Biomedical subjects

G Berton

Publications and source records attributed to G Berton.

At least 19 recordsLinked to original sources

PubMed2004

Albumin excretion in diabetic patients in the setting of acute myocardial infarction: association with 3-year mortality.

AIMS/HYPOTHESIS: Diabetes mellitus is associated with increased mortality in subjects with acute myocardial infarction (AMI). We aimed to estimate the risk of mortality in AMI patients with and without diabetes using the urinary albumin : creatinine ratio (ACR). METHODS: This is a prospective study of 121 consecutive, non-selected diabetic AMI patients, 121 age- and sex-matched non-diabetic AMI patients and 61 diabetic non-AMI outpatients as control subjects. All data were obtained during the first 7 days of hospitalisation and each AMI patient was followed for a period of exactly 3 years. Baseline ACR RIA measurements were made on the 1st, 3rd and 7th days of admission. RESULTS: Adjusted ACR values were significantly higher in the diabetic AMI patients than in the diabetic control outpatients ( p<0.0001), and a significant difference was observed between the weekly ACR slopes for these two groups ( p<0.0001). Microalbuminuria was more prevalent in the diabetic AMI patients than in the non-diabetic AMI patients on the 1st day (62% vs 46%, p=0.01) and 3rd day (41% vs 29%, p=0.04). Among the AMI patients with normoalbuminuria (ACR <30 microg/mg), the mortality rate was 11.6% for the patients without diabetes and 33.8% for those with diabetes ( p=0.001). The mortality rate was much higher among the AMI patients with microalbuminuria (ACR >/=30 microg/mg) and similar for the diabetic (68.0%) and non-diabetic patients (74.3%). In a multivariable Cox model, ACR ( p<0.0001) and diabetes status ( p=0.01) were associated with adverse outcome even when several other clinical variables were included in the model. Furthermore, a negative interaction was found between diabetes and ACR ( p=0.01). CONCLUSIONS/INTERPRETATION: Microalbuminuria frequently occurs in diabetic and non-diabetic AMI patients during the first 3 days of admission to hospital and can be used to identify subjects at high risk of mortality.

Aged↗

PubMed2001

Microalbuminuria during acute myocardial infarction; a strong predictor for 1-year mortality.

AIMS: Urinary albumin excretion increases during acute myocardial infarction but little is known on the prognostic significance and the pathophysiological mechanisms of microalbuminuria in this clinical setting. The primary aim of the study was to examine whether urinary albumin excretion has predictive power for 1-year mortality after acute myocardial infarction. A secondary objective was to gain insight into the pathophysiological mechanisms of increased urinary albumin in myocardial infarction. METHODS AND RESULTS: This is a prospective cohort study conducted in three coronary care units (Northeast Italy). Four hundred and thirty-two unselected, consecutively enrolled patients with acute myocardial infarction (66.3+/- 12.3 years of age) were studied. The incidence of mortality was related to the baseline urinary albumin:creatinine ratio. The best cut-off for total mortality approximated to 50 mg x g(-1)on the first day after myocardial infarction, 30 mg x g(-1)on the third day, and to 20 mg x g(-1)on the seventh day. At multivariable Cox analysis, the albumin:creatinine ratio was the strongest among several independent predictors of mortality (adjusted relative risks: 3.6 (95% CI, 2.1--6.2) on the first day, 4.9 (95% CI, 2.9--8.2) on the third day and 4.0 (95% CI, 2.3--6.8) on the seventh day). Independent determinants of urinary albumin were plasma aldosterone on the first day, and inflammatory markers on the third and seventh days. CONCLUSION: Urinary albumin assessed in the first week after acute myocardial infarction is a strong prognostic marker for 1-year mortality.

Aged↗

PubMed2001

K-Cl cotransport modulation by intracellular Mg in erythrocytes from mice bred for low and high Mg levels.

Mg is an important determinant of erythrocyte cation transport system(s) activity. We investigated cation transport in erythrocytes from mice bred for high (MGH) and low (MGL) Mg levels in erythrocytes and plasma. We found that K-Cl cotransport activity was higher in MGL than in MGH erythrocytes, and this could explain their higher mean corpuscular hemoglobin concentration, median density, and reduced cell K content. Although mouse KCC1 protein abundance was comparable in MGL and MGH erythrocytes, activities of Src family tyrosine kinases were higher in MGH than in MGL erythrocytes. In contrast, protein phosphatase (PP) isoform 1 alpha (PP1 alpha) enzymatic activity, which has been suggested to play a positive regulatory role in K-Cl cotransport, was lower in MGH than in MGL erythrocytes. Additionally, we found that the Src family kinase c-Fgr tyrosine phosphorylates PP1 alpha in vitro. These findings suggest that in vivo downregulation of K-Cl cotransport activity by Mg is mediated by enhanced Src family kinase activity, leading to inhibition of the K-Cl cotransport stimulator PP1.

Animals↗

PubMed2001

Role of Src kinases and Syk in Fcgamma receptor-mediated phagocytosis and phagosome-lysosome fusion.

Phagocytosis is increased by Fcgamma receptors (FcgammaRs), and studies with syk(-/-) macrophages demonstrated that Syk kinase is required for FcgammaR phagocytosis. Similar studies with macrophages lacking the Src family kinases Hck, Fgr, and Lyn showed that these kinases are not required for phagocytosis but that they enhance the rate of particle engulfment. In this report we show that both wild-type and hck(-/-)fgr(-/-) macrophages expressed Fyn, Src, and Yes and that these kinases were activated on ingestion of immunoglobulin G (IgG)-coated particles and redistributed, together with Syk, to actin-rich phagocytic cups and the phagosomal membrane. At doses blocking IgG-dependent phagocytosis, the tyrosine kinase inhibitors PP1 and piceatannol inhibited both Src family kinase and Syk activities, as well as their redistribution to actin-rich phagocytic cups. Hck, Fgr, and Lyn were dispensable for lysosome-phagosome fusion (PLF) induced by IgG-coated particles. However, PP1 or piceatannol hampered unopsonized yeast-induced PLF despite the fact that they did not block yeast internalization.

Actins↗

PubMed2001

Clinical features associated with pre-hospital time delay in acute myocardial infarction.

BACKGROUND: The pre-hospital time delay in acute myocardial infarction (AMI) is still a challenging problem since for many patients there are long intervals between the onset of symptoms and the initiation of therapy. The aim of this study was to verify which, among several clinical variables, are associated with a prolonged pre-hospital time delay. METHODS: Five hundred and twenty-six unselected patients with AMI and consecutively admitted to three coronary care units were enrolled. The pre-hospital time delay was defined as the time interval from the onset of symptoms to admission to the coronary care unit. Clinical variables included: age, gender, body mass index, level of education, alcohol consumption, smoking habits, regular physical activity, history of hypertension, diabetes mellitus, history of coronary artery disease (documented history of angina and/or previous myocardial infarction), chronic atrial fibrillation, Q-wave AMI and off hours onset of symptoms. After univariate analysis, multivariable regression analysis was used. RESULTS: The mean age of the patients was 66.6 +/- 12.1 years and 28.7% were female. The median pre-hospital time interval was 200 min (95% confidence interval 60-1140). For 342 patients the pre-hospital time interval was < or = 6 hours and for 184 patients it was > 6 hours. Those variables which, at univariate analysis, were found to significantly influence the pre-hospital delay were analyzed using a multivariable regression model where the dependent variable was the pre-hospital time interval. Chronic atrial fibrillation (p = 0.010), a history of coronary artery disease (p = 0.017), diabetes (p = 0.016) and age > or = 70 years (p = 0.009) were found to be independently associated with a prolonged prehospital time interval. Similar results were obtained when considering only Q-wave AMI. As expected, the thrombolytic therapy rate was much lower in patients with a longer pre-hospital time delay. CONCLUSIONS: The present study shows that, in case of AMI, the time interval between the onset of symptoms and a patient's arrival to hospital is still far from being optimal. This is especially true for older patients with diabetes, a history of coronary artery disease or chronic atrial fibrillation. Cardiologists should be aware of this problem and should implement adequate educational strategies addressed to those patients at highest risk.

Age Factors↗

PubMed2000

Kinase pathways in chemoattractant-induced degranulation of neutrophils: the role of p38 mitogen-activated protein kinase activated by Src family kinases.

The aim of the present study was to investigate the role of tyrosine phosphorylation pathways in fMLP-induced exocytosis of the different secretory compartments (primary and secondary granules, as well as secretory vesicles) of neutrophils. Genistein, a broad specificity tyrosine kinase inhibitor, blocked the exocytosis of primary and secondary granules, but had only a marginal effect on the release of secretory vesicles. Genistein also inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPK), raising the possibility that inhibition of ERK and/or p38 MAPK might be responsible for the effect of the drug on the degranulation response. Indeed, SB203580, an inhibitor of p38 MAPK, decreased the release of primary and secondary granules, but not that of secretory vesicles. However, blocking the ERK pathway with PD98059 had no effect on any of the exocytic responses tested. PP1, an inhibitor of Src family kinases, also attenuated the release of primary and secondary granules, and neutrophils from mice deficient in the Src family kinases Hck, Fgr, and Lyn were also defective in secondary granule release. Furthermore, activation of p38 MAPK was blocked by both PP1 and the hck-/-fgr-/-lyn-/- mutation. Taken together, our data indicate that fMLP-induced degranulation of primary and secondary granules of neutrophils is mediated by p38 MAPK activated via Src family tyrosine kinases. Although piceatannol, a reportedly selective inhibitor of Syk, also prevented degranulation and activation of p38 MAPK, no fMLP-induced phosphorylation of Syk could be observed, raising doubts about the specificity of the inhibitor.

Adjuvants, Immunologic↗

PubMed1999

Adhesion-dependent degranulation of neutrophils requires the Src family kinases Fgr and Hck.

Polymorphonuclear neutrophils (PMN) adherent to integrin ligands respond to inflammatory mediators by reorganizing their cytoskeleton and releasing reactive oxygen intermediates. As Src family tyrosine kinases are implicated in these responses, we investigated their possible role in regulating degranulation. Human PMN incubated on fibrinogen released lactoferrin in response to TNF-alpha and this response was inhibited by PP1, a Src family tyrosine kinase inhibitor. This drug had no effect on lactoferrin secretion induced by PMA, an adhesion-independent agonist of PMN degranulation. However, PP1 blocked secretion in PMN plated on plain tissue culture plastic, a surface inducing PMN spreading in the absence of any stimulus. Double knockout hck-/- fgr-/- PMN adherent to collagen or fibrinogen failed to release lactoferrin in response to TNF-alpha but responded to PMA as wild-type PMN. Degranulation induced by spreading over tissue culture plastic was also defective in hck-/- fgr-/- PMN. Defective adhesion-dependent degranulation required the absence of both kinases, because single knockout fgr-/- or hck-/- PMN responded as wild-type cells. Analysis of lactoferrin secretion in hck-/- fgr-/- or PP1-treated, suspended PMN showed that Src kinases are not implicated in degranulation dependent on activation of protein kinase C or increase in intracellular free Ca2+ but may play a role in the response to FMLP of cytochalasin B-treated PMN. These findings identify a role for Src family kinases in a signaling pathway leading to granule-plasma membrane fusion and suggest that Fgr and Hck would be targets for pharmacological control of adhesion-dependent degranulation in the inflammatory site.

Animals↗

PubMed1999

Integrin signal transduction in myeloid leukocytes.

Integrin-mediated adhesion serves as a powerful costimulus for neutrophil activation. Clustering of integrins at the leukocyte membrane by interaction with surface-bound ligands (extracellular matrix proteins or endothelial cell counter-receptors) leads to a number of signaling events that culminate in actin cytoskeletal rearrangement and neutrophil functional responses such as migration, degranulation, and respiratory burst. Although the signaling reactions elicited by integrin ligation are complex and the relative contribution of each pathway to neutrophil function is unclear, a large body of evidence suggests that activation of tyrosine kinases is a very proximal event in these signaling cascades. This review summarizes the role of adhesion in activating neutrophil functional properties and the contribution of leukocyte tyrosine kinases to regulation of integrin signaling in myeloid cells. Significant advances in our understanding of leukocyte integrin signaling have been afforded by studies using knockout mice lacking members of the Src-family of tyrosine kinases normally expressed in myeloid cells. These studies have demonstrated that these kinases (Hck, Fgr, and Lyn) are not required for myeloid cell development or for many of the functional properties of myeloid cells but are critical in controlling integrin-mediated signaling events. Absence of these kinases results in impaired adhesion-dependent neutrophil activation both in vivo and in vitro. These studies suggest that leukocyte-specific tyrosine kinases may be good therapeutic targets for controlling myeloid cell-dependent inflammatory disease.

Animals↗

PubMed1999

Integrin signalling in neutrophils and macrophages.

Integrins have been characterized extensively as adhesion receptors capable of transducing signals inside the cell. In myelomonocytic cells, integrin-mediated adhesive interactions regulate different selective cell responses, such as transmigration into the inflammatory site, cytokine secretion, production or reactive oxygen intermediates, degranulation and phagocytosis. In the last few years, great progress has been made in elucidating mechanisms of signal transduction by integrins in neutrophils and macrophages. This review summarises the current information on the role of integrins in regulating myelomonocytic cell functions and highlights the signalling pathways activated by integrin engagement in these cells. Also, exploiting the current knowledge of mechanisms of integrin signal transduction in other cell types, we propose a model to explain how integrins transduce signals inside neutrophils and macrophages, and how signaling pathways leading to regulation of selective cell functions may be coordinated.

Animals↗

PubMed1999

Tyrosine kinases in neutrophils.

Nonreceptor tyrosine kinases have been shown to represent essential components of several signal transduction pathways implicated in neutrophil activation. Engagement of phagocytic, cytokine, chemoattractant, and adhesion receptors transduces intracellular signals via distinct tyrosine kinases. This article discusses the role of distinct tyrosine kinases in mediating neutrophil responses.

Cell Adhesion↗

PubMed1999

Impaired integrin-mediated signal transduction, altered cytoskeletal structure and reduced motility in Hck/Fgr deficient macrophages.

Integrin-mediated adhesion of monocytes and macrophages initiates a signal transduction pathway that leads to actin cytoskeletal reorganization, cell migration and immunologic activation. This signaling pathway is critically dependent on tyrosine kinases. To investigate the role of the Src-family of tyrosine kinases in integrin signal transduction, we have examined the adhesive properties of macrophages isolated from hck-/-fgr-/- double knockout mice which lack two of the three predominant Src-family kinases expressed in myeloid cells. Previous examination of polymorphonuclear leukocytes from these animals indicated that these kinases were critical in initiating the actin cytoskeletal rearrangements that lead to respiratory burst and granule secretion following integrin ligation. Double mutant peritoneal exudate macrophages demonstrated markedly reduced tyrosine phosphorylation responses compared to wild-type cells following plating on fibronectin, collagen or vitronectin-coated surfaces. Tyrosine phosphorylation of several actin-associated proteins (cortactin, paxillin, and tensin), as well as the Syk and Pyk2 tyrosine kinases, were all significantly reduced in double mutant cells. The subcellular localization of focal-adhesion associated proteins was also dramatically altered in mutant macrophages cultured on fibronectin-coated surfaces. In wild-type cells, filamentous actin, paxillin, and talin were concentrated along leading edges of the plasma membrane, suggesting that these proteins contribute to cellular polarization during migration in culture. Double mutant cells failed to show the polarized subcellular localization of these proteins. Likewise, double mutant macrophages failed to form normal filopodia under standard culture conditions. Together, these signaling and cytoskeletal defects may contribute to the reduced motility observed in in vitro assays. These data provide biochemical and morphological evidence that the Src-family kinases Hck and Fgr are required for normal integrin-mediated signal transduction in murine macrophages.

Actins↗

PubMed1998

Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr.

Signal transduction through the leukocyte integrins is required for the processes of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory reactions. Neutrophils isolated from knockout mice that are deficient in the expression of p59/61(hck) (Hck) and p58(c-fgr) (Fgr), members of the Src-family of protein tyrosine kinases, have been shown to be defective in adhesion mediated activation. Cells from these animals have impaired induction of respiratory burst and granule secretion following plating on surfaces that crosslink beta2 and beta3 integrins. To determine if the defective function of hck-/-fgr-/- neutrophils observed in vitro also results in impaired inflammatory responses in vivo, we examined responses induced by lipopolysaccharide (LPS) injection in these animals. The hck-/-fgr-/- mice showed marked resistance to the lethal effects of high-dose LPS injection despite the fact that high levels of serum tumor necrosis factor alpha and interleukin 1alpha were detected. Serum chemistry analysis revealed a marked reduction in liver and renal damage in mutant mice treated with LPS, whereas blood counts showed a marked neutrophilia that was not seen in wild-type animals. Direct examination of liver sections from mutant mice revealed reduced neutrophil migration into the tissue. These data demonstrate that defective integrin signaling in neutrophils, caused by loss of Hck and Fgr tyrosine kinase activity, results in impaired inflammation-dependent tissue injury in vivo.

Animals↗

PubMed1998

Antibody-induced engagement of beta2 integrins in human neutrophils causes a rapid redistribution of cytoskeletal proteins, Src-family tyrosine kinases, and p72syk that precedes de novo actin polymerization.

Beta2 integrins mediate rearrangement of the cytoskeleton and activation of selective cell functions in neutrophils. To elucidate early events following beta2 integrin ligation, we analyzed redistribution of cytoskeletal and signaling proteins as a consequence of antibody-induced integrin clustering. Incubation of neutrophils on surface-bound anti-beta2 subunit antibodies induced a very rapid (within 1 min) redistribution of the cytoskeletal proteins talin, alpha-actinin, and paxillin, and the tyrosine kinases p58(c-fgr), p53/56(lyn), and p72(syk) to a cell fraction insoluble in Triton X-100. Cytoskeletal and signaling proteins redistribution preceded de novo actin polymerization because cytochalasin B did not inhibit this redistribution. Antibody engagement of all the three distinct beta2 integrins (CD11a, CD11b, CD11c) expressed by neutrophils induced redistribution of cytoskeletal proteins and tyrosine kinases. Several tyrosine phosphorylated proteins were also rapidly redistributed as a consequence of beta2 integrin engagement and this was not affected by blocking de novo actin polymerization with cytochalasin B. In addition, genistein, an inhibitor of tyrosine kinase activities which strongly reduced protein tyrosine phosphorylation, had no effect on redistribution of cytoskeletal proteins, Src-family kinases, and p72(syk). These findings suggest that integrin-dependent cytoskeleton rearrangement in neutrophils occurs in at least two distinct steps and nucleation of some cytoskeletal proteins together with tyrosine kinases precedes rearrangement of the actin-based cytoskeleton and tyrosine kinases activation. On the basis of these and previous findings we propose a model explaining mechanisms of integrin signaling in neutrophils.

Actins↗

PubMed1998

Structural abnormalities and not diastolic dysfunction are the earliest left ventricular changes in hypertension. HARVEST Study Group.

It has been claimed that diastolic dysfunction is the earliest cardiac abnormality in hypertension, preceding the development of left ventricular (LV) structural abnormalities. To detect early signs of hypertensive cardiac involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals of similar age and gender distributions were studied as controls. Significant, though modest, changes of LV mass and geometry were found in the participants in comparison with the normotensive controls. The increment was +10.4 g/m2 for LV mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall thickness. A slight increase in atrial filling peak velocity was found in the hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of early to atrial velocity of LV diastolic filling did not differ between the two groups. In multiple regression analyses, which included age, body mass index, heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a significant predictor of LV mass index (men, P = .003; women, P = .04) and wall thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas no index of diastolic filling was significantly associated with ambulatory blood pressure in either gender. The present data indicate that changes in LV anatomy are the earliest signs of hypertensive cardiac involvement. Left ventricular filling is affected only marginally in the initial phase of hypertension.

Adolescent↗

PubMed1998

ICAM-1 induction in respiratory cells exposed to a replication-deficient recombinant adenovirus in vitro and in vivo.

Administration of replication-deficient recombinant adenoviruses (Ad) designed as vectors for gene transfer to the airway tract of rats and monkeys has been associated with a dose-dependent inflammatory process a few days after viral exposure. Among the cellular mechanisms possibly involved, we investigated the expression of intercellular adhesion molecule-1 (ICAM-1), which is known to be induced by parainfluenza, adenovirus type 5 and respiratory syncytial viruses in vitro. To test this hypothesis, an Ad type 5-derived replication-deficient recombinant vector carrying the expression cassette for the cystic fibrosis gene (Ad.CFTR) was either incubated with A549 cells (a human-derived lung epithelial cell line) or instilled by bronchoscopic procedures into the airways of Rhesus monkeys. Ad.CFTR induced expression of ICAM-1 in A549 cells and up-regulated with time the basal levels of ICAM-1 mRNA in lung portions of Rhesus monkeys. These observations indicate that E1-E3-deleted replication-deficient adenoviral vectors are capable of inducing adhesion molecules known to play a role in inflammation.

Adenoviridae↗

PubMed1998

Prognostic significance of hypertension and albuminuria for early mortality after acute myocardial infarction.

OBJECTIVE: To assess the risk of mortality associated with hypertension and microalbuminuria in patients with acute myocardial infarction. DESIGN: A prospective study. SETTING: Intensive care units in three Italian general hospitals. PATIENTS: In total 309 consecutive patients (including 97 women) aged 66.6 +/- 12.5 years, admitted to hospital for acute myocardial infarction. MAIN OUTCOME MEASURES: Albumin excretion rate measured by radioimmunoassay of 24 h urine samples, on the first and third days after admission to hospital. In-hospital mortality rate among the patients stratified according to their history of hypertension and albumin excretion rate. RESULTS: Of the patients, 147 had histories of hypertension. Forty-four per cent of the normotensive and 43% of the hypertensive subjects had microalbuminuria on the first day. On the third day the percentages were 25 and 29%, respectively. Twenty-two patients died before discharge from hospital. Patients were divided into four groups according to whether they had microalbuminuria or not and likewise for hypertension. Mortality rate among the subjects with hypertension and microalbuminuria combined was greater than those among the other three groups (P < 0.0001 on the first and third days). The relative hazard ratio was 11.7 on the first day, and 15.6 on the third day. In a multivariate Cox's model hypertension and microalbuminuria combined had a greater predictive power for mortality than either variable alone. Killip class, age, and creatinine kinases MB level were other significant predictors of death. CONCLUSIONS: These results show that the combination of hypertension and microalbuminuria is associated with a greater risk of in-hospital mortality among subjects with acute myocardial infarction, independently of degree of heart failure and other possible confounders.

Aged↗

PubMed1997

Albumin excretion rate increases during acute myocardial infarction and strongly predicts early mortality.

BACKGROUND: This study was undertaken to assess whether albumin excretion rate (AER) increases during acute myocardial infarction (AMI) and whether it predicts in-hospital mortality. METHODS AND RESULTS: The study was carried out in 496 subjects admitted to hospital for suspected AMI. Of these, 360 had evidence of AMI. The other 136 were studied as control subjects. AER was assessed by radioimmunoassay in three 24-hour urine collections performed on the first, third, and seventh days after admission. Left ventricular ejection fraction was measured by two-dimensional echocardiography in 254 subjects. AER adjusted for several confounders was higher in the AMI than the non-AMI group on the first (69.2+/-5.2 versus 27.3+/-8.5 mg/24 h, P<.0001) and third (30.3+/-2.7 versus 12.5+/-4.4 mg/24 h, P=.001) days, whereas no difference was present on the seventh day. When the subjects with heart failure were excluded, the difference between the two groups remained significant (first day, P<.0001; third day, P=.001). On the basis of classification of the 26 AMI patients who died in hospital according to whether they had normal AER, microalbuminuria, or overt albuminuria, mortality rate progressively increased with increasing levels of AER (P<.0001). In a Cox's proportional hazards model, AER was a better predictor of in-hospital mortality than Killip class or echocardiographic left ventricular ejection fraction. A cutoff value of 50 mg/24 h for first-day AER and 30 mg/24 h for third-day AER yielded a sensitivity of 92.3% and of 88.5% and a specificity of 72.4% and of 79.3%, respectively, for mortality. Adjusted relative risks for the two cutoff values were 17.3 (confidence limits, 4.6 to 112.7) and 8.4 (confidence limits, 2.4 to 39.3), respectively. CONCLUSIONS: These data show that AER increases during AMI and that it yields prognostic information additional to that provided by clinical or echocardiographic evaluation of left ventricular performance.

Aged↗

PubMed1997

Signaling by adhesion in human neutrophils: activation of the p72syk tyrosine kinase and formation of protein complexes containing p72syk and Src family kinases in neutrophils spreading over fibrinogen.

Src family kinases are implicated in signaling by integrins in polymorphonuclear neutrophils (PMN). To identify proteins present in complexes with Src family kinases, we subjected p58(c-fgr) or p53/56(lyn) immunoprecipitates from Triton X-100 lysates of PMN incubated on fibrinogen-coated surfaces to in vitro kinase assays. Assays on p58(c-fgr) or p53/56(lyn) immunoprecipitates from Triton lysates of PMN induced to spread over fibrinogen in response to TNF-alpha showed that several proteins form complexes with Src family kinases and can be phosphorylated in vitro. Immunoblot analysis showed that the p72(syk) tyrosine kinase is one of these proteins. Formation of protein complexes containing Src family kinases and p72(syk) required PMN spreading because p72(syk) was not detected in p58(c-fgr) or p53/56(lyn) immunoprecipitates from PMN, which were stimulated with TNF-alpha, in suspension. In addition, induction of PMN spreading with Mn2+ in the absence of TNF-alpha promoted the formation of protein complexes containing Src family kinases and p72(syk). We also found that p72(syk)-autophosphorylating kinase activity was enhanced, and a fraction of p72(syk) was translocated to a Triton-insoluble cytoskeletal fraction in PMN induced to spread over fibrinogen by TNF-alpha or Mn2+. In vitro kinase assays on CD18 (beta 2 integrin subunit) immunoprecipitates from Triton lysates of spread PMN showed that several proteins formed complexes with CD18 and could be phosphorylated in vitro. Immunoblot analysis of CD18 immunoprecipitates allowed us to identify p72(syk) as one of these proteins. These findings show that PMN spreading is accompanied by activation of p72(syk) and formation of multimolecular complexes in which Src family kinases and p72(syk) colocalize.

CD18 Antigens↗