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61.
Zhang Q Zulfiqar F Xiao X Riazuddin SA Ahmad Z Caruso R MacDonald I Sieving P Riazuddin S Hejtmancik JF 《Human genetics》2007,122(3-4):293-299
Mutation in the PROM1 gene previously has been identified in one family with retinal degeneration for which neither ERG recordings
nor detailed information about visual impairment is available. A large family with multiple individuals affected by retinal
degeneration was ascertained in the Punjab province of Pakistan. The visual acuity of all affected patients in the family
was severely compromised beginning in early childhood. The retinal disease in this family is a severe form of retinitis pigmentosa
(RP) accompanied by macular degeneration. Fundus changes advanced with age. Choriocapillaris atrophy and posterior RPE atrophy
were obvious allowing visualization of the large choroidal vessels in patients over 40 years of age. Rod and cone responses
on ERG recordings were extinguished in patient’s teens. A genome-wide scan mapped the disease to a 34.7 cM region of chromosome
4p14–p16 between D4S1599 and D4S405. A maximum lod score of 3.96 with D4S403 and D4S391 is seen at θ = 0. Sequence analysis
of PROM1 located in the linkage interval identified a c.1726C>T homozygous transition in exon 15: resulting in p.Gln576X in
the translated protein. This mutation is found in a homozygous state in all six affected individuals and was heterozygous
in five of the six unaffected family members examined. The mutation was not detected in 192 chromosomes of unrelated control
individuals of the same ethnicity and from the same region. This delineates the phenotypic characteristics of retinopathy
caused by mutations in PROM1.
Qingjiong Zhang, Fareeha Zulfiqar, Xueshan Xiao, Sheikh Riazuddin and J. Fielding Hejtmancik contributed equally. 相似文献
62.
63.
Portincasa P Grattagliano I Testini M Caruso ML Wang DQ Moschetta A Calamita G Vacca M Valentini AM Renna G Lissidini G Palasciano G 《Free radical biology & medicine》2007,42(9):1381-1391
Whereas long-term cholestasis results in intestinal alterations and increased permeability to hepatotoxins, the effect of short-term cholestasis is less known and was investigated in bile duct ligated (BDL) rats. In the intestinal mucosa, at Day 7 BDL, total glutathione and protein sulfhydryl contents had decreased, oxidized glutathione levels increased (P<0.05 vs baseline), and a reduced epithelium thickness with dissolving crypt phenomena was observed in 40% of rats. At Day 10, total protein content, glutathione-related enzyme activities, and the transmural electrophysiological activity had decreased (-50%); by contrast, oxidized proteins doubled (P<0.05), and histological changes were extended to 70% of rats. In vitro exposure to taurodeoxycholate at micellar concentrations determined dysepithelization in normal gut but dissolving crypt phenomena and necrosis in cholestatic bowels. In the liver, ongoing cholestasis was associated with early oxidative changes especially in mitochondria, where protein sulfhydryls were decreased and negatively correlated with glutathione-protein mixed disulfides (r=-0.807, P<0.001). Daily oral administration of tauroursodeoxycholate, a hydrophilic bile salt, and glutathione to BDL rats improved intestinal histology, function, and redox state. In conclusion, short-term cholestasis results in distinctive functional, oxidative, and morphological changes of intestinal mucosa, determined increased vulnerability to toxic injury, and parallel hepatic oxidative damage. 相似文献
64.
Charlie Strange Felix JF Herth Kevin L Kovitz Geoffrey McLennan Armin Ernst Jonathan Goldin Marc Noppen Gerard J Criner Frank C Sciurba 《BMC pulmonary medicine》2007,7(1):1-12
Background
Lung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr® endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema.Methods
The trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV1) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV1 and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. George's Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV1 and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined.Conclusion
If endobronchial valves improve FEV1 and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease.Trial Registration
ClinicalTrials.gov: NCT00129584 相似文献65.
66.
L. Ruth Rivkin Andrea L. Case Christina M. Caruso 《Evolution; international journal of organic evolution》2015,69(5):1232-1243
Selection is frequency dependent when an individual's fitness depends on the frequency of its phenotype. Frequency‐dependent selection should be common in gynodioecious plants, where individuals are female or hermaphroditic; if the fitness of females is limited by the availability of pollen to fertilize their ovules, then they should have higher fitness when rare than when common. To test whether the fitness of females is frequency dependent, we manipulated the sex ratio in arrays of gynodioecious Lobelia siphilitica. To test whether fitness was frequency dependent because of variation in pollen availability, we compared open‐pollinated and supplemental hand‐pollinated plants. Open‐pollinated females produced more seeds when they were rare than when they were common, as expected if fitness is negatively frequency dependent. However, hand‐pollinated females also produced more seeds when they were rare, indicating that variation in pollen availability was not the cause of frequency‐dependent fitness. Instead, fitness was frequency dependent because both hand‐ and open‐pollinated females opened more flowers when they were rare than when they were common. This plasticity in the rate of anthesis could cause fitness to be frequency dependent even when reproduction is not pollen limited, and thus expand the conditions under which frequency‐dependent selection operates in gynodioecious species. 相似文献
67.
68.
Scapagnini G Vasto S Sonya V Abraham NG Nader AG Caruso C Calogero C Zella D Fabio G 《Molecular neurobiology》2011,44(2):192-201
In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies,
for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various
age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which
polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general
xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously
demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity
in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes,
and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death.
In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial
role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations
of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and
by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated
that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction.
These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against
cognitive decline. 相似文献
69.
70.
Reiners JJ Kleinman M Kessel D Mathieu PA Caruso JA 《Free radical biology & medicine》2011,50(2):281-294
Reactive oxygen species (ROS) can induce lysosomal membrane permeabilization (LMP). Photoirradiation of murine hepatoma 1c1c7 cultures preloaded with the photosensitizer NPe6 generates singlet oxygen within acidic organelles and causes LMP and the activation of procaspases. Treatment with the cationic amphiphilic drugs (CADs) U18666A, imipramine, and clozapine stimulated the accumulation of filipin-stainable nonesterified cholesterol/sterols in late endosomes/lysosomes, but not in mitochondria. Concentration-response studies demonstrated an inverse relationship between lysosomal nonesterified cholesterol/sterol contents and susceptibility to NPe6 photoirradiation-induced intracellular membrane oxidation, LMP, and activation of procaspase-9 and -3. Similarly, the kinetics of restoration of NPe6 photoirradiation-induced LMP paralleled the losses of lysosomal cholesterol that occurred upon replating U18666A-treated cultures in CAD-free medium. Consistent with the oxidation of lysosomal cholesterol, filipin staining in U18666A-treated cultures progressively decreased with increasing photoirradiating light dose. U18666A also suppressed the induction of LMP and procaspase activation by exogenously added hydrogen peroxide. However, neither U18666A nor imipramine suppressed the induction of apoptosis by agents that did not directly induce LMP. These studies indicate that lysosomal nonesterified cholesterol/sterol content modulates susceptibility to ROS-induced LMP and possibly does so by being an alternative target for oxidants and lowering the probability of damage to other lysosomal membrane lipids and/or proteins. 相似文献