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

Escherichia coli is a major cause of neonatal bacterial sepsis and meningitis. We recently identified a gene, traJ, which contributes to the ability of E. coli K1 to penetrate the blood-brain barrier in the neonatal rat. Because very little is known regarding the most critical step in disease progression, translocation to the gut and dissemination to the lymphoid tissues after a natural route of infection, we assessed the ability of a traJ mutant to cause systemic disease in the neonatal rat. Our studies determined that the traJ mutant is significantly less virulent than the wild type in the neonatal rat due to a decreased ability to disseminate from the mesenteric lymph nodes to the deeper tissues of the liver and spleen and to the blood during the early stages of systemic disease. Histopathologic studies determined that although significantly less or no mutant bacteria were recovered from the spleen and livers of infected neonatal rats, the inflammatory response was considerably greater than that in wild-type-colonized tissues. In vitro studies revealed that macrophages internalize the traJ mutant less frequently than they do the wild type and by a morphologically distinct process. Furthermore, we determined that tissue macrophages and dendritic cells within the liver and spleen are the major cellular targets of E. coli K1 and that TraJ significantly contributes to the predominantly intracellular nature of E. coli K1 within these professional phagocytes exclusively during the early stages of systemic disease. These data indicate that, contrary to earlier indications, E. coli K1 resides within professional phagocytes, and this is essential for the efficient progression of systemic disease.
 ...
PMID:TraJ-dependent Escherichia coli K1 interactions with professional phagocytes are important for early systemic dissemination of infection in the neonatal rat. 1468 29

Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer autoinducer peptide pheromone (competence-stimulating peptide [CSP]) for the control of competence for genetic transformation. Due to previous work linking CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect on virulence. Our data demonstrate a significant increase in the rates of survival of mice, reductions of blood S. pneumoniae counts, and prolonged times to death for mice treated with CSP. In vitro the dose of CSP used in the animal model produced a transitory inhibition of growth. When a mutant with a mutation in the CSP sensor histidine kinase was assayed, no bacteriostatic phenotype was detected in vitro and no change in disease outcome was observed in vivo. The data demonstrate that CSP, which induces in vitro a temporary growth arrest through stimulation of its cognate histidine kinase receptor, is able to block systemic disease in mice. This therapeutic effect is novel, in that the drug-like effect is obtained by stimulation, rather than inhibition, of a bacterial drug target.
 ...
PMID:Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae. 1556 50

A young female with Fisher-Evans' syndrome and a previous melanoma developed acute renal failure with generalized lymphoadenopathy and fever. The appearance of renal lesions is common in the course of several hematological disorders, but is unusual in Fisher-Evans' syndrome. Fisher-Evans' syndrome, defined as Coombs' positive hemolytic anemia and immune thrombocytopenia, is more frequently associated with the other autoimmune diseases, but not with renal involvement. In our case report, having excluded amyloidosis, myeloma, interstitial nephritis and sepsis, the rapid involvement of renal function with enlarged renal size seemed to suggest renal lymphoma. However, the lack of a monoclonal T-lymphocyte population in the renal tissue and peripheral blood, along with a clinical course characterized by a rapid reversibility of acute renal failure made this diagnosis rather an unlikely one. Polyclonal lymphocyte infiltration in a patient with a persistent autoimmune disease made us suspect a hyperimmune reaction. This syndrome is a non-neoplastic proliferation of B-cells involving an exaggeration of lymphocyte transformation. However, the clinical course is progressive and fatal, and can trigger a lymphoproliferative systemic disease. In our patient, two elements led us to suspect it was not a typical hyperimmune syndrome: first, polyclonal lymphocytes had massively infiltrated the kidney and, secondly, the clinical outcome was extremely favorable. Therefore, we were faced with an "atypical" and "singular" hyperimmune reaction with renal involvement, polyclonal proliferation of T-lymphocytes that had exhausted itself over time. Infective or toxic agents or drugs such as cyprofloxacin could have triggered the phenomenon, in the presence of a favorable condition such as Fisher-Evans' syndrome.
 ...
PMID:Acute renal failure in a young woman with Fisher-Evans' syndrome. 1559 44

Kikuchi-Fujimoto disease is a rare feverish disease characterised by lymphadenopathy, the most frequently cervical, exanthem, arthralgias and arthritis. It affects especially young women. Patients have high erythrocyte sedimentation rate (ES) and leucopenia, antibodies are missing. Course of the disease is usually very benign and can subside spontaneously. However, clinical picture is usually very dramatic and can suggest infectious, autoimmune or malign systemic disease; also association with some of autoimmune diseases was described. Its occurrence is sporadic in all the world, the most of cases were seen in Asia, in the Czech Republic it has not been yet described. Therapy consists in antibiotics administration followed with corticoid therapy and usually can restore patients to perfect health. However, exacerbations have also been described. We describe a case of a 60 year old man, a past top sportsman, who has never been seriously ill except sport traumas and prosthesis implantation for coxarthritis reasons. The last two years he has suffered from exanthem and leucopenia of an unclear origin. In May 2002 he become feverish and arthritis, lymphadenopathy, splenomegalia and exanthem progression, high ES rate and high serum level of C-reactive protein (CRP) appeared in him. His condition was first evaluated as septic condition (founded staphylococci in two blood cultures), however, cause of potential sepsis has not been identified. The patient was treated with antibiotics with improvement of his total health condition after second treatment regiment. A neck node biopsy was done because of suspicion on lymphoprolipherative disease and histiocytic necrotizing lymphadenitis of Kikuchi type was found. Autoantibodies assessment was completely negative. After antibiotic and corticoid therapies his clinical condition quite quickly standardized and ES rate and serum CPR level decreased. 4 month after lowering the dose of prednisolon a temporary exacerbation of the disease appeared and again disappeared after increasing the dose of corticoid.
 ...
PMID:[Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis). Case study and a literature review]. 1563 36

The clinical presentation of acute pancreatitis varies significantly from mild self-limiting discomfort to a severe life-threatening condition. Once the disease process is initiated, the severity of the disease is largely determined by a complex network of activated inflammatory mediators such as cytokines, proteolytic enzymes, reactive oxygen species, and many more which render the local injury to a systemic disease with multiple organ dysfunction, sepsis, and considerable mortality. Remarkable progress in diagnostic modalities, intensive care technologies, and organ preserving surgical techniques have decreased mortality of severe acute pancreatitis during the past decades. However, the treatment of acute pancreatitis still remains largely supportive and no specific approach exists to prevent evolving complications. A large body of clinical and experimental evidence suggests that cytokines are key factors in the pathomechanism of local and systemic complications of acute pancreatitis. Targeting cytokine activity as therapeutic approach to acute pancreatitis is a challenging concept and the results of modulating activation of TNF-alpha, IL-1beta, IL-2, IL-10, PAF and various chemokines has indeed been promising in the experimental setting even if tested under therapeutic conditions. However, experience from a limited number of clinical trials on anti cytokine strategies in acute pancreatitis has remarkably emphasized that translating successful experimental observations into reproducible clinical associations seems to be difficult.
 ...
PMID:Anti-cytokine strategies in acute pancreatitis: pathophysiological insights and clinical implications. 1635 48

To save their patients from dialysis and transplantation, neurologists need simply remain alert to the possibility of renal failure, particularly in the context of systemic disease, diabetes, sepsis and drugs. Of the numerous territories shared by our respective specialities, we outline a pragmatic approach to the diagnosis and treatment of the vasculitides, underpinned by knowing which questions to ask, equally importantly when to ask them, and in the art of obtaining a tissue diagnosis. We consider the current evolving trial evidence that directs the usage of a growing arsenal of therapies in the induction and maintenance stages of vasculitis treatment, and extend this consideration to Lupus and Sjogren's.
 ...
PMID:Notes on the kidney and its diseases for the neurologist. 1743 83

Theodore ("TR" or "Teddy") Roosevelt (1858-1919), who served as the twenty-sixth President of the United States from 1901 to 1909, was an "Icon of the American Century." Characterized by immense energy, numerous skills, zest for life, and enduring accomplishments, he made an impressive ascent to political importance. However, he also experienced serious, chronic, oral and systemic health problems. In spite of these significant health obstacles, he chose "the strenuous life," and cultivated a lifetime of joy, laughter and humor. TR was known as "the first president that smiled," and he was typically photographed and illustrated grinning from ear to ear. His flashing white teeth, wide smile, and engaging openness became welcome symbols of national and international acceptance. When Roosevelt died, suddenly and prematurely at the age of 60, dentists and physicians of that time began to investigate the probable medical causes of his untimely demise. The "focal infection hysteria" of the early 1900s convinced some of these health professionals that "a bad tooth", that previously had been endodontically treated, was the probable cause of death. Much of the early 20th century evidence-supporting the notion that oral sepsis was a "cause" of local or systemic disease-has now been proven, on closer inspection, to be anecdotal or of questionable scientific merit. Nevertheless, during those early days, it was common practice to extract all endodontically or periodontally involved teeth to eliminate any possible foci of infection that many clinicians believed could cause disease.
 ...
PMID:Theodore Roosevelt's "presidential smile" and questionable dental health. 1784 49

Striking individual differences in severity of group A streptococcal (GAS) sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL) on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%-30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases.
 ...
PMID:An unbiased systems genetics approach to mapping genetic loci modulating susceptibility to severe streptococcal sepsis. 1842 76

The ScpC protease of Streptococcus pyogenes degrades interleukin-8 (IL-8), a chemokine that mediates neutrophil transmigration and activation. The ability to degrade IL-8 differs dramatically among clinical isolates of S. pyogenes. Bacteria expressing ScpC overcome immune clearance by preventing the recruitment of neutrophils in soft tissue infection of mice. To study the role of ScpC in streptococcal sepsis, we generated an ScpC mutant that did not degrade IL-8 and thus failed to prevent the recruitment of immune cells as well as to cause disease after soft tissue infection. In a murine model of sepsis, challenge with the ScpC mutant resulted in more severe systemic disease with higher bacteremia levels and mortality than did challenge with the wild-type strain. As expected, the blood level of KC, the murine IL-8 homologue, increased in mice infected with the ScpC mutant. However, the elevated KC levels did not influence neutrophil numbers in blood, as it did in soft tissue, indicating that additional factors contributed to neutrophil transmigration in blood. In addition, the absence of ScpC increased tumor necrosis factor, IL-6, and C5a levels in blood, which contributed to disease severity. Thus, the ScpC mutant triggers high neutrophil infiltration but not lethal outcome after soft tissue infection, whereas intravenous infection leads to highly aggressive systemic disease.
 ...
PMID:The ScpC protease of Streptococcus pyogenes affects the outcome of sepsis in a murine model. 1857

Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.
 ...
PMID:Esophageal cancer associated with chronic mucocutaneous candidiasis. Could chronic candidiasis lead to esophageal cancer? 1879 15


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