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)

The tonsils are portal of entry and a site of multiplication and persistence for a variety of pathogens, including Streptococcus suis (S. suis), which is a common cause of meningitis, septicemia and arthritis in pigs. Understanding the early changes that occur in the first barrier of the tonsil, i.e. the crypt epithelium, in response to S. suis infection is critical in clarifying the pathogenesis of this disease and for the future development of efficient methods of mucosal vaccination. In this study, we investigated the early changes, from 18 to 72 h, that occur in leucocyte subpopulations of the crypt epithelium of the palatine tonsils of 3-week-old pigs in response to S. suis type 2 infection. Monoclonal antibodies against leucocyte markers CD3, CD4, CD8, gammadelta T cell receptor, lambda-immunoglobulin light-chain, myeloid cells, and major histocompatibility complex class II molecule (MHC-II) were used in an avidin-biotin immunoperoxidase technique. An increase in the number of lambda-immunoglobulin light-chain positive cells (B cell subset) was noticed in crypts of S. suis-infected animals from 18 h after infection onwards. This increase was significant at 18 and 48 h after infection. The number of CD4 and CD8 cells was greater from 18 h onwards, with a significant increase at 24 and 72 h post-infection. No significant difference in numbers of CD3, gammadelta T cell receptor and MHC-II positive cells was detected in the crypts of infected animals compared to controls. Macrophages, neutrophils and crypt epithelial cells stained positively with the myeloid marker, and the area of crypt epithelium positive for this marker was increased in the crypts of infected animals, with a significant difference detected at 24 and 72 h after infection. These results suggest that there is participation of the innate immunity in the early phase of S. suis infection, represented by neutrophils, macrophages and likely epithelial cells, and that there is a potential for the initiation of both humoral and cellular responses against S. suis within the crypt epithelium of the palatine tonsil.
 ...
PMID:Changes in the leucocyte subpopulations of the palatine tonsillar crypt epithelium of pigs in response to Streptococcus suis type 2 infection. 1205 42

Monocytes from many critically ill patients show a low level of major histocompatibility complex type II (MHC II) expression. This phenomenon is believed to play a role in these patients' increased susceptibility to secondary infections. In the present study, we show that the level of monocyte human leukocyte antigen (HLA)-DR expression inversely correlates with the degree of severity of the sepsis syndrome. The defect of the monocyte HLA-DR expression resides in an intracellular sequestration of the MHC II molecules, a posttranslational effect. No significant decrease in the rate of transcription of HLA-DR, or its major transcriptional inducer, Class II transactivator, was noted. The levels of HLA-DR protein produced by monocytes from patients with septic shock were comparable to those from healthy volunteers. Plasma from patients with septic shock induced significant HLA-DR endocytosis resulting in decreased surface HLA-DR expression of normal donor monocytes. This effect was partially blocked by anti-interleukin (IL)-10 monoclonal antibody, but not by antagonists to transforming growth factor-beta1, prostaglandins, or beta-adrenergic agonists. Altogether, these data suggest that HLA-DR molecules are re-endocytosed and retained intracellularly in monocytes from patients with septic shock, and that this phenomenon is partially mediated by IL-10. IL-10 may represent a future target for immunomodulating patients with the sepsis syndrome or critically ill patients at risk of developing infections.
 ...
PMID:Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. 1245 Sep 29

VDJ rearrangement at the teleost TCRbeta locus leads to a highly diverse repertoire of junctions for each VbetaJbeta combination. From a rainbow trout 5' RACE library of TCRbeta transcripts, 47 clones encompassing a full Vbeta-Dbeta-Jbeta-Cbeta sequence were selected and analyzed. A similarity analysis of the sequences evidenced 10 Vbeta families, of which 6 were not previously described. Immunoscope and sequence analysis of the Vbeta-Dbeta-Jbeta junctions of the new families confirmed that they create a polyclonal and diverse repertoire. Multiple alignments showed that rainbow trout Vbetas possess most of the conserved residues typical of Vbeta segments. However, this study revealed a high complementarity-determining region 2 (CDR2) and CDR1 length diversity among rainbow trout Vbeta families, suggesting that the spatial orientation of the TCR could fluctuate in the TCR/peptide/MHC complex, depending on the Vbeta expressed. Among the new Vbeta families, Vbeta6 displayed the strongest deviance from typical hypervariable CDR1 and CDR2 loops, with an unusually short CDR2. Moreover, the Vbeta6 sequence is overall divergent from typical Vbeta sequence, raising the question of its functional relevance. Immunoscope experiments identified a Vbeta6-Jbeta3 junction, which was amplified during the response against viral hemorrhagic septicemia virus, a fish rhabdovirus. Vbeta6 seems therefore to be expressed functionally in a selected TCR. However, the shorter Vbeta6 transcripts produced through an alternative splicing lack the C', C", D, and E strands of the Vbeta domain and are probably nonfunctional.
 ...
PMID:Primary structure and complementarity-determining region (CDR) 3 spectratyping of rainbow trout TCRbeta transcripts identify ten Vbeta families with Vbeta6 displaying unusual CDR2 and differently spliced forms. 1244 30

The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied -308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.
 ...
PMID:Is there a future for TNF promoter polymorphisms? 1497 48

In the last few years, many cytokine and other immune related genes have been identified in different teleost species, thus allowing their study at a molecular level. However, very little is known about their effect on fish antiviral responses. In the current work, we have studied the effect of viral haemorrhagic septicemia virus (VHSV) infection on the expression of different immune genes in rainbow trout (Oncorhynchus mykiss) through semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). We have studied the effect of the viral infection on the expression of different cytokines such as interleukin 1beta (IL-1beta) and transforming growth factor beta (TGF-beta), the CXC chemokine IL-8, and other immune genes such as inducible nitric oxide synthase (iNOS) and the class II major histocompatibility complex (MHC II). The virus induced an increased transcription of IL-1beta in the spleen, and to a lesser extent in the head kidney and liver at early times post-infection. IL-8 transcription was also significantly induced with the virus in the spleen at early times post-infection. TGF-beta transcription was significantly induced in VHSV infection in the spleen and liver. In the spleen, a significant induction of TGF-beta at day 1 post-infection was observed. A further significant increase occurred in the spleen and liver at day 7 post-infection. No effect of the virus on MHC II expression was ever observed while iNOS was induced in the spleen, head kidney and liver of VHSV-infected fish mostly at day 7 post-infection. These results constitute a first step towards the understanding of which molecules may have a role in antiviral defence in fish.
 ...
PMID:Expression of genes related to the early immune response in rainbow trout (Oncorhynchus mykiss) after viral haemorrhagic septicemia virus (VHSV) infection. 1578 92

The severity of infection with Streptococcus pyogenes is strongly influenced by the host's genetics. This observation extends to the murine model of streptococcal infection, where the background of the mouse strain determines the infection outcome (BALB/c are resistant, whereas C3H/HeN are susceptible). To determine the extent to which the MHC complex (H2) contributed to diseases susceptibility, the response to S. pyogenes of congenic BALB mice from a resistant background (BALB/c), but carrying the H2(k) region of susceptible C3H/HeN mice (BALB/k), was examined. BALB/k were as susceptible as the H2 donor strain (C3H/HeN). Linkage analysis performed in F(2) backcross ([BALB/c x C3H/HeN] x BALB/c) mice confirmed the presence of a susceptibility locus within the H2 region on proximal chromosome 17. The possibility that modulation of T cell responses to streptococcal superantigens (GAS-SAgs) by different H2 haplotypes may influence disease severity was examined. BALB/k exhibited a significantly stronger response at the level of cell proliferation and cytokine production to GAS-SAgs than did BALB/c mice. However, the fact that T cell-deficient SCID-C3H/HeN mice also exhibited a susceptible phenotype suggests a more important contribution of innate effector cells to disease susceptibility. Lower transcriptional levels of certain inflammation-related regulatory genes located on chromosome 17 were detected in macrophages from susceptible than in those from resistant mice in response to infection. These results suggest that susceptibility to S. pyogenes may be associated with an altered transcription of specific genes that may compromise the endogenous regulatory processes controlling the inflammatory cascade and favor the progression to sepsis.
 ...
PMID:The role of the MHC on resistance to group a streptococci in mice. 1614 32

The mechanisms governing the impairment of bacterial clearance and immune function in sepsis are not known. Adenosine levels are elevated during tissue hypoxia and damage associated with sepsis. Adenosine has strong immunosuppressive effects, many of which are mediated by A(2A) receptors (A(2A)R) expressed on immune cells. We examined whether A(2A)R are involved in the regulation of immune function in cecal ligation and puncture-induced murine polymicrobial sepsis by genetically or pharmacologically inactivating A(2A)R. A(2A)R knockout (KO) mice were protected from the lethal effect of sepsis and had improved bacterial clearance compared with wild-type animals. cDNA microarray analysis and flow cytometry revealed increased MHC II expression in A(2A)-inactivated mice, suggesting improved Ag presentation as a mechanism of protection. Apoptosis was attenuated in the spleen of A(2A) KO mice indicating preserved lymphocyte function. Levels of the immunosuppressive cytokines IL-10 and IL-6 were markedly lower following A(2A)R blockade. Similar to observations with A(2A)R KO mice, an A(2A)R antagonist increased survival even when administered in a delayed fashion. These studies demonstrate that A(2A)R blockade may be useful in the treatment of infection and sepsis.
 ...
PMID:Adenosine A2A receptor inactivation increases survival in polymicrobial sepsis. 1662 31

Sepsis, an infection-induced inflammatory syndrome, is a leading and increasing cause of mortality worldwide. Animal and human observational studies suggest statins may prevent the morbidity and mortality associated with the sepsis syndrome. In this Review, we describe the demonstrated mechanisms through which statins modulate the inflammatory response associated with sepsis. These mechanisms include effects on cell signalling with consequent changes at the transcriptional level, the induction of haem oxygenase, the direct alteration of leucocyte-endothelial cell interaction, and the reduced expression of MHC II. Since statins do not target individual inflammatory mediators, but possibly reduce the overall magnitude of the systemic response, this effect could prove an important distinguishing feature modulating the host response to septic insults. This work establishes the biological plausibility needed for future trials of statins in critical illness.
 ...
PMID:Statins and sepsis: multiple modifications at multiple levels. 1796 54

The spleen is a lymphatic organ that plays a fundamental role in protecting the body from invading pathogens. Being an organ that is interposed in the blood stream, it also stands as the body's largest blood filter that furthermore brings contribution to detecting senescent, mechanically damaged and aberrant cells. The spleen combines the innate and adaptive immune system in a unique way, releasing an immediate innate reaction to microbial penetration, but also an adaptive immune response that involves the interaction of cells that recognize a particular antigen, implicating MHC molecules presented by antigen-presenting cells. Clinical manifestations of some hematologic conditions can be controlled by splenectomy. The use of this procedure, although, has been restricted due to many observations of overwhelming post-splenectomy bacterial infections in splenectomized patients. After splenectomy, the mechanisms that play a fundamental role in bacterial clearance are altered, leading to gram-positive, but also gram-negative sepsis. Subtotal splenectomy is, therefore, a logical alternative that controls the manifestations of hematologic diseases while maintaining splenic function.
 ...
PMID:[Role of the spleen in immunity. Immunologic consequences of splenectomy]. 1871 73

Chitinase 3-Like-1 (CHI3L1) is a secreted 40 kDa glycoprotein that is upregulated in a number of human cancers and in non-neoplastic disease states characterized by chronic inflammation and tissue remodeling. Increased serum levels of CHI3L1 parallel disease severity, poorer prognosis, and shorter survival in many human neoplasias, including cancers of the breast, colon, prostate, ovaries, brain, thyroid, lung, and liver. Increased serum CHI3L1 also correlates with disease severity in rheumatoid arthritis, osteoarthritis, liver fibrosis, inflammatory bowel disease, and bacterial septicemia. CHI3L1 is a rheumatoid arthritis (RA) autoantigen, and MHC complexes containing specific CHI3L1 peptides have been found in RA patients; however, intranasal introduction of these same CHI3L1 peptides can induce tolerance towards them. CHI3L1 is a nonhydrolytic member of the human chitinase family that binds chitin tightly and heparin at lower affinity. Interactions with type I collagen, CHI3L1's only known protein-binding partner, helps regulate collagen fibril formation. The principal sources of CHI3L1 are activated macrophages and chondrocytes, neutrophils, and some tissue and tumor cells. CHI3L1 can act as a fibroblast mitogen and can activate several signaling pathways, however, no cell surface-binding partner for CHI3L1 has been identified. The ability of CHI3L1 to bind both proteins and carbohydrates allows potential interactions with a variety of cell-surface and extracellular-matrix proteins, proteoglycans, and polysaccharides, and thus CHI3L1 can interface between proteomics and glycomics.
 ...
PMID:Chitinase 3-Like-1 (CHI3L1): a putative disease marker at the interface of proteomics and glycomics. 1900 1


<< Previous 1 2 3 4 5 6 7 Next >>