Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Staphylococcus epidermidis releases factors that activate the HIV-1 long terminal repeat, induce cytokine release, and activate nuclear factor B in cells of macrophage lineage. The active material had a mass of 34,500 daltons, was inactivated by proteases and partitioned into the phenol layer on hot aqueous phenol extraction, and thus was termed phenol-soluble modulin (PSM). High performance liquid chromatography (HPLC) of crude PSM yielded two peaks of activity designated PSM peak 1 and peak 2. MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) mass spectroscopy indicated the presence of two components in peak 1, which were designated PSM and PSM. Peak 2 contained a single component, designated PSM. Separation of PSM and PSM in peak 1 could be achieved by a second HPLC procedure. The structure of each component was determined by amino acid sequence analysis and identification and sequencing of their genes. PSM, PSM, and PSM were 22-, 44-, and 25-amino acid, respectively, strongly hydrophobic polypeptides. PSM was identified as Staphylococcus epidermidis delta toxin, whereas PSM and PSM exhibited more distant homology to previously described staphylococcal toxins. They appeared to exist as a complex or aggregate with activity greater than the component parts. The properties of the S. epidermidis PSMs suggest that they may contribute to the systemic manifestations of Gram-positive sepsis.
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PMID:An inflammatory polypeptide complex from Staphylococcus epidermidis: isolation and characterization. 1007 74

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT and other calcitonin precursors are elevated in the serum of many conditions leading to systemic inflammatory response syndrome. The measurement of PCT in patients suffering from severe bacterial infections is a useful tool for the diagnosis of sepsis. Furthermore, therapeutic decisions are often based on the increase or decline of serum PCT levels. PCT was reported to have 116 amino acids. The aim of our study was the determination of the primary structure of serum PCT from septic patients. Sera containing high PCT-concentrations (>100 ng/ml) were collected from 22 patients with severe sepsis and were pooled for further purification (12.7 microg total concentration of PCT). Pooled PCT was purified on a CT 21-immunoaffinity column, further purified by reversed phase HPLC, and the resulting pure PCT was digested with endoproteinase Asp-N. N-terminal Edman sequencing showed that the first two amino acids (Ala-Pro) of the proposed pro-peptide were missing. Further analyses by MALDI-TOF mass spectroscopy resulted in a distinct mass signal of 12640 Da +/- 0.1%, which is in concordance with the theoretical molecular weight of the N-terminal truncated form (12628 Da). As opposed to previous suggestions, we could not detect any chemical modifications of PCT. In summary, we could demonstrate that PCT in the serum of septic patients is a peptide of only 114 amino acids, instead of the predicted 116 amino acids, lacking the N-terminal dipeptide Ala-Pro. This information on the primary structure of PCT might help in further studies on the physiological role of PCT during sepsis.
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PMID:Isolation and characterization of serum procalcitonin from patients with sepsis. 1178 96

Systemic inflammatory response conditions are associated with capillary leak and haemodynamic compromise. Fluid resuscitation to reverse the ensuing hypovolaemia is, however, complicated by the decreased endothelium reflection coefficient to albumin and other colloids. We developed PEG-Alb (albumin covalently linked to polyethylene glycol) as a potential resuscitative agent. PEG was covalently linked to human albumin at multiple sites on the protein. The modified protein was heterogeneous when examined by SDS/PAGE, size-exclusion chromatography and SELDI-TOF MS (surface-enhanced laser-desorption ionization-time of flight MS). Based on size-exclusion chromatography and osmotic pressure data, the effective volume of PEG-Alb is increased 13- to 16-fold compared with unmodified albumin. In an LPS (lipopolysaccharide) model of shock, rats treated with PEG-Alb showed better blood pressure, lower Hct (haematocrit) consistent with haemodilution and less lung injury than rats treated with unmodified albumin or saline. In a CLP (caecal ligation and puncture) model of sepsis, PEG-Alb was more effective than albumin or saline in maintaining blood pressure and in decreasing Hct. When fluorescein-labelled PEG-Alb and Texas Red-labelled albumin were administered to rats with LPS- or CLP-induced shock, PEG-Alb was retained within blood vessels, whereas albumin extravasates into the interstitial space. Based on these data, PEG-Alb appears to be retained within blood vessels in models of capillary leak. PEG-Alb may ultimately be effective in the clinical treatment of shock associated with capillary leak.
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PMID:Plasma expansion by polyethylene-glycol-modified albumin. 1504 8

Inter-alpha inhibitor proteins (IaIp) are a family of structurally related serine protease inhibitors found in relatively high concentrations in human plasma. Recent studies have implicated a role for IaIp in sepsis, and have demonstrated their potential as biomarkers in sepsis and cancer. For characterization of isolated IaI proteins and contaminating proteins during the last steps of the purification process, SELDI-TOF MS and HPLC-ESI-MS/MS were used. After separation by SDS-PAGE or 2-DE, polypeptide bands of 80, 125 and 250 kDa were excised from gels and digested by trypsin. The tryptic peptides were analyzed by both MS methods. The main contamination during the purification process, a band of 80 kDa, contains mainly IaIp heavy chain (HC) H3. HC H1 and H2 were also found in this band. In addition, some vitamin K-dependent clotting factors and inhibitors and other plasma proteins were identified. The 125-kDa band, representing the pre-alpha inhibitor, was found to contain both bikunin and HC H3. The presence of other HC H1, H2 and the recently described HC H4 was also detected by SELDI-TOF MS. The presence of HC H1, H2, and H3 in the 125-kDa band was confirmed by ESI-MS/MS, but not the presence of the H4. Three polypeptides, H1 and H2 together with bikunin, were identified in the 250-kDa band, representing the ITI, by both MS techniques. Once again, the presence of H4 was detected in this band only by SELDI-TOF MS, but the number of corresponding peptides was still not sufficient for final identification of this polypeptide. The importance of the application of proteomic methods for the proper evaluation of therapeutic drugs based on human plasma is discussed.
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PMID:Proteomic characterization of inter-alpha inhibitor proteins from human plasma. 1659 6

The vascular endothelium plays an important role in regulating immune and inflammatory responses to resist pathogens infection. Although it has been known that lipopolysaccharide (LPS) is a critical inducer of sepsis or endotoxemia, the systematic responses of LPS-stimulation in endothelial cells (ECs) are still unclear. The present study aims to analyze the late-phase responses of LPS-induced rat aortic ECs by using systematic biology approaches, including rat cDNA microarray, 2-DE and MALDI-TOF MS/MS, and cytokine protein array. Furthermore, to improve the efficiency of analysis of the bulk systematic data of rat, we designed a set of bioinformatic tools to convert and integrate these rat data into the corresponding human genes or proteins IDs based on BioCarta, KEGG, and Gene Ontology databases. Using the systematic analysis, it was shown that LPS could promote some signaling or metabolic pathways as well as pathophysiologic phenomena of proliferation, atherogenesis, inflammation, and apoptosis through activated nuclear factor-kappaB pathway in ECs. Interestingly, ECs also activated the mediators of anti-inflammation, antiapoptosis, and antioxidation to protect themselves. Moreover, the expressions of altered genes, proteins, and their involvement in the hypothetical signaling pathway can provide further understanding of inflammation associated responses in ECs.
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PMID:Lipopolysaccharide-stimulated responses in rat aortic endothelial cells by a systems biology approach. 1710 15

A fundamental issue for sepsis therapy is to control the development of inflammation at an early stage. With cecal ligation and puncture (CLP) surgery, the mouse model has clearly shown the septic signs triggered by chronic insult. To monitor the plasma proteomic responses to sepsis, the mouse blood was collected at intervals after sham and CLP surgery followed by the sample treatment to remove high abundance serum albumin. The treated mouse plasma proteins were well resolved by two-dimensional electrophoresis (2-DE). The image analysis revealed that these 2-DE spots observed from the sham and the CLP samples 4 h after surgery were comparable, whereas more than 30 different spots appeared on the 2-DE gels between the sham and CLP mouse plasma 24 h after surgery, indicating that some plasma proteins responded to the inflammatory development. These differential spots were verified by MALDI-TOF/TOF MS, resulting in 13 unique sepsis-responsive proteins. More importantly, most of them exhibited multiple spots as difference on the 2-DE gels. Furthermore, these isospots were incubated with PNGase F to eliminate N-linked oligosaccharides on proteins and then evaluated by Western blot as well as mass spectrometry. The results of PNGase F digestion suggested that most sepsis-associated proteins remained in N-glycosylation status but changed their N-glycans during septic development.
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PMID:The alterations of mouse plasma proteins during septic development. 1749 7

Sepsis is a systemic response to infection commonly found in critically ill patients and is associated with multi-organ failure and high mortality rate. Its pathophysiology and molecular mechanisms are complicated and remain poorly understood. In the present study, we performed a proteomics investigation to characterize early host responses to sepsis as determined by an altered plasma proteome in a porcine model of peritonitis-induced sepsis, which simulated several clinical characteristics of human sepsis syndrome. Haemodynamics, oxygen exchange, inflammatory responses, oxidative and nitrosative stress, and other laboratory parameters were closely monitored. Plasma samples were obtained from seven pigs before and 12 h after the induction of sepsis, and plasma proteins were resolved with two-dimensional gel electrophoresis (n=7 gels/group; before being compared with during sepsis). The resolved proteins were stained with the SYPRO Ruby fluorescence dye and subjected to quantitative and comparative analyses. From approx. 1500 protein spots visualized in each gel, levels of 36 protein spots were significantly altered in the plasma of animals with sepsis (sepsis/basal ratios or degrees of change ranged from 0.07 to 21.24). Q-TOF (quadrupole-time-of-flight) MS and MS/MS (tandem MS) identified 30 protein forms representing 22 unique proteins whose plasma levels were increased, whereas six forms of five unique proteins were significantly decreased during sepsis. The proteomic results could be related to the clinical features of this animal model, as most of these altered proteins have important roles in inflammatory responses and some of them play roles in oxidative and nitrosative stress. In conclusion, these findings may lead to a better understanding of the pathophysiology and molecular mechanisms underlying the sepsis syndrome.
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PMID:Altered plasma proteome during an early phase of peritonitis-induced sepsis. 1900 84

Hepcidin is a 25-residue hepatic peptide that regulates iron absorption from the diet and tissue iron distribution. Inappropriately low Hepcidin expression is implicated in the pathogenesis of hereditary hemochromatosis and iron-loading anemias, like the thalassemias. Increased hepcidin expression mediates iron retention in the anemias of inflammation and plays a pathogenic role in iron-refractory iron-deficiency anemia (IRIDA). Because of its clinical importance, Hepcidin is expected to be a useful biomarker for diagnosis and management of iron-related disorders. So far an ELISA for human hepcidin and SELDI-TOF-MS based approaches have been applied to monitor urinary and/or serum hepcidin levels. Here we report a modified protocol for SELDI-TOF based detection of human, urinary hepcidin. We show that CM10 Proteinchips are superior to NP20 Proteinchips commonly used in previously reported protocols to sensitively and accurately detect urinary hepcidin. Application of this modified hepcidin assay accurately detects increased hepcidin levels in the urine of sepsis patients.
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PMID:SELDI-TOF MS detection of urinary hepcidin. 1939 87

Lipid A structural modifications can substantially impact the host's inflammatory response to bacterial LPS. Bacteroides fragilis, an opportunistic pathogen associated with life-threatening sepsis and intra-abdominal abscess formation, and Bacteroides thetaiotaomicron, a symbiont pivotal for proper host intestinal tissue development, both produce an immunostimulatory LPS comprised of penta-acylated lipid A. Under defined conditions, Porphyromonas gingivalis, an oral pathogen associated with periodontitis, also produces an LPS bearing a penta-acylated lipid A. However, this LPS preparation is 100-1000 times less potent than Bacteroides LPS in stimulating endothelial cells. We analyzed Bacteroides and P. gingivalis lipid A structures using MALDI-TOF MS and gas chromatography to determine the structural basis for this phenomenon. Even though both Bacteroides and P. gingivalis lipid A molecules are penta-acylated and mono-phosphorylated, subtle differences in mass and fatty acid content could account for the observed difference in LPS potency. This fatty acid heterogeneity is also responsible for the peak "clusters" observed in the mass spectra and obfuscates the correlation between LPS structure and immunostimulatory ability. Further, we show the difference in potency between Bacteroides and P. gingivalis LPS is TLR4-dependent. Altogether, the data suggest subtle changes in lipid A structure may profoundly impact the host's innate immune response.
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PMID:The structurally similar, penta-acylated lipopolysaccharides of Porphyromonas gingivalis and Bacteroides elicit strikingly different innate immune responses. 1946 Apr 28

This study examines alterations in the plasma proteome in ten adults affected by sepsis caused by Acinetobacter baumannii as compared to paired healthy controls. 2-DE profiles of plasma from patients and paired healthy donors, depleted of the six most abundant proteins, were analysed by the DIGE technique. Protein spot detection and quantification were performed with the Differential In-gel Analysis and Biological Variation Analysis modules of the DeCyder() software. Differentially expressed proteins were identified by mass spectrometry (MALDI-TOF/TOF) after colloidal Coomassie blue staining. Almost 900 spots were detected on a unique 2-D gel by the DIGE technique. A total of 269 protein spots of differential abundance were shown to be statistically significant (2.5-fold) with p values of p< or =0.01 (135 spots) and p< or =0.05 (134 spots) as determined by the t test. Seventy-one spots were submitted to mass spectrometry and about 30% could be successfully identified. This multiplex approach significantly reduced experimental variability, allowing for the confident detection of small differences in protein levels. Results include differentially expressed lipoproteins as well as proteins belonging to inflammatory/coagulation pathways and the kallikrein-kinin system. These data improves the knowledge for future developments in sepsis diagnosis, staging and therapy.
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PMID:Differential proteomics of the plasma of individuals with sepsis caused by Acinetobacter baumannii. 1978 74


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