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)

Seventy three adults underwent orthotopic liver transplantations between February 1987 and November 1989 and were followed (54 retrospectively and 19 in a prospective study) with the aim of establishing the incidence of deep mycoses (3 disseminated candidiasis due to C. albicans, 1 invasive aspergillosis due to A. fumigatus and 1 invasive pulmonary aspergillosis due to A. niger and A. fumigatus). 4/5 of these infections occurred in the first month after transplantation. All the patients were associated with the following clinical risk factors: previous use of wide spectrum antibiotics (5/5); more than 1 abdominal laparotomy (4/5), due to primary failure of the graft (3/4) and thrombosis of the hepatic artery (1/4). Two of the three patients [corrected] with invasive candidiasis had previous episodes of documented fungemia. 24 patients of the group who didn't show MIP had some risk factor which in all of them was the previous use of high dose steroids and/or of wide spectrum antibiotics, in addition to the used in surgical prophylaxis. In our series, the one risk factor associated with MIP was more than one previous laparotomy (p less than 0.001). Other significant associated infections were 3 bacterial sepsis (2 due to Enterococcus faecalis and 1 due to Staphylococcus epidermidis) and one viral (Cytomegalovirus viremia). The mortality rate was 100%, however the cause of death was multifactorial.
 ...
PMID:[Invasive mycoses in liver transplantation]. 193 38

The chemokines are a superfamily of small proteins secreted primarily by leukocytes and related by a conserved four-cystein motif. In the present study we investigated the serum levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) and interleukin-8 (IL-8). MIP-1 alpha is a neutrophil chemotactic protein important in acute and chronic inflammation. Recent studies demonstrated that MIP-1 alpha may also act as potent inhibitor of hemopoetic stem cell proliferation, which may be important in the development of prolonged anemia in patients suffering from Plasmodium falciparum malaria. IL-8 serum concentrations correlate with severity and outcome of infectious diseases. Moreover, recent reports indicate that IL-8 plays a major role in fatal gram-negative sepsis. It was the aim of this study to investigate the time course of MIP-1 alpha and IL-8 concentrations in patients suffering from acute P. falciparum infection. Blood samples of 20 patients suffering from severe P. falciparum malaria were investigated. MIP-1 alpha and IL-8 concentrations were determined using ELISA technique at admission, on Days 7, 14, 21, and 28. Maximal concentrations of MIP-1 alpha and IL-8 were found on Day 14, at a time when parasites were not detected in the smears. The serum levels of IL-8 on the day of admission were correlated to the parasite count. No correlation was seen between the hematokrit values and the MIP-1 alpha concentrations at any time.
 ...
PMID:Serum concentrations of MIP-1 alpha and interleukin-8 in patients suffering from acute Plasmodium falciparum malaria. 760 66

Macrophage inflammatory proteins 1 alpha and beta (MIP-1 alpha and beta) and macrophage inflammatory protein 2 (MIP-2) are approximately 6-8 kd, heparin binding proteins that exhibit a number of inflammatory and immunoregulatory activities. The MIP proteins are members of a superfamily of cytokines called chemokines, many of which have been shown to possess chemotactic activity for inflammatory and immune effector cells. While MIPs were originally identified as secretory products of endotoxin-stimulated mouse macrophages, these chemokines are produced by a variety of cell types including neutrophils, fibroblasts, and epithelial cells. In addition, proteins with a high degree of structural and functional homology to murine MIP-1 alpha and beta and MIP-2 have been identified in other species including humans. MIP-1 alpha and beta are chemotactic for monocytes and lymphocytes and MIP-2 is a potent chemotactic factor for neutrophils. MIPs likely also play a role in regulating hematopoiesis and stimulating production of other inflammatory mediators such as IL-1, TNF alpha, and histamine. Studies using animal models of lung injury and inflammation have implicated MIPs as important mediators of lung defense. Increased MIP expression has been observed in models of bacterial sepsis, silicosis, and oxidant-induced lung injury. Studies in humans indicate MIP-1 alpha contributes to the inflammatory cell response associated with sarcoidosis and idiopathic pulmonary fibrosis. Given the bioactivities of MIP-1 alpha and beta and MIP-2 and the recent studies demonstrating their association with lung inflammation, it is likely these chemokines play a significant role in respiratory tract defenses and may contribute to the pathogenesis of inflammatory lung disease.
 ...
PMID:Macrophage inflammatory proteins: biology and role in pulmonary inflammation. 788 2

Seventy-two patients with advanced stage IIIB (42%) or stage IV (58%) non-small cell lung cancer (median age 57 years, Karnofsky PS 60-100) were treated with mitomycin C (6 mg/m2, day 1), ifosfamide (1500 mg/m2, days 1-3), and cisplatin (30 mg/m2, days 1-3) every 4 weeks. The objective response rate was 37% in the overall population; 50% in stage IIIB patients and 29% in stage IV patients. Twenty four patients achieved partial response (33%) and three patients achieved complete response. Despite this relatively high objective response rate, the overall median survival time was 32 weeks. The median survival was significantly better in stage IIIB patients (55 weeks) than in stage IV patients (25 weeks) (P = 0.003). MIP regimen was permanently suspended in 14 patients because of toxic events. Seventeen patients developed grade III or IV febrile neutropenia and two patients died from sepsis. Two patients experienced acute mitomycin peumonitis. Despite increased doses of cisplatin and ifosfamide, compared with the original description for MIC chemotherapy, with probably higher toxicity, no apparent increased response rate or median survival was observed in this study. The MIP regimen could be tested in a randomized trial in comparison with other administration plans in a comparable population.
 ...
PMID:Efficacy and toxicity of mitomycin, ifosfamide, and cisplatin (MIP) in patients with inoperable non-small cell lung cancer. 869 14

Endotoxin-induced lung injury is characterized by neutrophil infiltration of the lungs. The various mechanisms which mediate movement of neutrophils from vascular space to lung interstitium and alveoli remain unclear. Macrophage-inflammatory protein 2 (MIP-2) is a potent chemoattractant for neutrophils and may play a significant role in recruiting neutrophils in acute lung injury in rats. Experiments were performed in male Sprague Dawley rats to: (1) evaluate the kinetics of neutrophil influx in the lung following intraperitoneal administration of Salmonella enteritidis lipopolysaccharide (LPS); (2) determine the expression of transcripts for chemokines and adhesion molecules in the lung following intraperitoneal LPS; and (3) elucidate the effects of intra-alveolar instillation of recombinant rat MIP-2 on neutrophil influx into the lung. Intraperitoneal LPS resulted in an increase in neutrophil sequestration in the lung capillaries of rats as early as 45 min following administration, and there was a parallel increase in lung myeloperoxidase activity. There were also major increases in mRNA in whole-lung homogenates of LPS-treated rats for chemokines MIP-2 and KC (cytokine-induced neutrophil chemoattractant) and adhesion molecules P- and E-selectin at 1 and 2 h following LPS. When recombinant rat MIP-2 was instilled into the alveolar space of rats through a catheter wedged into a bronchus, there was profound neutrophil localization both in the vascular and alveolar space which significantly differed (P < 0.05) from the contralateral lungs of the same animals, and lungs of control animals instilled with control buffer. These observations reveal that MIP-2 is a potent chemoattractant in rat lungs, and suggest that chemoattractants locally released in alveoli can recruit neutrophils to those alveoli. This suggests that alveolar macrophages may play an important role in neutrophil sequestration in sepsis and other inflammatory lung diseases which produce a neutrophilic alveolitis.
 ...
PMID:Intra-alveolar macrophage-inflammatory peptide 2 induces rapid neutrophil localization in the lung. 891 72

Cytokines serve to initiate the acute inflammatory response and to integrate nonspecific and specific immunological responses to infections occurring in perioperative patients. Microbial substances induce macrophages to produce pivotal cytokines (TNF-alpha and IL-1 beta). This results in an activation of other cytokine productions including IL-2, IL-3, IL-4, IL-6, chemokines, and IL-10. Also, other host-originated humoral mediators are released from macrophages, neutrophils, platelets, and endothelial cells Various cytokines are also produced by helper-T (Th) cells, and the Th1/Th2 balance is regulated by cytokines and stress hormones. This nonspecific inflammatory response and specific immunological response which are mediated by cytokines are crucial for the host defense against invading pathogens. On the other hand, the blood levels of TNF-alpha, IL-6, IL-8, and MIP-1 alpha were correlated with the severity and mortality in patients with sepsis. Also we found that in patients with inhalation injury the high IL-8 levels in bronchoalveolar lavage fluid on admission predicted the development of respiratory insufficiency. In severe infection, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines cause an autodestructive systemic inflammatory response syndrome (SIRS). This condition is termed "Cytokine Storm" by the author. In cytokine storm, not only proinflamamtory cytokines, but also anti-inflammatory cytokines appear in circulating blood, leading to septic shock, multiple organ dysfunction, and immunosuppression. With further understanding of the roles of cytokines in sepsis, modulation of cytokine responses could be a new modality of the treatment.
 ...
PMID:[Cytokine-mediated biological response to severe infections in surgical patients]. 903 81

The roles of endotoxin (LPS) and tumor necrosis factor-alpha (TNF-alpha) in the causation of organ injury during sepsis are unclear. To study LPS and TNF-alpha in the genesis of lung inflammation after cecal ligation and puncture (CLP), we used endotoxin-resistant (C3H/HeJ) and endotoxin-sensitive mice (C3H/HeOuJ). We examined lung neutrophil sequestration, interleukin 1 (IL-1)beta mRNA expression, IL-1 beta protein expression, and injury. We also determined the expression of two C-X-C chemokine mRNAs, macrophage inflammatory protein-2 (MIP-2) and KC, in the lung to determine whether in vivo, endotoxin, or TNF-alpha are significant modulators of MIP-2 and KC mRNA expression. After CLP, increased neutrophils sequestrated in the lungs of both strains of mice and coincided with an increase in expression of IL-1 beta, MIP-2 and KC mRNAs, and IL-1 beta protein. Lung and serum TNF-alpha were significantly increased in the C3H/HeOuJ strain but not in the C3H/HeJ strain. Histologic studies of the lung revealed similar injury in both strains. Our results suggest that bacterial factors other than endotoxin cause lung neutrophil sequestration and injury after CLP and, further, that TNF-alpha production is not a prerequisite. Our findings also suggest a potential role for local pulmonary chemokine production in the control of neutrophil sequestration after CLP.
 ...
PMID:The pulmonary inflammatory response to experimental fecal peritonitis: relative roles of tumor necrosis factor-alpha and endotoxin. 927 63

We hypothesized that chemokines may play important roles in a cecal ligation and puncture (CLP) model of septic peritonitis in CD-1 mice. Concentrations of C-X-C (macrophage inflammatory protein 2 [MIP-2] and ENA-78) and C-C (MIP-1alpha and JE) chemokines were measured (by enzyme-linked immunosorbent assay) in serum, peritoneal lavage fluid, lung, and liver at 4, 8, 24, 48, and 96 h after CLP. Significant elevations in all measured chemokines occurred in peritoneal fluid after CLP (P < 0.05). MIP-2, in particular, increased dramatically (>400-fold, P < 0.001) in peritoneal fluid, serum, and to a lesser extent lung and liver (P < 0.05). Increased MIP-2 was correlated with severity of sepsis (P < 0.001). To determine the significance of this finding, mice were passively immunized prior to CLP with polyclonal antibody to MIP-2, which decreased mortality from 85 to 38% at 96 h (P < 0.01). To further understand the mechanism of the effect of MIP-2, additional measurements demonstrated that anti-MIP-2 prior to CLP decreased the percent neutrophils in peritoneal fluid (55% +/- 12%, compared with 82% +/- 10% in controls), but no significant changes in tumor necrosis factor alpha, interleukin-6, or interleukin-10 occurred. MIP-2 contributes to the inflammatory response and overall mortality in this model of severe septic peritonitis, possibly by increasing recruitment of neutrophils, which clear bacteria but may also injure the host.
 ...
PMID:Elevated levels of macrophage inflammatory protein 2 in severe murine peritonitis increase neutrophil recruitment and mortality. 928 62

Human alveolar macrophages (AMs) obtained from smokers and non-smokers by bronchoalveolar lavage (BAL) were subjected to various concentrations of NO2 in an inverted monolayer exposure model. Culture supernatants were collected 4 h after the exposure and assayed for secreted TNF-alpha, IL-1 beta, IL-8 and MIP-1 alpha. The steady state levels of the mRNAs for these cytokines were also analysed in the cells. The adherence of BAL cells to plastic prior to exposure to the gas elevated the steady state mRNA levels of all four cytokines tested in smoker's cells and that of TNF-alpha and IL-1 beta, but not IL-8 (MIP-1 alpha not tested), in non-smoker's cells. Interestingly, adherent cells from non-smokers released circa 15-, 3-, 1.5- and 3-fold the amounts of IL-1 beta, IL-8, TNF-alpha and MIP-1 alpha, respectively, than smoker's cells during control incubation or exposure to air. A 20 min exposure to NO2 (5 or 20 p.p.m.) did not increase the secretion of any of the cytokines from either cell type. In contrast, NO2 caused a concentration-dependent inhibition of the secretion of all cytokines except IL-1 beta from smoker's cells. Additionally, NO2 greatly diminished the release of all cytokines in response to further treatment with lipopolysaccharide (LPS). In contrast, only the secretion of TNF-alpha from non-smoker's cells was inhibited by the gas in a concentration-dependent manner, whilst LPS-induced secretion of the cytokines was not affected by the gas. The steady state levels of the respective mRNAs for each of the cytokines were not significantly affected in smoker's cells by exposure to NO2, except for a negative, dose-dependent trend in the case of TNF-alpha. Nitrogen dioxide also failed to elevate the levels of the mRNAs in non-smoker's cells but, again, tended to diminish the levels, particularly of IL-1 beta mRNA. However, exposure to the gas inhibited LPS-induced accumulation of cytokine mRNAs in smoker's cells only. The data suggest that macrophage-derived cytokine mediators of the sepsis response may not play a role in the generation of NO2-induced inflammation in the human lung. Conversely, the gas seems to non-specifically inhibit the release and/or production of cytokines, particularly from smoker's cells, at the post-transcriptional level, and impairs the ability of the cells to increase the transcription and release of the cytokines in response to bacterial LPS. The fact that NO2 seriously impaired the already diminished capacity of smoker's cells to release several important pro-inflammatory cytokines, both under control conditions and in response to LPS, strongly suggest that the inhalation of NO2 in cigarette smoke may contribute to impairing host defence against infection in the lung.
 ...
PMID:Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non-smokers by NO2. 936 75

Chemokines contribute to the inflammatory response by selective attraction of various leukocytic cell types. Human GCP-2 was originally identified by amino acid sequence analysis as a CXC chemokine co-produced with IL-8 by osteosarcoma cells. Furthermore, the complete coding domain of human GCP-2 was disclosed by means of RT-PCR. Similarly, mouse GCP-2 was isolated from fibroblastoid and epithelial cells and completely identified by sequence analysis. Human and mouse GCP-2 share 61% identical amino acids. Both chemokines occur as multiple NH2-terminally truncated forms. The shorter forms of mouse, but not those of human, GCP-2 showed a higher neutrophil chemotactic potency and gelatinase B releasing capacity. Mouse GCP-2 was a more potent neutrophil activator than human GCP-2, natural mouse KC, and MIP-2. Human GCP-2 was not chemotactic for monocytes, lymphocytes, or eosinophils. Quantitative studies of mRNA expression in diploid fibroblasts revealed GCP-2 induction by IL-1beta. Human GCP-2 induced [Ca2+]i increase in neutrophils, which was reciprocally desensitized by IL-8, GROalpha, and ENA-78. Human GCP-2 induced [Ca2+]i increases and chemotactic responses in both CXCR1- and CXCR2-transfected cells. Finally, GCP-2 provoked neutrophil accumulation and plasma extravasation in rabbit skin. In humans, GCP-2 complements the activity of IL-8 as neutrophil chemoattractant and activator but it constitutes a major neutrophil chemokine in the mouse. GCP-2 induces neutrophil chemotaxis and activation but it might also contribute to detrimental tissue damage in sepsis, acute respiratory distress syndrome, acute hypersensitivity reactions, and autoimmune diseases. It might also influence the invasive capacity of GCP-2-secreting tumor cells.
 ...
PMID:Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage. 936 9


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