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

The prophylactic and therapeutic efficacies of the immunomodulating agent RU 41.740 (a glycoprotein extract from Klebsiella pneumoniae) were studied in a murine model of intra-abdominal abscess formation with Bacteroides fragilis, Escherichia coli, and bran as an abscess-potentiating agent. Parenteral injection of RU 41.740, either before or after injection of an abscess-inducing mixture (AIM), was associated with significantly diminished incidence and size of abscesses. Abscess incidence and size were significantly decreased by oral administration of RU 41.740 after, but not before, AIM injection. Abscess formation and resolution are the results of complex interactions of host defence mechanisms with bacteria and potentiating agent, and RU 41.740 has been shown previously to activate both macrophage and neutrophil function. These results indicate that activation of non-specific defences may protect against abscess development in chronic sepsis.
 ...
PMID:The effects of RU 41.740, a glycoprotein immunomodulating agent derived from Klebsiella pneumoniae, on intra-abdominal abscess formation in mice. 851 Jan 39

Plasma fibronectic (pFN) is a high molecular weight multifunction glycoprotein, which augments neutrophil and macrofage phagocytosis and acts as a nonspecific opsonin for the reticuloendothelial system. In this study we have determined pFN concentrations in fifty eight preterm infants to discriminate infected from non infected ones. Concentrations of pFN decreased from baselin in babies with early or late onset infections. The changes in pFN concentrations were not found before sepsis, but on day 1. By day 5 pFN concentrations have increased and have been no longer different from controls. We have calculated sensitivity (73.68%), specificity (74.36%), positive (58.35%) and negative (85.29%) predictive values of pFN and of other markers of infections (C-reactive protein--CRP-, Immature/Mature neutrophil ratio--I/M n. ratio-). Adding these tests to pFN, provided equal specificity and positive predictive value, but increased sensitivity (94.73%) and negative predictive value (96.43%). Thus, low concentrations of pFN may be a valuable but not early marker for neonatal infections. The combination of pFN, CRP and I/M n. ratio increase the precision of diagnostic testing.
 ...
PMID:[Decreased plasma fibronectin (pFN) level in preterm infants with infections]. 866 94

Sepsis after surgery, trauma, or burn contributes to altered lung endothelial permeability and respiratory failure. Fibronectin (Fn), an opsonic and adhesive glycoprotein, exists in both a soluble form in plasma and an insoluble form in the extracellular matrix (ECM). Recent studies [E. M. Wheatley, P. J. McKeown-Longo, P. A. Vincent, and T. M. Saba, Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L148-L157, 1993] suggest that the ECM content of Fn may influence lung vascular permeability. We evaluated the incorporation of plasma-derived Fn (pFn) into the ECM of the lung during postoperative sepsis. Postoperative nonseptic and postoperative septic rats were compared, using a model of laparotomy followed by cecal ligation and puncture. To label the pFn pool, rats received intravenously 3 micrograms of purified rat 125I-labeled Fn/100 g body weight 6 h after surgery (laparotomy). 125I-Fn in the deoxycholate detergent-insoluble fraction of tissues was used to quantify matrix-incorporated Fn at 4 h after infusion with 125I-Fn. Septic rats exhibited a peripheral leukopenia as well as reduction in plasma volume, Fn halflife, and total pFn pool. Incorporation of pFn in the liver and spleen of postsurgical septic rats was not different (P > 0.05) from sham-operated (postsurgical nonseptic) rats, but incorporation was significantly decreased (P < 0.05) in vivo in the lung. However, under controlled in vitro conditions, lung tissue harvested from septic or sham-operated rats demonstrated a similar tissue incorporation of soluble 125I-pFn as well as similar rates of retention/turnover of ECM 125I-Fn, based on pulse-chase experiments. These data suggest that the in vivo inflammatory environment in the lung during postoperative sepsis, which cannot be reproduced in vitro, may alter the Fn content of the ECM of the lung. Such reduced levels of pFn in the lung ECM may be a factor influencing lung vascular integrity during postoperative sepsis.
 ...
PMID:Reduced in vivo plasma fibronectin content of lung matrix during postoperative sepsis. 884 89

Acquired growth hormone (GH) resistance is an increasingly recognized feature of catabolic states. Low circulating levels of the insulin-like growth factors (IGF-I and II) have been shown to be associated with changes in the IGF binding proteins (IGFBP-1 to -6) that may significantly impact on IGF bioactivity. IGFBP-3 binds IGF and a third glycoprotein, the acid labile subunit (ALS), to form a stable 150 kDa ternary complex that serves as an intravascular store for IGFs and prolongs IGF half-life. IGFBP-1 is present at much lower concentration in serum but levels fluctuate acutely, suggesting regulation of IGF bioactivity in response to short-term metabolic changes. The function of IGFBP-2 remains unclear, but studies suggest that this protein may act as an alternative carrier for IGF when IGFBP-3 levels are low. Multiple regulatory influences on circulating IGFBP levels have been identified but three appear prominent. Nutritional influences, in particular substrate availability, appear to be a central regulatory influence on IGFBP levels in catabolic states. Low substrate availability increases IGFBP-1 levels acutely and decreases IGFBP-3 and IGFBP-2 levels in the intermediate term, with each of these changes likely to further limit IGF bioactivity. End organ failure, particularly of liver and kidney significantly affects production and clearance rates of the circulating IGFBPs and may contribute to the catabolism frequently seen in these states. Severe protein catabolism often accompanies malignancy and chronic sepsis and it is likely that additional ill-defined factors influence IGF bioactivity in this setting. Recent studies have identified post-translational modifications to the IGFBPs such as proteolysis and phosphorylation, which appear to further impact on IGF bioactivity. The relative contributions of these changes to the overall impairment of IGF bioactivity in GH-resistant states remains to be fully elucidated.
 ...
PMID:Insulin-like growth factor bioactivity and its modification in growth hormone resistant states. 885 49

Bacterial lipopolysaccharide (LPS) plays a central role in the pathogenesis of gram-negative sepsis and shock. The glycosylphoshatidyl inositol (GPI) anchored glycoprotein CD14 on mononuclear cells binds LPS, especially in the presence of an LPS binding serum protein, activating the production of pro-inflammatory cytokines, i.e. TNF-alpha. However, since GPI anchorage to the cell membrane lacks the intracellular signalling capacity, the existence of at least a second receptor has been postulated. In attempt to identify additional LPS receptors, we used the human myelomonocytic cell line THP-1. This undifferentiated cell line did not respond to LPS in terms of TNF-alpha release, but when induced with 250 U/ml of IFN-gamma for 48 h, the cells released TNF-alpha (174 +/- 58.6 U/ml. L929 cell bioassay) in response to 10 vg/ml of E. coli 0111 LPS, in the absence of serum. Blockade of either HLA-DR or CD14 receptors with specific MAbs did not reduce the amount of cytokine released. However, when both the receptors were sequentially blocked involved on the effector cells a remarkable inhibition of TNF-alpha release was observed (8.6 +/- 1.4). It seems therefore, that HLA-DR receptor may be with CD14 in triggering TNF-alpha release by IFN-gamma, induced THP-1 cells.
 ...
PMID:The release of tumor necrosis factor alpha (TNF-alpha) by interferon gamma (IFN-gamma) induced THP-1 cells stimulated with smooth lipopolysaccharide is inhibited by MAbs against HLA-DR and CD14 receptors on the effector cell. 903 62

The functions of thyroid cells are regulated by a number of cytokines and growth factors in addition to TSH. Recent studies have revealed that several cytokines including interleukin (IL)-6 are involved in thyroid dysfunction. Oncostatin M (OSM) is a glycoprotein belonging to the same family of cytokines as IL-6, to which it is related by sequence and structural homology and the use of the signal-transducing receptor component gp130. We, therefore, studied the effect of OSM on iodide uptake and DNA synthesis by porcine thyroid cells in culture. OSM increased c-fos and c-jun mRNA levels but did not stimulate DNA synthesis. OSM inhibited iodide uptake stimulated by TSH; while IL-6 also inhibited iodide uptake, it was only about one-tenth as potent. IL-6 had about the same potency as OSM when it was added with soluble IL-6 receptor. OSM had no effect on cAMP production but inhibited iodide uptake stimulated by 8-bromo-cAMP and forskolin. These findings suggest that OSM exerts its inhibitory effects at the post-cAMP production step(s). OSM also inhibited thyroid peroxidase mRNA levels but had little effect on thyroglobulin mRNA levels. Investigations of the signal transduction system showed that gp130 and leukemia inhibitory factor (LIF) receptor beta subunit mRNA were detectable in porcine thyroid cells by reverse transcription (RT)-polymerase chain reaction (PCR). Together with the report that serum OSM and IL-6 concentrations are elevated to the same levels in patients with sepsis, these results suggest that OSM may contribute to the thyroid dysfunction in this condition.
 ...
PMID:Oncostatin M: a new potent inhibitor of iodine metabolism inhibits thyroid peroxidase gene expression but not DNA synthesis in porcine thyroid cells in culture. 908 75

The use of leukocyte-depleted blood components has become the standard therapy for multiply transfused patients during the past few years, as a measure to reduce the frequency of alloimmunization and refractoriness. We assessed frequency and causes of refractoriness, defined as a repeated 24-h post-transfusion platelet count below 20,000/microliters, in 145 consecutive patients who received three or more single-donor platelet concentrates during a 1-year period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein-specific ELISA were applied for the diagnosis of alloimmunization. Forty patients (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were the cause. In 15 refractory patients alloantibodies were detected. In seven patients (17.5%), alloimmunization alone caused an inadequate transfusion response, while in eight refractory patients (20.0%) alloimmunization and fever or sepsis were present. HLA antibodies were detected in 17 patients (11.7%); three patients (2%) had platelet-specific antibodies in addition to HLA antibodies; in two patients panreactive platelet antibodies were detectable. All 17 patients had a history of previous transfusions or pregnancy. We did not observe primary immunization in patients transfused exclusively with filtered (leukodepleted) blood products. Our data suggest that alloimmunization in patients with a negative risk history can be prevented by the exclusive use of leukodepleted blood components.
 ...
PMID:Frequency and causes of refractoriness in multiply transfused patients. 917 47

Neutrophils are important in ischemia and reperfusion injury. Multiple factors may be responsible for the adhesion of granulocytes to endothelial cells. P-selectin is a carbohydrate-binding glycoprotein that is stored preformed in endothelial cells as Weibel-Palade bodies. This preformation implies a very early role of P-selectin in the leukocyte adhesion process. Previous studies of P-selectin have not quantified its expression. The purpose of this study is to quantitate the expression and time course of P-selectin in response to renal ischemia and reperfusion injury. P-selectin was measured in 34 C57BL-6 mice after 30 minutes of occlusive left renal ischemia followed by 20 minutes, 2, 5, 10, and 24 hours of reperfusion. This was also performed in control and sham laparotomy groups. P-selectin was quantified using a new double radiolabeled 125I/131I monoclonal antibody technique and reported as percent injected dose per gram of tissue. P-selectin expression peaked at 20 minutes, plateaued up to 5 hours, and fell at 10 hours. Additionally, genetically altered mice that do not express P-selectin showed no up regulation after 5 hours of reperfusion. Pathology results confirmed significant renal injury. Renal ischemia and reperfusion injury caused significant upregulation of P-selectin. Expression of P-selectin at the short reperfusion time of 20 minutes reinforces the premise that P-selectin is one of the earliest adhesion molecules expressed. This early peak is probably caused by the release of preformed P-selectin. The delineation of these mechanisms of injury may be important in understanding and preventing renal injury in transplantation, sepsis, and shock.
 ...
PMID:Quantification of P-selectin expression after renal ischemia and reperfusion. 924 23

Antithrombin (AT) is a single-chain glycoprotein in plasma and belongs to the family of the serpins. It is synthesized in liver parenchymal cells, and its plasma concentration is between 112-140 mg/L. AT is a unique inhibitor of the clotting system and neutralizes most of the enzymes generated during activation of the clotting cascade, especially thrombin, factors Xa and IXa. Equimolar, irreversible complexes are formed between AT and the enzymes. The interaction between AT and the activated clotting factors is at least 1,000-fold increased in the presence of heparins. Heparins bind to multiple sites of the AT molecule resulting in a steric reconfiguration. Heparins contain a specific pentasaccharide unit which is the minimum requirement for AT binding. The glycosaminoglycan (GAG) heparan sulfate found on endothelial cell surfaces also contains this pentasaccharide and can thus "activate" AT. It is believed that much of the physiological inactivation of enzymes by AT occurs on the endothelium, mediated by heparan sulfate. The binding of AT to the GAGs also releases prostacyclin which possesses strong antiinflammatory properties. Deficiencies of AT are inherited or acquired. Only acquired defects due to increased consumption are discussed, most notably AT in DIC, especially DIC in sepsis. During acute DIC, clotting factors and inhibitors are consumed faster than they can be reproduced. This consumption of AT is of great significance in DIC and sepsis, and plasma AT levels predict outcome. AT levels drop early in sepsis and laboratory signs of DIC can already be found in patients with SIRS and early sepsis. The important role of AT in DIC and sepsis is the basis for considering antithrombin concentrates as an additional therapeutic modality.
 ...
PMID:Antithrombin: its physiological importance and role in DIC. 951 76

1. Sepsis was induced in rats by an intravenous injection of live bacteria. Infected and pair-fed animals were studied before the infection, in an acute septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a late septic phase (day 10). Protein synthesis rates were measured in vivo after administration of a flooding dose of L[1-13C]valine. 2. During the acute phase, muscle protein loss associated with infection resulted from both a decrease in protein synthesis and an increase in proteolysis. During the chronic phase and the late phase, the increase of proteolysis in infected rats as compared with pair-fed animals persisted, worsening muscle atrophy. Skin protein synthesis rates were not significantly modified by infection. However, skin protein content decreased 6 and 10 days after infection, suggesting an increased proteolysis in response to sepsis. 3. Protein synthesis in liver of infected rats was twice that of pair-fed animals. Liver protein synthesis remained elevated in infected rats compared with pair-fed animals until day 10. Hypoalbuminaemia and high plasma concentrations of fibrinogen were evident at all periods studied. alpha 2-Macroglobulin and alpha 1-acid glycoprotein reached peak concentrations during the acute phase (concentrations increased 50 times in infected rats). On day 10, the levels of these proteins were still about 12-fold higher. 4. Protein synthesis rates were significantly increased in the digestive tract and lung of infected rats compared with pair-fed groups on days 2 and 6, but were similar in the two groups on day 10 post-infection. The fractional protein synthesis rate was increased 3-fold over the entire experimental period in the spleen. 5. The results show that sepsis stimulates protein synthesis in various tissues over a long time, and that skin, like muscle, can provide amino acids to the rest of the body.
 ...
PMID:Sustained modifications of protein metabolism in various tissues in a rat model of long-lasting sepsis. 964 Mar 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>