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73.
Brand RM Hannah TL Mueller C Cetin Y Hamel FG 《Annals of biomedical engineering》2000,28(10):1210-1217
Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epithelia, which can alter their kinetic and metabolic profiles. It is, therefore, important to understand diffusion kinetics across barrier membranes when choosing a dosing regime that will elicit the greatest cellular response. An in vitro system that combines membrane transport studies with a downstream cell culture chamber has been developed. The system has been tested with skin and a small intestine model (Caco-2 cell monolayers) as barriers, the peroxovanadium compound [VO(O2)2 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumption as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in diabetic rats when administered transdermally. A dose of 10 mM bpV(phen) placed on the skin epidermis with a continuous iontophoretic current of 0.5 mA/cm2 for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23%. This system is highly versatile and can be used to study many other processes, involving a variety of biological membranes, cell types, chemicals and assays, making it a valuable research tool. © 2000 Biomedical Engineering Society.
PAC00: 8716Uv, 8715Vv 相似文献
74.
Eva Libman Catherine S. Fichten Sally Bailes Rhonda Amsel 《International Journal of Rehabilitation and Health》2000,5(3):205-209
One questionnaire about a typical week's sleep is more convenient than asking individuals to complete daily sleep diaries. Yet, most clinical evaluations and much sleep and insomnia research rely upon self monitoring via daily sleep diaries. These are often problematic to administer and can be reactive. Therefore, we investigated comparability of two measurement modalities (self monitoring and questionnaire) in a sample of 156 community dwelling older adults, both good and poor sleepers. Results indicate significant and high correlations between corresponding scores on a retrospective sleep questionnaire and on 7 days of self monitoring on a daily sleep diary, thereby suggesting that the two measurement modalities are tapping the same domains. There were, however, significant differences between means on several variables, but there was no systematic pattern to the differences. These findings illustrate the need to tailor measurement modality—retrospective or ongoing—to the setting and the purpose of the evaluation. 相似文献
75.
An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133 总被引:5,自引:0,他引:5
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76.
Rhonda C. Kines Cynthia D. Thompson Douglas R. Lowy John T. Schiller Patricia M. Day 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(48):20458-20463
Using a murine challenge model, we previously determined that human papillomavirus (HPV) pseudovirions initially bind preferentially to the cervicovaginal basement membrane (BM) at sites of trauma. We now report that the capsids undergo a conformational change while bound to the BM that results in L2 cleavage by a proprotein convertase (PC), furin, and/or PC5/6, followed by the exposure of an N-terminal cross-neutralization L2 epitope and transfer of the capsids to the epithelial cell surface. Prevention of this exposure by PC inhibition results in detachment of the pseudovirions from the BM and their eventual loss from the tissue, thereby preventing infection. Pseudovirions whose L2 had been precleaved by furin can bypass the PC inhibition of binding and infectivity. Cleavage of heparan sulfate proteoglycans (HSPG) with heparinase III prevented infection and BM binding by the precleaved pseudovirions, but did not prevent them from binding robustly to cell surfaces. These results indicate that the infectious process has evolved so that the initial steps take place on the BM, in contrast to the typical viral infection that is initiated by binding to the cell surface. The data are consistent with a dynamic model of in vivo HPV infection in which a conformational change and PC cleavage on the BM allows transfer of virions from HSPG attachment factors to an L1-specific receptor on basal keratinocytes migrating into the site of trauma. 相似文献
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78.
Rhonda K Yantiss Marcus W Bosenberg Donald A Antonioli Robert D Odze 《The American journal of surgical pathology》2002,26(2):206-215
Adenomas with misplaced epithelium in the submucosa of the polyp stalk ("pseudoinvasion") may be difficult to distinguish from adenomas that harbor invasive adenocarcinoma by morphologic analysis. Recently, several epithelial and stromal proteins, such as matrix metalloproteinase-1 (MMP-1), p53, E-cadherin, and collagen IV, have been shown to be altered in colonic adenocarcinomas in comparison with adenomas and normal colonic mucosa. Therefore, the purpose of this study was to evaluate the diagnostic use of several epithelial (p53, E-cadherin) and stromal (MMP-1, collagen IV) markers in distinguishing adenomas with misplaced epithelium from those with invasive adenocarcinoma. Routinely processed polypectomy specimens from 23 patients with an adenoma with misplaced epithelium (male/female ratio 12/11; mean age 65 years) and 23 patients with an adenocarcinoma arising in an adenoma (male/female ratio 13/10; mean age 63 years) were immunohistochemically stained (avidin-biotin complex method) for monoclonal antibodies to MMP-1 (epithelial and stromal cell collagenase), p53 (tumor suppression gene), E-cadherin (intercellular adhesion protein), and collagen IV (basement membrane collagen component), and the results were compared between the two polyp groups. Where appropriate, immunopositivity was evaluated in the epithelium (MMP-1, p53, E-cadherin), stroma (MMP-1), and/or basement membrane (collagen IV). Cases were considered positive if an increase (MMP-1, p53) or decrease (E-cadherin, collagen IV) in either the intensity or proportion of cells staining was noted in the submucosal epithelial component compared with the intramucosal portion of the polyp head for each individual polyp. In adenomas with invasive adenocarcinoma, MMP-1 staining of the stroma surrounding submucosal epithelium and p53 nuclear staining within the epithelium were increased in 21 (91%) and 14 (61%) cases, respectively, whereas decreased or discontinuous E-cadherin and collagen IV staining was noted in 15 (65%) and 22 (96%) cases, respectively. All these values were significantly different (p < 0.005) from those observed in adenomas with misplaced epithelium [MMP-1, 11 of 23 (48%); p53, 1 of 23 (4%); E-cadherin, 0 of 23 (0%); collagen IV, 0/23 (0%)]. Furthermore, in three diagnostically difficult cases that contained foci of misplaced epithelium with high-grade dysplasia, the immunohistochemical results confirmed the impression that the lesions represented epithelial misplacement rather than invasive adenocarcinoma. In conclusion, the degree and/or pattern of MMP-1, p53, E-cadherin, and collagen IV staining in the submucosal epithelial elements in comparison with the intramucosal adenomatous tissue may help distinguish adenomas with misplaced epithelium from those with invasive adenocarcinoma. 相似文献
79.
PURPOSE: To determine how glaucoma and glaucoma suspect patients' rating of their vision correlates with Esterman binocular visual field testing and other visual function tests. METHODS: One hundred ninety-one glaucoma patients and 46 glaucoma suspect patients underwent binocular visual field testing and evaluated their vision using the linear rating scale and time-tradeoff utility tests, the National Eye Institute Visual Functional Questionnaire (NEI VFQ-25), and the Short Form 36 (SF-36) quality-of-life instruments. RESULTS: The mean Esterman score was 88.2 +/- 17.4 for the glaucoma subjects and 95.2 + 6.9 for glaucoma suspect subjects (maximum score 100). On a scale from 0 (blind) to 100 (ideal), the mean rating of vision for glaucoma patients and glaucoma suspect patients was 74.8 +/- 17.3 and 78.9 +/- 18.5, respectively. The Esterman test correlated moderately with the overall NEI VFQ-25 score (partial correlation coefficient (PCC) = 0.32, P = 0.001), but only weakly with the linear rating scale (PCC = 0.17, P = 0.02), and the time-tradeoff (PCC = 0.14, P = 0.06). CONCLUSION: Utility values that glaucoma and glaucoma suspect patients assign to their vision do not correlate well with Esterman results. A challenge for the future is the design of clinical tests of vision that better correlate with patient perceptions. 相似文献
80.
An analysis of glyphosate data from the California Environmental Protection Agency Pesticide Illness Surveillance Program 总被引:1,自引:0,他引:1
Goldstein DA Acquavella JF Mannion RM Farmer DR 《Journal of toxicology. Clinical toxicology》2002,40(7):885-892
Glyphosate is among the pesticides most frequently reported to the California EPA Pesticide Illness Surveillance Program. We analyzed glyphosate-related calls to the Pesticide Illness Surveillance Program in order to assess the number of reports involving systemic symptoms and to better understand the nature and severity of reported cases. Data on glyphosate and other pesticides are available for the years 1982-1997 including: type of exposure (agricultural/other); target organ(s) affected (skin/eye/respiratory/systemic); exposure(s); an assessment of causal relationship (possible, probable, or definite); and limited medical text. Of 815 total glyphosate calls, most involved topical irritation of the eye (n = 399), skin (n = 250), upper airway (n = 7), or combinations of these sites (n = 32) without systemic symptoms. Of the 187 systemic cases, only 22 had symptoms recorded as probably or definitely related to glyphosate exposure alone. The reported symptoms were not severe, expected to be limited in duration, and frequently inconsistent with the route of exposure and/or previous experience with glyphosate. We conclude that call volume is not a reliable indicator of the actual incidence or severity of glyphosate-related incidents in California. 相似文献