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排序方式: 共有442条查询结果,搜索用时 15 毫秒
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R.P. Butt J.P. Huggins D. Greiling B. Hopkins S. Gaboardi D. Winslow M. Ronald S. Lewis S. Ward E. Levett J. Owen F. Burslem M. Collis S. Bailey P.V. Fish G. Whitlock S. Billotte K. James A. Mcelroy J. Blagg 《International journal of experimental pathology》2004,85(1):A20-A21
Introduction Fibrosis is a component of many tissue pathologies leading to loss of normal tissue function, primarily due to excessive collagen deposition. Collagen is deposited following cleavage of the C- and N- terminal peptides from the pro-collagen molecule. The cleavage of the globular C-peptide by PCP reduces solubility of the fibrillar collagen molecule, resulting in deposition of insoluble collagen. Increased insoluble collagen deposition is a feature of all organ fibroses, with inhibition of this process, a key potential anti-fibrotic mechanism. The aim of this work was to discover potent and selective PCP inhibitors as experimental, topically applied, anti-fibrotic drugs for clinical evaluation.
Materials and methods PCP was cloned from human osteosarcoma cells and enzymatic activity demonstrated using a PCP-specific peptide cleavage assay. Activities were confirmed by measuring cleavage of [3 H]C-peptide from type-I pro-collagen. A cell-based fibroplasias model was employed to demonstrate compound efficacy using collagen deposition, liberated C-peptide and histological endpoints. The activities of PCP inhibitors in fibroblast and epithelial in vitro cell proliferation and migration assays, and selectivity vs. a panel of MMPs were also determined.
Discussion In summary, we have identified and characterized potent and selective inhibitors of PCP for progression to clinical studies for investigation as a treatment paradigm for fibrotic disease.
Materials and methods PCP was cloned from human osteosarcoma cells and enzymatic activity demonstrated using a PCP-specific peptide cleavage assay. Activities were confirmed by measuring cleavage of [
Discussion In summary, we have identified and characterized potent and selective inhibitors of PCP for progression to clinical studies for investigation as a treatment paradigm for fibrotic disease.
Results 相似文献
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The vascularity of 49 renal masses (26 malignant and 23 benign lesions) was investigated with duplex Doppler ultrasound. Doppler signals obtained at the margins of renal masses were defined as "tumor signals" when the Doppler-shifted frequency of the lesion exceeded the frequency shift in the ipsilateral main renal artery. These exceeded 2.5 kHz with a 3-MHz insonating frequency. Among the 26 renal masses that subsequently proved to be malignant, tumor signals were obtained in 15 of 18 (83%) untreated renal cell carcinomas, in three of four Wilms tumors, and in two patients with metastases to the kidney, but not in the one patient with lymphoma. None of the 23 benign renal masses demonstrated tumor signals. Tumor vascularity in malignant lesions gives rise to abnormal, high-velocity, Doppler-shifted signals that can help in the differential diagnosis of renal masses. 相似文献
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Isolation of a fastidious Bergeyella species associated with cellulitis after a cat bite and a phylogenetic comparison with Bergeyella zoohelcum strains 下载免费PDF全文
Shukla SK Paustian DL Stockwell PJ Morey RE Jordan JG Levett PN Frank DN Reed KD 《Journal of clinical microbiology》2004,42(1):290-293
Bergeyella zoohelcum is an uncommon zoonotic pathogen typically associated with cat or dog bites. Previously, only five cases of B. zoohelcum infection have been reported. We report the isolation and characterization of a fastidious Bergeyella species from acute cellulitis in the upper extremity of a 60-year-old woman. The organism was too fastidious for identification and susceptibility testing with traditional culture methods. The isolate was characterized further by PCR amplification and sequencing of the 16S rRNA gene with broad-range eubacterial primers. Phylogenetic analysis of the 16S ribosomal DNA sequence indicated that this isolate was a member of the species B. zoohelcum (previously Weeksella zoohelcum), a gram-negative bacillus that is rarely associated with infections in humans. Despite sharing a close genetic relationship with other B. zoohelcum strains, this isolate was extremely fastidious in nature, raising the possibility that similar strains from cat or dog bite wound infections have been underreported. 相似文献
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Use of 16S rRNA gene sequencing for rapid identification and differentiation of Burkholderia pseudomallei and B. mallei 下载免费PDF全文
Gee JE Sacchi CT Glass MB De BK Weyant RS Levett PN Whitney AM Hoffmaster AR Popovic T 《Journal of clinical microbiology》2003,41(10):4647-4654
Burkholderia pseudomallei and B. mallei, the causative agents of melioidosis and glanders, respectively, are designated category B biothreat agents. Current methods for identifying these organisms rely on their phenotypic characteristics and an extensive set of biochemical reactions. We evaluated the use of 16S rRNA gene sequencing to rapidly identify these two species and differentiate them from each other as well as from closely related species and genera such as Pandoraea spp., Ralstonia spp., Burkholderia gladioli, Burkholderia cepacia, Burkholderia thailandensis, and Pseudomonas aeruginosa. We sequenced the 1.5-kb 16S rRNA gene of 56 B. pseudomallei and 23 B. mallei isolates selected to represent a wide range of temporal, geographic, and origin diversity. Among all 79 isolates, a total of 11 16S types were found based on eight positions of difference. Nine 16S types were identified in B. pseudomallei isolates based on six positions of difference, with differences ranging from 0.5 to 1.5 bp. Twenty-two of 23 B. mallei isolates showed 16S rRNA gene sequence identity and were designated 16S type 10, whereas the remaining isolate was designated type 11. This report provides a basis for rapidly identifying and differentiating B. pseudomallei and B. mallei by molecular methods. 相似文献
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The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection 总被引:44,自引:0,他引:44 下载免费PDF全文
Haake DA Chao G Zuerner RL Barnett JK Barnett D Mazel M Matsunaga J Levett PN Bolin CA 《Infection and immunity》2000,68(4):2276-2285
We report the cloning of the gene encoding the 32-kDa lipoprotein, designated LipL32, the most prominent protein in the leptospiral protein profile. We obtained the N-terminal amino acid sequence of a staphylococcal V8 proteolytic-digest fragment to design an oligonucleotide probe. A Lambda-Zap II library containing EcoRI fragments of Leptospira kirschneri DNA was screened, and a 5.0-kb DNA fragment which contained the entire structural lipL32 gene was identified. Several lines of evidence indicate that LipL32 is lipid modified in a manner similar to that of other procaryotic lipoproteins. The deduced amino acid sequence of LipL32 would encode a 272-amino-acid polypeptide with a 19-amino-acid signal peptide, followed by a lipoprotein signal peptidase cleavage site. LipL32 is intrinsically labeled during incubation of L. kirschneri in media containing [(3)H]palmitate. The linkage of palmitate and the amino-terminal cysteine of LipL32 is acid labile. LipL32 is completely solubilized by Triton X-114 extraction of L. kirschneri; phase separation results in partitioning of LipL32 exclusively into the hydrophobic, detergent phase, indicating that it is a component of the leptospiral outer membrane. CaCl(2) (20 mM) must be present during phase separation for recovery of LipL32. LipL32 is expressed not only during cultivation but also during mammalian infection. Immunohistochemistry demonstrated intense LipL32 reactivity with L. kirschneri infecting proximal tubules of hamster kidneys. LipL32 is also a prominent immunogen during human leptospirosis. The sequence and expression of LipL32 is highly conserved among pathogenic Leptospira species. These findings indicate that LipL32 may be important in the pathogenesis, diagnosis, and prevention of leptospirosis. 相似文献
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Manolio TA Barnes KC Naidu RP Levett PN Beaty TH Wilson AF 《International archives of allergy and immunology》2003,131(2):119-126
BACKGROUND: Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but correlates of sensitivity to B. tropicalis and its relationship to Dermatophagoides pteronyssinus sensitivity have not been widely examined in families with asthma. The main objective of this study was to determine prevalence and correlates of sensitivity to these mites in families with asthma and characteristics of persons sensitized to both. METHODS: Antibodies to major antigens (Blo t 5 and Der p 1) of these mites were measured by immunochemiluminescent assay in 481 members of 29 families from Barbados ascertained through two asthmatic siblings. RESULTS: Blo t 5 sensitivity was present in 261 subjects (46%) and was associated with younger age, higher total serum IgE level, and more than a three-fold increased prevalence of asthma (42 vs. 13%). Der p 1 sensitivity was less common (27%) and showed similar associations with age, IgE, and asthma. Of the 261 subjects sensitized to Blo t 5, 116 were also sensitized to Der p 1; they were younger, had higher total and Blo t 5 specific IgE levels, and had more than twice the asthma prevalence as those sensitized to Blo t 5 alone (59 vs. 29%). Der p 1 sensitivity without Blo t 5 sensitivity was uncommon; 90% of those sensitized to Der p 1 were also sensitized to Blo t 5. Geometric mean total IgE levels were lowest in the 207 participants without any mite sensitization (102 U/ml), intermediate in 158 sensitized to either Blo t 5 OR Der p 1 (609 U/ml), and highest in 116 sensitized to both (1,869 U/ml). CONCLUSIONS: Blo t 5 is the predominant sensitizing mite allergen in these Barbadian families with correlates similar to Der p 1. Concomitant sensitization to Der p 1 appears to identify a more reactive subgroup of individuals at a higher risk of asthma. 相似文献
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Flaherty JD Levett PN Dewhirst FE Troe TE Warren JR Johnson S 《Journal of clinical microbiology》2003,41(5):2237-2239
This is the first reported case of endocarditis due to the Lactobacillus-like vancomycin-resistant gram-positive bacillus Weissella confusa. Full identification and susceptibility testing of Lactobacillus-like organisms recovered in blood culture should be performed for patients with clinical presentations that suggest endocarditis. 相似文献