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[PMID]: 24856311
[Au] Autor:Zarranz-Ventura J; Sim DA; Keane PA; Patel PJ; Westcott MC; Lee RW; Tufail A; Pavesio CE
[Ad] Address:Medical Retina Service, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom; Department of Ophthalmology, Clínica Universidad de Navarra, Pampl...
[Ti] Title:Characterization of punctate inner choroidopathy using enhanced depth imaging optical coherence tomography.
[So] Source:Ophthalmology;121(9):1790-7, 2014 Sep.
[Is] ISSN:1549-4713
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: To perform qualitative and quantitative analyses of retinal and choroidal morphology in patients with punctate inner choroidopathy (PIC) using enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Cross-sectional, consecutive series. PARTICIPANTS: A total of 2242 patients attending 2 tertiary referral uveitis clinics at Moorfields Eye Hospital were screened; 46 patients with PIC diagnosis were identified, and 35 eyes (35 patients) had clinically inactive PIC had EDI-OCT images that met the inclusion criteria. METHODS: Punctate inner choroidopathy lesions were qualitatively assessed for retinal features, such as (1) focal elevation of the retinal pigment epithelium (RPE), (2) focal atrophy of the outer retina/RPE, and (3) presence of sub-RPE hyperreflective deposits and choroidal features: (a) presence of focal hyperreflective dots in the inner choroid and (b) focal thinning of the choroid adjacent to PIC lesions. Quantitative analyses of the retina, choroid, and choroidal sublayers were performed, and associations with clinical and demographic data were examined. MAIN OUTCOME MEASURES: Prevalence of each lesion pattern and thickness of retinal and choroidal layers. RESULTS: A total of 90 discrete PIC lesions were captured; 46.6% of PIC lesions consisted of focal atrophy of the outer retina and RPE; 34.4% consisted of sub-RPE hyperreflective deposits; and 18.8% consisted of localized RPE elevation with underlying hyporeflective space. Focal hyperreflective dots were seen in the inner choroid of 68.5% of patients, with 17.1% of eyes presenting focal choroidal thinning underlying PIC lesions. By excluding high myopes, patients with "atypical" PIC had reduced retinal thickness compared with patients with "typical" PIC (246.65±30.2 vs. 270.05±24.6 µm; P = 0.04), and greater disease duration was associated with decreases in retinal thickness (r = -0.53; P = 0.01). A significant correlation was observed between best-corrected visual acuity and foveal retinal thickness (r = -0.40; P = 0.03). CONCLUSIONS: In a large series of patients with clinically inactive PIC, one fifth of the lesions analyzed revealed RPE elevation with underlying hyporeflective space, described before as a sign of activity and suggesting subclinical inflammation. Retinal thickness seems to be associated with disease type and duration of disease in non-highly myopic eyes. Improved visualization of the inner choroid using EDI-OCT may allow noninvasive assessment of inflammatory status.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  2 / 249923 MEDLINE  
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[PMID]: 24835759
[Au] Autor:Keane PA; Karampelas M; Sim DA; Sadda SR; Tufail A; Sen HN; Nussenblatt RB; Dick AD; Lee RW; Murray PI; Pavesio CE; Denniston AK
[Ad] Address:NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom....
[Ti] Title:Objective measurement of vitreous inflammation using optical coherence tomography.
[So] Source:Ophthalmology;121(9):1706-14, 2014 Sep.
[Is] ISSN:1549-4713
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: To obtain measurements of vitreous signal intensity from optical coherence tomography (OCT) image sets in patients with uveitis, with the aim of developing an objective, quantitative marker of inflammatory activity in patients with this disease. DESIGN: Retrospective, observational case-control series. PARTICIPANTS: Thirty patients (30 eyes) with vitreous haze secondary to intermediate, posterior, or panuveitis; 12 patients (12 eyes) with uveitis but without evidence of vitreous haze; and 18 patients (18 eyes) without intraocular inflammation or vitreoretinal disease. METHODS: Clinical and demographic characteristics were recorded, including visual acuity (VA), diagnosis, and anatomic type of uveitis. In each eye, the anterior chamber (AC) was graded for cellular activity and flare according to standardized protocols. The presence and severity of vitreous haze were classified according to the National Eye Institute system. Spectral-domain OCT images were analyzed using custom software. This software provided an "absolute" measurement of vitreous signal intensity, which was then compared with that of the retinal pigment epithelium (RPE), generating an optical density ratio with arbitrary units ("VIT/RPE-Relative Intensity"). MAIN OUTCOME MEASURES: Correlation between clinical vitreous haze scores and OCT-derived measurements of vitreous signal intensity. RESULTS: The VIT/RPE-Relative Intensity was significantly higher in uveitic eyes with known vitreous haze (0.150) than in uveitic eyes without haze or in healthy controls (0.0767, P = 0.0001). The VIT/RPE-Relative Intensity showed a significant, positive correlation with clinical vitreous haze scores (r = 0.566, P = 0.0001). Other ocular characteristics significantly associated with VIT/RPE-Relative Intensity included VA (r = 0.573, P = 0.0001), AC cells (r = 0.613, P = 0.0001), and AC flare (r = 0.385, P = 0.003). Measurement of VIT/RPE-Relative Intensity showed a good degree of intergrader reproducibility (95% limits of agreement, -0.019 to 0.016). CONCLUSIONS: These results provide preliminary evidence that OCT-derived measurements of vitreous signal intensity may be useful as an outcome measure in patients with uveitis. If validated in future studies, such measures may serve as an objective, quantitative disease activity end point, with the potential to improve the "signal:noise" ratio of clinical trials in this area, thus enabling smaller studies for the same power. The incorporation of automated vitreous analysis in commercial OCT systems may, in turn, facilitate monitoring and re-treatment of patients with uveitis in clinical practice.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 249923 MEDLINE  
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[PMID]: 24811962
[Au] Autor:Tsang SH; Burke T; Oll M; Yzer S; Lee W; Xie YA; Allikmets R
[Ad] Address:Department of Ophthalmology, Columbia University, New York, New York; Department of Pathology & Cell Biology, Columbia University, New York, New York....
[Ti] Title:Whole Exome Sequencing Identifies CRB1 Defect in an Unusual Maculopathy Phenotype.
[So] Source:Ophthalmology;121(9):1773-82, 2014 Sep.
[Is] ISSN:1549-4713
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To report a new phenotype caused by mutations in the CRB1 gene in a family with 2 affected siblings. DESIGN: Molecular genetics and observational case studies. PARTICIPANTS: Two affected siblings and 3 unaffected family members. METHODS: Each subject received a complete ophthalmic examination together with color fundus photography, fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT). Microperimetry 1 (MP-1) mapping and electroretinogram (ERG) analysis were performed on the proband. Screening for disease-causing mutations was performed by whole exome sequencing in 3 family members followed by segregation analyses in the entire family. MAIN OUTCOME MEASURES: Appearance of the macula as examined by clinical examination, fundus photography, FAF imaging, SD-OCT, and visual function by MP-1 and ERG. RESULTS: The proband and her affected brother exhibited unusual, previously unreported, findings of a macular dystrophy with relative sparing of the retinal periphery beyond the vascular arcades. The FAF imaging showed severely affected areas of hypoautofluorescence that extended nasally beyond the optic disc in both eyes. A central macular patch of retinal pigment epithelium (RPE) sparing was evident in both eyes on FAF, whereas photoreceptor sparing was documented in the right eye only using SD-OCT. The affected brother presented with irregular patterns of autofluorescence in both eyes characterized by concentric rings of alternating hyper- and hypoautofluorescence, and foveal sparing of photoreceptors and RPE, as seen on SD-OCT, bilaterally. After negative results in screening for mutations in candidate genes including ABCA4 and PRPH2, DNA from 3 members of the family, including both affected siblings and their mother, was screened by whole exome sequencing resulting in identification of 2 CRB1 missense mutations, c.C3991T:p.R1331C and c.C4142T:p.P1381L, which segregated with the disease in the family. Of the 2, the p.R1331C CRB1 mutation has not been described before and the p.P1381L variant has been described in 1 patient with Leber congenital amaurosis. CONCLUSIONS: This report illustrates a novel presentation of a macular dystrophy caused by CRB1 mutations. Both affected siblings exhibited a relatively well-developed retinal structure and preservation of generalized retinal function. An unusual 5-year progression of macular atrophy alone was observed that has not been described in any other CRB1-associated phenotypes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 249923 MEDLINE  
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[PMID]: 24930713
[Au] Autor:Li JY; Yu T; Xia ZS; Chen GC; Yuan YH; Zhong W; Zhao LN; Chen QK
[Ad] Address:Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong 510120, People's Republic of China....
[Ti] Title:Enhanced proliferation in colorectal epithelium of patients with type 2 diabetes correlates with ß-catenin accumulation.
[So] Source:J Diabetes Complications;28(5):689-97, 2014 Sep-Oct.
[Is] ISSN:1873-460X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:AIMS: ß-Catenin accumulation promotes proliferation. However, the correlation between proliferation of colorectal epithelium and ß-catenin in type 2 diabetes mellitus (DM) patients remains unclear. METHODS: Colorectal epithelium samples from distal ends of colorectal adenocarcinomas without histological aberrances were divided into two groups: DM patients with type 2 DM for more than 1year (n=27) and non-DM patients without hyperglycemia (n=20). Samples from patients without colorectal epithelial disease or hyperglycemia served as a control group (n=6). Proliferative index was calculated as the percentage of proliferating cell nuclear antigen positive cells. Wnt/ß-catenin signaling was assessed immunohistochemically and phosphorylation of ß-catenin was assessed by immunofluorescence. RESULTS: Compared with the non-DM or control group, the proliferative index and expression of lactate dehydrogenase A and Wnt/ß-catenin signaling were significantly higher in the DM group (all p<0.01). The proliferative index correlated positively with ß-catenin expression (Spearman correlation coefficient=0.55; p<0.01). Reduced phosphorylation at serine 33/37 and increased phosphorylation at serine 675 of ß-catenin were detected in the DM group (all p<0.01). CONCLUSIONS: Enhanced proliferation, accompanied by increased aerobic glycolysis, was detected in colorectal epithelium of patients with diabetes. ß-Catenin accumulation with altered phosphorylation correlated with the proliferative changes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  5 / 249923 MEDLINE  
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[PMID]: 24487059
[Au] Autor:Nasi M; Pinti M; Mussini C; Cossarizza A
[Ad] Address:Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy....
[Ti] Title:Persistent inflammation in HIV infection: Established concepts, new perspectives.
[So] Source:Immunol Lett;161(2):184-8, 2014 Oct.
[Is] ISSN:1879-0542
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Immune activation is now considered a main driving force for the progressive immune failure in HIV infection. During the early phases of infection, a rapid depletion of gastrointestinal CD4+ T cells occurs that is followed by a deterioration of the gut epithelium and by the subsequent translocation of microbial products into the blood. Activation of innate immunity results in massive production of proinflammatory cytokines, which can trigger activation induced cell death phenomena among T lymphocytes. Moreover, persistent antigenic stimulation and inflammatory status causes immune exhaustion. The chronic immune activation also damages lymphoid tissue architecture, so contributing to the impairment of immune reconstitution. Recently, new mechanisms were identified, so opening new perspective on the innate immune sensing in HIV-1 infection. Cell death is followed by the release of molecules containing "damage-associated molecular patterns", that trigger a potent innate immune response through the engagement of Toll-like receptors. Then, also different types of HIV-related nucleic acids can act as potent stimulators of innate immunity. All these events contribute to the loss of T cell homeostatic regulation and to the failure of adaptive immunity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 249923 MEDLINE  
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[PMID]: 25152361
[Au] Autor:Boulton ME
[Ad] Address:Department of Ophthalmology, Indiana University School of Medicine, USA. Electronic address: mboulton@iupui.edu.
[Ti] Title:Studying melanin and lipofuscin in RPE cell culture models.
[So] Source:Exp Eye Res;126:61-7, 2014 Sep.
[Is] ISSN:1096-0007
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The retinal pigment epithelium contains three major types of pigment granules; melanosomes, lipofuscin and melanolipofuscin. Melanosomes in the retinal pigment epithelium (RPE) are formed during embryogenesis and mature during early postnatal life while lipofuscin and melanolipofuscin granules accumulate as a function of age. The difficulty in studying the formation and consequences of melanosomes and lipofuscin granules in RPE cell culture is compounded by the fact that these pigment granules do not normally occur in established RPE cell lines and pigment granules are rapidly lost in adult human primary culture. This review will consider options available for overcoming these limitations and permitting the study of melanosomes and lipofuscin in cell culture and will briefly evaluate the advantages and disadvantages of the different protocols.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  7 / 249923 MEDLINE  
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[PMID]: 25152360
[Au] Autor:Reichhart N; Strauß O
[Ad] Address:Experimentelle Ophthalmologie, Augenklinik, Charité Universitätsmedizin Berlin, Germany.
[Ti] Title:Ion channels and transporters of the retinal pigment epithelium.
[So] Source:Exp Eye Res;126:27-37, 2014 Sep.
[Is] ISSN:1096-0007
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Ion channels and ion transporters play essential roles in the function of the retinal pigment epithelium (RPE). The use of cell cultures has been exploited as a key method for successfully identifying and studying ion channels and transporters of the RPE. Cultured RPE cells enable robust and long-lasting patch-clamp recordings, Ussing chamber investigations of the transepithelial transport within the isolated RPE, and analyses of the intracellular Ca(2+) or pH with fluorescent probes. Furthermore, cultured RPE can be transfected at high success rates, permitting the easy use of siRNA to study the involvement of ion channels on the molecular level. However, the expression patterns of the ion channels in the RPE appear to be a very sensitive marker reflecting the extent of RPE differentiation in vitro. Having originated from the neuroectoderm, cultured RPE cells seem to retain some capacity to change into a more neuronal phenotype expressing TTX-blockable Na(+) channels or synaptic Ca(2+) channels. Therefore, the identification of ion channels and transporters in cultured cells should be verified in freshly isolated RPE cells and in situ preparations of the RPE, via immunohistochemistry and the analysis of RPE-specific signals in the electroretinogram from transgenic animals.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  8 / 249923 MEDLINE  
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[PMID]: 24060345
[Au] Autor:Hu J; Bok D
[Ad] Address:Department of Ophthalmology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
[Ti] Title:The use of cultured human fetal retinal pigment epithelium in studies of the classical retinoid visual cycle and retinoid-based disease processes.
[So] Source:Exp Eye Res;126:46-50, 2014 Sep.
[Is] ISSN:1096-0007
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Human fetal retinal pigment epithelium (hfRPE), when harvested by mechanical dissection and cultured initially under low calcium conditions, will proliferate and tolerate cryopreservation for future use. Cryopreserved cells can be subsequently thawed and cultured in standard calcium and in the presence of appropriate nutrients to a high state of differentiation, allowing recapitulation of multiple in vivo functions. In this review we briefly discuss some of our previous studies of the classical retinoid visual cycle and introduce current studies in our laboratory that involve two new areas of investigation; the dynamic response of the receptor for retinol binding protein, STRA6 to the addition of holo-retinol binding protein to the culture medium and the protective complement-based response of hfRPE to the ingestion of toxic byproducts of the visual cycle. This response is studied in the context of genotyped hfRPE expressing either predisposing or protective variants of complement factor H.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Data-Review

  9 / 249923 MEDLINE  
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[PMID]: 24971615
[Au] Autor:Jun HJ; Roy J; Smith TB; Wood LB; Lane K; Woolfenden S; Punko D; Bronson RT; Haigis KM; Breton S; Charest A
[Ad] Address:Molecular Oncology Research Institute (H.J.J., S.W., D.P., A.C), Tufts Medical Center, Boston, Massachusetts 02111; Center for Cancer Research (K.L., A.C.), Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Program in Membrane Biology and Division of Nephrology and Center for Systems Biology (J.R., T.B.S., S.B.) and Molecular Pathology Unit (L.B.W., K.M.H.), Massachusetts General Hospital, Boston, Massachusetts 02114; Department of Pathology (R.T.B), Harvard Medical School, Boston, Massachusetts 02115; and Department of Neurosurgery and Program in Genetics (A.C), Tufts University School of Medicine, Boston, Massachusetts 02111.
[Ti] Title:ROS1 Signaling Regulates Epithelial Differentiation in the Epididymis.
[So] Source:Endocrinology;155(9):3661-73, 2014 Sep.
[Is] ISSN:1945-7170
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The initial segment (IS) of the epididymis plays an essential role in male fertility. The IS epithelium is undifferentiated and nonfunctional at birth. Prior to puberty, the epithelium undergoes differentiation that leads to the formation of a fully functional organ. However, the mechanistic details of this program are not well understood. To explore this further, we used genetic engineering to create a kinase dead allele of the ROS1 receptor tyrosine kinase in mice and studied the effects of ROS1 tyrosine kinase activity on the differentiation of the IS epithelium. We show that the expression and activation of ROS1 coincides with the onset of differentiation and is exclusively located in the IS of the maturing and adult mouse epididymides. Here we demonstrate that the differentiation of the IS is dependent on the kinase activity of ROS1 and its downstream effector MEK1/2-ERK1/2 signaling axis. Using genetic engineering, we show that germ line ablation of ROS1 kinase activity leads to a failure of the IS epithelium to differentiate, and as a consequence sperm maturation and infertility were dramatically perturbed. Pharmacological inhibition of ROS1 kinase activity in the developing epididymis, however, only delayed differentiation transiently and did not result in infertility. Our results demonstrate that ROS1 kinase activity and the ensuing MEK1/2-ERK1/2 signaling are necessary for the postnatal development of the IS epithelium and that a sustained ablation of ROS1 kinase activity within the critical window of terminal differentiation abrogate the function of the epididymis and leads to sterility.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.1210/en.2014-1341

  10 / 249923 MEDLINE  
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[PMID]: 25152774
[Au] Autor:Sala PC; Torrinhas RS; Giannella-Neto D; Waitzberg DL
[Ad] Address:Medical School, Department of Gastroenterology, Digestive Surgery Discipline (LIM 35), University of São Paulo, Av. Dr. Arnaldo, 455, Cerqueira César, CEP: 01246-903, São Paulo, Brazil....
[Ti] Title:Relationship between gut hormones and glucose homeostasis after bariatric surgery.
[So] Source:Diabetol Metab Syndr;6(1):87, 2014.
[Is] ISSN:1758-5996
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Type 2 diabetes mellitus (T2D) is emerging as a worldwide public health problem, and is mainly associated with an increased incidence of obesity. Bariatric surgery is currently considered the most effective treatment for severely obese patients. After bariatric surgery, T2D patients have shown a significant improvement in glycemic control, even before substantial weight loss and often discontinuation of medication for diabetes control. A central role for enteroendocrine cells from the epithelium of the gastrointestinal tract has been speculated in this postoperative phenomenon. These cells produce and secrete polypeptides - gut hormones - that are associated with regulating energy intake and glucose homeostasis through modulation of peripheral target organs, including the endocrine pancreas. This article reviews and discusses the biological actions of the gut hormones ghrelin, cholecystokinin, incretins, enteroglucagon, and Peptide YY, all of which were recently identified as potential candidates for mediators of glycemic control after bariatric surgery. In conclusion, current data reinforce the hypothesis that T2D reversion after bariatric surgery may be related to glycemic homeostasis developed by the intestine.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1408
[Da] Date of entry for processing:140825
[St] Status:PubMed-not-MEDLINE
[do] DOI:10.1186/1758-5996-6-87


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