Mechanisms of speciation: proceedings from the International Meeting on Mechanisms of Speciation , Mechanisms of speciation: proceedings from the International Meeting on Mechanisms of Speciation , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Discusses how she experienced research processes as a way of opening up a dialogue about racial inter-subjective relations in feminist research, in order to use the process as a means of enabling greater understanding on how race and whiteness work. She explores some of the contradictions and ambiguities that arose from feminism, and argues that feminism is the outcome of the operations of racialized and gendered social relations. Moreover, she opines that as researchers of whiteness, indigenous and white women need to be conscious of feminist academics and need to unmask it in the process of developing methodologies to be better equipped to critique patriarchal whiteness
Enzymes of Lipid A Biosynthesis: Target for the Design of New Antibiotics (C. Raetz). Biosynthesis of Escherichia coli 09 Polysaccharide and its Evolution (N. Kido). Core Structure, of Enterobacterial Lipopolysaccharides (O. Holst, et al.). Unique Structural and Biological Features of Helicobacter pylori Lipopolysaccharides (A. Moran & G. Aspinall). What We Know and Don't Know about the Chemical and Physical Structure of Lipopolysaccharides in Relation to Biological Activity (S. Muller--Loennies, et al.). Roles for LBP and Soluble Cd14 in Cellular Uptake of LPS (R. Tapping, et al.). Structure--Function Analysis of Soluble and Membrane--Bound CD14 (T. Kirkland & S. Viriyakosol). Roles of CD14 in LPS Signaling and Scavenging: Analysis of CD14--Transgenic and Non--Transgenic Mice and Rats in Response to LPS (S. Yamamoto, et al.). The Role of Scavenger Receptors in LPS--Induced Macrophage Activation (T. Kirikae, et al.). The CD11/CD18 Integrins: Characterization of Three Novel LPS Signaling Receptors (R. Ingalls, et al.). The Role of Tyrosine Kinases and MAP Kinases in LPS--Induced Signaling (A. DeFranco, et al.). CD14 Dependent and Independent Signaling Pathways in Murine Macrophages from Normal and CD14 "Knockout" (CD14KO) Mice Stimulated with LPS or Taxol (S. Vogel, et al.). ADP--Ribosylation: Role in LPS--Induced Phosphorylation of Two Cytosolic Proteins (p36/38) in Monocytes (S. Hauschildt, et al.). CD14 Dependent Mechanisms of Cell Activation (J. Han, et al.). Cytokine Regulation of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells (J. Cohen, et al.N). Detoxification of Lipopolysaccharide by Lysozyme (N. Ohno, et al.). Role of Hepatocytes in the Clearance of Lipopolysaccharide and its Clinical Significance (K. Tanikawa, et al.). Antibiotic--Mediated Release of Endotoxin and the Pathogenesis of Gram--Negative Sepsis (D. Morrison). Molecular Mechanisms Responsible for Endotoxin Tolerance (B. Yoza, et al.N). Endotoxin Tolerance Alters Macrophage Membrane Regulatory G Proteins (M. Makhlouf, et al.). Lipopolysaccharide (LPS) Antibodies Regulate Cellular Uptake of LPS and LPS Induced Proinflammatory Responses (C. Ohl & M. Pollack). Apoptotic Cell Death in Response to LPS (T. Yokochi, et al.). Stimulation of Human T Lymphocytes by Lipopolysaccharide (LPS) in the Presence of Autologous and Heterologous Monocytes (T. Mattern, et al.). Role of CD14 in Infection: Studies in CD14--Deficient Mice (A. Haziot, et al.). Reconciling the Concepts of Endotoxin Sensitization and Tolerance (M. Freudenberg, et al.). Production of Nontoxic Lipid A by Chemical Modification and its Antagonistic Effect on LPS Activity (K. Tanamoto). The Protective Effect of Prostaglandin E 1 on Endotoxin--Induced Hepatocyte Injury (H. Shimada, et al.). Natural and Synthetic LPS and Lipid A Analogs or Partial Structures that Antagonize or Induce Tolerance to LPS (N. Qureshi, et al.). The Molecular Basis for Therapeutic Concepts Utilizing CD14 (F. Stelter, et al.). Natural and Synthetic Polypeptides that Recoggnize the Conserved Lipid A Binding Site of Lipoplysaccharides (M. Porro, et al.). Prevention of Endotoxin Shock through Targeting Leukocytes Adhesion Molecules (H. Higashi, et al.). Suppression of TNF and other Proinflammatory Cytokines by the Tetravalent Guanylhydrazone CNI--1493 (K. Tracey). Interaction of Lipopolysaccharide with a Mammalian Lyso--phosphatidate Acyltransferase (LPAAT) Tranfected into E. coli, and Effect of Lisofylline on LPAAT Transfected into Mammalian Cells (S. Bursten). Role of Nitric Oxide and Reactive Oxygen Species in Endotoxin Shock (T. Yoshikawa, et al.). The Role of Interleukin 6 in Endotoxin--Induced Inflammatory Responses (T. van der Poll & S. van Deventer). The Pathogenic Role of LBP in Gram--Negative Sepsis and Septic Shock (D. Heumann, et al.). Index.
Since the earliest days of antibiotic chemotherapy to treat infection with Gram-negative microbes, investigators have recognized that such treatments may result in the release of microbial constituents that might, in turn, exacerbate the pathophysiological manifestations of disease. Both in vitro studies and in vivo animal experiments have over the years provided evidence in support of this concept; however, the actual clinical importance of this phenomenon to patients with Gram-negative sepsis is unclear. Recently published reports from a number of laboratories have shown that cell wall-active antibiotics that differ in their fundamental mechanisms of action in disrupting microbial growth (via selective interactions with various penicillin binding proteins) also differ in their relative ability to induce the release of biologically active endotoxin both in vitro and in vivo. Further, quantitative differences in total endotoxin release correlate well with antibiotic-initiated morphological changes in the microbe. Of potential significance is the finding that these differences are also reflected in differential production of cytokines from endotoxin-stimulated mononuclear phagocytes and other host target cells, including 11-6 and TNF. Since these immunologic hormones have been strongly implicated as contributing factors to the pathogenesis of Gram-negative sepsis, interest in the potential use of this chemotherapeutic approach as a means of controlling the host immunopathologic response has increased. Carefully controlled clinical trials in which different antibiotic treatments are correlated with production of cytokines will be of significant potential value in evaluating the actual significance of this phenomenon in the Gram-negative septic patient.
Administration of sublethal doses of endotoxin (LPS) or tumor necrosis factor-alpha (TNF alpha) renders rats tolerant to supralethal doses of LPS. Peritoneal macrophages from tolerant rats are refractory to LPS induced arachidonic acid (AA) metabolism and cytokine production in vivo, and exhibit reduced membrane GTPase activity and GTP gamma S binding. Since LPS stimulated AA metabolism is mediated by Gi alpha proteins, we sought to determine whether Gi alpha and/or other G proteins are reduced in LPS tolerance. Rats were rendered tolerant by two daily sublethal doses of Salmonella enteritidis LPS, 100 micrograms/kg and 500 micrograms/kg administered intraperitoneally. Animals were allowed to rest for 72 hours. Alternatively, tolerance to LPS was induced by sublethal administration of human recombinant TNF alpha (10 micrograms/kg) intraperitoneally 24 hrs before the experiments. Macrophage membrane G protein content was determined by immunoblot analysis with specific antisera to Gi1,2 alpha, Gi3 alpha, Gs alpha and the G protein beta subunits (G beta). Membrane G proteins were differentially decreased in tolerant macrophages. In macrophages from rats rendered tolerant by sublethal doses of LPS, Gi3 alpha was reduced the most to 48 +/- 8% of control (n = 3, P < 0.05) and this reduction was significant compared to those of other G proteins. Gi1,2 alpha and G beta were reduced to 73 +/- 5% (n = 3, P < 0.05) and 65 +/- 4% (n = 3, P < 0.05) of control respectively. Gs alpha(L) and Gs alpha(H) were also reduced to 61 +/- 5% (n = 3, P < 0.05) and 68 +/- 3% (n = 3, P < 0.05) of control, respectively. In contrast, only Gi3 alpha was reduced in macrophage membranes from rats pretreated with TNF alpha. Gi3 alpha was reduced to 57 +/- 11% of control (n = 4, P < 0.05) whereas Gi1,2 alpha and G beta were not significantly affected. These results demonstrate selective changes in tolerant macrophage membrane G proteins and suggest a potential role for Gi3 alpha in mediating LPS tolerance. The molecular mechanisms underlying these changes and their significance in LPS tolerance merit further investigation.
1. Lipid A and LPS stimulate LPAAT activity (and hence unsaturated PA formation) in RMC membranes and whole cells. 2. This correlates with cell phenotypic and membrane changes associated with small G proteins. 3. Unsaturated PA and Lipid A have similar effects on cells when given exogenously. 4. Human LPAAT-alpha and -beta isoforms were cloned and transfected into E. coli, demonstrating the ability to restore PA synthesis and reduce lyso-PA accumulation in plsC strains (LPAAT deficient mutants), as well as restoring growth at high temperatures. 5. LPAAT transfection into E. coli plsC (JC201) strains results in an increase in LPS content, suggesting stimulation of LPS synthesis. 6. LPAAT transfection into human A549 lung epithelial carcinoma and endothelial ECV304 cells results in increased cytokine mRNA transcription at baseline, and a significant increase in stimulated cytokine mRNA transcription. In addition, LPAAT transfection also results in increased cytokine release in response to IL-1 beta. 7. LSF, which reduces rodent deaths in sepsis models, reduces unsaturated acyl incorporation into PA in monoblastic cell lines, and reduces serum FFA increase in human sepsis, also reduces unsaturated acyl incorporation into PA in ECV304 cells. LPAAT-alpha transfection increases linolenate incorporation into PA at the expense of linoleate incorporation, which is reversed by LSF. LPAAT-beta increases both linoleate and linolenate incorporation into PA, which is also reduced by LSF. We conclude that LPAAT and PA remodeling may play a role in diffuse renal toxicity in sepsis due to induction of cellular phenotype changes associated with PA induction by Lipid A and/or LPS. Two human isoforms of LPAAT have been cloned, and apparently address C18 unsaturated acyl chains somewhat selectively. LSF causes functional reduction in LPAAT activity in transfected systems. This does not yet imply a direct effect of LSF on LPAAT. LPAAT and LPS may interact in the membrane in a not-yet-understood manner.
Human monocytes respond to LPS by releasing proinflammatory cytokines such as TNF-alpha, IL-1 and IL-6. Here we show that inhibitors of ADP-ribosylation namely nicotinamide and meta-iodobenzylguanidine prevent production of TNF-alpha and IL-6 at the protein and mRNA level. The inhibitors also influence the LPS-induced phosphorylation pattern of cytosolic proteins. They consistently lead to changes of the phosphorylation state of two proteins with an apparent molecular mass of 36 kDa and 38 kDa. The changes are both time and dose dependent. The data suggest that the conditions leading to altered phosphorylation of p36/38 may correlate with conditions initiating and regulating TNF-alpha and IL-6 production.
Bacterial lipopolysaccharide (LPS) is present on the outer membranes of all gram-negative bacteria and causes the systemic inflammatory response syndrome and septic shock, which finally develop to multiorgan failure, accompanied by extensive cell death. This chapter focuses on apoptotic cell death in in vivo response to LPS. The administration of LPS into normal mice induced marked apoptotic cell death in lymphoid organs. The reduction of peritoneal CD5+ B cells might be caused by their apoptotic cell death. When LPS was administered to normal mice, apoptotic cell death was hardly detected in the liver, kidney, heart, and lung. The characterization of LPS-induced apoptosis in D-GalN-sensitized mice might be also useful for understanding the role of apoptotic cell death in clinical endotoxin shock or septic shock.
