The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform

Herbert A Lassiter - One of the best experts on this subject based on the ideXlab platform.

  • The administration of Complement Component C9 augments post-ischemic cerebral infarction volume in neonatal rats
    Neuroscience letters, 2002
    Co-Authors: Mitchell D. Imm, Richard C Feldhoff, Pamela W. Feldhoff, Herbert A Lassiter
    Abstract:

    To determine whether ischemic cerebral infarction is mediated in part by Complement Component C9, C9-deficient neonatal rats were subjected to unilateral cerebral ischemia. Brains were harvested 24 h later, stained with 2,3,5-triphenyl tetrazolium chloride, and cerebral infarct volumes were quantified by computer-based planimetry. Compared with buffer, prophylactic intraperitoneal (i.p.) administration of the Complement inhibitors soluble Complement receptor type 1 (sCR1), a molecular hybrid of sCR1 and the selectin inhibitor sialyl Lewis x (sCR1-sLex), or cobra venom factor did not affect the cerebral infarct volume. In contrast, i.p. human C9 (75 microg/g body weight) significantly increased the volume of infarct located 6 through 10 mm posterior to the frontal pole. Therefore, in the post-ischemic brain, C9 was neurotoxic and augmented the focal cerebral infarct volume.

  • Complement Component C9 Enhances the Capacity of Beta-Lactam Antibiotics to Kill Escherichia coli In Vitro and In Vivo
    The American journal of the medical sciences, 1998
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, John Q. Buchheit, Herbert A Lassiter
    Abstract:

    Complement Component C9 is required for rapid Complement-mediated killing of Escherichia coli. In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels. Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05). Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These observations may contribute to the development of new strategies, such as augmentation of Complement Component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis.

  • supplemental Complement Component C9 C9 potentiates the protective effect of ivig in neonatal rats infected with e coli 1316
    Pediatric Research, 1997
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard G. Feldhoff, Linda J. Goldsmith, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli. Previous studies revealed that 1) a diminished C9 concentration restricts the capacity of neonatal serum to kill E. coli and 2) pooled immunoglobulin G (IVIG) enhanced the capacity of human neonatal serum to deposit supplemental C9 onto E. coli and to kill the bacteria. Whether the administration of C9 potentiates the bactericidal and protective effect of IVIG in neonates infected with E. coli is not known. Therefore, in vitro and in vivo animal experiments were designed. Undegraded and hemolytically active human C9 was purified from Cohn Fraction III. IVIG was dialyzed against PBS without bacteriostatic agents. By rocket immunoelectrophoresis, the concentration of intrinsic C9 in serum pooled from two-day-old rats (NeoRS) was only 19% of adult controls. First, the survival of E. coli 07:K1:NM (5×104 cfu/ml) was quantitated in vitro during 60 min of incubation with 50% NeoRS. The bacteria proliferated in NeoRS (bacteria survival [±SEM]=170±14% of the original inoculum), and in NeoRS supplemented with 500 μg IVIG/ml(bacteria survival=122±13%). In NeoRS supplemented with C9 (100μg/ml), 79±14% of the bacteria survived. In contrast, only 30±10% of the bacteria survived in NeoRS supplemented with both IVIG and C9 (P<.04). Next, the survival of two-day-old rats was quantitated one wk after transthoracic injections of E. coli (5×103/g body wt [bw]). The bacteria were injected into each neonate 1 h after the intraperitoneal (ip) administration of IVIG (115 μg/g bw) or an equal volume of placebo (PBS). Each animal also received ip C9 (75 μg/g bw) or PBS 4 h prior to the bacterial injections. Of the 37 animals which received only placebo, none survived. 20 of 40 IVIG recipients and 20 of 38 C9 recipients survived. In contrast, 33 of the 40 neonates which received both IVIG and C9 survived (P<.01). Conclusion: Supplemental C9 potentiated 1) the bactericidal activity of IVIG in NeoRS and 2) the protective effect of IVIG in neonatal rats infected with an otherwise lethal dose of E. coli. These data may contribute to new strategies to reduce the morbidity and mortality of neonatal E. coli sepsis.Funded by the Alliant Community Trust Fund

  • The administration of Complement Component C9 enhances the survival of neonatal rats with Escherichia coli sepsis
    Pediatric research, 1997
    Co-Authors: Herbert A Lassiter, B. Paul Morgan, Brent M Walz, Jessica L Wilson, Elizabeth Jung, Cynthia R Calisi, L. Jane Goldsmith, Richard Wilson, Richard C Feldhoff
    Abstract:

    The Administration of Complement Component C9 Enhances the Survival of Neonatal Rats with Escherichia coli Sepsis1

  • Supplemental Complement Component C9 (C9) Potentiates the Protective Effect of IVIG in Neonatal Rats Infected with E. coli † 1316
    Pediatric Research, 1997
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard G. Feldhoff, Linda J. Goldsmith, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli. Previous studies revealed that 1) a diminished C9 concentration restricts the capacity of neonatal serum to kill E. coli and 2) pooled immunoglobulin G (IVIG) enhanced the capacity of human neonatal serum to deposit supplemental C9 onto E. coli and to kill the bacteria. Whether the administration of C9 potentiates the bactericidal and protective effect of IVIG in neonates infected with E. coli is not known. Therefore, in vitro and in vivo animal experiments were designed. Undegraded and hemolytically active human C9 was purified from Cohn Fraction III. IVIG was dialyzed against PBS without bacteriostatic agents. By rocket immunoelectrophoresis, the concentration of intrinsic C9 in serum pooled from two-day-old rats (NeoRS) was only 19% of adult controls. First, the survival of E. coli 07:K1:NM (5×104 cfu/ml) was quantitated in vitro during 60 min of incubation with 50% NeoRS. The bacteria proliferated in NeoRS (bacteria survival [±SEM]=170±14% of the original inoculum), and in NeoRS supplemented with 500 μg IVIG/ml(bacteria survival=122±13%). In NeoRS supplemented with C9 (100μg/ml), 79±14% of the bacteria survived. In contrast, only 30±10% of the bacteria survived in NeoRS supplemented with both IVIG and C9 (P

Anthony K. Campbell - One of the best experts on this subject based on the ideXlab platform.

  • mutation of recombinant Complement Component C9 reveals the significance of the n terminal region for polymerization
    Immunology, 1997
    Co-Authors: Kathryn Mary Taylor, Andrew R. Trimby, Anthony K. Campbell
    Abstract:

    Complement Component C9 binds to C5b-8 sites on target cells and polymerizes to form the membrane attack complex (MAC). The aim of the work reported here was to discover which region within C9 was responsible for protecting the globular protein against self-polymerization. Computer prediction modelling highlighted the domain at the N-terminus of C9, which was then investigated by site-directed mutagenesis. The mutated proteins were expressed using insect cells infected with baculovirus. Removal of 16, 20 or 23 amino acids at the N-terminus of C9 resulted in inactivation due to self-polymerization. In contrast, removal of 4, 8 or 12 amino acids resulted in a C9 that did not polymerize spontaneously, had two to threefold enhanced lytic activity on erythrocytes, and had increased binding to C5b-8 sites on rat neutrophils. These results suggest that the domain within the first 16 amino acids at the N-terminus of C9 is crucial in preventing the self-polymerization of the globular protein. We have also found that C9 contains a motif (27WSEWS31) common to a family of cytokine receptors that is similar to a tryptophan-rich motif (WEWWR) of the membrane pore formers, thiol-activated cytolysins. Mutation of this motif in C9 resulted in polymerized protein, consistent with this site keeping the N-terminus in a protected conformation and preventing premature self-polymerization.

  • Mutation of recombinant Complement Component C9 reveals the significance of the N‐terminal region for polymerization
    Immunology, 1997
    Co-Authors: Kathryn Mary Taylor, Andrew R. Trimby, Anthony K. Campbell
    Abstract:

    Complement Component C9 binds to C5b-8 sites on target cells and polymerizes to form the membrane attack complex (MAC). The aim of the work reported here was to discover which region within C9 was responsible for protecting the globular protein against self-polymerization. Computer prediction modelling highlighted the domain at the N-terminus of C9, which was then investigated by site-directed mutagenesis. The mutated proteins were expressed using insect cells infected with baculovirus. Removal of 16, 20 or 23 amino acids at the N-terminus of C9 resulted in inactivation due to self-polymerization. In contrast, removal of 4, 8 or 12 amino acids resulted in a C9 that did not polymerize spontaneously, had two to threefold enhanced lytic activity on erythrocytes, and had increased binding to C5b-8 sites on rat neutrophils. These results suggest that the domain within the first 16 amino acids at the N-terminus of C9 is crucial in preventing the self-polymerization of the globular protein. We have also found that C9 contains a motif (27WSEWS31) common to a family of cytokine receptors that is similar to a tryptophan-rich motif (WEWWR) of the membrane pore formers, thiol-activated cytolysins. Mutation of this motif in C9 resulted in polymerized protein, consistent with this site keeping the N-terminus in a protected conformation and preventing premature self-polymerization.

  • Complement Component C9-dependent cytosolic free Ca2+ rise and recovery in neutrophils.
    Cell calcium, 1995
    Co-Authors: Iraj Laffafian, Anthony K. Campbell, E. V. Davies, Maurice Bartlett Hallett
    Abstract:

    The cytosolic free Ca2+ concentration in rat neutrophils was determined by ratiometric fluorometry and imaging of Fura-2. Transient elevations of cytosolic free Ca2+ concentration were provoked by addition of C9 to neutrophils pre-coated with C5b-8. The rate of rise of the cytosolic free Ca2+ concentration was dependent upon the concentration of C9. These changes in cytosolic free Ca2+ concentration occurred in the absence of cell lysis, since there was no release of Fura-2, and were the result of increased permeability to extracellular Ca2+. More than 96% of the rise in cytosolic free Ca2+ generation by C9 was dependent upon the presence of extracellular Ca2+, but did not occur via channels which were inhibited by the Ca2+ channel blocker SKF96365. The decrease in the permeability of the membrane to Ca2+ after C9 was not triggered by the rise in cytosolic free Ca2+. After attack by C9, individual neutrophils remained responsive to f-met-leu-phe, or further attack by C9, both producing Ca2+ transients. The recovery of the Ca2+ signal was consistent with the Complement membrane attack complex generating a series of permeability thresholds in the plasma membrane. These data have implications for the understanding of the mechanisms underlying the inappropriate responsiveness of neutrophils at inflammatory sites.

  • A method for in vitro synthesis of unglycosylated recombinant Complement Component C9
    Journal of immunological methods, 1994
    Co-Authors: Kathryn Mary Taylor, J. P. Luzio, Anthony K. Campbell
    Abstract:

    A method for in vitrosynthesis of human Complement Component C9 has been established in order to generate unglycosylated normal and mutant proteins without the need to sub-clone. One or two step polymerase chain reaction (PCR) was used to add the T7 RNA polymerase promoter and introduce multiple mutations within the cDNA. The cDNA was then transcribed by T7 RNA polymerase and the mRNA translated in a rabbit reticulocyte lysate or wheat germ system. Successful synthesis was confirmed by: the correct size of PCR product DNA on agarose gel electrophoresis, incorporation of [α-32P]UTP into mRNA, and formation of [35S]methionine-labelled protein of the correct molecular mass for full length C9. The wheat germ extract generated up to 1.5 μg of recombinant C9. This unglycosylated C9 had at least 10% of the haemolytic activity of native C9. Unglycosylated C9 polymerised more readily than the native protein. This spontaneous polymerisation was increased by removal of the first 23 amino acids or mutating two cysteines at positions 33 and 36. This therefore provides a rapid method for screening the effect of multiple mutations on the biological activity and polymerisation of pore forming proteins.

  • Altered glycosylation and selected mutation in recombinant human Complement Component C9: effects on haemolytic activity.
    Immunology, 1994
    Co-Authors: Kathryn Mary Taylor, Bryan Paul Morgan, Anthony K. Campbell
    Abstract:

    Recombinant wild-type and mutated forms of human Complement Component C9 have been synthesized in baculovirus-infected insect cells. Wild-type recombinant C9 was indistinguishable from native C9, as judged by haemolytic activity, trypsin and alpha-thrombin digestion, reaction with antibodies to C9, enzymatic deglycosylation to the same core size and polymerization in the presence of Zn2+. Replacement of the native signal peptide with the honey-bee melittin signal peptide, and replacement of Spodoptera frugiperda (Sf9) cells with Trichoplusia ni cells produced yields of 5 micrograms C9/ml supernatant. Three C9 mutants were generated; one mutant, with four acidic residues changed to alanines in a putative calcium-binding site, had the same biological activity as recombinant C9. Another mutant, lacking 23 N-terminal amino acids, previously showing increased polymerization when produced in vitro, polymerized on secretion, rendering it inactive. It was not possible to demonstrate haemolytic activity of the third mutant, cysteines 33 and 36 mutated to alanine, as it was secreted a hundredfold less than the wild-type protein.

Elizabeth Jung - One of the best experts on this subject based on the ideXlab platform.

  • Complement Component C9 Enhances the Capacity of Beta-Lactam Antibiotics to Kill Escherichia coli In Vitro and In Vivo
    The American journal of the medical sciences, 1998
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, John Q. Buchheit, Herbert A Lassiter
    Abstract:

    Complement Component C9 is required for rapid Complement-mediated killing of Escherichia coli. In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels. Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05). Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These observations may contribute to the development of new strategies, such as augmentation of Complement Component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis.

  • supplemental Complement Component C9 C9 potentiates the protective effect of ivig in neonatal rats infected with e coli 1316
    Pediatric Research, 1997
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard G. Feldhoff, Linda J. Goldsmith, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli. Previous studies revealed that 1) a diminished C9 concentration restricts the capacity of neonatal serum to kill E. coli and 2) pooled immunoglobulin G (IVIG) enhanced the capacity of human neonatal serum to deposit supplemental C9 onto E. coli and to kill the bacteria. Whether the administration of C9 potentiates the bactericidal and protective effect of IVIG in neonates infected with E. coli is not known. Therefore, in vitro and in vivo animal experiments were designed. Undegraded and hemolytically active human C9 was purified from Cohn Fraction III. IVIG was dialyzed against PBS without bacteriostatic agents. By rocket immunoelectrophoresis, the concentration of intrinsic C9 in serum pooled from two-day-old rats (NeoRS) was only 19% of adult controls. First, the survival of E. coli 07:K1:NM (5×104 cfu/ml) was quantitated in vitro during 60 min of incubation with 50% NeoRS. The bacteria proliferated in NeoRS (bacteria survival [±SEM]=170±14% of the original inoculum), and in NeoRS supplemented with 500 μg IVIG/ml(bacteria survival=122±13%). In NeoRS supplemented with C9 (100μg/ml), 79±14% of the bacteria survived. In contrast, only 30±10% of the bacteria survived in NeoRS supplemented with both IVIG and C9 (P<.04). Next, the survival of two-day-old rats was quantitated one wk after transthoracic injections of E. coli (5×103/g body wt [bw]). The bacteria were injected into each neonate 1 h after the intraperitoneal (ip) administration of IVIG (115 μg/g bw) or an equal volume of placebo (PBS). Each animal also received ip C9 (75 μg/g bw) or PBS 4 h prior to the bacterial injections. Of the 37 animals which received only placebo, none survived. 20 of 40 IVIG recipients and 20 of 38 C9 recipients survived. In contrast, 33 of the 40 neonates which received both IVIG and C9 survived (P<.01). Conclusion: Supplemental C9 potentiated 1) the bactericidal activity of IVIG in NeoRS and 2) the protective effect of IVIG in neonatal rats infected with an otherwise lethal dose of E. coli. These data may contribute to new strategies to reduce the morbidity and mortality of neonatal E. coli sepsis.Funded by the Alliant Community Trust Fund

  • The administration of Complement Component C9 enhances the survival of neonatal rats with Escherichia coli sepsis
    Pediatric research, 1997
    Co-Authors: Herbert A Lassiter, B. Paul Morgan, Brent M Walz, Jessica L Wilson, Elizabeth Jung, Cynthia R Calisi, L. Jane Goldsmith, Richard Wilson, Richard C Feldhoff
    Abstract:

    The Administration of Complement Component C9 Enhances the Survival of Neonatal Rats with Escherichia coli Sepsis1

  • Supplemental Complement Component C9 (C9) Potentiates the Protective Effect of IVIG in Neonatal Rats Infected with E. coli † 1316
    Pediatric Research, 1997
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard G. Feldhoff, Linda J. Goldsmith, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli. Previous studies revealed that 1) a diminished C9 concentration restricts the capacity of neonatal serum to kill E. coli and 2) pooled immunoglobulin G (IVIG) enhanced the capacity of human neonatal serum to deposit supplemental C9 onto E. coli and to kill the bacteria. Whether the administration of C9 potentiates the bactericidal and protective effect of IVIG in neonates infected with E. coli is not known. Therefore, in vitro and in vivo animal experiments were designed. Undegraded and hemolytically active human C9 was purified from Cohn Fraction III. IVIG was dialyzed against PBS without bacteriostatic agents. By rocket immunoelectrophoresis, the concentration of intrinsic C9 in serum pooled from two-day-old rats (NeoRS) was only 19% of adult controls. First, the survival of E. coli 07:K1:NM (5×104 cfu/ml) was quantitated in vitro during 60 min of incubation with 50% NeoRS. The bacteria proliferated in NeoRS (bacteria survival [±SEM]=170±14% of the original inoculum), and in NeoRS supplemented with 500 μg IVIG/ml(bacteria survival=122±13%). In NeoRS supplemented with C9 (100μg/ml), 79±14% of the bacteria survived. In contrast, only 30±10% of the bacteria survived in NeoRS supplemented with both IVIG and C9 (P

  • Complement Component C9 C9 potentiates the protective effect of cefotaxime in neonatal rats septic with e coli bull 1759
    Pediatric Research, 1996
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli by serum. Previous studies revealed that a diminished C9 concentration restricts the bactericidal capacity of serum from neonatal humans and neonatal rats. Also, significant morbidity and mortality from E. coli sepsis persist in neonates despite the use of bactericidal antibiotics, such as cefotaxime (CEF). Therefore, in vitro and in vivo experiments were designed to determine whether supplemental C9 potentiates the bactericidal and protective effects of CEF in neonatal rats. Undegraded and hemolytically active human C9 was purified from Cohn fraction III paste. First, the survival of E. coli (5 × 104 cfu/ml) was quantitated in vitro during 60 min of incubation with 20% serum pooled from neonatal rats (NeoRS). The bacteria proliferated in NeoRS(bacterial survival [x±SEM] = 199±15% of the original inoculum). Similarly, the bacteria proliferated in NeoRS supplemented with 2.5 ng/ml CEF(bacterial survival = 170±26%) or with 20 μg/ml C9 (147±11%). In contrast, only 54±27% of the bacteria survived in serum supplemented with both CEF and C9 (P .11 vs recipients of only PBS). In contrast, 36/45 recipients of both CEF and C9 survived (P<.05 vs only PBS, vs CEF alone, and vs C9 alone). In conclusion, supplemental C9 potentiated the bactericidal activity of CEF against E. coli in NeoRS and potentiated the protective effect of CEF in septic neonatal rats. These observations may contribute to the development of new strategies to reduce the morbidity and mortality associated with E. coli sepsis in human neonates. Funded by the Alliant Community Trust Fund.

Richard C Feldhoff - One of the best experts on this subject based on the ideXlab platform.

  • The administration of Complement Component C9 augments post-ischemic cerebral infarction volume in neonatal rats
    Neuroscience letters, 2002
    Co-Authors: Mitchell D. Imm, Richard C Feldhoff, Pamela W. Feldhoff, Herbert A Lassiter
    Abstract:

    To determine whether ischemic cerebral infarction is mediated in part by Complement Component C9, C9-deficient neonatal rats were subjected to unilateral cerebral ischemia. Brains were harvested 24 h later, stained with 2,3,5-triphenyl tetrazolium chloride, and cerebral infarct volumes were quantified by computer-based planimetry. Compared with buffer, prophylactic intraperitoneal (i.p.) administration of the Complement inhibitors soluble Complement receptor type 1 (sCR1), a molecular hybrid of sCR1 and the selectin inhibitor sialyl Lewis x (sCR1-sLex), or cobra venom factor did not affect the cerebral infarct volume. In contrast, i.p. human C9 (75 microg/g body weight) significantly increased the volume of infarct located 6 through 10 mm posterior to the frontal pole. Therefore, in the post-ischemic brain, C9 was neurotoxic and augmented the focal cerebral infarct volume.

  • Complement Component C9 Enhances the Capacity of Beta-Lactam Antibiotics to Kill Escherichia coli In Vitro and In Vivo
    The American journal of the medical sciences, 1998
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, John Q. Buchheit, Herbert A Lassiter
    Abstract:

    Complement Component C9 is required for rapid Complement-mediated killing of Escherichia coli. In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels. Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05). Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These observations may contribute to the development of new strategies, such as augmentation of Complement Component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis.

  • The administration of Complement Component C9 enhances the survival of neonatal rats with Escherichia coli sepsis
    Pediatric research, 1997
    Co-Authors: Herbert A Lassiter, B. Paul Morgan, Brent M Walz, Jessica L Wilson, Elizabeth Jung, Cynthia R Calisi, L. Jane Goldsmith, Richard Wilson, Richard C Feldhoff
    Abstract:

    The Administration of Complement Component C9 Enhances the Survival of Neonatal Rats with Escherichia coli Sepsis1

  • Complement Component C9 C9 potentiates the protective effect of cefotaxime in neonatal rats septic with e coli bull 1759
    Pediatric Research, 1996
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli by serum. Previous studies revealed that a diminished C9 concentration restricts the bactericidal capacity of serum from neonatal humans and neonatal rats. Also, significant morbidity and mortality from E. coli sepsis persist in neonates despite the use of bactericidal antibiotics, such as cefotaxime (CEF). Therefore, in vitro and in vivo experiments were designed to determine whether supplemental C9 potentiates the bactericidal and protective effects of CEF in neonatal rats. Undegraded and hemolytically active human C9 was purified from Cohn fraction III paste. First, the survival of E. coli (5 × 104 cfu/ml) was quantitated in vitro during 60 min of incubation with 20% serum pooled from neonatal rats (NeoRS). The bacteria proliferated in NeoRS(bacterial survival [x±SEM] = 199±15% of the original inoculum). Similarly, the bacteria proliferated in NeoRS supplemented with 2.5 ng/ml CEF(bacterial survival = 170±26%) or with 20 μg/ml C9 (147±11%). In contrast, only 54±27% of the bacteria survived in serum supplemented with both CEF and C9 (P .11 vs recipients of only PBS). In contrast, 36/45 recipients of both CEF and C9 survived (P<.05 vs only PBS, vs CEF alone, and vs C9 alone). In conclusion, supplemental C9 potentiated the bactericidal activity of CEF against E. coli in NeoRS and potentiated the protective effect of CEF in septic neonatal rats. These observations may contribute to the development of new strategies to reduce the morbidity and mortality associated with E. coli sepsis in human neonates. Funded by the Alliant Community Trust Fund.

  • Complement Component C9 (C9) POTENTIATES THE PROTECTIVE EFFECT OF CEFOTAXIME IN NEONATAL RATS SEPTIC WITH E. COLI. |[bull]| 1759
    Pediatric Research, 1996
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli by serum. Previous studies revealed that a diminished C9 concentration restricts the bactericidal capacity of serum from neonatal humans and neonatal rats. Also, significant morbidity and mortality from E. coli sepsis persist in neonates despite the use of bactericidal antibiotics, such as cefotaxime (CEF). Therefore, in vitro and in vivo experiments were designed to determine whether supplemental C9 potentiates the bactericidal and protective effects of CEF in neonatal rats. Undegraded and hemolytically active human C9 was purified from Cohn fraction III paste. First, the survival of E. coli (5 × 104 cfu/ml) was quantitated in vitro during 60 min of incubation with 20% serum pooled from neonatal rats (NeoRS). The bacteria proliferated in NeoRS(bacterial survival [x±SEM] = 199±15% of the original inoculum). Similarly, the bacteria proliferated in NeoRS supplemented with 2.5 ng/ml CEF(bacterial survival = 170±26%) or with 20 μg/ml C9 (147±11%). In contrast, only 54±27% of the bacteria survived in serum supplemented with both CEF and C9 (P .11 vs recipients of only PBS). In contrast, 36/45 recipients of both CEF and C9 survived (P

Brent M Walz - One of the best experts on this subject based on the ideXlab platform.

  • Complement Component C9 Enhances the Capacity of Beta-Lactam Antibiotics to Kill Escherichia coli In Vitro and In Vivo
    The American journal of the medical sciences, 1998
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, John Q. Buchheit, Herbert A Lassiter
    Abstract:

    Complement Component C9 is required for rapid Complement-mediated killing of Escherichia coli. In this report, the influence of supplemental C9 on the bactericidal and protective effects of beta-lactam antibiotics in neonates was assessed. By rocket immunoelectrophoresis, the intrinsic C9 concentrations of pooled serum from both human and rat neonates was less than 20% of adult levels. Supplemental C9 purified from human plasma enhanced the capacity of ampicillin-treated serum from human neonates to impair the survival of E coli O7:K1:NM (P < 0.02). Similarly, supplemental C9 enhanced the capacity of cefotaxime-treated neonatal rat serum to impair the survival of E coli O1:K1:NM (P < 0.05). Moreover, the intraperitoneal administration of C9 enhanced the survival of cefotaxime-treated neonatal rats that were septic with E coli (P < 0.05). These observations may contribute to the development of new strategies, such as augmentation of Complement Component serum concentrations, to reduce the morbidity and mortality of neonatal E coli sepsis.

  • supplemental Complement Component C9 C9 potentiates the protective effect of ivig in neonatal rats infected with e coli 1316
    Pediatric Research, 1997
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard G. Feldhoff, Linda J. Goldsmith, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli. Previous studies revealed that 1) a diminished C9 concentration restricts the capacity of neonatal serum to kill E. coli and 2) pooled immunoglobulin G (IVIG) enhanced the capacity of human neonatal serum to deposit supplemental C9 onto E. coli and to kill the bacteria. Whether the administration of C9 potentiates the bactericidal and protective effect of IVIG in neonates infected with E. coli is not known. Therefore, in vitro and in vivo animal experiments were designed. Undegraded and hemolytically active human C9 was purified from Cohn Fraction III. IVIG was dialyzed against PBS without bacteriostatic agents. By rocket immunoelectrophoresis, the concentration of intrinsic C9 in serum pooled from two-day-old rats (NeoRS) was only 19% of adult controls. First, the survival of E. coli 07:K1:NM (5×104 cfu/ml) was quantitated in vitro during 60 min of incubation with 50% NeoRS. The bacteria proliferated in NeoRS (bacteria survival [±SEM]=170±14% of the original inoculum), and in NeoRS supplemented with 500 μg IVIG/ml(bacteria survival=122±13%). In NeoRS supplemented with C9 (100μg/ml), 79±14% of the bacteria survived. In contrast, only 30±10% of the bacteria survived in NeoRS supplemented with both IVIG and C9 (P<.04). Next, the survival of two-day-old rats was quantitated one wk after transthoracic injections of E. coli (5×103/g body wt [bw]). The bacteria were injected into each neonate 1 h after the intraperitoneal (ip) administration of IVIG (115 μg/g bw) or an equal volume of placebo (PBS). Each animal also received ip C9 (75 μg/g bw) or PBS 4 h prior to the bacterial injections. Of the 37 animals which received only placebo, none survived. 20 of 40 IVIG recipients and 20 of 38 C9 recipients survived. In contrast, 33 of the 40 neonates which received both IVIG and C9 survived (P<.01). Conclusion: Supplemental C9 potentiated 1) the bactericidal activity of IVIG in NeoRS and 2) the protective effect of IVIG in neonatal rats infected with an otherwise lethal dose of E. coli. These data may contribute to new strategies to reduce the morbidity and mortality of neonatal E. coli sepsis.Funded by the Alliant Community Trust Fund

  • The administration of Complement Component C9 enhances the survival of neonatal rats with Escherichia coli sepsis
    Pediatric research, 1997
    Co-Authors: Herbert A Lassiter, B. Paul Morgan, Brent M Walz, Jessica L Wilson, Elizabeth Jung, Cynthia R Calisi, L. Jane Goldsmith, Richard Wilson, Richard C Feldhoff
    Abstract:

    The Administration of Complement Component C9 Enhances the Survival of Neonatal Rats with Escherichia coli Sepsis1

  • Supplemental Complement Component C9 (C9) Potentiates the Protective Effect of IVIG in Neonatal Rats Infected with E. coli † 1316
    Pediatric Research, 1997
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard G. Feldhoff, Linda J. Goldsmith, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli. Previous studies revealed that 1) a diminished C9 concentration restricts the capacity of neonatal serum to kill E. coli and 2) pooled immunoglobulin G (IVIG) enhanced the capacity of human neonatal serum to deposit supplemental C9 onto E. coli and to kill the bacteria. Whether the administration of C9 potentiates the bactericidal and protective effect of IVIG in neonates infected with E. coli is not known. Therefore, in vitro and in vivo animal experiments were designed. Undegraded and hemolytically active human C9 was purified from Cohn Fraction III. IVIG was dialyzed against PBS without bacteriostatic agents. By rocket immunoelectrophoresis, the concentration of intrinsic C9 in serum pooled from two-day-old rats (NeoRS) was only 19% of adult controls. First, the survival of E. coli 07:K1:NM (5×104 cfu/ml) was quantitated in vitro during 60 min of incubation with 50% NeoRS. The bacteria proliferated in NeoRS (bacteria survival [±SEM]=170±14% of the original inoculum), and in NeoRS supplemented with 500 μg IVIG/ml(bacteria survival=122±13%). In NeoRS supplemented with C9 (100μg/ml), 79±14% of the bacteria survived. In contrast, only 30±10% of the bacteria survived in NeoRS supplemented with both IVIG and C9 (P

  • Complement Component C9 C9 potentiates the protective effect of cefotaxime in neonatal rats septic with e coli bull 1759
    Pediatric Research, 1996
    Co-Authors: Elizabeth Jung, Brent M Walz, Richard C Feldhoff, Molly M. Drehs, Herbert A Lassiter
    Abstract:

    C9 is required for rapid Complement-mediated killing of E. coli by serum. Previous studies revealed that a diminished C9 concentration restricts the bactericidal capacity of serum from neonatal humans and neonatal rats. Also, significant morbidity and mortality from E. coli sepsis persist in neonates despite the use of bactericidal antibiotics, such as cefotaxime (CEF). Therefore, in vitro and in vivo experiments were designed to determine whether supplemental C9 potentiates the bactericidal and protective effects of CEF in neonatal rats. Undegraded and hemolytically active human C9 was purified from Cohn fraction III paste. First, the survival of E. coli (5 × 104 cfu/ml) was quantitated in vitro during 60 min of incubation with 20% serum pooled from neonatal rats (NeoRS). The bacteria proliferated in NeoRS(bacterial survival [x±SEM] = 199±15% of the original inoculum). Similarly, the bacteria proliferated in NeoRS supplemented with 2.5 ng/ml CEF(bacterial survival = 170±26%) or with 20 μg/ml C9 (147±11%). In contrast, only 54±27% of the bacteria survived in serum supplemented with both CEF and C9 (P .11 vs recipients of only PBS). In contrast, 36/45 recipients of both CEF and C9 survived (P<.05 vs only PBS, vs CEF alone, and vs C9 alone). In conclusion, supplemental C9 potentiated the bactericidal activity of CEF against E. coli in NeoRS and potentiated the protective effect of CEF in septic neonatal rats. These observations may contribute to the development of new strategies to reduce the morbidity and mortality associated with E. coli sepsis in human neonates. Funded by the Alliant Community Trust Fund.