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)

Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.
 ...
PMID:The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes. 1004 17

Twenty clinical isolates of Staphylococcus aureus were examined to elucidate the virulence factors which are directly related to lethality in a mouse septic model. Heat or formalin treatment of the organism abolished the lethal activity of the live organism during challenge intravenously administered via the tail vein. Nevertheless, injection of ten times concentrated culture supernatant fluid (SUP) showed lethal activity in the mouse. However, there was no lethality when SUP was heated at 60 degrees C for 15 min. To examine variations of SUP lethality among strains, we collected 20 strains of S. aureus from four different hospitals. Then, we compared several factors for SUP lethality, which were the extracellular toxins and enzymes, such as toxic shock syndrome toxin 1, enterotoxin A, B, D, and hemolysins (alpha,beta,gamma), and also cytotoxic activity to human polymorphonuclear leukocytes and Vero cells. No difference was found among these factors except cytotoxic activity to Vero cells. Furthermore, we compared two strains in a mouse septic model according to the grade of bacteremia and lethal events. We found that mortality was higher with challenge by the strain whose SUP was lethal in comparison to the strain whose SUP was not lethal, even though the viable bacteria counts in the septic blood in both strains were not significantly different. This strongly supports the possibility that extracellular products, not the cell wall components, of S. aureus play the key role in the lethal event in this mouse septic model. In addition, among the extracellular products, those which have cytotoxic activity to Vero cells may contribute to the lethality in sepsis caused by S. aureus in this murine model.
 ...
PMID:Possible virulence factors of Staphylococcus aureus in a mouse septic model. 1007 10

The pyrogenic exotoxins of Group A Streptococci and enterotoxins of Staphylococcus aureus constitute a family of related toxins that acts as "superantigens" because of their ability to stimulate large numbers of T-cell subsets. These toxins have been implicated in gastrointestinal food poisoning, toxic shock syndromes, Gram-positive sepsis, and, possibly, septic shock. There is increasing evidence that Gram-positive infections frequently coexist in septic shock and that bacterial superantigens play a major role.
 ...
PMID:Structure and function of streptococcal and staphylococcal superantigens in septic shock. 1034 Jan 73

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.
 ...
PMID:[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure]. 1036 25

Group A streptococcal infections, ranging from necrotizing fasciitis and myositis to toxic shock syndrome, have increased over the last 10 years. We developed the first primate model of necrotizing fasciitis and myositis. Thirteen baboons were inoculated intramuscularly with group A streptococci (GAS). Eleven animals survived for > or = 11 days before sacrifice, and two animals died within 2 days. The site of inoculation of the survivors exhibited an intense neutrophilic influx (stage I), followed by a lymphoplasmacytic influx (stages II and III). This was accompanied by the appearance of markers of an acute and then a chronic systemic inflammatory response. In contrast, the site of inoculation of the two nonsurvivors exhibited intravascular aggregates of neutrophils at its margin with no influx of neutrophils and with extensive bacterial colonization. We conclude that GAS inoculation induces a local and systemic acute neutrophilia followed by a chronic lymphoplasmacytic response; failure, initially, of neutrophilic influx into the site of inoculation predisposes to systemic GAS sepsis and death; and this three-stage primate model approximates the human disease.
 ...
PMID:Staging of the baboon response to group A streptococci administered intramuscularly: a descriptive study of the clinical symptoms and clinical chemical response patterns. 1091 29

The aim of this study was to assess the importance of complement receptor 1 (CR1, CD35) in Staphylococcus aureus arthritis and sepsis. The murine model of haematogenously acquired septic arthritis was used, injecting toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus LS-1 intravenously. CR1 was blocked using immunoglobulin G (IgG) rat antimouse CR1 monoclonal antibody (MoAb) (8C12). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of blocking CR1 was assessed on the phagocytic activity of leucocytes and on T-cell dependent and independent inflammation. Seven days after inoculation with bacteria, 96% of CR1 MoAb-treated mice had clinical symptoms of arthritis compared with 58% of the control animals (P < 0.01). The severity of arthritis, expressed as mean arthritic index, was 2.9 +/- 0.5 and 1.4 +/- 0.5, respectively (P = 0.004). Fifteen days after bacterial inoculation, all CR1 MoAb-treated mice had severe arthritis (mean arthritic index 6.3 +/- 0.6), while only 77% of controls were affected (mean arthritic index 2.9 +/- 0.6; P = 0.002). The potential explanation of these findings is that treatment with CR1 MoAb significantly increases the polymorphonuclear cell-dependent inflammatory response as a result of enhanced vasodilatation in treated animals. We conclude that treatment with CR1 MoAb leads to amelioration of sepsis-induced mortality during S. aureus infection, possibly as a result of the increased phagocytic activity of peripheral phagocytes.
 ...
PMID:Interaction with complement receptor 1 (CD35) leads to amelioration of sepsis-triggered mortality but aggravation of arthritis during Staphylococcus aureus infection. 1044 33

A 5-year-old boy presented with primary varicella zoster virus infection, group A streptococcal sepsis, toxic shock, and multisite osteonecrosis. An association between osteonecrosis and group A streptococcal sepsis has not been previously reported. Clinical recognition with supportive radiologic and pathologic findings are presented. Therapeutic guidelines are suggested.
 ...
PMID:Varicella complicated by group A streptococcal sepsis and osteonecrosis. 1050 43

Streptococcal toxic shock syndrome (STSS) is caused by infection with a toxicogenic strain of Streptococcus pyogenes. Clinical manifestations may be those of a mild illness, characterized by malaise, fever, and muscle pain, to severe sepsis and multisystem organ failure. The syndrome may be associated with several invasive infections including necrotizing fasciitis. Treatment is primarily surgical debridement of infected tissue with supportive care, antibiotics, and hemodynamic monitoring. Intravenous immunoglobulin (IVIG) is reported to have beneficial effects in the management of STSS associated with necrotizing fasciitis. The agent was successful in conjunction with surgical excision and antibiotics in a patient with necrotizing fasciitis, toxic shock, and multisystem organ failure. On the basis of this experience and a thorough literature review, we concur that IVIG may be a useful adjunct in the treatment of STSS associated with necrotizing fasciitis.
 ...
PMID:Intravenous immunoglobulin as adjunctive treatment for streptococcal toxic shock syndrome associated with necrotizing fasciitis: case report and review. 1061 17

To investigate the role of B cells in experimental, superantigen-mediated Staphylococcus aureus arthritis and sepsis, we used gene-targeted B-cell-deficient mice. The mice were inoculated intravenously with a toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus strain. The B-cell-deficient and thus agamma-globulinemic mice showed striking similarities to the wild-type control animals with respect to the development of arthritis, the mortality rate, and the rate of bacterial clearance. Surprisingly, we found that the levels of gamma interferon in serum were significantly lower (P < 0. 0001) in B-cell-deficient mice than in the controls, possibly due to impaired superantigen presentation and a diminished expression of costimulatory molecules. In contrast, the levels of interleukin-4 (IL-4), IL-6, and IL-10 in serum were equal in both groups. Our findings demonstrate that neither mature B cells nor their products significantly contribute to the course of S. aureus-induced septic arthritis.
 ...
PMID:Are B lymphocytes of importance in severe Staphylococcus aureus infections? 1076 27

Fluorescence in situ hybridisation (FISH) targeted to ribosomal RNA is well established for studies in environmental microbiology. Initial applications of this technique in the field of medical microbiology showed that FISH is also a suitable means for the rapid, reliable and cultivation-independent identification of bacterial pathogens. In particular, for infectious diseases that follow a fulminant live-threatening course, such as sepsis or necrotising fasciitis (NF), a fast and reliable detection technique is of great importance. This study describes the development of an rRNA-targeted oligonucleotide set covering more than 95% of the pathogens associated with NF. These probes were tested with a broad collection of target and non-target organisms and found to be highly specific. Subsequently, the FISH approach was applied for the direct detection of bacterial pathogens in clinical samples. Two cases of NF and one case of streptococcal toxic shock syndrome (STSS) were analysed. FISH correctly identified almost all pathogens present in the samples examined within 2-3 h. However, Proteus mirabilis, which was identified in one sample by conventional methods was detected as a rod-shaped bacteria but could not be identified by FISH, since no specific probe was available for this particular organism. In contrast, identification of pathogens in these samples by conventional laboratory methods took 48-72 h. Furthermore, in one patient with pre-sampling antimicrobial therapy bacteria could not be grown from any of the samples. FISH unequivocally revealed the presence of Streptococcus pyogenes in affected tissue samples from this patient. In an experimental setting we demonstrated that FISH readily identifies S. pyogenes cells rendered non-cultivable by antibiotic treatment.
 ...
PMID:Culture independent and rapid identification of bacterial pathogens in necrotising fasciitis and streptococcal toxic shock syndrome by fluorescence in situ hybridisation. 1091 53


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