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Dharmarajan Sriram Narasimharaghavan Srichakravarthy Tanushree R Bal Perumal Yogeeswari 《Biomedicine & Pharmacotherapy》2005,59(8):456-459
A series of nevirapine derivatives has been synthesized in an effort to enhance the spectrum of chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. The nevirapine derivative bearing isoniazid moiety (3a) was found to be the most potent compound with EC50 of<0.0636 microM, CC50 of>1000 microM and selectivity index of>15,723 which also exhibited 90% inhibition against Mycobacterium tuberculosis at 6.25 microg/ml. Compound 3c showed 100% inhibition against M. tuberculosis and also exhibited potent antibacterial activity against 24 pathogenic bacteria with MIC less than 1 microg/ml. 相似文献
13.
A report of a patient who developed acute suppurative parotitis while on total parenteral nutrition for small bowel fistula is presented. The importance of early detection of parotitis as a cause of fever is emphasized. Attention to oral hygiene and early resumption of oral intake, whenever possible, are to be encouraged. 相似文献
14.
Summary Hypodermic needle shields may be used as tip protectors for several types of microsurgical instruments. These provide an inexpensive alternative to commercially available tip covers. 相似文献
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Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site 总被引:2,自引:0,他引:2
M S Allen Y C Tan M L Trudell K Narayanan L R Schindler M J Martin C Schultz T J Hagen K F Koehler P W Codding 《Journal of medicinal chemistry》1990,33(9):2343-2357
The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
17.
R B Narayanan A Girdhar B K Girdhar 《International archives of allergy and applied immunology》1990,92(1):94-96
A comparison was made of the numbers of epidermal Langerhans cells in active and regressed lesions of tuberculoid and lepromatous leprosy using the OKT6 and OKIa monoclonal antibodies. A reduction in the numbers of CD1+ epidermal Langerhans cells was noticed in the regressed lesions of both the tuberculoid and lepromatous leprosy lesions unlike the active lesions. The majority of infiltrates in both types of regressed lesions were HLA-DR+ and CD1-. 相似文献
18.
Type I collagen gene expression in human atherosclerosis. Localization to specific plaque regions. 总被引:4,自引:2,他引:4
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M. D. Rekhter K. Zhang A. S. Narayanan S. Phan M. A. Schork D. Gordon 《The American journal of pathology》1993,143(6):1634-1648
Because collagen is a major component of the human atherosclerotic plaque, factors controlling collagen synthesis may have a profound influence on the volume growth of these intimal lesions. In human arteries, we compared normal vs atherosclerotic media vs intimas for type I collagen gene expression using immunocytochemistry and in situ messenger RNA hybridization with subsequent correlations with plaque topographical features. We also determined the associations of such collagen gene expression with proximity to monocyte/macrophages and T lymphocytes. Type I collagen synthesis appears to be upregulated in atherosclerotic plaques compared with their underlying medias and normal internal mammary arteries and coronary diffuse intimal thickenings. At least in established and advanced coronary and carotid plaques, type I collagen gene expression is focal and especially prevalent in fibrous cap and vascularized regions. Although macrophages and type I procollagen messenger RNA and protein are both found in atherosclerotic plaques, no apparent spatial correlation between macrophage presence and type I procollagen presence was found within these atherosclerotic intimas. Type I procollagen presence appears to be negatively associated with the spatial presence of T cells. Thus, human atherosclerotic plaques exhibit nonuniform patterns of type I collagen gene expression. Although the biochemical determinants of this focal gene expression have yet to be determined, it is conceivable that stimulatory/inhibitory cytokines and other factors (eg hemodynamics) play important roles in determining the focal nature of collagen synthesis in atherosclerosis. 相似文献
19.
Collagens synthesized in vitro by diploid fibroblasts obtained from chronically inflamed human connective tissue 总被引:5,自引:0,他引:5
A S Narayanan R C Page F Kuzan 《Laboratory investigation; a journal of technical methods and pathology》1978,39(1):61-65
Collagen synthesis by fibroblasts obtained from healthy and diseased human gingiva was compared. The cells were labeled with radioactive amino acids and the collagenous proteins synthesized were characterized after NaCl fractionation by CM-cellulose chromatography and cyanogen bromide peptide analysis. Fourteen cell lines, six from healthy gingiva, six from gingiva with chronic inflammatory periodontitis, and two from acutely inflamed gingiva were studied. All of the cell lines synthesized predominantly type I collagen. Type III collagen was a minor product of all cell lines except one from diseased tissue. Five of six cell lines from diseased gingiva and two of two from acutely inflamed tissue synthesized a collagen that was soluble in 2.5 M NaCl. The alpha1/alpha2 ratio and cyanogen bromide peptide pattern indicated that this fraction contained a collagen of the type alpha1[I]3. The alpha1[I]3 collagen was not detectable in the fibroblast lines obtained from healthy gingiva. It appears that inflamed human gingivae contain fibroblasts which differ phenotypically from cells from normal tissue in that they are capable of synthesizing alpha1[I]3 collagen. 相似文献
20.
Elkins MK Vittinghoff E Baranzini SE Hecht FM Sriram U Busch MP Levy JA Oksenberg JR;San Francisco Primary Infection Group 《Genes and immunity》2005,6(1):66-69
In chronically HIV infected individuals, a number of functional B cell abnormalities have been described. However, the immediate changes that occur in the B cell compartment following viral exposure and how they affect the long-term course of infection are not well understood. We report the longitudinal analysis of B cell repertoires during early infection in untreated and treated individuals receiving highly active antiretroviral therapy (HAART). Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement and relationship with CD4/CD8 counts, viral load, and total serum IgG, and anti-HIV antibodies levels. Repertoires were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. The findings indicate a stable peripheral B cell repertoire during the first 72 weeks following infection, particularly in the HAART treated patients. A modest association between B cell repertoire integrity and viremia levels as well as treatment was detected. 相似文献