Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro experiments have suggested that interleukin (IL)-6 may contribute to human immunodeficiency virus (HIV) burden and to immunological abnormalities in HIV-infected patients. We had the opportunity to directly address this question in vivo through the virological and immunological monitoring of HIV-infected patients treated with an anti-IL-6 monoclonal antibody (mAb) for a lymphoma (ANRS 018 trial). Sixteen courses of anti-IL-6 mAb administration, performed in 11 patients, were studied. All patients were at a late stage of HIV infection. The HIV load and the immunological status were determined at the initiation of each course and at its end, 21 days later. The mAb induced no significant change of HIV load, as evaluated by p24 antigenemia, plasma viremia, and quantification of circulating HIV RNA by reverse transcriptase-polymerase chain reaction and branched DNA techniques. The anti-IL-6 mAb also did not affect CD4+, CD8+, and CD19+ circulating cell counts, nor the serum concentrations of sIL-2R and of sCD8. In contrast, the mAb completely abrogated acute-phase reaction, as demonstrated by the normalization of C-reactive protein and fibrinogen circulating levels (p = 0.013 and p = 0.008, respectively). It increased serum albumin concentration. The latter effect was restricted to patients with a spontaneously low albuminemia (p = 0.01). It decreased B-lymphocyte hyperactivity, as reflected by decreased IgG and IgA serum levels (p = 0.008 and p < 0.001, respectively), and by a decreased production of IgG in vitro (p = 0.017). In contrast, the IgM hyperproduction was not affected by the mAb. Therefore, increased IL-6 production in HIV-infected patients at a late stage of the infection may not stimulate HIV replication in vivo, but it may represent a key mechanism contributing to the metabolic and immunological dysbalance of the disease.
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PMID:In vivo role of IL-6 on the viral load and on immunological abnormalities of HIV-infected patients. 852 34

A case of thymic squamous cell carcinoma producing interleukin-6 (IL-6) is reported. C-reactive protein (CRP), white blood cell (WBC) count, and serum IL-6 had been elevated, and normalized immediately after tumorectomy. IL-6 in the culture supernatant from the tumor was significantly elevated and the expression of IL-6 mRNA was demonstrated in the tumor by a reverse transcriptase polymerase chain reaction method. Immunohistochemical study demonstrated that tumor cells were stained positive with an anti-IL-6 antibody. IL-6 derived from the tumor cells reflected the increase CRP and WBC counts. This case suggested that asymptomatic elevation of acute-phase reactants might be clues for the diagnosis of an IL-6 producing tumor.
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PMID:Thymic carcinoma associated with a high serum level of interleukin 6 diagnosed through the evaluation for asymptomatic elevation of acute-phase reactants. 963 Feb 6

It is well known that cases with multiple myeloma reveal various clinical manifestations such as pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, hypercalcemia and immunodeficiency. Recently, a few more clinical features associated with myeloma, such as salivary type hyperamylasemia and elevated serum C-reactive protein (CRP) concentration, have been reported. The elevation of CRP is thought to be related to interleukin-6 (IL-6) production by myeloma cells, because of identification of IL-6 as an autocrine and/or paracrine growth factor for myeloma cells. More recently, there have been several reports of cases with myeloma associated with hyperammonemia. This hyperammonemia is not considered to be due to liver dysfunction, because in most of these cases tests revealed normal hepatic function, and some cases showed different patterns of serum amino acid distribution than that associated with hepatic failure. However, there have been no apparent observations of ammonia production by myeloma cells. In this study, we used six human myeloma cell lines including KMS-18, which was recently established from a myeloma case associated with hyperammonemia. These lines were treated with MRA (mycoplasma removal agent) to observe ammonia production in vitro. They produced and released significantly higher levels of ammonia into culture medium than non-myeloma hematological cell lines or the HepG2 human hepatic carcinoma cell line. Although attempts to analyze the relative expression levels of the enzymes related to ammonia biosynthesis using the reverse transcriptase-polymerase chain reaction assay failed to detect any differences between these myeloma lines and other cell lines, in vitro excess ammonia production by the myeloma cells was confirmed and the relevance to clinical manifestations is discussed.
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PMID:In vitro excess ammonia production in human myeloma cell lines. 966 3

There is increasing evidence that nitric oxide (NO) is an important factor in the pathogenesis of septic shock. It is known that polymorphonuclear neutrophils (PMNs) are activated during sepsis or after surgical stress, and they then release various toxic mediators including free radicals. It has not been clear whether NO synthesis can be induced in circulating PMNs. Blood samples were obtained from 11 patients with sepsis, 23 patients with systemic inflammatory response syndrome (SIRS), and 16 patients without SIRS (nonSIRS) who underwent operation. We examined mRNA expression of inducible NO synthase (iNOS) in circulating PMNs from those patients pre- and postoperatively using the reverse transcriptase polymerase chain reaction (RT-PCR) method and measured their serum nitrate (NO2-) + nitrate (NO3-) concentration, peripheral blood white cell (WBC) count, and serum C-reactive protein (CRP) level. The frequency of iNOS expression in PMNs increased in sepsis (100%) and SIRS (70%) patients compared to that in nonSIRS patients (18%) (p < 0.001). The peripheral WBC count and CRP level were significantly higher in iNOS-positive patients than in iNOS-negative patients (p < 0.05 and p < 0.01, respectively). Postoperatively, the serum NO2- + NO3- concentration increased in 87% of septic patients and in 56% of patients with SIRS (p < 0.05 for both). Our study indicated that iNOS mRNA expression is induced in human circulating PMNs of patients with postoperative sepsis and SIRS and may be involved in the pathogenesis of the sepsis syndrome.
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PMID:Expression of inducible nitric oxide synthase in circulating neutrophils of the systemic inflammatory response syndrome and septic patients. 967 45

Italian investigations have shown an association between Chlamydia pneumoniae infection and atherosclerosis. With the use of several diagnostic techniques, including serology, a microimmunofluorescence test, and nucleic acid amplification methods, a temporal association was found between acute C. pneumoniae reinfection and acute myocardial infarction, suggesting that an acute infection superimposed on a chronic or latent infection may trigger the onset of acute myocardial infarction. C. pneumoniae but not Helicobacter pylori or Mycoplasma pneumoniae was found in atherosclerotic plaques of abdominal aortic aneurysms and the carotid artery. A reverse transcriptase-polymerase chain reaction process confirmed the presence of viable C. pneumoniae in carotid atheromas. Nucleic amplification of peripheral blood mononuclear cells may enable the identification of subjects carrying C. pneumoniae in the vascular wall. Macrolide treatment reduced fibrinogen and C-reactive protein plasma levels and C. pneumoniae burden in patients with atherosclerotic diseases.
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PMID:Chlamydia pneumoniae detection in atherosclerotic plaques in Italy. 1102 90

C-reactive protein (CRP) and amyloid P (AP) are pentraxins which are associated with many pathological lesions, including the amyloid deposits and neurofibrillary tangles (NFTs) of Alzheimer disease (AD). It has always been assumed that they are generated by liver and delivered to their sites of action by serum. Here we report by in situ hydridization, reverse transcriptase-polymerase chain reaction analysis, Western blotting and immunohistochemistry that the mRNAs and proteins of both CRP and AP are concentrated in pyramidal neurons and are upregulated in affected areas of AD brain. Controlling pentraxin production at the tissue level may be important in reducing inflammatory damage in AD.
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PMID:Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer's disease. 1113 92

C-reactive protein (CRP) is a normal constituent of human sera synthesized by hepatocytes and induced by proinflammatory cytokines. The function of this acute-phase reactant includes activation of complement and enhancement of opsonophagocytosis. CRP binds to phosphorylcholine (ChoP), a constituent of eukaryotic membranes that is also found on the cell surface of major bacterial pathogens of the human respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae. The presence of CRP on mucosal surfaces and role in innate immunity in the human respiratory tract where ChoP-containing organisms reside have not been previously studied. We have shown using a monoclonal antibody to CRP that CRP is present in inflamed (0.17 to 42 microg/ml) and uninflamed (<0.05 to 0.88 microg/ml) secretions from the human respiratory tract in sufficient quantities for an antimicrobial effect. In addition, the CRP gene was expressed in epithelial cells of the human respiratory tract using in situ hybridization on nasal polyps and reverse transcriptase PCR of pharyngeal cells in culture. The complement-dependent bactericidal activity of normal nasal airway surface fluid and sputum against ChoP-expressing H. influenzae was abolished when the secretions were pretreated to remove CRP. In summary, the results indicate that CRP is present in secretions of the human respiratory tract, that human respiratory epithelial cells are capable of CRP expression, and that this protein may contribute to bacterial clearance in the human respiratory tract.
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PMID:Expression of C-reactive protein in the human respiratory tract. 1117 52

C-reactive protein (CRP) and complement are hypothesized to be major mediators of inflammation in atherosclerotic plaques. We used the reverse transcriptase-polymerase chain reaction technique to detect the mRNAs for CRP and the classical complement components C1 to C9 in both normal arterial and plaque tissue, establishing that they can be endogenously generated by arteries. When the CRP mRNA levels of plaque tissue, normal artery, and liver were compared in the same cases, plaque levels were 10.2-fold higher than normal artery and 7.2-fold higher than liver. By Western blotting, we showed that the protein levels of CRP and complement proteins were also up-regulated in plaque tissue and that there was full activation of the classical complement pathway. By in situ hybridization, we detected intense signals for CRP and C4 mRNAs in smooth muscle-like cells and macrophages in the thickened intima of plaques. By immunohistochemistry we showed co-localization of CRP and the membrane attack complex of complement. We also detected up-regulation in plaque tissue of the mRNAs for the macrophage markers CD11b and HLA-DR, as well as their protein products. We showed by immunohistochemistry macrophage infiltration of plaque tissue. Because CRP is a complement activator, and activated complement attacks cells in plaque tissue, these data provide evidence of a self-sustaining autotoxic mechanism operating within the plaques as a precursor to thrombotic events.
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PMID:Generation of C-reactive protein and complement components in atherosclerotic plaques. 1123 52

C-reactive protein (CRP) is frequently deposited in the lesions of the arterial intima; however, the origin and pathological significance of CRP in these lesions are not completely understood. In this study, we measured CRP levels in the plasma of hypercholesterolemic rabbits and investigated CRP expression at both the mRNA and protein levels using rabbit and human atherosclerotic specimens. CRP levels were significantly elevated in both cholesterol-fed and Watanabe heritable hyperlipidemic rabbits, and CRP levels were clearly correlated with aortic atherosclerotic lesion size. Immunohistochemical staining coupled with Western blotting analysis revealed that CRP-immunoreactive proteins were found at all stages of atherosclerosis from the early to advanced lesions. CRP was present extracellularly and co-localized with apolipoprotein B but was rarely associated with the cytoplasm of macrophages and foam cells. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that CRP mRNA in atherosclerotic lesions was barely detectable, and isolated macrophages did not express CRP mRNA, suggesting that CRP proteins found in the lesions were essentially derived from the circulation rather than synthesized de novo by vascular cells. These results suggest that there is a link between plasma CRP and the degree of atherosclerosis and that inhibition of plasma CRP may represent a therapeutic modality for the treatment of cardiovascular disease.
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PMID:C-reactive protein in atherosclerotic lesions: its origin and pathophysiological significance. 1650 18

Neointima formation after vascular injury is exaggerated in ovariectomized (OVX) human C-reactive protein transgenic mice (CRPtg) compared to nontransgenic mice (NTG). We tested the hypothesis that this CRP-mediated exacerbation requires IgG Fc receptors (Fc gamma Rs). OVX NTG, CRPtg, and CRPtg lacking Fc gamma RI, Fc gamma RIIb, Fc gamma RIII, or the common gamma chain (FcR gamma) had their common carotid artery ligated. Twenty-eight days later neointimal thickening in CRPtg/Fc gamma RI(-/-) and CRPtg/FcR gamma (-/-) was significantly less than in CRPtg and no worse than in NTG, whereas in CRPtg/Fc gamma RIIb(-/-) and CRPtg/Fc gamma RIII(-/-) neointimal thickness was equal to or greater than in CRPtg. Immunohistochemistry revealed human CRP in the neointima of CRPtg, but little or none was observed in those lacking Fc gamma RI or FcR gamma. Real-time reverse transcriptase-polymerase chain reaction demonstrated that Fc gamma R types I to III were expressed in the CRPtg arteries, with Fc gamma RI expression increasing by threefold after ligation injury. Levels of serum complement (C3), neointimal deposition of complement (C3d), and cellular composition (monocytes, macrophages, lymphocytes) in the neointima did not differ among the different CRPtg genotypes. However, by immunofluorescence a neointimal population of F4/80+CRP+ cells was revealed only in OVX CRPtg. The exaggerated response to vascular injury provoked by CRP in OVX CRPtg depends on Fc gamma RI and probably requires its expression by F4/80+ cells.
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PMID:Exaggerated neointima formation in human C-reactive protein transgenic mice is IgG Fc receptor type I (Fc gamma RI)-dependent. 1806 1


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