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)

A profoundly immunosuppressed HIV-infected man developed sepsis syndrome with multi-organ failure. A septic screen failed to identify a bacterial or fungal cause and despite empirical treatment for these pathogens the patient remained unwell. Investigations revealed disseminated tuberculosis. With specific anti-tuberculosis therapy the patient rapidly recovered. Although most cases of sepsis syndrome in HIV-infected patients are due to bacteria, tuberculosis should be added to the differential diagnosis of this presentation.
Int J STD AIDS 2006 Aug
PMID:Septic shock and multi-organ failure in HIV infection-'sepsis tuberculosa gravissima'. 1692 7

X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5'-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand.
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PMID:Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations. 1695 17

Intestinal epithelial cells are subject to repetitive deformation during peristalsis and villous motility, whereas the mucosa atrophies during sepsis or ileus when such stimuli are abnormal. Such repetitive deformation stimulates intestinal epithelial proliferation via focal adhesion kinase (FAK) and extracellular signal-regulated kinases (ERK). However, the upstream mediators of these effects are unknown. We investigated whether Src and Rac1 mediate deformation-induced FAK and ERK phosphorylation and proliferation in human Caco-2 and rat IEC-6 intestinal epithelial cells. Cells cultured on collagen-I were subjected to an average 10% cyclic strain at 10 cycles/min. Cyclic strain activated Rac1 and induced Rac1 translocation to cell membranes. Mechanical strain also induced rapid sustained phosphorylation of c-Src at Tyr(418), Rac1 at Ser(71), FAK at Tyr(397) and Tyr(576), and ERK1/2 at Thr(202)/Tyr(204). The mitogenic effect of cyclic strain was blocked by inhibition of Src (PP2 or short interfering RNA) or Rac1 (NSC23766). Src or Rac1 inhibition also prevented strain-induced FAK phosphorylation at Tyr(576) and ERK phosphorylation but not FAK phosphorylation at Tyr(397). Reducing FAK using short interfering RNA blocked strain-induced mitogenicity and attenuated ERK phosphorylation but not Src or Rac1 phosphorylation. Src inhibition blocked strain-induced Rac1 phosphorylation, but Rac inhibition did not alter Src phosphorylation. Transfection of a two-tyrosine phosphorylation-deficient FAK mutant Y576F/Y577F prevented activation of cotransfected myc-ERK2 by cyclic strain. Repetitive deformation induced by peristalsis or villus motility may support the gut mucosa by a pathway involving Src, Rac1, FAK, and ERK. This pathway may present important targets for interventions to prevent mucosal atrophy during prolonged ileus or fasting.
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PMID:Repetitive deformation activates focal adhesion kinase and ERK mitogenic signals in human Caco-2 intestinal epithelial cells through Src and Rac1. 1708 51

Signal transduction mechanism in the regulation of high mobility group box protein 1 (HMGB1) has not yet been well elucidated. Our data showed for the first time that Janus kinase-signal transduction and activator of transcription (JAK/STAT) pathway played a major role in the regulation of expression and inflammatory effect of HMGB1. The study was carried out in the following sequence. Firstly, the role of JAK/STAT pathway in the regulation of expression of HMGB1 was examined. After stimulation with 75 ng/mL LPS in vitro, significant increases in HMGB1 expression and prompt activation of JAK/STAT pathway were demonstrated in cultured macrophages. On the other hand, administration of AG490 (specific inhibitor for JAK2), fludarabine (specific inhibitor for STAT1) or rapamycin (specific inhibitor for STAT3) markedly suppressed HMGB1 expression. Secondly, the role of JAK/STAT pathway in the regulation of TNF-alpha expression induced by HMGB1 was examined. When macrophages were stimulated with 10 microg/mL HMGB1 in vitro, significant increases in TNF-alpha expression and prompt activation of JAK/STAT pathway were demonstrated, whereas inhibitors of JAK/STAT pathway significantly suppressed TNF-alpha expression. Taken together, our data strongly indicated that expression and inflammatory effect of HMGB1 could be mediated by JAK/STAT pathway and suggested a possible clinical strategy to control an inflammatory effect of HMGB1 in sepsis.
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PMID:Role of Janus kinase/signal transducer and activator of transcription pathway in regulation of expression and inflammation-promoting activity of high mobility group box protein 1 in rat peritoneal macrophages. 1717 81

Mucosal repair is a complex event that immediately follows acute injury induced by ischemia and noxious luminal contents such as bile. In the small intestine, villous contraction is the initial phase of repair and is initiated by myofibroblasts that reside immediately beneath the epithelial basement membrane. Subsequent events include crawling of healthy epithelium adjacent to the wound, referred to as restitution. This is a highly regulated event involving signaling via basement membrane integrins by molecules such as focal adhesion kinase and growth factors. Interestingly, however, ex vivo studies of mammalian small intestine have revealed the importance of closure of the interepithelial tight junctions and the paracellular space. The critical role of tight junction closure is underscored by the prominent contribution of the paracellular space to measures of barrier function such as transepithelial electrical resistance. Additional roles are played by subepithelial cell populations, including neutrophils, related to their role in innate immunity. The net result of reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian tissues to prevent the onset of sepsis.
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PMID:Restoration of barrier function in injured intestinal mucosa. 1742 41

A 30-year-old HIV-infected intravenous drug user presented with sepsis, acute renal failure, oedema, proteinuria and iron deficiency anaemia. After extensive investigation, a diagnosis of reactive systemic AA (amyloid, serum amyloid A protein) amyloidosis was made on the basis of renal, gastric and duodenal biopsies.
Int J STD AIDS 2007 May
PMID:Renal and gastrointestinal amyloidosis in an HIV-infected injection drug user. 1752 3

Kaposi's sarcoma (KS) usually presents with typical skin lesions. We report two cases that presented with illnesses suggesting major sepsis, but were found to have disseminated KS at postmortem with little in the way of cutaneous involvement.
Int J STD AIDS 2007 Nov
PMID:Septic illness and Kaposi's sarcoma. 1800 17

Endothelial cells control the passage of plasma constituents and circulating cells from blood to the underlying tissues. This specialized function is lost or impaired in several pathological conditions - including inflammation, sepsis, ischemia and diabetes - which leads to severe, and sometimes fatal, organ dysfunction. Endothelial permeability is regulated in part by the dynamic opening and closure of cell-cell adherens junctions (AJs). In endothelial cells, AJs are largely composed of vascular endothelial cadherin (VE-cadherin), an endothelium-specific member of the cadherin family of adhesion proteins that binds, via its cytoplasmic domain, to several protein partners, including p120, beta-catenin and plakoglobin. Endogenous pathways that increase vascular permeability affect the function and organization of VE-cadherin and other proteins at AJs in diverse ways. For instance, several factors, including vascular endothelial growth factor (VEGF), induce the tyrosine phosphorylation of VE-cadherin, which accompanies an increase in vascular permeability and leukocyte diapedesis; in addition, the internalization and cleavage of VE-cadherin can cause AJs to be dismantled. From the knowledge of how AJ organization can be modulated, it is possible to formulate several pharmacological strategies to control the barrier function of the endothelium. We discuss the possible use of inhibitors of SRC and other kinases, of agents that increase cAMP levels, and of inhibitors of lytic enzymes as pharmacological tools for decreasing endothelial permeability.
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PMID:The role of adherens junctions and VE-cadherin in the control of vascular permeability. 1856 24

Tigecycline belong to glycylcycline antibiotics. This new group of antibiotics was derived from lipophilic tetracyclines but differs from them by higher effectivity, lower affinity to bacterial resistance mechanisms, and very long half-time. Tigecycline is registered for treatment two groups of infections: skin and soft tissue infections and complicated intra-abdominal infections. Nevertheless, its therapeutic use probably can be enlarged to pneumonia, STD, infections caused by multi-resistant Helicobacter pylori, subacute and chronic infections associated with biofilm formation, and serious infections caused by intracellular pathogens (serious brucellosis, Q-fever, rickettsial infections). By contrast, tigecycline seems not appropriate for treatment sepsis and similar acute life-threatening bacterial diseases.
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PMID:[Tigecycline: Its position between other antibiotics, features, clinical usage]. 1939 24

Respiratory failure is a major cause of mortality during septic shock and is due in part to decreased ventilatory muscle contraction. Ventilatory muscles have high energy demands; fatty acid (FA) oxidation is an important source of ATP. FA oxidation is regulated by nuclear hormone receptors; studies have shown that the expression of these receptors is decreased in liver, heart, and kidney during sepsis. Here, we demonstrate that lipopolysaccharide (LPS) decreases FA oxidation and the expression of lipoprotein lipase (LPL), FA transport protein 1 (FATP-1), CD36, carnitine palmitoyltransferase beta, medium chain acyl-CoA dehydrogenase (MCAD), and acyl-CoA synthetase, key proteins required for FA uptake and oxidation, in the diaphragm. LPS also decreased mRNA levels of PPARalpha and beta/delta, RXRalpha, beta, and gamma, thyroid hormone receptor alpha and beta, and estrogen related receptor alpha (ERRalpha) and their coactivators PGC-1alpha, PGC-1beta, SRC1, SRC2, Lipin 1, and CBP. Zymosan resulted in similar changes in the diaphragm. Finally, in PPARalpha deficient mice, baseline CPT-1beta and FATP-1 levels were markedly decreased and were not further reduced by LPS suggesting that a decrease in the PPARalpha signaling pathway plays an important role in inducing some of these changes. The decrease in FA oxidation in the diaphragm may be detrimental, leading to decreased diaphragm contraction and an increased risk of respiratory failure during sepsis.
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PMID:Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm. 1944 62


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