Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proinflammatory phenotype activation in macrophages (MPhis) after sepsis orchestrates an inflammatory response leading to multiple organ dysfunction. Trehalose preserves cell viability during exposure to a range of environmental stresses. We investigated whether trehalose may inhibit endotoxin-induced activation of the inflammatory phenotype in MPhis. Rat peritoneal MPhis were stimulated with 50 microg/mL of Salmonella enteritidis lipopolysaccharide (LPS). Stimulated MPhis were coincubated with trehalose (25, 50, and 100 mmol), sucrose (100 mmol), or RPMI alone. Macrophages cultures were used for Western blot analysis of extracellular-regulated kinase, c-jun-N terminal kinase, and inducible nitric oxide synthase; interleukin (IL) 1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) gene expression by real-time reverse transcriptase-polymerase chain reaction, and supernatants for measuring the release of inflammatory cytokines and nitrite content. In vitro trehalose significantly blunted LPS-induced extracellular-regulated kinase (LPS = 21 +/- 6 integrated intensity; LPS + trehalose 100 mmol = 2 +/- 0.3 integrated intensity), c-jun-N terminal kinase (LPS = 15 +/- 5 integrated intensity; LPS + trehalose 100 mmol = 3.5 +/- 0.9 integrated intensity), and inducible nitric oxide synthase activation (LPS = 12 +/- 3 integrated intensity; LPS + trehalose 100 mmol = 1 +/- 0.09 integrated intensity), blunted IL-1beta (LPS = 5 +/- 1.9 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.5 +/- 0.8 n-folds/beta-actin), IL-6 (LPS = 4 +/- 1.5 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.4 +/- 0.5 n-folds/beta-actin), and TNF-alpha (LPS = 4.2 +/- 1.6 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.1 +/- 0.7 n-folds/beta-actin) gene expression, and markedly reduced the release of inflammatory cytokines and nitrite content. Furthermore, in vivo trehalose prevented mortality in rats challenged with a lethal dose (20 mg/kg; LD90) of LPS (80% survival rate and 70% survival rate 24 and 72 h after LPS injection, respectively) and reduced serum TNF-alpha. Sucrose did not modified inflammatory phenotype in vitro nor in vivo protected against endotoxin-induced mortality. Our study suggests that trehalose inhibits proinflammatory phenotype activation in MPhis and prevents endotoxin-induced mortality.
...
PMID:The disaccharide trehalose inhibits proinflammatory phenotype activation in macrophages and prevents mortality in experimental septic shock. 1717 86

We have demonstrated that volatile anesthetics reduce inflammation after renal ischemia/reperfusion injury in vivo. As hyperactive uncontrolled inflammation can lead to mortality and morbidity during early sepsis, we questioned whether the volatile anesthetic isoflurane could reduce mortality and protect against sepsis induced renal and hepatic dysfunction. Mice were anesthetized with isoflurane or with pentobarbital and subjected to cecal ligation and puncture (CLP) to induce septic peritonitis. Mice were anesthetized for an additional 3 h after CLP with either isoflurane or pentobarbital. Renal and hepatic function was assessed 24 h later and survival after CLP was assessed for 7 days. To determine if isoflurane protects by reducing inflammation, we quantified renal tubular expression of pro-inflammatory (intercellular adhesion molecule 1, tumor necrosis factor alpha [TNF-alpha], and interleukin [IL] 1beta) messenger RNA with reverse transcriptase-polymerase chain reaction. We also measured the plasma levels of the pro-inflammatory cytokines TNF-alpha, keratinocyte-derived chemokine (KC), and IL-6 and an anti-inflammatory cytokine IL-10. Renal cortical apoptosis was also assessed 24 h after CLP. Twenty-four hours after the septic insult, isoflurane-treated mice had significantly improved renal and hepatic function compared with mice anesthetized with pentobarbital. Renal cortices of isoflurane-treated mice had significantly reduced expression of intercellular adhesion molecule 1, TNF-alpha, and IL-1beta messenger RNA and showed less apoptosis. Isoflurane-treated mice had lower plasma levels of TNF-alpha, KC, and IL-6. Isoflurane-anesthetized mice also had significantly prolonged and increased survival compared with pentobarbital-anesthetized mice. Therefore, isoflurane anesthesia conferred significant protection against renal and hepatic dysfunction and death after septic peritonitis and attenuated renal inflammation and apoptosis compared with pentobarbital anesthesia.
...
PMID:Isoflurane improves survival and protects against renal and hepatic injury in murine septic peritonitis. 1741 19

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis.
...
PMID:Sepsis-induced coagulation in the baboon lung is associated with decreased tissue factor pathway inhibitor. 1764 Sep 67

Postoperative or posttraumatic sepsis remains one of the leading causes of morbidity and mortality in hospital populations, especially in populations in intensive care units (ICUs). Central to the successful control of sepsis-associated infections is the ability to rapidly diagnose and treat disease. The ability to identify sepsis patients before they show any symptoms would have major benefits for the health care of ICU patients. For this study, 92 ICU patients who had undergone procedures that increased the risk of developing sepsis were recruited upon admission. Blood samples were taken daily until either a clinical diagnosis of sepsis was made or until the patient was discharged from the ICU. In addition to standard clinical and laboratory parameter testing, the levels of expression of interleukin-1beta (IL-1beta), IL-6, IL-8, and IL-10, tumor necrosis factor-alpha, FasL, and CCL2 mRNA were also measured by real-time reverse transcriptase PCR. The results of the analysis of the data using a nonlinear technique (neural network analysis) demonstrated discernible differences prior to the onset of overt sepsis. Neural networks using cytokine and chemokine data were able to correctly predict patient outcomes in an average of 83.09% of patient cases between 4 and 1 days before clinical diagnosis with high sensitivity and selectivity (91.43% and 80.20%, respectively). The neural network also had a predictive accuracy of 94.55% when data from 22 healthy volunteers was analyzed in conjunction with the ICU patient data. Our observations from this pilot study indicate that it may be possible to predict the onset of sepsis in a mixed patient population by using a panel of just seven biomarkers.
...
PMID:Presymptomatic prediction of sepsis in intensive care unit patients. 1848 Feb 35

High-tidal volume (Vt) ventilation induces lung injury and systemic inflammation, and small doses of endotoxin have been shown to increase the susceptibility to ventilation-induced lung injury. We studied whether high-Vt ventilation increases organ injury in a model of bacterial sepsis and whether an anti-inflammatory treatment averts those changes. Anesthetized rats, monitored with an arterial catheter and a blood flow probe in the aorta, were assigned to one of four different groups: nonseptic low-Vt group (Vt = 9 mL/kg, positive end-expiratory pressure = 8 cm H2O, control group), septic low-Vt group, septic overventilated group (Vt = 35 mL/kg, positive end-expiratory pressure = 0), and septic overventilated group pretreated with dexamethasone (6 mg/kg i.p., 30 min before mechanical ventilation). Rats were ventilated for 75 min. Septic rats had undergone cecal ligation and puncture 48 h before mechanical ventilation. We measured hemodynamics, lung mechanics, blood chemistry and gas exchange, liver and heart expression of cyclooxygenase 2 (COX-2) and iNOS (reverse transcriptase-polymerase chain reaction), and lung histopathology. Septic rats showed metabolic acidosis, hyperlactatemia, lung and liver injury, increased liver and heart COX-2, and liver iNOS expression. High-Vt ventilation of septic rats was associated with more marked liver injury and heart COX-2 upregulation, as well as lung inflammation and dysfunction (impaired oxygenation, increased bronchoalveolar lavage fluid protein and IL-6 concentration, decreased thoracic system compliance) and systemic hypotension. All inflammatory changes, as well as pulmonary and vascular dysfunctions, were abrogated by dexamethasone. High-Vt ventilation in bacterial sepsis upregulates the inflammatory response and aggravates the sepsis-induced cardiovascular, pulmonary, and liver dysfunction. Dexamethasone averts mechanical ventilation-induced changes under conditions of bacterial sepsis.
...
PMID:High-tidal volume ventilation aggravates sepsis-induced multiorgan dysfunction in a dexamethasone-inhibitable manner. 1879 91

The pneumococcal histidine triad (Pht) proteins are a recently recognized family of surface proteins, comprising 4 members: PhtA, PhtB, PhtD, and PhtE. They are being promoted for inclusion in a multicomponent pneumococcal protein vaccine currently under development, but to date, their biological functions and their relative contributions to pathogenesis have not been clarified. In this study, the involvement of these proteins in pneumococcal virulence was investigated in murine models of sepsis and pneumonia by using defined, nonpolar mutants of the respective genes in Streptococcus pneumoniae D39. In either challenge model, mutagenesis of all 4 genes was required to completely abolish virulence relative to the wild-type, suggesting significant functional redundancy among Pht proteins. The in vivo expression of pht genes was significantly up-regulated in the nasopharynx and lungs compared with blood. We provide unequivocal molecular evidence for Zn(2+)-dependent, AdcR-mediated, regulation of pht gene expression by real-time reverse transcriptase-polymerase chain reaction, Western blotting, and electrophoretic mobility-shift assays. We also present the first direct evidence for the biological function of this protein family by demonstrating that Pht proteins are required for inhibition of complement deposition on the pneumococcal surface through the recruitment of complement factor H.
...
PMID:Pneumococcal histidine triad proteins are regulated by the Zn2+-dependent repressor AdcR and inhibit complement deposition through the recruitment of complement factor H. 1897 Dec 60

Streptococcus suis serotype 2 is a zoonotic Gram-positive bacterium responsible for arthritis, meningitis, pneumonia and septicemia in swine and humans. Little information about the regulation of iron on its gene expression had been reported. In this study, 63 S. suis genes upregulated under an iron-restricted condition were identified using selective capture of transcribed sequences (SCUTS) technique: 23 genes involved in metabolism, 22 genes responsible for the replication and genetic information proceeding of the bacteria, eight genes relative to the construction of the cell wall, five ATP-binding cassette transporters, four transcriptional regulators and one uncharacterized gene conserved among streptococcal species. To adapt to the stress, S. suis modulated its physiological activities, which were validated by the upregulation of RelA (a crucial enzyme in stringent response), ArcA (a component of the arginine deiminase system catalyzing the conversion of arginine to ornithine) and CpdB (a cell surface protein that is a substrate of sortase A). All of them were reported to be virulence factors in S. suis or other bacteria. Besides, together with the results of quantitative reverse transcriptase PCR, we found that several homologous genes (fur, fhuGBDA operons) associated with iron uptake as reported in other bacteria were also upregulated under an iron-restricted condition in S. suis.
...
PMID:Identification of Streptococcus suis genes preferentially expressed under iron starvation by selective capture of transcribed sequences. 1919 74

Sepsis causes impaired vascular reactivity, hypotension and acute renal failure. The ability of the Escherichia coli endotoxin (lipopolysaccharide [LPS]) to impair agonist-induced contractility in mesangial cells, which contributes to LPS-induced renal dysfunction, was evaluated. Agonist-induced intracellular calcium ([Ca(2+)]i) mobilization was analyzed using angiotensin II (AngII). The effect of LPS on the levels of the renin-angiotensin system (RAS) components and the roles of vasodilatation-inducing molecules including AT2 receptor (AT2R) and nitric oxide (NO) in the cell reactivity were also evaluated. Confluent human mesangial cells (HMCs) were stimulated with LPS (0111-B4, 100 microg/mL). AngII-induced [Ca(2+)]i mobilization was measured by fluorometric analysis using Fura-2AM in the absence and presence of an AT2R antagonist (PD123319). The mRNA and protein levels for angiotensinogen, renin, angiotensin-converting enzyme, AT1R and AT2R were analyzed by realtime reverse transcriptase-polymerase chain reaction and Western blot, respectively. NO production was measured by the chemiluminescence method in the culture media after 24, 48 and 72 h of LPS incubation. After 24 h, LPS-stimulated HMCs displayed lower basal [Ca(2+)]i and an impaired response to AngII-induced rise in [Ca(2+)]i. LPS significantly increased AT2R levels, but did not cause significant alterations of RAS components. PD123319 restored both basal and AngII-induced [Ca(2+)]i peak, suggesting an involvement of AT2R in these responses. The expected increase in NO production was significant only after 72 h of LPS incubation and it was unaffected by PD123319. Results showed that LPS reduced the reactivity of HMCs to AngII and suggest that the vasodilatation induced by AT2R is a potential mediator of this response through a pathway independent of NO.
...
PMID:Escherichia coli lipopolysaccharide impairs the calcium signaling pathway in mesangial cells: role of angiotensin II receptors. 2051 80

The present study compared the susceptibility of representative Laurentian Great Lakes fish species to the emerging viral hemorrhagic septicemia virus (VHSV) Genotype IVb. The median lethal dose of infection by intraperitoneal injection (IP-LD50) was obtained from fish that were experimentally infected with the MI03 index strain of VHSV-IVb. Fish were injected at doses ranging from 7 x 10(7) to 7 x 10(-2) plaque-forming units (pfu) and maintained at 12 +/- 1 degrees C. The infection trials identified species of high, medium, and low susceptibility based on the IP-LD50 values. Pathogenicity of VHSV-IVb was highest in largemouth bass Micropterus salmoides, which resulted in an IP-LD50 of 1.5 x 10(2) pfu, while also demonstrating the clinical diathesis of VHSV-infected fish. The virus was moderately pathogenic in yellow perch Perca flavescens (IP-LD50 of 2.5 x 10(5) pfu), but also showed the classical signs of VHSV infection. Salmonids were the least susceptible to VHSV-IVb with IP-LD50 values of no less than 1.4 x 106 pfu; however, in fish that succumbed to infection, characteristic VHSV lesions were observed. Histopathologic alterations were most profound in gill, skin, muscle, gonads, and liver of largemouth bass and yellow perch, while in salmonids, hemorrhages in the swimbladder and/or degenerative changes in the liver were the most common lesions noticed. VHSV was isolated from infected fish, and its identity was confirmed by the reverse transcriptase polymerase chain reaction. These results highlight the variations among fish species susceptibility to this emerging strain of VHSV and offer insights into the potential impact of VHSV-IVb on the Laurentian Great Lakes fish community.
...
PMID:Comparative susceptibility of representative Great Lakes fish species to the North American viral hemorrhagic septicemia virus Sublineage IVb. 2085 39

A novel viral hemorrhagic septicemia virus (VHSV) (genotype IVb) has been isolated from mortality events in a range of wild freshwater fish from the Great Lakes since 2005. In 2005 and 2006, numerous new freshwater host species (approximately 90 fish from 12 different species) were confirmed to have VHSV by cell culture and reverse transcriptase polymerase chain reaction. A prominent feature observed in infected fish were the petechial and ecchymotic haemorrhages on the body surface and in visceral organs, as well as serosanguinous ascites; however, many fish had few and subtle, gross lesions. Histologically, virtually all fish had a vasculitis and multifocal necrosis of numerous tissues. Excellent correlation was found between the presence of VHSV IVb antigen detected by immunohistochemistry and the pathological changes noted by light microscopy. Intact and degenerate leukocytes, including cells resembling lymphocytes and macrophages, also had cytoplasmic viral antigen. By contrast, renal tubules and gonadal tissues (ovary and testis), were strongly immunopositive for VHSV IVb, but no lesions were noted.
...
PMID:Immunohistochemistry and pathology of multiple Great Lakes fish from mortality events associated with viral hemorrhagic septicemia virus type IVb. 2138 18


<< Previous 1 2 3 4 5 6 7 Next >>

---