Excessive use of antibiotics contributes to the selection of resistant bacteria and intestinal colonization with multiresistant pathogens poses a risk factor for subsequent infections. The present study assessed vancomycin-resistant enterococci (VRE) carriage rates in patients admitted to our tertiary care hospital. Stool samples sent for routine culturing were screened with vancomycin containing solid or broth enrichment media. VRE isolates were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and antibiotic susceptibilities were tested by E-test. Vancomycin resistance genes were detected by polymerase chain reaction. Medical records of carriers were examined for suspected risk factors for colonization. Altogether 3025 stool specimens were analyzed. Solid media identified a VRE carriage rate of 2.2% while broth enrichment detected 5.8%. Seventy percent of the isolates were Enterococcus faecium. VanB genotype was detected in 38.2%, VanA in 37.3%, VanC1 in 22.6%, and VanC2 in 1.9%. All VRE were sensitive to linezolid, daptomycin, and tigecycline. Collective risk factors for carriage were diabetes, normal flora absence, Clostridioides difficile positivity, longer hospital stay, and advanced age. 78.5% of the carriers received antibiotic therapy which was metronidazole in most cases (47.3%). We recommend regular screening of risk groups such as patients with diabetes, history of recent hospitalization, or former C. difficile infection as an imperative step for preventing VRE dissemination.
- MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Tertiary Care Centers MeSH
- Child MeSH
- Adult MeSH
- Vancomycin-Resistant Enterococci isolation & purification MeSH
- Feces microbiology MeSH
- Genotype MeSH
- Gram-Positive Bacterial Infections drug therapy epidemiology microbiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Adolescent MeSH
- Young Adult MeSH
- Child, Preschool MeSH
- Carrier State epidemiology microbiology MeSH
- Retrospective Studies MeSH
- Vancomycin Resistance genetics MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Intestines microbiology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Hungary MeSH
The Epstein-Barr virus (EBV) is found almost exclusively in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focused on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCLs and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this, we found that LMP1-expressing primary ABC-DLBCLs were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- MeSH
- Phosphatidylinositol 3-Kinase metabolism MeSH
- CD40 Antigens genetics metabolism MeSH
- Databases, Genetic MeSH
- Lymphoma, Large B-Cell, Diffuse genetics metabolism mortality virology MeSH
- Epstein-Barr Virus Infections mortality virology MeSH
- Host-Pathogen Interactions MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prognosis MeSH
- Viral Matrix Proteins genetics metabolism MeSH
- Proto-Oncogene Proteins c-akt metabolism MeSH
- Sphingosine-1-Phosphate Receptors genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Signal Transduction MeSH
- Cell Transformation, Viral MeSH
- Herpesvirus 4, Human genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with a poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 is expressed in preneoplastic lesions, and its expression is maintained in most colorectal cancers (CRC). High TROP2 positivity correlated with lymph node metastases and poor tumor differentiation and was a negative prognostic factor. To investigate the role of TROP2 in intestinal tumors, we analyzed two mouse models with conditional disruption of the adenomatous polyposis coli (Apc) tumor-suppressor gene, human adenocarcinoma samples, patient-derived organoids, and TROP2-deficient tumor cells. We found that Trop2 is produced early after Apc inactivation and its expression is associated with the transcription of genes involved in epithelial-mesenchymal transition, the regulation of migration, invasiveness, and extracellular matrix remodeling. A functionally similar group of genes was also enriched in TROP2-positive cells from human CRC samples. To decipher the driving mechanism of TROP2 expression, we analyzed its promoter. In human cells, this promoter was activated by β-catenin and additionally by the Yes1-associated transcriptional regulator (YAP). The regulation of TROP2 expression by active YAP was verified by YAP knockdown in CRC cells. Our results suggest a possible link between aberrantly activated Wnt/β-catenin signaling, YAP, and TROP2 expression.
- Publication type
- Journal Article MeSH
... 271 -- Transcription Initiation by Bacterial RNA Polymerase -- Requires Association with a Sigma Factor ... ... and Activators 273 -- Transcription Initiation from Some Promoters -- Requires Alternative Sigma Factors ... ... Transcription Factors 703 -- Ligand-Activated Notch Is Cleaved Twice, Releasing a Transcription Factor ... ... -- MPF Activity 853 -- Maturation-Promoting Factor (MPF) Stimulates Meiotic Maturation in Oocytes and ... ... 941 -- Some Trophic Factors Induce Inactivation of a Pro-Apoptotic Regulator 942 -- Tumor Necrosis Factor ...
6th ed. xxxvii, 1150 s. : il., tab. ; 29 cm
- MeSH
- Cell Biology MeSH
- Molecular Biology MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- cytologie, klinická cytologie
... Grown in a Culture Dish 161 -- Chemically Defined Media Permit Identification of Specific Growth Factors ... ... -- Chromatin-bound Factors Ensure That Each Region of the DNA Is Replicated Only Once During Each S - ... ... Species-specific Cell Aggregation in Sponges Is -- Mediated by a Large Extracellular Aggregation Factor ... ... Than as Neurotransmitters 726 -- Some Hormones and Local Chemical Mediators Act as Specific Growth Factors ... ... Cells -- New Capillaries Form by Sprouting -- Growth of the Capillary Network Is Controlled by -- Factors ...
xxxix, 1146 s. : il., tab. ; 28 cm
- MeSH
- Cell Biology MeSH
- Molecular Biology MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- NML Fields
- biologie
- cytologie, klinická cytologie
... Neuroglial Cells in Axonal Con duction 140 -- Glial Cells, CNS Development, and Secretion of Growth -- Factors ... ... Receptors 507 -- Agrin-induced Synaptic Differentiation 508 -- Formation of CNS Synapses 511 -- Growth Factors ... ... and Survival of Neurons 512 -- Nerve Growth Factor 512 -- Uptake and Retrograde Transport of NGF 512 ... ... -- The Neurotrophin Family of Growth Factors 514 -- Neurotrophins in the CNS 514 -- Neurotrophin Receptors ... ... Pruning 520 -- General Considerations of Neural Specificity 520 -- BOX 23.1 Discovery of Nerve Growth Factor ...
4th ed. XIX,580,A-8,B-5,C-8,G-7,BB-60,I-10 : obr.,tab.,grafy.
... depend on the function and mobility of the element 713 -- Soil characteristics are key environmental factors ... ... from the adaptations of organisms to the dynamics of ecosystems 1062 -- Climate and other abiotic factors ... ... any population are its density and the spacing of individuals 1094 -- Demography is the study of factors ... ... carrying capacity 1106 -- XXVi DETAILED CONTENTS -- Both density-dependent and density-independent factors ... ... community structure: science as a process 1118 -- Community interactions can provide strong selection factors ...
Fourth edition 1206, 32 stran : ilustrace ; 29 cm
