Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe trauma threatens the life of the victim, both directly and indirectly via immunological dysregulation during the subsequent clinical course. Inflammatory or infectious episodes may complicate the clinical course and ultimately result in sepsis and multiple organ failure, which have mortality rates of up to 80%. Immunomodulatory intervention aims to ameliorate the early hyperinflammatory phase (systemic inflammatory response syndrome, SIRS) to avoid the development of sepsis. One of the immunomodulation strategies is enteral feeding supplemented with specific nutrients, such as glutamine, n-3-polyunsaturated fatty acids, and nucleotides ('immunonutrition'), because changes in the GALT (gut-associated lymphoid tissue) immune response may contribute to intestinal dysfunction and increase susceptibility to post injury gut-derived sepsis. In a prospective, randomized, double-blind, controlled study in twenty-nine patients suffering severe trauma we were able to show that immunonutrition (arginine, n-3-fatty acids, and nucleotides) significantly reduces the number of SIRS days per patient, and also lowers the multiple organ failure (MOF) score on day 3 and days 8-11 (P<0.05). Other studies have reported a reduction in septic complications and MOF rates, shortened hospital stay, and reduction in the use of antibiotics in patients randomized to the immune-enhancing diet. This improved clinical outcome was reflected in a reduction in hospital costs. In the recovery period after trauma (1-72 h after injury) a limitation of the inflammatory response of immunocompetent cells must be achieved as quickly as possible (<72 h). The only strategy available to clinicians caring for trauma patients is immunonutrition, and this should be strongly considered as a rational approach improving immune function and reducing septic complications in critically ill or injured patients.
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PMID:Immunonutrition in patients after multiple trauma. 1189 49

Hematopoietic stem cells represent a long term reservoir of cells to populate blood with multiple formed cells. These hematopoietic stem cells proliferate and mature into lymphoid, erythroid, and myeloid precursor cells, with the balance of these cell populations modulated by major thermal injury, with or without sepsis. Recent studies indicate that thermal injury shifts this balance to favor the monocyte/macrophage lineage at the expense of neutrophil production. The mechanisms for these changes are now being elucidated with the results of clinical importance, because understanding the dynamics of the different precursor pools could be used to identify patients at greater risk for systemic inflammatory sequelae following major thermal injury.
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PMID:Bone marrow stem cell and progenitor response to injury. 1189 91

The dendritic cell (DC) is the most potent APC of the immune system, capable of stimulating naive T cells to proliferate and differentiate into effector T cells. Recombinant adenovirus (Adv) readily transduces DCs in vitro allowing directed delivery of transgenes that modify DC function and immune responses. In this study we demonstrate that footpad injection of a recombinant Adv readily targets transduction of myeloid and lymphoid DCs in the draining popliteal lymph node, but not in other lymphoid organs. Popliteal DCs transduced with an empty recombinant Adv undergo maturation, as determined by high MHC class II and CD86 expression. However, transduction with vectors expressing human IL-10 limit DC maturation and associated T cell activation in the draining lymph node. The extent of IL-10 expression is dose dependent; transduction with low particle numbers (10(5)) yields only local expression, while transduction with higher particle numbers (10(7) and 10(10)) leads additionally to IL-10 appearance in the circulation. Furthermore, local DC expression of human IL-10 following in vivo transduction with low particle numbers (10(5)) significantly improves survival following cecal ligation and puncture, suggesting that compartmental modulation of DC function profoundly alters the sepsis-induced immune response.
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PMID:Increased survival in sepsis by in vivo adenovirus-induced expression of IL-10 in dendritic cells. 1190 99

Nitric oxide (NO) produced by NO synthase (NOS) serves as a ubiquitous mediator molecule involved in many physiologic lung functions, including regulation of vascular and bronchial tone, immunocompetence, and neuronal signaling. On the other hand, excessive and inappropriate NO synthesis in inflammation and sepsis has been implicated in vascular abnormalities and cell injury. At least three different NOS isoforms (neuronal/brain [bNOS], inducible [iNOS], and endothelial [eNOS]) have been described, which are all expressed in normal lung tissue. We investigated the cell-specific expression of bNOS, iNOS, and eNOS in perfused control rat lungs and lungs undergoing stimulation with endotoxin in the presence and absence of plasma constituents. Lung immunohistochemistry and quantitative evaluation of staining intensity showed endotoxin-induced increase in iNOS expression in particular in bronchial epithelial cells, cells of the bronchus-associated lymphoid tissue (BALT), alveolar macrophages, and vascular smooth muscle cells in a time- and dose-dependent fashion. In endothelial cells, which did not express iNOS at baseline, newly induced iNOS was found in response to endotoxin. In contrast, expression of eNOS was markedly suppressed under endotoxin challenge, particularly in bronchial epithelium, BALT, and alveolar macrophages but also in vascular smooth muscle cells and endothelial cells. eNOS expression in bronchial smooth muscle cells was not altered. In contrast to iNOS and eNOS, cellular expression of bNOS in epithelial cells, nerve fibers, BALT, and endothelial cells did not change in response to endotoxin. All changes in NOS regulation were found to be independent of plasma constituents. We conclude that endotoxin exerts a profound impact on the cell-specific NOS regulation in a large number of lung cell types. Prominent features include de novo synthesis or up-regulation of iNOS, in contrast to down-regulation of eNOS, which may well contribute to vascular abnormalities, inflammatory sequelae, and loss of physiologic functions in septic lung failure.
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PMID:Cell-specific nitric oxide synthase-isoenzyme expression and regulation in response to endotoxin in intact rat lungs. 1195 Sep

The aim of the study was to investigate the mobilization of T cells in response to a stressful challenge (adrenalin stimulation), and to access T cells resided in the peripheral lymphoid organs in HIV infected patients. Seventeen patients and eight HIV seronegative controls received an adrenalin infusion for 1 h. Blood was sampled before, during and 1 h after adrenalin infusion. Proliferation and mean telomere restriction fragment length (telomeres) of blood mononuclear cells (BMNC) and purified CD8+ and CD4+ cells were investigated at all time points. In patients, the proliferation to pokeweed mitogens (PWM) was lower and decreased more during adrenalin infusion. After adrenalin infusion the proliferation to PWM was restored only in the controls. In all subjects telomeres in CD4+ cells declined during adrenalin infusion. Additionally, the patients had shortened telomeres in their CD8+ cells, and particularly HAART treated patients had shortened telomeres in all cell-subtypes. The finding that patients mobilized cells with an impaired proliferation to PWM during and after adrenalin infusion has possible clinical relevance for HIV infected patients during pathological stressful conditions, such as sepsis, surgery and burns. However, this study did not find a correlation between impaired proliferation and telomeres. It is concluded that physiological stress further aggravates the HIV-induced immune deficiency.
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PMID:Proliferation and telomere length in acutely mobilized blood mononuclear cells in HIV infected patients. 1196 67

Bacterial infection alters whole-body protein homeostasis. Although immune cells are of prime importance for host defense, the effect of sepsis on their protein synthesis rates is poorly documented. We analyzed protein synthesis rates in rat primary lymphoid tissues and circulating lymphocytes after infection. Male Sprague-Dawley rats were studied 1, 2, 6 or 10 d after an intravenous injection of live Escherichia coli. Control healthy rats consumed food ad libitum (d 0) or were pair-fed to infected rats. Protein synthesis was quantified using a flooding dose of L-(4,4,4-(2)H(3))valine. Sepsis induced a delayed increase in total blood leukocytes and a rapid and persistent inversion of the counts. Basal fractional rates of protein synthesis (ks) were 117, 73 and 29%/d in bone marrow, thymus and circulating lymphocytes, respectively. Pair-feeding strongly depressed the absolute protein synthesis rates (ASR) of bone marrow (d 2 and 10) and thymus (d 2-10). The infection per se increased bone marrow, thymus and circulating lymphocyte ks but at various postinfection times. It decreased bone marrow (d 1) and thymus (d 1 and 2) ASR but increased lymphocyte (d 2 and 10) and bone marrow (d 10) ASR. Our results reflect the deleterious effect of anorexia on primary lymphoid tissues. The host defense against bacterial infection exhibited time- and tissue-dependent modifications of protein synthesis, indicating that blood lymphocyte protein data are not representative of the immune system as a whole. Optimization of nutritional supports would be facilitated by including protein synthesis measurements of the immune system.
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PMID:Bacterial infection affects protein synthesis in primary lymphoid tissues and circulating lymphocytes of rats. 1209 87

Breast pathology that is characteristic of patients infected with human immunodeficiency virus (HIV) has not been addressed in the literature. HIV may directly and indirectly affect the glandular, mesenchymal, and intramammary lymphoid tissue in seropositive patients. Likely infections in this setting include tuberculous mastitis and pyogenic abscesses that may lead to fatal septicemia. Benign stromal changes include gynecomastia, adipose tissue deposition as part of the fat maldistribution syndrome, and pseudoangiomatous stromal hyperplasia. Breast carcinoma in HIV-infected patients occurs at a relatively early age, with increased bilateral disease, unusual histology, and early metastatic spread with a poor outcome. However, the link between breast cancer and HIV remains controversial. Kaposi's sarcoma and non-Hodgkin's lymphoma may also be localized to the breast in patients with acquired immunodeficiency syndrome (AIDS). This article reviews benign and malignant breast diseases that are likely to be encountered in patients with HIV/AIDS.
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PMID:Pathology of the breast associated with HIV/AIDS. 1210 Jan 17

The prevalence of different pathogens detected in combination with porcine circovirus type 2 (PCV-2) was studied retrospectively in field cases of postweaning multisystemic wasting syndrome (PMWS) diagnosed at the Iowa State University Veterinary Diagnostic Laboratory, Ames, Iowa, between January 2000, and September 2001. The presence of PCV-2 antigen in lymphoid tissues and/or lung, demonstrated by immunohistochemistry, together with moderate to severe lymphoid depletion and/or granulomatous lymphadenitis, was used as the criteria for the diagnosis of PMWS. A total of 484 cases fulfilled these criteria. Most of the cases (294/369) of PMWS occurred in pigs between the ages of 8 and 18 weeks, with a peak at 10 weeks of age. Porcine reproductive and respiratory syndrome virus was detected in 51.9% of the cases, Mycoplasma hyopneumoniae in 35.5%, bacterial septicemia in 14.0%, bacterial pneumonia in 7.6%, swine influenza virus in 5.4%, and PCV-2 alone in 1.9%. In cases with bacterial septicemia the most frequently isolated pathogen was Streptococcus suis. In cases with bacterial pneumonia, Pasteurella multocida was the most prevalent.
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PMID:Porcine circovirus type 2 (PCV-2) coinfections in US field cases of postweaning multisystemic wasting syndrome (PMWS). 1242 38

The role of lymphocyte apoptosis in septic shock remains a controversial issue. Using Annexin V and flow cytometry analysis on freshly isolated cells, we evaluated circulating lymphocyte apoptosis in 23 septic shock, 25 sepsis without shock, 7 nonseptic critically ill, and 25 control patients. In patients with sepsis, we compared day 1 lymphocyte apoptosis (i.e., within 3 days of the onset of infection) with that observed 5-7 days after (day 6) according to shock state, mortality, and seventy factors. At day 1, patients in septic shock exhibited higher lymphocyte apoptosis than that present in controls (16.5% +/- 3.5% vs. 3% +/- 0.5%, respectively, P = 0.0001). At day 6, patients with sepsis without shock restored undamaged CD4+ T and CD8+ T lymphocyte counts, whereas patients in septic shock increased only CD4+ T cells. Similarly, survivors restored undamaged lymphocyte count at day 6 (+70%, P < 0.001), whereas nonsurvivors did not. Day 6 undamaged lymphocyte count negatively correlated with day 1 SAPS II, day 6 LOD score, mechanical ventilation, and ICU stay duration. We observed no apoptotic effect of septic shock plasma or septic shock circulating mononuclear cells on target lymphoid cell lines. We found no alteration in any death receptors Fas, TRAIL-R1, TRAIL-R2, or in their ligands on circulating blood cells. Catecholamines and interleukin 10 levels significantly increased in patients with septic shock, but did not correlate with apoptosis levels. We conclude that lymphocyte apoptosis is rapidly increased in blood of patients in septic shock and that lymphocyte apoptosis leads to a profound and persistent lymphopenia associated with poor outcome. These results suggest that lymphocyte apoptosis is one of the main components of human septic shock immune dysfunction and could be related more to microcirculatory disturbance than to circulating factors.
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PMID:Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome. 1246 54

Inflammatory lesions in bone marrow, observed during a 2 year period at the College of Veterinary Medicine, University of Minnesota, were reviewed. Of 24 bone marrow specimens with evidence of inflammation, six were classified as acute inflammation, nine as fibrinous inflammation, five as chronic inflammation/hyperplasia, three as granulomatous inflammation and one as nodular lymphoid hyperplasia. Acute inflammation commonly accompanied bacterial sepsis. Two patterns of acute inflammation were identified. One pattern consisted of multifocal microabscesses. The other pattern of acute inflammation consisted of perivascular infiltrates of neutrophils, fibrin, edema, and hemorrhage. The most common disorder associated with fibrinous inflammation was disseminated intravascular coagulopathy. Chronic inflammation was difficult to differentiate from chronic immune stimulation. Discrete granulomas were identified in the marrow of animals with systemic mycotic disease, idiopathic systemic granulomatous disease, and serous atrophy of fat. This study indicates that a broad variety of inflammatory disorders occur in animal bone marrow and that these disorders can be classified based on general categories of inflammation described in other tissues.
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PMID:Inflammatory disorders of bone marro. 1267 95


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