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11.
High Rates of Clustering of Strains Causing Tuberculosis in Harare,Zimbabwe: a Molecular Epidemiological Study 下载免费PDF全文
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Twells RC Mein CA Phillips MS Hess JF Veijola R Gilbey M Bright M Metzker M Lie BA Kingsnorth A Gregory E Nakagawa Y Snook H Wang WY Masters J Johnson G Eaves I Howson JM Clayton D Cordell HJ Nutland S Rance H Carr P Todd JA 《Genome research》2003,13(5):845-855
Patterns of linkage disequilibrium (LD) in the human genome are beginning to be characterized, with a paucity of haplotype diversity in "LD blocks," interspersed by apparent "hot spots" of recombination. Previously, we cloned and physically characterized the low-density lipoprotein-receptor-related protein 5 (LRP5) gene. Here, we have extensively analysed both LRP5 and its flanking three genes, spanning 269 kb, for single nucleotide polymorphisms (SNPs), and we present a comprehensive SNP map comprising 95 polymorphisms. Analysis revealed high levels of recombination across LRP5, including a hot-spot region from intron 1 to intron 7 of LRP5, where there are 109 recombinants/Mb (4882 meioses), in contrast to flanking regions of 14.6 recombinants/Mb. This region of high recombination could be delineated into three to four hot spots, one within a 601-bp interval. For LRP5, three haplotype blocks were identified, flanked by the hot spots. Each LD block comprised over 80% common haplotypes, concurring with a previous study of 14 genes that showed that common haplotypes account for at least 80% of all haplotypes. The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination. 相似文献
14.
Elodie Mordelet Heather A Davies Philippa Hillyer Ignacio A Romero David Male 《Endothelium》2007,14(1):7-15
Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma-inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP]-1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface. 相似文献
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Evidence for cell-specific changes with age in expression of oestrogen receptor (ER) alpha and beta in bone fractures from men and women 总被引:7,自引:0,他引:7
Batra GS Hainey L Freemont AJ Andrew G Saunders PT Hoyland JA Braidman IP 《The Journal of pathology》2003,200(1):65-73
Oestrogen is recognized as important for maintaining bone mass in men and women. Oestrogen receptor (ER) alpha and the recently described ER-beta are both expressed in bone cells, but have different affinities for oestrogen agonists and plant oestrogens, which could be important in developing treatments for bone loss in both men and women. It is unclear, however, which isoform predominates in bone; cell type and age may influence their relative expression. The present study has compared ER-alpha and ER-beta expression in serial sections of human fracture callus from males (n = 19, age range 5-72 years) and females (n = 15, age range 3-86 years) by indirect immunoperoxidase. Fracture callus was used as it can be readily obtained from individuals over a wide age range and contains a variety of bone cells. Antibody specificity was confirmed by western blotting and comparison of immunoreactivity in sections of breast tumour and benign prostate hyperplasia. No gender difference in ER expression was found in bone from individuals less than 40 years old. Proliferative chondrocytes were positive for both isoforms, but few larger hypertrophic cells were immunoreactive. ER-alpha and ER-beta were co-expressed in osteoclasts, suggesting that oestrogen may act directly on these cells. Osteoblasts, osteocytes, and mesenchymal cells also expressed both isoforms. In women over 40 years of age, however, relatively fewer biopsies contained osteocytes positive for ER-alpha and ER-beta. Likewise, the proportions of osteoblasts and mesenchymal cells expressing ER-beta were reduced but ER-alpha remained unaffected. In contrast, in men over 40 years, only the proportion of biopsies containing ER-beta-positive mesenchymal cells was lower. In these older men and women, ER-alpha and ER-beta expression was retained by the small proliferative chondrocytes. These results demonstrate that gender, age, and cell type are important determinants of ER isoform expression in skeletal cells. 相似文献
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Eshleman SH Guay LA Wang J Mwatha A Brown ER Musoke P Mmiro F Jackson JB 《Journal of acquired immune deficiency syndromes (1999)》2005,40(1):24-29
BACKGROUND: The HIVNET 012 trial in Uganda demonstrated that single-dose nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. NVP resistance (NVPR) mutations were detected in 25% of women 6 to 8 weeks after NVP, with a higher rate of NVPR in women with subtype D than A. This study examined emergence and fading of specific NVPR mutations in women with these subtypes. METHODS: Plasma HIV-1 was analyzed with the ViroSeq genotyping system (Celera Diagnostics, Alameda, CA). Genotypes were obtained from paired samples collected 7 days and 6 to 8 weeks after NVP from 140 women, 83 with subtype A and 57 with subtype D. RESULTS: The rate of NVPR was similar in women with subtype A vs. D at 7 days but was higher in subtype D than A at 6 to 8 weeks. The higher rate of NVPR in subtype D was explained by at least 2 factors: Y181C faded from detection at a greater rate in women with subtype A (odds ratio = 3.06; 95% CI, 1.04, 8.90) and K103N accumulated at a greater rate in women with subtype D (odds ratio = 1.74; 95% CI, 0.62, 4.87). CONCLUSIONS: HIV-1 subtype influences selection and fading of HIV-1 variants with specific drug resistance mutations after antiretroviral drug exposure. 相似文献
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We identified dish-based dietary patterns for breakfast, lunch, and dinner and assessed the diet quality of each pattern. Dietary data were obtained from 392 Japanese adults aged 20–69 years in 2013, using a 4 d dietary record. K-means cluster analysis was conducted based on the amount of each dish group, separately for breakfasts (n = 1462), lunches (n = 1504), and dinners (n = 1500). The diet quality of each dietary pattern was assessed using the Healthy Eating Index 2015 (HEI-2015) and Nutrient-Rich Food Index 9.3 (NRF9.3). The extracted dietary patterns were as follows: ‘bread-based’ and ‘rice-based’ for breakfast; ‘bread’, ‘rice-based’, ‘ramen’, ‘udon/soba’, and ‘sushi/rice bowl dishes’ for lunch; and ‘miscellaneous’, ‘meat dish and beer’, and ‘hot pot dishes’ for dinner. For breakfast, the HEI-2015 and NRF9.3 total scores were higher in the ‘rice-based’ pattern than the ‘bread-based’ pattern. For lunch, the HEI-2015 and NRF9.3 total scores were relatively high in the ‘rice-based’ pattern and low in the ‘ramen’ pattern. For dinner, the HEI-2015 total score was the highest in the ‘meat dish and beer’ pattern, and the NRF9.3 total score was higher in the ‘hot pot dishes’ than the ‘miscellaneous’ pattern. These results suggested that breakfast, lunch, and dinner have distinctive dietary patterns with different diet qualities. 相似文献
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Paolo Dell’Oglio Philippa Meershoek Tobias Maurer Esther M.K. Wit Pim J. van Leeuwen Henk G. van der Poel Fijs W.B. van Leeuwen Matthias N. van Oosterom 《European urology》2021,79(1):124-132
BackgroundThe DROP-IN gamma probe was introduced to overcome the restricted manoeuvrability of traditional laparoscopic gamma probes. Through enhanced manoeuvrability and surgical autonomy, the DROP-IN promotes the implementation of radioguided surgery in the robotic setting.ObjectiveTo confirm the utility and safety profile of the DROP-IN gamma probe and to perform a comparison with the traditional laparoscopic gamma probe and fluorescence guidance.Design, setting, and participantsTwenty-five prostate cancer patients were scheduled for a robot-assisted sentinel lymph node (SN) procedure, extended pelvic lymph node dissection, and prostatectomy at a single European centre.Surgical procedureAfter intraprostatic injection of indocyanine green (ICG)-99mTc-nanocolloid (n = 12) or 99mTc-nanocolloid + ICG (n = 13), SN locations were defined using preoperative imaging. Surgical excision of SNs was performed under image guidance using the DROP-IN gamma probe, the traditional laparoscopic gamma probe, and fluorescence imaging.MeasurementsIntraoperative SN detection was assessed for the different modalities and related to anatomical locations. Patient follow-up was included (a median of 18 mo).Results and limitationsOverall, 47 SNs were pursued in vivo by the DROP-IN gamma probe, of which 100% were identified. No adverse events related to its use were observed. In vivo fluorescence imaging identified 91% of these SNs. The laparoscopic gamma probe identified only 76% of these SNs, where the detection inaccuracies appeared to be related to specific anatomical regions.ConclusionsOwing to improved manoeuvrability, the DROP-IN probe yielded improved SN detection rates compared with the traditional gamma probe and fluorescence imaging. These findings underline that the DROP-IN technology provides a valuable tool for radioguided surgery in the robotic setting.Patient summaryRadioguided robot-assisted surgery with the novel DROP-IN gamma probe is feasible and safe. It enables more efficient intraoperative identification of sentinel lymph nodes than can be achieved with a traditional laparoscopic gamma probe. The use of the DROP-IN probe in combination with fluorescence imaging allows for a complementary optical confirmation of node localisations. 相似文献