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The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED50 values in the range 20–30 mg/kg/3 days. Both were also equiptent in suppression of PMN infiltration induced by PAF with ED50 values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen-induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis. 相似文献
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Effect of twenty-three chemotherapeutic agents on the adherence and growth of Giardia lamblia in vitro 总被引:3,自引:0,他引:3
A A Crouch W K Seow Y H Thong 《Transactions of the Royal Society of Tropical Medicine and Hygiene》1986,80(6):893-896
The sensitivity of Giardia lamblia to 23 chemotherapeutic agents was evaluated in vitro with a Growth Inhibition Assay and a recently developed Adherence Inhibition Assay. Of the four established anti-giardia drugs, tinidazole, metronidazole, and furazolidone were found to have strong inhibitory effects on both growth and adherence, while mepacrine had a strong effect on growth only. Three drugs (mefloquine, doxycycline and rifampin) not previously used in giardiasis were found to have significant activity in vitro and may deserve consideration for clinical evaluation of efficacy. Also, the concurrent use of these two in vitro methods provided significant insights into the modes of action of some of these drugs on G. lamblia. 相似文献
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Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients 下载免费PDF全文
Hart PS Zhang Y Firatli E Uygur C Lotfazar M Michalec MD Marks JJ Lu X Coates BJ Seow WK Marshall R Williams D Reed JB Wright JT Hart TC 《Journal of medical genetics》2000,37(12):927-932
INTRODUCTION—Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity.
AIM—To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families.
METHODS—Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene.
RESULTS—The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region.
CONCLUSION—Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.
Keywords: cathepsin C; genetics; severe early onset periodontitis; hyperkeratosis 相似文献
AIM—To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families.
METHODS—Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene.
RESULTS—The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region.
CONCLUSION—Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.
Keywords: cathepsin C; genetics; severe early onset periodontitis; hyperkeratosis 相似文献
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Geok Hun Tan Khatijah Yusoff Heng Fong Seow Wen Siang Tan 《Journal of clinical virology》2007,38(1):49-56
BACKGROUND: Phage display is an alternative method for constructing and selecting antibodies with desired specificity towards an antigen. OBJECTIVES: To construct a library of single chain variable fragment (ScFv) towards hepatitis B core antigen (HBcAg). To isolate a ScFv phage clone that interacts with HBcAg and to develop a phage-ELISA for detecting the antigen. STUDY DESIGN: Mice were inoculated with HBcAg and RNA was extracted from their spleen cells. The genes encoding heavy (V(H)) and light (V(L)) chains were amplified, linked via PCR and cloned into a phagemid vector. Phage particles displaying ScFv were panned against HBcAg and a selected clone was characterized and employed as a diagnostic reagent for detecting HBcAg in serum samples. RESULTS: A phage clone that interacts with HBcAg was selected from the antibody library. The binding of the phage to HBcAg was inhibited by a cyclic peptide bearing the WSFFSNI sequence. A phage-ELISA was established using the recombinant phage and as low as 10ng of HBcAg can be detected by the assay. CONCLUSION: The ScFv displayed on the surface of filamentous phage is an alternative choice for diagnosis of HBcAg in serum samples. 相似文献
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W K Seow Y H Thong J G McCormack A Ferrante 《International archives of allergy and applied immunology》1988,85(1):63-68
Human neutrophil adherence was enhanced by recombinant human tumour necrosis factor-beta (TNF beta) but suppressed by recombinant human interleukin-2 (IL-2). The opposite effects of these two lymphokines were observed over a range of concentrations consistent with their other biological activities, occurred within 15 min of incubation, and were still evident after 60 min. Pretreatment of neutrophils with both IL-2 and TNF beta resulted in adherence values intermediate between the values obtained with the individual lymphokines. IL-2 suppressed the stimulatory effects of both the chemotactic peptide formyl-methionyl-leucyl-phenyl-alanine (FMLP) and the phorbol ester phorbol myristate acetate (PMA). The combination of TNF beta with either FMLP or PMA produced enhancement of neutrophil adherence which exceeded that of either agent alone. These effects of the lymphokines were not due to endotoxin contamination since their effects were sensitive to heating and insensitive to polymyxin B treatment. These experiments provide further evidence for the critical role of these lymphokines in the regulation of acute and chronic inflammatory processes. 相似文献
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Byron H Hartman Toshinori Hayashi Branden R Nelson Olivia Bermingham-McDonogh Thomas A Reh 《Developmental dynamics》2007,236(10):2875-2883
Notch mediates the process of lateral inhibition that controls the production of hair cells in the inner ear. Hair cells are known to express Notch ligands Dll1 and Jag2, which signal through Notch1 in adjacent supporting cells. However, recent genetic and pharmacological studies indicate that the level of Notch-mediated lateral inhibition is greater than can be accounted for by Dll1 and Jag2. Here, we report that another Notch ligand, Dll3, is expressed in developing hair cells, in a pattern that overlaps that of Dll1 and Jag2. We analyzed the cochleae of Dll3(pu) mutant mice, but did not detect any abnormalities. However, earlier studies have demonstrated that there is functional redundancy among Notch ligands in cochlear development and loss of one ligand can be at least partially compensated for by another. Thus Dll3 may play a role in lateral inhibition similar to that of Dll1 and Jag2. 相似文献
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F. Lechner H. R. Vogt H. F. Seow G. Bertoni W. P. Cheevers U. von Bodungen A. Zurbriggen E. Peterhans 《The American journal of pathology》1997,151(4):1053-1065
Infection of goats with the lentivirus caprine arthritis encephalitis virus (CAEV) leads to persistent infection and development of chronic arthritis. We analyzed the expression of cytokines and viral RNA in the joints of goats at early time points after experimental infection with CAEV and in those of animals suffering from chronic arthritis as a result of natural infection. In situ hybridization experiments showed that the pattern of cytokine expression in caprine arthritis was similar to that found in rheumatoid arthritis (RA), with a few cells expressing the lymphocyte-derived cytokines interferon (IFN)-gamma and interleukin (IL)-2 and rather more cells expressing monocyte chemoattractant protein (MCP)-1, IL-6, and tumor necrosis factor (TNF)-alpha. IFN-gamma mRNA expression in experimentally infected joints peaked at day 12 and was mostly detected in areas containing viral RNA. At later time points, no IFN-gamma- or virus-expressing cells were found in inflamed joints but both were again detected in goats with severe arthritis. Interestingly, at the clinical stage of arthritis reflecting the chronic stage of infection, the inflammatory lesion was found to be immunologically compartmentalized. Humoral immune responses and cell-mediated immune responses appeared to concurrently occur in distinct areas of the synovial membrane. 相似文献