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1.
Mechanisms for the transport of unconjugated bilirubin in human trophoblastic BeWo cells 总被引:3,自引:0,他引:3
To evaluate mechanisms that mediate passage of unconjugated bilirubin (UCB) across placenta, the transport of [3H]UCB was studied in the human trophoblastic, BeWo cell line. When plotted against the unbound UCB concentration [Bf], uptake exhibited saturative kinetics with a similar apparent Km ( approximately 30 nM) for BeWo cells grown either in polarized (Transwell) or non-polarized fashion (dish). UCB release from cells, but not uptake, was inhibited by sulfobromophthalein but not by taurocholate, and almost abolished by MK571, a specific inhibitor of the activity of multidrug resistance-associated proteins (MRPs). MRP1 and MRP5 were both present in BeWo cells and the expression of MRP1, but not MRP5, was markedly higher in polarized cells. These data indicate that UCB is taken up from the fetal circulation by a still undefined, saturative process not shared by other organic anions and is then excreted to maternal circulation by proteins of the MRP family. 相似文献
2.
Mediavilla MG Pascolo L Rodriguez JV Guibert EE Ostrow JD Tiribelli C 《FEBS letters》1999,463(1-2):143-145
Hepatocytic transport of physiological concentrations of unconjugated bilirubin (UCB) has not been determined in isolated liver cells. Initial uptake of highly purified [(3)H]UCB was measured in rat hepatocytes in the presence of human serum albumin at various free, unbound UCB concentrations, [UCB]. At [UCB]=42 nM (below aqueous solubility of 70 nM), uptake was strictly temperature dependent; this was much less evident at [UCB]=166 nM (supersaturated). At low, physiological UCB concentrations, specific UCB uptake showed saturative kinetics with an apparent K(m) of 41 nM, indicating carrier-mediated transport. With aqueous supersaturation, UCB entered hepatocytes mainly by passive diffusion. 相似文献
3.
Background
Most diabetic foot amputations are caused by ulcers on the skin of the foot i.e. diabetic foot ulcers. Early identification of patients at high risk for diabetic foot ulcers is crucial. The ‘Simplified 60-Second Diabetic Foot Screening Tool’ has been designed to rapidly detect high risk diabetic feet, allowing for timely identification and referral of patients needing treatment. This study aimed to determine the clinical performance and inter-rater reliability of ‘Simplified 60 Second Diabetic Foot Screening Tool’ in order to evaluate its applicability for routine screening.Methods and Findings
The tool was independently tested by n=12 assessors with n=18 Guyanese patients with diabetes. Inter-rater reliability was assessed by calculating Cronbach’s alpha for each of the assessment items. A minimum value of 0.60 was considered acceptable. Reliability scores of the screening tool assessment items were: ‘monofilament test’ 0.98; ‘active ulcer’ 0.97; ‘previous amputation’ 0.97; ‘previous ulcer’ 0.97; ‘fixed ankle’ 0.91; ‘deformity’ 0.87; ‘callus’ 0.87; ‘absent pulses’ 0.87; ‘fixed toe’ 0.80; ‘blisters’ 0.77; ‘ingrown nail’ 0.72; and ‘fissures’ 0.55. The item ‘stiffness in the toe or ankle’ was removed as it was observed in only 1.3% of patients. The item ‘fissures’ was also removed due to low inter-rater reliability. Clinical performance was assessed via a pilot study utilizing the screening tool on n=1,266 patients in an acute care setting in Georgetown, Guyana. In total, 48% of patients either had existing diabetic foot ulcers or were found to be at high risk for developing ulcers.Conclusions
Clinicians in low and middle income countries such as Guyana can use the Simplified 60-Second Diabetic Screening Tool to facilitate early detection and appropriate treatment of diabetic foot ulcers. Implementation of this screening tool has the potential to decrease diabetes related disability and mortality. 相似文献4.
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6.
Pan JJ Chang WJ Barone TA Plunkett RJ Ostrow PT Greenberg SJ 《Cancer immunology, immunotherapy : CII》2006,55(8):918-927
The role that transforming growth factor β1 (TGF-β1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF-β1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF-β1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF-β1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF-β1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF-β1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF-β receptor. Cells expressing high levels of truncated TGF-β receptor were less sensitive to TGF-β1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF-β1. These results also would tend to support the possibility that TGF-β1 may be useful in treating some high-grade gliomas. 相似文献
7.
Clingan JM Ostrow K Hosiawa KA Chen ZJ Matloubian M 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(9):4432-4440
The necessity for pathogen recognition of viral infection by the innate immune system in initiating early innate and adaptive host defenses is well documented. However, little is known about the role these receptors play in the maintenance of adaptive immune responses and their contribution to resolution of persistent viral infections. In this study, we demonstrate a nonredundant functional requirement for both nucleic acid-sensing TLRs and RIG-I-like receptors in the control of a mouse model of chronic viral infection. Whereas the RIG-I-like receptor pathway was important for production of type I IFNs and optimal CD8(+) T cell responses, nucleic acid-sensing TLRs were largely dispensable. In contrast, optimal anti-viral Ab responses required intact signaling through nucleic acid-sensing TLRs, and the absence of this pathway correlated with less virus-specific Ab and deficient long-term virus control of a chronic infection. Surprisingly, absence of the TLR pathway had only modest effects on Ab production in an acute infection with a closely related virus strain, suggesting that persistent TLR stimulation may be necessary for optimal Ab responses in a chronic infection. These results indicate that innate virus recognition pathways may play critical roles in the outcome of chronic viral infections through distinct mechanisms. 相似文献
8.
Mariana Brait Myriam Loyo Eli Rosenbaum Kimberly L. Ostrow Alina Markova Silvana Papagerakis Marianna Zahurak Steven M. Goodman Martha Zeiger David Sidransky Christopher B. Umbricht Mohammad O. Hoque 《Epigenetics》2012,7(7):710-719
Our aim was to comprehensively analyze promoter hypermethylation of a panel of novel and known methylation markers for thyroid neoplasms and to establish their relationship with BRAF mutation and clinicopathologic parameters of thyroid cancer. A cohort of thyroid tumors, consisting of 44 cancers and 44 benign thyroid lesions, as well as 15 samples of adjacent normal thyroid tissue, was evaluated for BRAF mutation and promoter hypermethylation. Genes for quantitative methylation specific PCR (QMSP) were selected by a candidate gene approach. Twenty-two genes were tested: TSHR, RASSF1A, RARβ2, DAPK, hMLH1, ATM, S100, p16, CTNNB1, GSTP1, CALCA, TIMP3, TGFßR2, THBS1, MINT1, CTNNB1, MT1G, PAK3, NISCH, DCC, AIM1 and KIF1A. The PCR-based “mutector assay” was used to detect BRAF mutation. All p values reported are two sided. Considerable overlap was seen in the methylation markers among the different tissue groups. Significantly higher methylation frequency and level were observed for KIF1A and RARß2 in cancer samples compared with benign tumors. A negative correlation between BRAF mutation and RASSF1A methylation, and a positive correlation with RARß2 methylation were observed in accordance with previous results. In addition, positive correlation with TIMP3 and a marginal correlation with DCC methylation were observed. The present study constitutes a comprehensive promoter methylation profile of thyroid neoplasia and shows that results must be analyzed in a tissue-specific manner to identify clinically useful methylation markers. Integration of genetic and epigenetic changes in thyroid cancer will help identify relevant biologic pathways that drive its development. 相似文献
9.
Human papillomavirus type 27: detection of a novel human papillomavirus in common warts of a renal transplant recipient. 总被引:2,自引:1,他引:1 下载免费PDF全文
The cloning and partial characterization of the genome of human papillomavirus type 27 (HPV-27) is described. Hybridization analyses reveal that this is a new HPV type, with the strongest homology to HPV-2. 相似文献
10.
Julia C Jones Carmelo Fruciano Falk Hildebrand Hasan Al Toufalilia Nicholas J Balfour Peer Bork Philipp Engel Francis LW Ratnieks William OH Hughes 《Ecology and evolution》2018,8(1):441-451
There is growing recognition that the gut microbial community regulates a wide variety of important functions in its animal hosts, including host health. However, the complex interactions between gut microbes and environment are still unclear. Honey bees are ecologically and economically important pollinators that host a core gut microbial community that is thought to be constant across populations. Here, we examined whether the composition of the gut microbial community of honey bees is affected by the environmental landscape the bees are exposed to. We placed honey bee colonies reared under identical conditions in two main landscape types for 6 weeks: either oilseed rape farmland or agricultural farmland distant to fields of flowering oilseed rape. The gut bacterial communities of adult bees from the colonies were then characterized and compared based on amplicon sequencing of the 16S rRNA gene. While previous studies have delineated a characteristic core set of bacteria inhabiting the honey bee gut, our results suggest that the broad environment that bees are exposed to has some influence on the relative abundance of some members of that microbial community. This includes known dominant taxa thought to have functions in nutrition and health. Our results provide evidence for an influence of landscape exposure on honey bee microbial community and highlight the potential effect of exposure to different environmental parameters, such as forage type and neonicotinoid pesticides, on key honey bee gut bacteria. This work emphasizes the complexity of the relationship between the host, its gut bacteria, and the environment and identifies target microbial taxa for functional analyses. 相似文献