Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

<p>Abstract</p> <p>Background</p> <p>Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of <it>E. coli </it>activates the expression of <it>atoDAEB </it>operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that <it>atoSC </it>is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the <it>atoDAEB </it>promoter as the single, <it>cis</it>-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the <it>E. coli </it>genome.</p> <p>Results</p> <p>Through the implementation of a computational <it>de novo </it>motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the <it>E. coli </it>genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the <it>in vivo </it>binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences.</p> <p>Conclusions</p> <p>This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.</p

Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

Torsades de Pointes due to multihormonal deficiency induced long QT syndrome

A 70-year-old patient suffering from multihormonal insufficiency presented several episodes of polymorphic ventricular tachycardia Torsades de pointes. A long QT interval was diagnosed which was due to hypoparathyroidism-induced hypocalcaemia refractory to the replacement therapy. Although several antiarrythmic drugs were used, only the administration with magnesium sulfate provided electrical stability. The multihormonal deficiency was due to ‘empty sella turcica syndrome’. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved

PERCUTANEOUS PULMONARY VALVULOPLASTY IN AN OCTOGENARIAN WITH CALCIFIC PULMONARY STENOSIS

We describe a patient in whom calcific pulmonary vascular stenosis was diagnosed at the age of 84 years. Valve stenosis was relieved by percutaneous transluminal pulmonary valvuloplasty. To our knowledge, PTPV performed at this age bas not been previously reported

IMPROVED DIAGNOSTIC-ACCURACY WITH THE EVALUATION OF ECG-CHANGES IN EXERCISE-INDUCED SUPRAVENTRICULAR EXTRASYSTOLES

The clinical value of exercise-induced ST segment depression (STx) and R wave amplitude (R(x)) in supraventricular extrasystoles, in the preceding sinus beat (STs and R(s) respectively), as well as the combination of the differences between the two of them (STx-s + R(x-s)) was studied in 96 patients with angiographically documented coronary artery disease (CAD) (group A) - 34 with myocardial infarction (group A(1)) and 62 without (group A(2)) - compared to 37 subjects with normal coronary arteries (group B). ST,, had greater values in group A than in group B (0.4 +/- 0.5 vs. -0.2 +/- 0.4 mm; p &lt; 0.0001) as did R(x-s) (0.6 +/- 0.5 vs. -1.1 +/- 0.8 mm; p &lt; 0.0001) and their combination (1.0 +/- 0.7 vs. -1.3 +/- 1.0 mm; p &lt; 0.0001), while STx-s had similar values in groups A(1) and A(2) but R(x-s) values were higher in A(1) than in A(2) (P &lt; 0.001). R(x-s), STx-s, and especially their sum (STx-s + R(x-s)) value was directly related to the number of vessel disease(0.7 +/- 0.5 mm for 1-, 1.1 +/- 0.7 mm for 2-, and 1.4 +/- 0.7 mm for 3-vessel disease; p &lt; 0.0001), while it was significantly higher in patients with left ventricular dysfunction (-0.01 +/- 1.2 vs. 1.5 +/- 0.8 mm; p &lt; 0.0001). The value of (STx-s + R(x-s)) improved sensitivity compared to the sinus signs (from 66 to 87%) as well as specificity (from 82 to 95%) for CAD detection, while for detection of left ventricular dysfunction it improved sensitivity (from 85 to 91%)with no gain in specificity. It is concluded that ST segment depression and R wave amplitude changes in exercise-induced supraventricular extrasystoles may be of greater diagnostic significance than in sinus beats, for the detection of CAD and left ventricular dysfunction

45,X TURNER SYNDROME WITH NORMAL OVARIAL FUNCTION AND MULTIPLE MALFORMATIONS OF THE AORTA

We present a case of a female patient with monosomy of X chromosome in peripheral lymphocytes and skin fibroblasts, normal ovarian function and associated multiple congenital abnormalities of the aorta: bicuspid aortic valve, dilatation of the ascending aorta and multiple cystic structures of the aortic wail, complicated by endarteritis. We review the literature on fertile women with 45,X karyotype and the possible pathogenetic mechanisms of the aortic defects described as ‘cystic medial necrosis of the aorta’

RELATION BETWEEN CHANGES IN BLOOD-FLOW OF THE CONTRALATERAL CORONARY-ARTERY AND THE ANGIOGRAPHIC EXTENT AND FUNCTION OF RECRUITABLE COLLATERAL VESSELS ARISING FROM THIS ARTERY DURING BALLOON CORONARY-OCCLUSION

Objectives. The purpose of this study was to investigate changes in the magnitude of blood flow through the contralateral coronary artery in relation to the development of recruitable collateral vessels arising from this artery to supply a balloon occluded coronary vessel. Background. Recruitable collateral vessels have been shown to emerge suddenly to supply an occluded coronary artery, but their physiologic effect cannot always be predicted angiographically. Methods. Twenty four patients were studied during four successive balloon dilations for single left anterior descending coronary artery stenosis. Before and during each balloon occlusion, blood flow in the proximal right coronary artery was measured by intracoronary Doppler flow velocimetry and quantitative coronary angiography. Estimates of chest pain and ST segment elevation were also obtained. Results. Fourteen patients developed angiographically visible recruitable collateral vessels (high grade in 6 [group III], low grade in 8 [group II]), whereas 10 patients (group I) did not. During the four successive balloon occlusions, the right coronary artery how showed transient reproducible increases in group In (first occlusion 66.4 +/- 36.8%, fourth occlusion 64 +/- 23.9%, all p = 0.036), progressive increases in group II (from first occlusion 17.9 +/- 26.6% [p = 0.08] to fourth occlusion 60.4 +/- 35.9% [p = 0.014]) and no significant changes in group I. Between the first and the fourth occlusion, the severity of chest pain and the magnitude of ST segment elevation declined significantly in group II but did not change in groups I and III. Conclusions. During balloon coronary artery occlusion, the transient appearance of recruitable collateral vessels is associated with a transient increase in blood flow through the collateral donor artery. This increase in coronary flow appears to reflect collateral function better than the angiographic assessment, especially in patients with poor collateral vessel recruitment

Fibrinolytic/hemostatic variables in arterial hypertension: Response to treatment with irbesartan or atenolol

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta(1)-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol. (C) 2000 American Journal of Hypertension, Ltd

Resistance to activated protein C and FV Leiden mutation in patients with a history of acute myocardial infarction or primary hypertension

This study was designed to investigate both resistance to activated protein C (APC-R) and the factor FV Q506 mutation incidence in patients with a history of acute myocardial infarction (AMI) and patients with primary hypertension (PH), a highrisk group for arterial thrombosis. Eighty patients with a history of AMI (group A), 160 patients with a history of PH (group B), and 124 age-matched controls without arterial disease (group C) were studied. APC-R was determined using the Coatest APC Resistance Kit of Chromagenix, Sweden. The prevalence of the FV Q506 mutation was estimated by DNA analysis (Bertina method). The prevalence of the FV Q506 mutation was 20%, 13.75%, and 8% in groups A, B, and C, respectively (A v C P = .0466). The prevalence of APC-R was 47.5% in group A v 13% in group C (P &lt; .0001) and 36.25% in group B v13% in group C (P &lt; .0001). The response to activated protein C expressed as mean value +/- SD was 2.05 +/- 0.33 in group A v 2.56 +/- 0.46 in group C (P &lt; .05) and 2 +/- 0.22 in group B v 2.56 +/- 0.46 in group C (P &lt; .05). These findings suggest that patients with a history of AMI or PH have a significantly increased incidence of both APC-R and FV Q506 mutation compared with the control group. These findings support the hypothesis that these anticoagulant defects may be risk factors for arterial thrombosis. (C) 2000 American Journal of Hypertension, Ltd