25763772|t|DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis
25763772|a|Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre. Polymerase chain reaction and direct sequencing were used to screen DNA samples for DCTN4 variants. A total of 121 adult CF patients from the Cochin Hospital CF centre have been included, all of them carrying two CFTR defects: 103 developed at least 1 pulmonary infection with Pa, and 68 patients of them had CPA. DCTN4 variants were identified in 24% (29/121) CF patients with Pa infection and in only 17% (3/18) CF patients with no Pa infection. Of the patients with CPA, 29% (20/68) had DCTN4 missense variants vs 23% (8/35) in patients without CPA. Interestingly, p.Tyr263Cys tend to be more frequently observed in CF patients with CPA than in patients without CPA (4/68 vs 0/35), and DCTN4 missense variants tend to be more frequent in male CF patients with CPA bearing two class II mutations than in male CF patients without CPA bearing two class II mutations (P = 0.06). Our observations reinforce that DCTN4 missense variants, especially p.Tyr263Cys, may be involved in the pathogenesis of CPA in male CF.
25763772	0	5	DCTN4	T103	UMLS:C4308010
25763772	23	63	chronic Pseudomonas aeruginosa infection	T038	UMLS:C0854135
25763772	67	82	cystic fibrosis	T038	UMLS:C0010674
25763772	83	120	Pseudomonas aeruginosa (Pa) infection	T038	UMLS:C0854135
25763772	124	139	cystic fibrosis	T038	UMLS:C0010674
25763772	141	143	CF	T038	UMLS:C0010674
25763772	189	206	pulmonary disease	T038	UMLS:C0024115
25763772	233	253	chronic Pa infection	T038	UMLS:C0854135
25763772	255	258	CPA	T038	UMLS:C0854135
25763772	302	329	faster rate of lung decline	T033	UMLS:C3160731
25763772	350	363	exacerbations	T033	UMLS:C4086268
25763772	395	411	exome sequencing	T062	UMLS:C3640077
25763772	469	477	isoforms	T103	UMLS:C0597298
25763772	481	491	dynactin 4	T103	UMLS:C4308010
25763772	493	498	DCTN4	T103	UMLS:C4308010
25763772	514	526	Pa infection	T038	UMLS:C0854135
25763772	530	532	CF	T038	UMLS:C0010674
25763772	551	570	respiratory disease	T038	UMLS:C0035204
25763772	592	597	study	T062	UMLS:C2603343
25763772	629	634	DCTN4	T103	UMLS:C4308010
25763772	644	652	variants	T103	UMLS:C0597298
25763772	656	668	Pa infection	T038	UMLS:C0854135
25763772	693	705	Pa infection	T038	UMLS:C0854135
25763772	710	730	chronic Pa infection	T038	UMLS:C0854135
25763772	746	752	cohort	T098	UMLS:C0599755
25763772	762	764	CF	T038	UMLS:C0010674
25763772	788	794	centre	T092	UMLS:C0475309
25763772	796	821	Polymerase chain reaction	T062	UMLS:C0032520
25763772	826	843	direct sequencing	T062	UMLS:C3899368
25763772	864	875	DNA samples	T017	UMLS:C0444245
25763772	880	885	DCTN4	T103	UMLS:C4308010
25763772	886	894	variants	T103	UMLS:C0597298
25763772	917	919	CF	T038	UMLS:C0010674
25763772	938	963	Cochin Hospital CF centre	T092	UMLS:C0019994
25763772	1009	1013	CFTR	T017	UMLS:C1413365
25763772	1048	1067	pulmonary infection	T038	UMLS:C0876973
25763772	1073	1075	Pa	T007	UMLS:C0033809
25763772	1105	1108	CPA	T038	UMLS:C0854135
25763772	1110	1115	DCTN4	T103	UMLS:C4308010
25763772	1116	1124	variants	T103	UMLS:C0597298
25763772	1157	1159	CF	T038	UMLS:C0010674
25763772	1174	1186	Pa infection	T038	UMLS:C0854135
25763772	1210	1212	CF	T038	UMLS:C0010674
25763772	1230	1242	Pa infection	T038	UMLS:C0854135
25763772	1265	1268	CPA	T038	UMLS:C0854135
25763772	1286	1291	DCTN4	T103	UMLS:C4308010
25763772	1301	1309	variants	T103	UMLS:C0597298
25763772	1344	1347	CPA	T038	UMLS:C0854135
25763772	1364	1375	p.Tyr263Cys	T103	UMLS:C0597298
25763772	1415	1417	CF	T038	UMLS:C0010674
25763772	1432	1435	CPA	T038	UMLS:C0854135
25763772	1461	1464	CPA	T038	UMLS:C0854135
25763772	1485	1490	DCTN4	T103	UMLS:C4308010
25763772	1500	1508	variants	T103	UMLS:C0597298
25763772	1542	1544	CF	T038	UMLS:C0010674
25763772	1559	1562	CPA	T038	UMLS:C0854135
25763772	1575	1593	class II mutations	T038	UMLS:C0026882
25763772	1607	1609	CF	T038	UMLS:C0010674
25763772	1627	1630	CPA	T038	UMLS:C0854135
25763772	1643	1661	class II mutations	T038	UMLS:C0026882
25763772	1706	1711	DCTN4	T103	UMLS:C4308010
25763772	1721	1729	variants	T103	UMLS:C0597298
25763772	1742	1753	p.Tyr263Cys	T103	UMLS:C0597298
25763772	1778	1790	pathogenesis	T038	UMLS:C0699748
25763772	1794	1797	CPA	T038	UMLS:C0854135
25763772	1806	1808	CF	T038	UMLS:C0010674

25847295|t|Nonylphenol diethoxylate inhibits apoptosis induced in PC12 cells
25847295|a|Nonylphenol and short-chain nonylphenol ethoxylates such as NP2 EO are present in aquatic environment as wastewater contaminants, and their toxic effects on aquatic species have been reported. Apoptosis has been shown to be induced by serum deprivation or copper treatment. To understand the toxicity of nonylphenol diethoxylate, we investigated the effects of NP2 EO on apoptosis induced by serum deprivation and copper by using PC12 cell system. Nonylphenol diethoxylate itself showed no toxicity and recovered cell viability from apoptosis. In addition, nonylphenol diethoxylate decreased DNA fragmentation caused by apoptosis in PC12 cells. This phenomenon was confirmed after treating apoptotic PC12 cells with nonylphenol diethoxylate, whereas the cytochrome c release into the cytosol decreased as compared to that in apoptotic cells not treated with nonylphenol diethoxylate s. Furthermore, Bax contents in apoptotic cells were reduced after exposure to nonylphenol diethoxylate. Thus, nonylphenol diethoxylate has the opposite effect on apoptosis in PC12 cells compared to nonylphenol, which enhances apoptosis induced by serum deprivation. The difference in structure of the two compounds is hypothesized to be responsible for this phenomenon. These results indicated that nonylphenol diethoxylate has capability to affect cell differentiation and development and has potentially harmful effect on organisms because of its unexpected impact on apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1389-1398, 2016.
25847295	34	43	apoptosis	T038	UMLS:C0162638
25847295	55	65	PC12 cells	T017	UMLS:C0085262
25847295	137	144	present	T033	UMLS:C0150312
25847295	206	219	toxic effects	T037	UMLS:C0600688
25847295	259	268	Apoptosis	T038	UMLS:C0162638
25847295	301	306	serum	T031	UMLS:C0229671
25847295	322	328	copper	T103	UMLS:C0009968
25847295	437	446	apoptosis	T038	UMLS:C0162638
25847295	458	463	serum	T031	UMLS:C0229671
25847295	480	486	copper	T103	UMLS:C0009968
25847295	496	512	PC12 cell system	T017	UMLS:C0085262
25847295	579	593	cell viability	T038	UMLS:C0007620
25847295	599	608	apoptosis	T038	UMLS:C0162638
25847295	658	675	DNA fragmentation	T038	UMLS:C0376669
25847295	686	695	apoptosis	T038	UMLS:C0162638
25847295	699	709	PC12 cells	T017	UMLS:C0085262
25847295	766	776	PC12 cells	T017	UMLS:C0085262
25847295	820	832	cytochrome c	T103	UMLS:C0010749
25847295	850	857	cytosol	T017	UMLS:C1383501
25847295	891	906	apoptotic cells	T017	UMLS:C0007634
25847295	965	968	Bax	T103	UMLS:C0219474
25847295	981	996	apoptotic cells	T017	UMLS:C0007634
25847295	1112	1121	apoptosis	T038	UMLS:C0162638
25847295	1125	1135	PC12 cells	T017	UMLS:C0085262
25847295	1176	1185	apoptosis	T038	UMLS:C0162638
25847295	1197	1202	serum	T031	UMLS:C0229671
25847295	1234	1243	structure	T082	UMLS:C0678594
25847295	1255	1264	compounds	T103	UMLS:C0220806
25847295	1326	1333	results	T033	UMLS:C2825142
25847295	1399	1419	cell differentiation	T038	UMLS:C0007589
25847295	1424	1435	development	T038	UMLS:C0243107
25847295	1456	1470	harmful effect	T037	UMLS:C0600688
25847295	1520	1529	apoptosis	T038	UMLS:C0162638

26316050|t|Prevascularized silicon membranes for the enhancement of transport to implanted medical devices
26316050|a|Recent advances in drug delivery and sensing devices for in situ applications are limited by the diffusion -limiting foreign body response of fibrous encapsulation. In this study, we fabricated prevascularized synthetic device ports to help mitigate this limitation. Membranes with rectilinear arrays of square pores with widths ranging from 40 to 200 μm were created using materials (50 μm thick double-sided polished silicon) and processes (photolithography and directed reactive ion etching) common in the manufacturing of microfabricated sensors. Vascular endothelial cells responded to membrane geometry by either forming vascular tubes that extended through the pore or completely filling membrane pores after 4 days in culture. Although tube formation began to predominate overgrowth around 75 μm and continued to increase at even larger pore sizes, tubes formed at these large pore sizes were not completely round and had relatively thin walls. Thus, the optimum range of pore size for prevascularization of these membranes was estimated to be 75-100 μm. This study lays the foundation for creating a prevascularized port that can be used to reduce fibrous encapsulation and thus enhance diffusion to implanted medical devices and sensors. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1602-1609, 2016.
26316050	16	23	silicon	T103	UMLS:C0037114
26316050	70	95	implanted medical devices	T033	UMLS:C2828363
26316050	115	128	drug delivery	T074	UMLS:C0085104
26316050	153	160	in situ	T082	UMLS:C0444498
26316050	161	173	applications	T058	UMLS:C0185125
26316050	213	234	foreign body response	T033	UMLS:C1708386
26316050	400	406	square	T082	UMLS:C0205120
26316050	506	522	polished silicon	T103	UMLS:C0037114
26316050	647	673	Vascular endothelial cells	T017	UMLS:C1257792
26316050	723	737	vascular tubes	T017	UMLS:C0005847
26316050	743	751	extended	T082	UMLS:C0231449
26316050	876	886	overgrowth	T033	UMLS:C1849265
26316050	1012	1017	round	T082	UMLS:C0332490
26316050	1042	1047	walls	T082	UMLS:C0442069
26316050	1164	1169	study	T062	UMLS:C2603343
26316050	1305	1330	implanted medical devices	T033	UMLS:C2828363
