of hindering apoptosis in HEp-2 cells. In addition to the promotion of cell spreading, CNF1 protects cells from the experimentally-induced rounding up and detachment and improves the ability of cells to adhere to each other and to the extracellular matrix by modulating the expression of proteins related to cell adhesion. In particular, the expression of integrins such as alpha 5, alpha 6 and alpha v, as well as of some heterotypic and homotypic adhesion-related proteins such as the Focal Adhesion Kinase, E-cadherin, alpha and beta catenins were significantly increased in cells exposed to CNF1. Our results suggest, however, that the promotion of Rho-dependent cell spreading is the key mechanism in protecting cells against apoptosis rather than cell adhesion per se. A toxin inducing cell spreading without activating Rho, such as Cytochalasin B, was in fact ineffective in favouring cell survival. These data are of relevance (i) for the understanding of the role of the actin-dependent and especially Rho-dependent cellular activities involved in apoptosis regulation and (ii) in providing some clues to understanding the mechanisms by which bacteria, by controlling cell fate, might exert their pathogenic activity.

Actins↗
PubMed1998

Occurrence, diversity and pathogenicity of mesophilic Aeromonas in estuarine waters of the Italian coast of the Adriatic Sea.

A total of 208 strains of Aeromonas were isolated by monthly sampling from two estuaries (one provided with, and the other devoid of a waste-water treatment system) on the Italian coast of the Adriatic sea between September 1994 and August 1995. Biotyping at the species level allowed the identification of 96 strains (46%) as Aer. caviae, 46 (22%) as Aer. sobria, 33 (16%) as Aer. hydrophila and 25 (12%) as Aer. veronii. Eight strains (4%) were regarded as unnamed aeromonads. Aeromonas caviae was the most prevalent species in water with a high degree of pollution, while Aer. hydrophila strains were more commonly isolated from cleaner water. Aeromonas sobria and Aer. veronii were equally distributed in both estuaries. There was no correlation between temperature and numbers of aeromonads in either estuary. Using a biochemical fingerprinting method, strains were divided into similarity groups (PhP-types) based on their biochemical phenotypes. Several different PhP-types were found in each estuary, yielding a high diversity for these strains. However, some identical PhP-types were also found in both estuaries and at different times of the year, indicating that certain Aeromonas strains can survive more widely varying physico-chemical conditions. The production of toxins capable of causing cytoskeletal-dependent changes in the morphology of Chinese hamster ovary (CHO) cells was detected in 14 strains and appeared to be dependent on the season.

Aeromonas↗
PubMed1998

Phlebotomus-transmitted toscana virus infections of the central nervous system: a seven-year experience in Tuscany.

Toscana virus (TOSv) is a recently discovered Phlebotomus-transmitted human pathogen involved in acute infections of the central nervous system (CNS) occurring during the summer in natural foci in Italy. The purpose of this prospective study was to investigate the role of this virus in 170 patients with meningitis-meningoencephalitis of suspected viral origin, admitted to the Departments of Infectious Diseases at the Siena Hospital from 1990 to 1996. Infections caused by tick-borne encephalitis virus (TBEv) and TOSv or other neurotropic viruses were routinely diagnosed by means of conventional virological methods. 89 cases were attributed to TOSv, about 10% of which were Europeans on vacation in Tuscany. All of the TOSv-positive cases were observed during the summer and were residents of hilly areas in Siena and its province at an altitude not above 500 m. An increase in the number of cases was observed over the years, with a higher incidence among younger people. The clinical picture was similar to that observed in other viral infections of the CNS. Evolution was benign in all cases; in 2 subjects symptoms and signs of encephalitis were present.

Acute Disease↗
PubMed1998

Assessment of the coupling between RTapex and RR interval as an index of temporal dispersion of ventricular repolarization.

To evaluate the dynamic characteristics of the relationship between the RT and RR intervals we analyzed the RR/RTapex variability interaction with a dynamic parametric model whose parameters can be directly estimated from the beat-to-beat series RR and RTapex intervals. The model is designed to separate the fraction of RTapex variability driven by RR changes from that independent of RR variations and to quantify the gain and phase of the relationship between RR and RTapex intervals. The percentage of RTapex variability driven by RR variability was significantly greater in young normal subjects in comparison with postmyocardial infarction patients as well as with age-matched control subjects. This new approach based on the quantification of the RTapex variability dependent and independent of beat-to-beat RR interval changes could be used to quantify the degree of uncoupling between the two signals thus providing a new and noninvasive index of temporal dispersion of ventricular repolarization.

Adult↗
PubMed1998

Escherichia coli cytotoxic necrotizing factor 1 effaces microvilli and decreases transmigration of polymorphonuclear leukocytes in intestinal T84 epithelial cell monolayers.

Cytotoxic necrotizing factor type 1 (CNF1), a 110-kDa toxin-like protein from pathogenic Escherichia coli strains, induces an actin cytoskeleton reorganization consisting of the formation of prominent stress fibers by permanent activation of the small GTP-binding protein Rho. Since p21Rho regulates tight-junction permeability and perijunctional actin reorganization in epithelial intestinal cells (A. Nusrat, M. Giry, J. R. Turner, S. P. Colgan, C. A. Parkos, E. Lemichez, P. Boquet, and J. L. Madara, Proc. Natl. Acad. Sci. USA 92:10629-10633, 1995), we used polarized T84 epithelial intestinal cell monolayers to examine whether CNF1 could affect microvillus structure, transepithelial resistance, and polymorphonuclear leukocyte (PMN) transmigration. Incubation of T84 cells with CNF1 did not influence transepithelial resistance, suggesting that barrier function and surface polarity were not affected by the toxin. However, CNF1 effaced intestinal cell microvilli and induced a strong decrease of PMN transepithelial migration in either the luminal-to-basolateral or the basolateral-to-luminal direction. CNF1 could thus be a virulence factor exhibiting a new type of combined activity consisting of effacing of microvilli and occlusion of the epithelial barrier to PMNs. Attenuated transepithelial migration of PMNs could result in the enhanced growth and protection of luminal bacteria.

Bacterial Toxins↗
PubMed1998

Clostridium difficile toxin B induces apoptosis in intestinal cultured cells.

Toxigenic strains of the anaerobic bacterium Clostridium difficile produce at least two large, single-chain protein exotoxins involved in the pathogenesis of antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic activity. This study dealt with CdB, providing the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportion of the treated cells displayed nuclear fragmentation and chromatin condensation. In keeping with ultrastructural data, CdB-treated cells showed the typical flow cytometric hallmark of apoptosis consisting of a distinct sub-G1 peak. The CdB-induced apoptotic response was dose and time dependent and not simply due to the actin-disrupting effect of the toxin or to the subsequent impairment of cell anchorage. Rather, the inhibition of proteins belonging to the Rho family due to CdB seems to play a role in the induction of apoptosis in intestinal cells. The origin of cells and the growth rate may also be cofactors relevant to such a response.

Actins↗
PubMed1998

Carcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure.

A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide--a somatostatin analogue--followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, nonmetastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.

Carcinoid Heart Disease↗
PubMed1998

Early assessment of viable myocardium after acute myocardial infarction by low-dose echo-dobutamine.

BACKGROUND: The aim of the study was to evaluate the usefulness of low-dose dobutamine echocardiographic testing performed within 48 hours from anterior AMI in order to identify the extent of viable myocardium and predict its functional outcome. The early echo-dobutamine test was also compared with a predischarge test in order to evaluate the effects of different timing on the accuracy of the test. METHODS: Nineteen consecutive patients, aged 54 +/- 11 years, with a first anterior AMI entered the study. All patients underwent a low-dose dobutamine echocardiographic test within 48 hours from hospital admission and at predischarge. In all the patients, a rest follow-up echocardiogram was performed three months after hospital discharge. Eleven patients underwent a revascularization procedure (7 underwent PTCA and 4 CABG). RESULTS: Of the 159 dyssynergic segments, 26% improved spontaneously at predischarge and 51% improved at the three-month follow-up. Of the 145 predischarge dyssynergic segments, 38% improved at three months. Considering the results on a segmental basis, early low-dose dobutamine echocardiography showed a sensitivity of 52%, a specificity of 87%, a positive predictive value of 81%, a negative predictive value of 64% and a diagnostic accuracy of 69% for wall-motion improvement at three months. The predischarge test showed very similar values. A slight enhancement of the sensitivity of both tests was observed considering the akinetic segments only. Finally, considering the amount of segmental reversible dysfunction inside the infarct area in the single patients, early low-dose dobutamine echocardiography showed a sensitivity of 86% and a specificity of 80%. CONCLUSIONS: Our results indicate that: 1) recovery of regional wall motion after AMI is slow and progressive, with substantial improvement ensuing within the first days after infarction; 2) considering results on a segmental basis, low-dose dobutamine echocardiography performed within 48 hours of AMI shows a high specificity but a low sensitivity for late recovery of regional function, although it gave information similar to what was obtained performing the test at predischarge; 3) the efficiency of test can be improved by considering the amount of reversible segmental dysfunction inside the infarct area in the single patients.

Adult↗
PubMed1997

Hinderance of apoptosis and phagocytic behaviour induced by Escherichia coli cytotoxic necrotizing factor 1: two related activities in epithelial cells.

Several microbial factors are recognized able to modulate apoptosis. In this work, we analyze the activity of a toxin from pathogenic strains of Escherichia coli, the Cytotoxic Necrotizing Factor 1 (CNF1), which influences epithelial cell structure and function. This toxin activates the Rho GTP-binding protein leading to actin filament reorganization, membrane ruffling and multinucleation. Functionally, CNF1 induces a phagocytic activity in non-professional phagocytes. Surprisingly, we found that the increase of phagocytic activity induced by CNF1 corresponds to a decrease of apoptotic cell death. We therefore hypothesize that the two activities together might have a finalistic role in the pathogenesis of bacterial infection.

Actins↗
PubMed1997

Actin cytoskeleton as a target for 2-chloro adenosine: evidence for induction of apoptosis in C2C12 myoblastic cells.

Recent results for various cell types have shown that adenosine is capable of inducing relevant cytophatological alterations which can eventually lead to apoptosis. No data are available regarding the involvement of adenosine in apoptosis of muscle cells. In this work, we studied the effect of the relatively hydrolysis-resistant adenosine analog 2-chloro adenosine on a cultured myogenic cell line, C2C12, which is able to differentiate in vitro, leading to the formation of syncythia, giant multinucleated cells called myotubes. Results indicated that 2-chloro adenosine induces apoptotic cell death in both myoblasts and myotubes; this was preceded by a derangement of actin microfilaments, which represent the main cytoskeletal component and play a pivotal role in the physiology of such cell line. The time-dependency of cytoskeletal alterations suggested a causal relationship between these changes and the induction of apoptosis. These results implicate adenosine as an endogenous regulator of apoptosis in muscle cells and validate this cell model system as a useful tool for studying human muscle cell pathologies.

2-Chloroadenosine↗
PubMed1997

Dissection of pathways implicated in integrin-mediated actin cytoskeleton assembly. Involvement of protein kinase C, Rho GTPase, and tyrosine phosphorylation.

A panel of antibodies to the alphaIIbbeta3 integrin was used to promote adhesion of Chinese hamster ovary cells transfected with the alphaIIbbeta3 fibrinogen receptor. While some alphaIIbbeta3 antibodies were not able to induce p125 focal adhesion kinase (p125FAK) tyrosine phosphorylation, all the antibodies equally support cell adhesion but not spreading and assembly of actin stress fibers. Absence of stress fibers was also obtained by plating on antibodies directed to the hamster beta1 integrin. In contrast, cells plated on matrix proteins spread organizing actin stress fibers. Treatment with phorbol esters phorbol 12-myristate 13-acetate (PMA) induced cells to spread on antibodies-coated dishes but not to organize actin in stress fibers. The combination of PMA and cytotoxic necrotizing factor 1 (CNF1), a specific Rho activator, induced cell spreading and organization of stress fibers. PMA or the combination of PMA and CNF1 also increases tyrosine phosphorylation of p125FAK in response to antibodies that were otherwise unable to trigger this response. These data show that: 1) matrix proteins and antibodies differ in their ability to induce integrin-dependent actin cytoskeleton organization (while matrix induced stress fibers formation, antibodies did not); 2) p125FAK tyrosine phosphorylation is insufficient per se to trigger actin stress fibers formation since antibodies that activate p125FAK tyrosine phosphorylation did not lead to actin stress fibers assembly; and 3) the inability of anti-integrin antibodies to trigger stress fibers organization is overcome by concomitant activation of the protein kinase C (PKC) and Rho pathways; PKC activation leads to cell spreading and Rho activation is required to organize actin stress fibers.

Actins↗
PubMed1997

Escherichia coli cytotoxic necrotizing factor 1 (CNF1), a toxin that activates the Rho GTPase.

Cytotoxic necrotizing factor 1 (CNF1), a 110-kDa protein toxin from pathogenic Escherichia coli induces actin reorganization into stress fibers and retraction fibers in human epithelial cultured cells allowing them to spread. CNF1 is acting in the cytosol since microinjection of the toxin into HEp-2 cells mimics the effects of the externally applied CNF1. Incubation in vitro of CNF1 with recombinant small GTPases induces a modification of Rho (but not of Rac, Cdc42, Ras, or Rab6) as demonstrated by a discrete increase in the apparent molecular weight of the molecule. Preincubation of cells with CNF1 impairs the cytotoxic effects of Clostridium difficile toxin B, which inactivates Rho but not those of Clostridium sordellii LT toxin, which inhibits Ras and Rac. As shown for Rho-GTP, CNF1 activates, in a time- and dose-dependent manner, a cytoskeleton-associated phosphatidylinositol 4-phosphate 5-kinase. However, neither the phosphatidylinositol 4,5-bisphosphate (PIP2) nor the phosphatidylinositol 3,4-bisphosphate (PI 3,4-P2) or 3,4,5-trisphosphate (PIP3) cellular content were found increased in CNF1 treated HEp-2 cells. Cellular effects of CNF1 were not blocked by LY294002, a stable inhibitor of the phosphoinositide 3-kinase. Incubation of HEp-2 cells with CNF1 induces relocalization of myosin 2 in stress fibers but not in retraction fibers. Altogether, our data indicate that CNF1 is a toxin that selectively activates the Rho GTP-binding protein, thus inducing contractility and cell spreading.

Actins↗
PubMed1997

Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine.

Pathogenic Escherichia coli are responsible for a variety of diseases, including diarrhoea, haemolytic uraemic syndrome, kidney infection, septicaemia, pneumonia and meningitis. Toxins called cytotoxic necrotizing factors (CNFs) are among the virulence factors produced by uropathogenic (CNF1) or enteropathogenic (CNF2) E. coli strains that cause diseases in humans and animals, respectively. CNFs induce an increase in the content of actin stress fibres and focal contacts in cultured cells. Effects of CNFs on the actin cytoskeleton correlated with a decrease in the electrophoretic mobility of the GTP-binding protein Rho and indirect evidence indicates that CNF1 might constitutively activate Rho. Here we show that CNF1 catalyses the deamidation of a glutamine residue at position 63 of Rho, turning it into glutamic acid, which inhibits both intrinsic GTP hydrolysis and that stimulated by its GTPase-activating protein (GAP). Thus, this deamidation of glutamine 63 by CNF1 leads to the constitutive activation of Rho, and induces the reorganization of actin stress fibres. To our knowledge, CNF1 is the first example of a bacterial toxin acting by deamidation of a specific target protein.

Actins↗
PubMed1997

Dobutamine-induced ST-segment elevation in patients with acute myocardial infarction and the role of myocardial ischemia, viability, and ventricular dyssynergy.

We analyzed the relation between dobutamine-induced Q-wave ST-segment elevation and regional contraction during low (5 to 10 microg/kg/min) and high doses (20 to 40 microg/kg/min) of dobutamine in a series of 391 dobutamine echocardiographic tests performed 10 +/- 2 days after a first uncomplicated acute myocardial infarction (AMI). ST-segment elevation was defined as > or = 1 mm new or additional J-point elevation with a horizontal or upsloping ST segment lasting 80 ms. Wall motion score index at rest was derived using a 16 segment-4 grade score model. Patients with dobutamine-induced ST-segment elevation had a higher wall motion score index at rest (anterior wall AMI: 1.67 +/- 0.27 vs 1.43 +/- 0.30, p = 0.0001; inferior wall AMI: 1.44 +/- 0.27 vs 1.30 +/- 0.18, p = 0.0001) and similar incidence and extent of myocardial viability and homozonal ischemia in comparison with those without ST-segment elevation. The sensitivity, specificity, and accuracy of dobutamine-induced ST-segment elevation for detecting residual homozonal ischemia were 51%, 55%, and 54%, respectively, in patients with anterior wall AMI, and 42%, 68%, and 58%, respectively, in patients with inferior wall AMI. In conclusion, dobutamine-induced ST-segment elevation is not associated with higher incidence and extent of viable or jeopardized myocardium but rather to a greater extent of wall motion abnormalities at rest. Thus, this finding does not represent a clinically reliable discriminator for selecting patients for coronary angiography and possible revascularization procedures.

Adult↗