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1.
Role of the Salmonella pathogenicity island 1 effector proteins SipA, SopB, SopE, and SopE2 in Salmonella enterica subspecies 1 serovar Typhimurium colitis in streptomycin-pretreated mice 下载免费PDF全文
Hapfelmeier S Ehrbar K Stecher B Barthel M Kremer M Hardt WD 《Infection and immunity》2004,72(2):795-809
Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium) induces enterocolitis in humans and cattle. The mechanisms of enteric salmonellosis have been studied most extensively in calf infection models. The previous studies established that effector protein translocation into host cells via the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (TTSS) is of central importance in serovar Typhimurium enterocolitis. We recently found that orally streptomycin-pretreated mice provide an alternative model for serovar Typhimurium colitis. In this model the SPI-1 TTSS also plays a key role in the elicitation of intestinal inflammation. However, whether intestinal inflammation in calves and intestinal inflammation in streptomycin-pretreated mice are induced by the same SPI-1 effector proteins is still unclear. Therefore, we analyzed the role of the SPI-1 effector proteins SopB/SigD, SopE, SopE2, and SipA/SspA in elicitation of intestinal inflammation in the murine model. We found that sipA, sopE, and, to a lesser degree, sopE2 contribute to murine colitis, but we could not assign an inflammation phenotype to sopB. These findings are in line with previous studies performed with orally infected calves. Extending these observations, we demonstrated that in addition to SipA, SopE and SopE2 can induce intestinal inflammation independent of each other and in the absence of SopB. In conclusion, our data corroborate the finding that streptomycin-pretreated mice provide a useful model for studying the molecular mechanisms of serovar Typhimurium colitis and are an important starting point for analysis of the molecular events triggered by SopE, SopE2, and SipA in vivo. 相似文献
2.
K M Connolly V J Stecher E Danis D J Pruden T LaBrie 《International journal of immunopharmacology》1988,10(6):717-728
The purpose of the paper was to determine whether two clinically active antirheumatic compounds, cyclosporin-A (CS-A) and methotrexate (MTX) were efficacious in the treatment of adjuvant arthritis (AA) in rats, as measured by reduction of paw inflammation, lymphocyte activating factor (LAF) activity and the acute phase response. Parameters of the acute phase response consisted of plasma fibronectin (Fn), C-reactive protein (CRP), albumin and iron. Rats injected with Freund's complete adjuvant on day 1, developed systemic arthritis, which was quantitated by measuring non-injected paw swelling on day 17. When compared to normal animals, AA rats had significantly (P less than or equal to 0.01) increased: (1) splenic LAF activity (100% increase), (2) plasma Fn (58%), and (3) CRP (122%), as well as abnormally reduced levels of: (1) plasma albumin (53% reduction), and (2) iron (54%). Orally dosing AA rats from days 3 to 17 with the immunoregulatory drugs, CS-A (3 and 5 mg/kg) or MTX (0.5 and 1 mg/kg), significantly (P less than or equal to 0.01) reduced paw inflammation (100% reduction), increased final body wt 40-50 g over arthritic controls and decreased LAF activity from splenic leukocytes. The acute phase response, often associated with a high degree of LAF activity, was significantly (P less than or equal to 0.01) decreased by dosing with CS-A (3 and 5 mg/kg) and MTX (0.5 and 1 mg/kg). The inhibition of the acute phase response was measured by reduction of high plasma Fn levels (42-79% decrease) and CRP levels (57-100% decrease) as well as elevation of subnormal levels of plasma albumin (57-101% increase) and iron (40-114% increase). Dosing with the nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin (50 and 100 mg/kg) or phenylbutazone (10 and 30 mg/kg), significantly inhibited paw inflammation (29-85%), but did not decrease the high rate of splenic LAF activity, nor did aspirin (55, 100 and 200 mg/kg) or phenylbutazone (1, 10 and 30 mg/kg) alter the acute phase response in AA rats, as measured by levels of plasma Fn, CRP, albumin and iron. Since CS-A and MTX have been reported to be effective in the treatment of RA, their activity in the LAF, Fn, CRP, albumin and iron assays of the AA rat suggests that these immunological and serological parameters may be useful in identifying potential antirheumatic drugs and distinguishing them from standard NSAIDs. 相似文献
3.
Introduction: Quantitative DNA cytophotometry, the study of morphology of chromosomes and cell kinetics are important approaches toward characterization of genetic information. Each approach has its own problems and limits. Difficulties with interpretation of DNA histograms arise from a lack of proper terminology, and from attempting to interpret them in terms of the existing terminologies for chromosomal analysis and cell kinetics. Aim of this research was to develop a computerized mathematical analysis of DNA histograms. Materials and methods: As a basis for the comparison of normal with those of tumor cell populations the DNA histograms of heart muscle cells were selected for the normal cell population from 14 normal hearts of adults, 16 hypertrophic hearts, 14 non-polyploidized hearts of children, and 14 hypertrophic hearts of children with congenital malformations. Normal diploid cell populations from 7 effusions were also included. The 24 populations of malignant cells consisted of primary tumors and metastatic effusions. DNA cytophotometry was performed on single nuclei in Feulgen stained preparations by means of the UMSP/XD 50 ZEISS. The approximation of the DNA histograms by linear combination of normal distributions was done according to spline-function and calculated by means of the IBM-375. Results: The nuclear classes 2C, 4C, and 8C show no differences between the normal, left and right heart with respect to mean values (X), standard deviations (sx), variances (sX) and coefficients of variance (sx/X). However, coefficients of variance are smaller in hypertrophic (2.15 to 8.37%) than in normal hearts of adults (8.90 to 10.85%), and larger in hypertrophic heart of children (4.06 to 7.09%). The mean values of the DNA classes 2C, 4C, 8C, and 16C vary witin +/- 18.6% with a probability of 95.5%. Benign effusions contain only 2C and 4C nuclei with a variance of 4.00% and 8.75%, respectively. In DNA histograms of malignant cells, only one third has a first peak outside of 2C +/- 18.6%. In approximately one fifth of the histrograms the position of the second or third peaks deviates significantly from normal polyploid values. Since a large proportion of polyploid nuclei is limited to only a few normal tissues, pronounced polyploidy is suggestive of malignancy in all other tissues. If in the cases containing only two DNA classes, 2C and 4C, the populations are malignant, the proportion of 4C is more than 8% while in the corresponding benign populations the proportion of 4C atains only 2.97 +/- 2.5%. In some cases a few highly polyploidized nuclei not taken into a account by our computer program are suggestive of malignancy. In only one DNA histogram out of the 24 analysed, all of these criteria are negative. In six cases the computer analyses reveal two stemlines of tumor cells with corresponding polyploid values. 相似文献
4.
5.
Schwartz BG Levine LA Comstock G Stecher VJ Kloner RA 《Journal of the American College of Cardiology》2012,59(1):9-15
Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynaud's phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases. 相似文献
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7.
Jordan Brophy Kyle Summerfield Jiashi Yin Jon Kephart Joshua T. Stecher Jeramie Adams Takashi Yanase Jason Brant Katie Dongmei Li-Oakey John O. Hoberg Bruce A. Parkinson 《Materials》2021,14(1)
Two-dimensional covalent organic frameworks (2D-COFs) have been of increasing interest in the past decade due to their porous structures that ideally can be highly ordered. One of the most common routes to these polymers relies on Schiff-base chemistry, i.e., the condensation reaction between a carbonyl and an amine. In this report, we elaborate on the condensation of 3,6-dibromobenzene-1,2,4,5-tetraamine with hexaketocyclohexane (HKH) and the subsequent carbonylation of the resulting COF, along with the possibility that the condensation reaction on HKH can result in a trans configuration resulting in the formation of a disordered 2D-COF. This strategy enables modification of COFs via bromine substitution reactions to place functional groups within the pores of the materials. Ion-sieving measurements using membranes from this COF, reaction of small molecules with unreacted keto groups along with modeling studies indicate disorder in the COF polymerization process. We also present a Monte Carlo simulation that demonstrates the influence of even small amounts of disorder upon both the 2D and 3D structure of the resulting COF. 相似文献
8.
Schlumberger MC Müller AJ Ehrbar K Winnen B Duss I Stecher B Hardt WD 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(35):12548-12553
Many pathogenic and symbiotic Gram-negative bacteria employ type III secretion systems to inject "effector" proteins into eukaryotic host cells. These effectors manipulate signaling pathways to initiate symbiosis or disease. By using time-lapse microscopy, we have imaged delivery of the Salmonella type III effector protein SipA/SspA into animal cells in real time. SipA delivery mostly began 10-90 sec after docking and proceeded for 100-600 sec until the bacterial SipA pool (6 +/- 3 x 10(3) molecules) was exhausted. Similar observations were made for the effector protein SopE. This visualization of type III secretion in real time explains the efficiency of host cell manipulation by means of this virulence system. 相似文献
9.
Cristián Biscayart María Eugenia Pérez Carrega Sandra Sagradini Ángela Gentile Daniel Stecher Tomás Orduna Silvia Bentancourt Salvador García Jiménez Luis Pedro Flynn Gabriel Pirán Arce María Andrea Uboldi Laura Bugna María Alejandra Morales Clara Digilio Cintia Fabbri Delia Enría Máximo Diosque Carla Vizzotti 《Vaccine》2014
10.
Lena M. Biehl Paul G. Higgins Jannik Stemler Meyke Gilles Silke Peter Daniela Drfel Wichard Vogel Winfried V. Kern Hanna Glz Hartmut Bertz Holger Rohde Eva-Maria Klupp Philippe Schafhausen Jon Salmanton-García Melanie Stecher Julia Wille Blasius Liss Kyriaki Xanthopoulou Janine Zweigner Harald Seifert Maria J.G.T. Vehreschild 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2022,27(2)
BackgroundEvidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition of vancomycin-resistant enterococci (haVRE) is limited.AimWe assessed the impact of SCP on haVRE and their transmission.MethodsWe conducted a prospective, multicentre cohort study in German haematological/oncological departments during 2016. Two sites performed SCP for VRE patients and two did not (NCP). We defined a 5% haVRE-risk difference as non-inferiority margin, screened patients for VRE, and characterised isolates by whole genome sequencing and core genome MLST (cgMLST). Potential confounders were assessed by competing risk regression analysis.ResultsWe included 1,397 patients at NCP and 1,531 patients at SCP sites. Not performing SCP was associated with a significantly higher proportion of haVRE; 12.2% (170/1,397) patients at NCP and 7.4% (113/1,531) patients at SCP sites (relative risk (RR) 1.74; 95% confidence interval (CI): 1.35–2.23). The difference (4.8%) was below the non-inferiority margin. Competing risk regression analysis indicated a stronger impact of antimicrobial exposure (subdistribution hazard ratio (SHR) 7.46; 95% CI: 4.59–12.12) and underlying disease (SHR for acute leukaemia 2.34; 95% CI: 1.46–3.75) on haVRE than NCP (SHR 1.60; 95% CI: 1.14–2.25). Based on cgMLST and patient movement data, we observed 131 patient-to-patient VRE transmissions at NCP and 85 at SCP sites (RR 1.76; 95% CI: 1.33–2.34).ConclusionsWe show a positive impact of SCP on haVRE in a high-risk population, although the observed difference was below the pre-specified non-inferiority margin. Importantly, other factors including antimicrobial exposure seem to be more influential. 相似文献