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1.
J A Mancini P Prasit M G Coppolino P Charleson S Leger J F Evans J W Gillard P J Vickers 《Molecular pharmacology》1992,41(2):267-272
An 18-kDa leukocyte membrane protein, termed 5-lipoxygenase-activating protein (FLAP), has recently been shown to be the target of two structurally distinct classes of leukotriene biosynthesis inhibitors. These classes of inhibitors are based on indole and quinoline structures and are represented by MK-886 and L-674,573, respectively. A novel class of hybrid structure based on the indole and quinoline classes of inhibitors, termed quindoles, has recently been developed. These compounds, exemplified by L-689,037, are potent inhibitors of leukotriene biosynthesis, both in vitro and in vivo. In the present study, we have developed and characterized a potent radioiodinated photoaffinity analogue of L-689,037, termed [125I]L-691,678. This compound was used in immunoprecipitation studies with FLAP antisera to show that the quindole series of leukotriene biosynthesis inhibitors interact directly with FLAP. In addition, we show that MK-886, L-674,573, and L-689,037 specifically compete, in a concentration-dependent manner, with both [125I]L-691,678 and [125I]L-669,083, a photoaffinity analogue of MK-886, for binding to FLAP. These results suggest that these three classes of leukotriene biosynthesis inhibitors share a common binding site on FLAP, providing further evidence that FLAP represents a suitable target for structurally diverse classes of leukotriene biosynthesis inhibitors. 相似文献
2.
Emergence of rifampin-resistant Rhodococcus equi with several types of mutations in the rpoB gene among AIDS patients in northern Thailand
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Asoh N Watanabe H Fines-Guyon M Watanabe K Oishi K Kositsakulchai W Sanchai T Kunsuikmengrai K Kahintapong S Khantawa B Tharavichitkul P Sirisanthana T Nagatake T 《Journal of clinical microbiology》2003,41(6):2337-2340
The antimicrobial susceptibilities of 30 Rhodococcus equi isolates obtained from 30 patients between 1993 and 2001 in northern Thailand were investigated. The MICs showed a tendency toward resistance to various antibiotics but sensitivity to imipenem, minocycline, vancomycin, and teicoplanin (MICs, =0.5 micro g/ml) and relative sensitivity to meropenem, clarithromycin, and ciprofloxacin (MICs, =2 micro g/ml). Of the 30 isolates, 26 were susceptible (MICs, =1 micro g/ml), 1 showed low-level resistance (MIC, 8 micro g/ml), and 3 showed high-level resistance (MICs, >/=64 micro g/ml) to rifampin. PCR amplification and DNA sequencing of the rpoB gene and molecular typing by pulsed-field gel electrophoresis (PFGE) were performed for eight R. equi isolates from eight AIDS patients with pneumonia or lung abscess caused by R. equi between 1998 and 2001, including one low- and three high-level rifampin-resistant isolates. As a result, two high-level rifampin-resistant strains with PFGE pattern A had a Ser531Trp (Escherichia coli numbering) mutation, and one high-level rifampin-resistant strain with PFGE pattern B had a His526Tyr mutation, whereas one low-level rifampin-resistant strain with PFGE pattern C had a Ser509Pro mutation. Four rifampin-susceptible strains with PFGE patterns D and E showed an absence of mutation in the rpoB region. Our results indicate the presence of several types of rifampin-resistant R. equi strains among AIDS patients in northern Thailand. 相似文献
3.
The immunopathogenic and immunomodulatory effects of interleukin‐12 in periodontal disease
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Benjar Issaranggun Na Ayuthaya Vincent Everts Prasit Pavasant 《European journal of oral sciences》2018,126(2):75-83
Interleukin 12 (IL‐12) is an inflammatory cytokine that promotes the response of the immune system. This cytokine has been implicated as a potent stimulator of several diseases characterized by inflammatory‐induced bone destruction, such as rheumatoid arthritis and periodontitis. Yet, the exact role of IL‐12 in the development and progress of periodontitis has not been clarified. Several studies have demonstrated a positive correlation between the level of IL‐12 and the severity of periodontal destruction. Deletion of IL‐12 in mice with periodontitis significantly suppressed the level of bone destruction. Interestingly, next to a role in modulating the pathogenesis, IL‐12 also has immunological‐regulatory properties. This cytokine induces expression of immunosuppressive molecules, such as indoleamine‐pyrrole 2,3‐dioxygenase (IDO). Thus, these findings suggest both negative and positive influences of IL‐12 in periodontal disease. It is currently proposed that the diversity of action of cytokines is a molecular key which regulates biological development and homeostasis. Accordingly, the actions of IL‐12 might be one of the mechanisms that regulate homeostasis of periodontal tissue during and following inflammation. Therefore, this article aims to review both destructive and protective functionalities of IL‐12 with an emphasis on periodontal disease. 相似文献
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Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1?mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60?mL/min/1.73?m2, is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function. 相似文献
6.
Boonsak Hanterdsith Prasit Tharavichitkul Pongsak Mahanupab Wannisa Raksamat 《Journal of Forensic and Legal Medicine》2013,20(4):347-349
Streptococcus suis causes meningitis, septicemia, arthritis, endocarditis and death in both pigs and humans. Sudden death is rarely documented in the forensic field and almost all cases were diagnosed pre-mortem. Here we report a 49-year-old man who died from S. suis type 2 infection. S. suis was identified as the causative pathogen using bacterial culture, standard biochemical and coagglutination tests, specific DNA amplification by polymerase chain reaction, and histopathologic examination. We discuss the postmortem investigation of a suspected S. suis infection. 相似文献
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Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process. 相似文献
9.
Background. A continuous increase in number of CKD patients entering ESRD is a growing public health threat, which reflects the present therapeutic failure usually initiating at the late stage of CKD. Objective. To study the mechanism of vascular repair in CKD patients associated with mildly impaired renal function, which included angiogenic factors such as VEFG, angiopoietin-1, and flt-1 (VEGFR1); and antiangiogenic factors such as angiopoietin-2 and KDR (VEGFR2). Results. A mild defect in angiogenic factor—namely, angiopoietin-1—was observed, whereas VEGF and flt-1 (VEGFR1) were within normal limit. Also, antiangiogenic factor—namely, angiopoietin-2—was mildly elevated, whereas KDR (VEGFR2) remained within normal limit. Conclusion. The mechanism of vascular repair appears to be adequately functional in the early stage of CKD. Therapeutic intervention at this stage can improve renal perfusion and restore renal function as indicated in normoalbuminuric, type 2 diabetic nephropathy. The authors encourage changing the conceptual view of treatment under common treatment at late stage of CKD to treatment at early stage of CKD under an environment favorable for renal regeneration. 相似文献
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