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991.
Anita Wadagni Michael Frimpong Delphin Mavinga Phanzu Anthony Ablordey Emmanuel Kacou Mirabelle Gbedevi Estelle Marion Yalan Xing Vaddela Sudheer Babu Richard Odame Phillips Mark Wansbrough-Jones Yoshito Kishi Kingsley Asiedu 《PLoS neglected tropical diseases》2015,9(11)
Introduction
Mycobacterium ulcerans infection, known as Buruli ulcer, is a disease of the skin and subcutaneous tissues which is an important but neglected tropical disease with its major impact in rural parts of West and Central Africa where facilities for diagnosis and management are poorly developed. We evaluated fluorescent thin layer chromatography (f-TLC) for detection of mycolactone in the laboratory using samples from patients with Buruli ulcer and patients with similar lesions that gave a negative result on PCR for the IS2404 repeat sequence of M. ulceransMethodology/Principal findings
Mycolactone and DNA extracts from fine needle aspiration (FNA), swabs and biopsy specimen were used to determine the sensitivity and specificity of f-TLC when compared with PCR for the IS2404. For 71 IS2404 PCR positive and 28 PCR negative samples the sensitivity was 73.2% and specificity of 85.7% for f-TLC. The sensitivity was similar for swabs (73%), FNAs (75%) and biopsies (70%).Conclusions
We have shown that mycolactone can be detected from M. ulcerans infected skin tissue by f-TLC technique. The technique is simple, easy to perform and read with minimal costs. In this study it was undertaken by a member of the group from each endemic country. It is a potentially implementable tool at the district level after evaluation in larger field studies. 相似文献992.
Shantashri Vaidya Babu Rao Vundinti Chandrakala Shanmukhaiah Prantar Chakrabarti Kanjaksha Ghosh 《PloS one》2015,10(1)
Background
Mutations in the ABL kinase domain and SH3-SH2 domain of the BCR/ABL gene and amplification of the Philadelphia chromosome are the two important BCR/ABL dependent mechanisms of imatinib resistance. Here, we intended to study the role played by TKI, imatinib, in selection of gene mutations and development of chromosomal abnormalities in Indian CML patients.Methods
Direct sequencing methodology was employed to detect mutations and conventional cytogenetics was done to identify Philadelphia duplication.Results
Among the different mechanisms of imatinib resistance, kinase domain mutations (39%) of the BCR/ABL gene were seen to be more prevalent, followed by mutations in the SH3-SH2 domain (4%) and then BCR/ABL amplification with the least frequency (1%). The median duration of occurrence of mutation was significantly shorter for patients with front line imatinib than those pre-treated with hydroxyurea. Patients with high Sokal score (p = 0.003) showed significantly higher incidence of mutations, as compared to patients with low/intermediate score. Impact of mutations on the clinical outcome in AP and BC was observed to be insignificant. Of the 94 imatinib resistant patients, only 1 patient exhibited duplication of Philadelphia chromosome, suggesting a less frequent occurrence of this abnormality in Indian CML patients.Conclusion
Close monitoring at regular intervals and proper analysis of the disease resistance would facilitate early detection of resistance and thus aid in the selection of the most appropriate therapy. 相似文献993.
Subhash Gaddipati Qingxian Lu Ramesh Babu Kasetti M. Clarke Miller Qingjun Lu John O. Trent Henry J. Kaplan Qiutang Li 《PloS one》2015,10(3)
The inhibition of NF-κB by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV). To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) (MW: 279.29), we developed a biodegradable poly-lactide-co-glycolide (PLGA) polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model. The solvent-evaporation method produced spherical TPCA-1-loaded PLGA microparticles characterized with a mean diameter of 2.4 ¼m and loading efficiency of 80%. Retrobulbar administration of the TPCA-1-loaded PLGA microparticles maintained a sustained drug level in the retina during the study period. No detectable TPCA-1 level was observed in the untreated contralateral eye. The anti-CNV effect of retrobulbarly administrated TPCA-1-loaded PLGA microparticles was assessed by retinal fluorescein leakage and isolectin staining methods, showing significantly reduced CNV development on day 7 after laser injury. Macrophage infiltration into the laser lesion was attenuated as assayed by choroid/RPE flat-mount staining with anti-F4/80 antibody. Consistently, laser induced expressions of Vegfa and Ccl2 were inhibited by the TPCA-1-loaded PLGA treatment. This TPCA-1 delivery system did not cause any noticeable cellular or functional toxicity to the treated eyes as evaluated by histology and optokinetic reflex (OKR) tests; and no systemic toxicity was observed. We conclude that retrobulbar injection of the small-molecule IKK2 inhibitor TPCA-1, delivered by biodegradable PLGA microparticles, can achieve a sustained and controllable drug release into choroid/retina and attenuate laser-induced CNV development without causing apparent systemic toxicity. Our results suggest a potential clinical application of TPCA-1 delivered by microparticles in treatment of CNV in the patients with age-related macular degeneration and other retinal neovascularization diseases. 相似文献
994.
Nripendra Vikram Singh Venkata Lakshmi Abburi D. Ramajayam Ravinder Kumar Ram Chandra Kuldeep Kumar Sharma Jyotsana Sharma K. Dhinesh Babu Ram Krishna Pal Dhananjay M. Mundewadikar Thangasamy Saminathan Robert Cantrell Padma Nimmakayala Umesh K. Reddy 《Molecular genetics and genomics : MGG》2015,290(4):1393-1402
995.
996.
Islam I Bryant J Chou YL Kochanny MJ Lee W Phillips GB Yu H Adler M Whitlow M Ho E Lentz D Polokoff MA Subramanyam B Wu JM Zhu D Feldman RI Arnaiz DO 《Bioorganic & medicinal chemistry letters》2007,17(14):3814-3818
HTS screening identified 1 with micromolar inhibitory activity against PDK1. Optimization of 1 afforded 4i (BX-517) which has single-digit nanomolar activity against PDK1 and excellent selectivity against PKA. 相似文献
997.
Islam I Brown G Bryant J Hrvatin P Kochanny MJ Phillips GB Yuan S Adler M Whitlow M Lentz D Polokoff MA Wu J Shen J Walters J Ho E Subramanyam B Zhu D Feldman RI Arnaiz DO 《Bioorganic & medicinal chemistry letters》2007,17(14):3819-3825
Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds. 相似文献
998.
We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient. 相似文献
999.
Singh K Agarwal A Khan SI Walker LA Tekwani BL 《Journal of biomolecular screening》2007,12(8):1109-1114
In vitro cultivation of Plasmodium falciparum has been extremely useful in understanding the biology of the human malaria parasite as well as research on the discovery of new antimalarial drugs and vaccines. A chemically defined serum-free medium supplemented with lipid-rich bovine serum albumin (AlbuMAX I) offers the following advantages over human serum-supplemented media for the in vitro culture of P. falciparum: 1) improved growth profile, with more than a 2-fold higher yield of the parasites at any stage of the growth cycle; 2) suitability for in vitro antimalarial screening, as the parasites grown in AlbuMAX and human serum-supplemented media show similar sensitivity to standard and novel antimalarials as well as natural product extracts in the in vitro drug susceptibility assays; and 3) DNA microarray analysis comparing the global gene expression profile of sorbitol-synchronized P. falciparum trophozoites grown in the 2 different media, indicating minimal differences. 相似文献
1000.
Triplex-forming ability of modified oligonucleotides 总被引:1,自引:0,他引:1
Højland T Babu BR Bryld T Wengel J 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1411-1414
We present our studies on the ability of several different nucleotide analogs as triplex-forming oligonucleotides. The modifications tested include 4'-C-hydroxymethyl, LNA, 2'-amino-LNA and N2'-functionalized 2'-amino-LNA. Triplexes containing monomers of N2'-glycyl-functionalized 2'-amino-LNA are particularly stable. 相似文献