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Results: 1 to 5 of 5

Publication Record


Fractalkine and CX3CR1 mediate leukocyte capture by endothelium in response to Shiga toxin.
Zanchi C, Zoja C, Morigi M, Valsecchi F, Liu XY, Rottoli D, Locatelli M, Buelli S, Pezzotta A, Mapelli P, Geelen J, Remuzzi G, Hawiger J
(2008) J Immunol 181: 1460-9
MeSH Terms: Animals, CX3C Chemokine Receptor 1, Cell Adhesion, Cells, Cultured, Chemokine CX3CL1, Disease Models, Animal, Endothelial Cells, Escherichia coli O157, Hemolytic-Uremic Syndrome, Humans, Kidney Glomerulus, Leukocytes, Lipopolysaccharides, Male, Mice, Mice, Inbred C57BL, NF-kappa B, Receptors, Chemokine, Shiga Toxin 2, Signal Transduction, Transcription Factor AP-1, Up-Regulation, p38 Mitogen-Activated Protein Kinases
Show Abstract · Added December 10, 2013
Shiga toxins (Stx) are the virulence factors of enterohemorrhagic Escherichia coli O157:H7, a worldwide emerging diarrheal pathogen, which precipitates postdiarrheal hemolytic uremic syndrome, the leading cause of acute renal failure in children. In this study, we show that Stx2 triggered expression of fractalkine (FKN), a CX3C transmembrane chemokine, acting as both adhesion counterreceptor on endothelial cells and soluble chemoattractant. Stx2 caused in HUVEC expression of FKN mRNA and protein, which promoted leukocyte capture, ablated by Abs to either endothelial FKN or leukocyte CX3CR1 receptor. Exposure of human glomerular endothelial cells to Stx2 recapitulated its FKN-inducing activity and FKN-mediated leukocyte adhesion. Both processes required phosphorylation of Src-family protein tyrosine kinase and p38 MAPK in endothelial cells. Furthermore, they depended on nuclear import of NF-kappaB and other stress-responsive transcription factors. Inhibition of their nuclear import with the cell-penetrating SN50 peptide reduced FKN mRNA levels and FKN-mediated leukocyte capture by endothelial cells. Adenoviral overexpression of IkappaBalpha inhibited FKN mRNA up-regulation. The FKN-mediated responses to Stx2 were also dependent on AP-1. In mice, both virulence factors of Stx-producing E. coli, Stx and LPS, are required to elicit hemolytic uremic syndrome. In this study, FKN was detected within glomeruli of C57BL/6 mice injected with Stx2, and further increased after Stx2 plus LPS coadministration. This was associated with recruitment of CX3CR1-positive cells. Thus, in response to Stx2, FKN is induced playing an essential role in the promotion of leukocyte-endothelial cell interaction thereby potentially contributing to the renal microvascular dysfunction and thrombotic microangiopathy that underlie hemolytic uremic syndrome due to enterohemorrhagic E. coli O157:H7 infection.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Clostridium septicum myonecrosis complicating diarrhea-associated hemolytic uremic syndrome.
Hunley TE, Spring MD, Peters TR, Weikert DR, Jabs K
(2008) Pediatr Nephrol 23: 1171-5
MeSH Terms: Amputation, Anti-Bacterial Agents, Arm, Clostridium Infections, Clostridium septicum, Combined Modality Therapy, Debridement, Diarrhea, Infantile, Hemolytic-Uremic Syndrome, Humans, Infant, Male, Muscle, Skeletal, Muscular Diseases, Necrosis, Treatment Outcome
Show Abstract · Added February 25, 2014
We report the case of a 19-month-old male child with diarrhea-associated hemolytic uremic syndrome (HUS) who developed swelling of the right arm at the site of a peripherally inserted central venous catheter (PICC), fever, and later, ecchymosis. Wound cultures at the time of surgical debridement grew Clostridium septicum. The child subsequently required amputation of the right arm and prolonged therapy with parenteral penicillin and clindamycin. Clostridium septicum infections in children with HUS have been associated with a high rate of mortality. Along with colon cancer, diarrhea-associated HUS comprises a clinical entity which appears to predispose to atraumatic C. septicum infection, where acidic and anaerobic conditions in the diseased colon favor C. septicum invasion. Though not well recognized among pediatric nephrologists, C. septicum infection constitutes a severe, albeit rare, complication of diarrhea-associated HUS, but one in which a high index of suspicion is warranted as aggressive surgical and antibiotic therapy may be life-saving.
0 Communities
2 Members
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16 MeSH Terms
Fever, thrombocytopenia, anasarca, and acute renal failure in a 50-year-old woman.
Goral S, Horn R, Brouillette J, Fogo A
(1998) Am J Kidney Dis 31: 890-5
MeSH Terms: Acute Kidney Injury, Diagnosis, Differential, Edema, Female, Fever, Hemolytic-Uremic Syndrome, Humans, Kidney, Middle Aged, Pleural Effusion, Thrombocytopenia
Added January 20, 2012
1 Communities
1 Members
0 Resources
11 MeSH Terms
Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis.
Hakim RM, Schulman G, Churchill WH, Lazarus JM
(1985) Am J Kidney Dis 5: 170-6
MeSH Terms: Acute Kidney Injury, Adult, Creatinine, Female, Hemolytic-Uremic Syndrome, Humans, Kidney, Middle Aged, Plasmapheresis, Platelet Count, Purpura, Thrombotic Thrombocytopenic, Time Factors, Uremia
Show Abstract · Added May 20, 2014
We report on the outcome of six consecutive adult patients who presented with microangiopathic anemia and thrombocytopenia. Clinical parameters on admission included platelet counts less than 45,000/mm3, microangiopathic red blood cell morphology, mental status abnormalities, and in three, rapidly progressive azotemia requiring dialysis. All patients underwent plasma exchange therapy as part of their treatments. Patients with renal failure underwent plasma exchange with a hollow fiber plasma separator, while those without renal failure were treated with a cytocentrifuge. All received fresh frozen plasma as replacement solution and were treated with glucocorticoids as well. For all six patients, plasmapheresis and conventional drug therapy resulted in remission that has lasted for 16 +/- 5 months (range 8 to 24 months). Early cessation of plasmapheresis in two patients resulted in rapid relapse. Patients who required dialysis now have a mean creatinine of 2.0 +/- 0.9 mg/dL (range 1.2 to 3.5). With similar volumes of exchange, and the same number of treatments, less fresh frozen plasma was used in the three patients treated with the hollow fiber separator than in patients treated with the cytocentrifuge (6.3 +/- 3.7 v 14.8 +/- 4.3 U/exchange, P less than 0.05). We conclude that plasmapheresis is a useful therapeutic modality for the treatment of thrombocytopenia and microangiopathic hemolytic anemia. In addition the use of a hollow fiber plasma separator for plasmapheresis is safe and efficient, particularly when concurrent dialysis is required.
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1 Members
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13 MeSH Terms
Prolongation of acute renal failure in two patients with hemolytic-uremic syndrome due to excessive plasma infusion therapy.
Eddy AA, Geary DF, Balfe JW, Clark WF, Baumal R
(1989) Pediatr Nephrol 3: 420-3
MeSH Terms: Acute Kidney Injury, Blood Proteins, Child, Preschool, Female, Hemolytic-Uremic Syndrome, Humans, Male, Peritoneal Dialysis, Plasma, Plasma Exchange, Transfusion Reaction
Show Abstract · Added February 3, 2012
Two children with prototypic hemolytic-uremic syndrome had prolonged acute dialysis-dependent renal failure (74 and 84 days) associated with a state of hyperproteinemia induced by extensive infusion of fresh frozen plasma (283 and 307 units). We believe that the hyperproteinemia prolonged the duration of renal failure. Following cessation of plasma therapy, the hyperproteinemic state reversed, the degree of proteinuria decreased and renal function quickly recovered. Although the pathophysiological mechanism requires further evaluation, we speculate that an alteration in the colloid oncotic pressure and/or aggravation of tubulointerstitial injury due to overload-proteinuria may have increased the duration of renal failure.
0 Communities
1 Members
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11 MeSH Terms