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1.	Karpman, Diana (författare) Studies of the pathogenesis of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura 1997 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract This study investigated the pathogenesis of hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). (1) The relative roles of lipopolysaccharide and Shiga-like toxin-2 were studied in a mouse model of Escherichia coli O157:H7 infection. Both factors were found to be important for the virulence of the strain and contributed in an additive manner. The mouse model mimicked certain aspects of human HUS. (2) Apoptotic cell death in HUS was demonstrated in a human renal biopsy, kidneys of mice infected with E. coli O157:H7 and in pediatric renal cortical tubular cells stimulated with Shiga toxin and E. coli O157:H7 supernatants in culture. (3) The cytokine response to HUS was analyzed in serum and urine showing that interleukin 6 (IL-6) was elevated both in serum and urine and could be used to monitor disease activity. Both IL-6 and tumor necrosis factor alpha were detected in urine indicating cytokine production in the urinary tract. Cytokine levels correlated to the degree of renal injury. (4) Increased platelet retention was found in two siblings with recurrent TTP. This activity was mediated by the patients' von Willebrand factor (vWF) and treatment with plasma or factor VIII/vWF concentrate decreased platelet retention and was beneficial for the patients' clinical state.

Karpman, Diana (författare)
Studies of the pathogenesis of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura
1997
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study investigated the pathogenesis of hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). (1) The relative roles of lipopolysaccharide and Shiga-like toxin-2 were studied in a mouse model of Escherichia coli O157:H7 infection. Both factors were found to be important for the virulence of the strain and contributed in an additive manner. The mouse model mimicked certain aspects of human HUS. (2) Apoptotic cell death in HUS was demonstrated in a human renal biopsy, kidneys of mice infected with E. coli O157:H7 and in pediatric renal cortical tubular cells stimulated with Shiga toxin and E. coli O157:H7 supernatants in culture. (3) The cytokine response to HUS was analyzed in serum and urine showing that interleukin 6 (IL-6) was elevated both in serum and urine and could be used to monitor disease activity. Both IL-6 and tumor necrosis factor alpha were detected in urine indicating cytokine production in the urinary tract. Cytokine levels correlated to the degree of renal injury. (4) Increased platelet retention was found in two siblings with recurrent TTP. This activity was mediated by the patients' von Willebrand factor (vWF) and treatment with plasma or factor VIII/vWF concentrate decreased platelet retention and was beneficial for the patients' clinical state.

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