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[PMID]: 27797139
[Au] Autor:Switon K; Kotulska K; Janusz-Kaminska A; Zmorzynska J; Jaworski J
[Ad] Address:Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland.
[Ti] Title:Tuberous sclerosis complex: From molecular biology to novel therapeutic approaches.
[So] Source:IUBMB Life;, 2016 Oct 31.
[Is] ISSN:1521-6551
[Cp] Country of publication:England
[La] Language:ENG
[Ab] Abstract:Tuberous sclerosis complex (TSC) is a rare multi-system disorder, primary manifestations of which are benign tumors and lesions in various organs of the body, including the brain. TSC patients often suffer from epilepsy, mental retardation, and autism spectrum disorder (ASD). Therefore, TSC serves as a model of epilepsy, ASD, and tumorigenesis. TSC is caused by the lack of functional Tsc1-Tsc2 complex, which serves as a major cellular inhibitor of mammalian Target of Rapamycin Complex 1 (mTORC1). mTORC1 is a kinase controlling most of anabolic processes in eukaryotic cells. Consequently, mTORC1 inhibitors, such as rapamycin, serve as experimental or already approved drugs for several TSC symptoms. However, rapalogs, although quite effective, need to be administered chronically and likely for a lifetime, since therapy discontinuation results in tumor regrowth and epilepsy recurrence. Recent studies revealed that metabolism and excitability (in the case of neurons) of cells lacking Tsc1-Tsc2 complex are changed, and these features may potentially be used to treat some of TSC symptoms. In this review, we first provide basic facts about TSC and its molecular background, to next discuss the newest findings in TSC cell biology that can be used to improve existing therapies of TSC and other diseases linked to mTORC1 hyperactivation. © 2016 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 2016.
[Pt] Publication type:REVIEW; JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher
[do] DOI:10.1002/iub.1579

  2 / 205789 MEDLINE  
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[PMID]: 27797002
[Au] Autor:Lysandropoulos AP; Racapé J; Holovska V; Toungouz M
[Ad] Address:Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium. andreas.lysandropoulos@erasme.ulb.ac.be.
[Ti] Title:Human leucocyte antigen (HLA) class I and II typing in Belgian multiple sclerosis patients.
[So] Source:Acta Neurol Belg;, 2016 Oct 28.
[Is] ISSN:2240-2993
[Cp] Country of publication:Italy
[La] Language:ENG
[Ab] Abstract:This is one of the first studies to compare the frequencies of different human leucocyte antigen (HLA) class I and II alleles and haplotype HLA-DRB1*15-DQB1*06 in a cohort of 119 patients with multiple sclerosis (MS) and a cohort of 124 healthy controls in Belgium. An association with MS was found for the HLA-DRB1*15 (odds ratio [OR] 2.60 [95% confidence interval (CI) 1.51-4.50]) and HLA-DQB1*06 (OR 1.97 [95% CI 1.18-3.29]) alleles, and for haplotype DRB1*15-DQB1*06 (OR 2.63 [95% CI 1.52-4.56]). The HLA-B*07 allele also tended to be more frequent in MS patients (OR 1.46 [95% CI 0.80-2.65]) and more frequent among MS patients with than in those without the HLA-DRB1*15 allele (26/54 [48.1%] versus 6/65 [9.2%]; p value <0.0001). Other alleles were underrepresented in MS patients, such as the HLA-DRB1*07 (OR 0.39 [95% CI 0.21-0.73]) and HLA-A*02 (OR 0.56 [95% CI 0.34-0.94]), showing a protective role against the disease. The HLA-B*44 (OR 0.58 [95% CI 0.31-1.09]) and HLA-DRB1*04 (OR 0.75 [95% CI 0.42-1.34]) alleles tended to be less frequent in MS patients. Altogether, the significant results observed in this population are in line with those from other countries and confirm that propensity to MS can be due to a complex presence of various HLA class I and class II alleles.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher

  3 / 205789 MEDLINE  
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[PMID]: 27796896
[Au] Autor:Manole CG; Simionescu O
[Ad] Address:1st Clinic of Dermatology, 'Carol Davila' University of Medicine and Pharmacy, Colentina Clinical Hospital, Bucharest, Romania. catalin.manole@jcmm.org.
[Ti] Title:The Cutaneous Telocytes.
[So] Source:Adv Exp Med Biol;913:303-323, 2016.
[Is] ISSN:0065-2598
[Cp] Country of publication:United States
[La] Language:ENG
[Ab] Abstract:Telocytes (TCs) are interstitial cells found in stroma of many organs, including the skin dermis. Ultrastructurally, normal skin TCs recapitulates all the previously documented features in interstitum of other organs. Their (ultra)structural hallmark is the presence of particular shaped cellular prolongations (termed telopodes), along other features as cellular organelles representation and their distribution within cell body and its prolongations. Transmission electron microscopy (TEM) or high magnification light microscopy indicated that the particular shape of telopodes alternate characteristically thin segments (termed podomeres) and dilated segments (called podoms). A new and powerful technique, focused ion beam scanning electron microscopy (FIB-SEM), indicated that, ultrastructurally, telopodes could be either irregular ribbon-like structures, or uneven tubular-like structures. TEM images shown that podoms consists mitochondria, elements of endoplasmic reticulum and caveolae. Immunohisochemical studies on skin TCs revealed their positive expression for CD34 and PDGFRα, but for vimentin and c-kit, also. In normal dermis, TCs are involved in junctions, either homocellular (TCs-TCs), or heterocellular (TCs - other type of cells). The junctional attribute of TCs underlies their ability of forming a 3D network within dermis. Beyond the physical interactions, the connections between TCs and other cells could be also chemical, by paracrine secretion via shed vesicles as ultrastructural studies demonstrated. In normal dermis, TCs were found distributed in particular spatial relationships with other interstitial structures and/or cells: vascular structures, nerves, skin adnexa, stem cells and immune reactive cells.To date, the study of TCs was approached into two pathologic conditions: systemic sclerosis and psoriasis. In both diseases, the normal ultrastructure of TCs and also their distribution were shown to be altered. Moreover, the pattern of TCs ultrastructural changes differs in systemic sclerosis (cytoplasmic vacuolization, swollen mitochondria, lipofuscin bodies) from those appeared in psoriasis, characterized by important dystrophic changes (telopodes fragmentation, cytoplasmic disintegration, apoptotic nuclei, nuclear extrusions). Furthermore, in psoriasis, the lesional remission is (ultra)structurally displaying a recovery of dermal TCs at values similar to normal.Considering TCs ultrastructural features, their connections and spatiality in normal dermis and also their pathologic changes, TCs are credited with roles in skin homeostasis and/or pathogeny of dermatological disorders. In our opinion, further researches should be focused on identifying a specific marker for TCs and also on comprehending the pattern of their response in different dermatoses.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:In-Data-Review

  4 / 205789 MEDLINE  
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[PMID]: 27796790
[Au] Autor:Gabr RE; Tefera GB; Allen WJ; Pednekar A; Narayana PA
[Ad] Address:Departments of Diagnostic and Interventional Imaging, University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. refaat.e.gabr@uth.tmc.edu.
[Ti] Title:GRAPE: a graphical pipeline environment for image analysis in adaptive magnetic resonance imaging.
[So] Source:Int J Comput Assist Radiol Surg;, 2016 Oct 28.
[Is] ISSN:1861-6429
[Cp] Country of publication:Germany
[La] Language:ENG
[Ab] Abstract:PURPOSE: We present a platform, GRAphical Pipeline Environment (GRAPE), to facilitate the development of patient-adaptive magnetic resonance imaging (MRI) protocols. METHODS: GRAPE is an open-source project implemented in the Qt C++ framework to enable graphical creation, execution, and debugging of real-time image analysis algorithms integrated with the MRI scanner. The platform provides the tools and infrastructure to design new algorithms, and build and execute an array of image analysis routines, and provides a mechanism to include existing analysis libraries, all within a graphical environment. The application of GRAPE is demonstrated in multiple MRI applications, and the software is described in detail for both the user and the developer. RESULTS: GRAPE was successfully used to implement and execute three applications in MRI of the brain, performed on a 3.0-T MRI scanner: (i) a multi-parametric pipeline for segmenting the brain tissue and detecting lesions in multiple sclerosis (MS), (ii) patient-specific optimization of the 3D fluid-attenuated inversion recovery MRI scan parameters to enhance the contrast of brain lesions in MS, and (iii) an algebraic image method for combining two MR images for improved lesion contrast. CONCLUSIONS: GRAPE allows graphical development and execution of image analysis algorithms for inline, real-time, and adaptive MRI applications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher

  5 / 205789 MEDLINE  
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[PMID]: 27796661
[Au] Autor:Botou A; Bangeas A; Alexiou I; Sakkas LI
[Ad] Address:Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41 110, Larissa, Greece.
[Ti] Title:Acro-osteolysis.
[So] Source:Clin Rheumatol;, 2016 Oct 29.
[Is] ISSN:1434-9949
[Cp] Country of publication:Germany
[La] Language:ENG
[Ab] Abstract:Acro-osteolysis is an osteolysis of the distal phalanges of the hands and feet and can affect the terminal tuft or the shaft of the distal phalanx (transverse or band acro-osteolysis). It is often associated with distal digital ischemia, digital calcinosis, or severe sensory neuropathy. Acro-osteolysis has been associated with a heterogeneous group of disorders, including occupational activities, infections, rheumatic disorders (systemic sclerosis, psoriatic arthritis), endocrinopathies, genetic disorders, and lysosomal storage disorders. Plain radiography is the gold standard for the detection of acro-osteolysis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher

  6 / 205789 MEDLINE  
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[PMID]: 27796537
[Au] Autor:Dal-Bianco A; Grabner G; Kronnerwetter C; Weber M; Höftberger R; Berger T; Auff E; Leutmezer F; Trattnig S; Lassmann H; Bagnato F; Hametner S
[Ad] Address:Department of Neurology, Medical University of Vienna, Vienna, Austria.
[Ti] Title:Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging.
[So] Source:Acta Neuropathol;, 2016 Oct 27.
[Is] ISSN:1432-0533
[Cp] Country of publication:Germany
[La] Language:ENG
[Ab] Abstract:In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher

  7 / 205789 MEDLINE  
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[PMID]: 27796473
[Au] Autor:Becker MO
[Ad] Address:Klinik für Rheumatologie, Universitätsspital Zürich, Gloriastr. 25, 8091, Zürich, Schweiz. mikeoliver.becker@usz.ch.
[Ti] Title:Systemische Sklerose : Was ist gesichert in der Therapie? [Systemic sclerosis : What is currently available for treatment?]
[So] Source:Internist (Berl);, 2016 Oct 31.
[Is] ISSN:1432-1289
[Cp] Country of publication:Germany
[La] Language:GER
[Ab] Abstract:Systemic sclerosis (scleroderma) is a rheumatologic disease characterised not only by inflammation/autoimmunity, but also by tissue fibrosis and vascular lesions. The therapeutic approach to patients is dictated by the organ involvement and includes treatment of vascular and fibrotic disease features beyond mere immunosuppression. Fibrotic features in particular, are still inadequately treated, whereas many drugs have been tested for vascular complications within recent years. In this review, the currently available treatment options for this rare disease are presented. Therapy options in systemic sclerosis have changed over the past 10 years and this trend will also continue in the future.
[Pt] Publication type:JOURNAL ARTICLE; ENGLISH ABSTRACT
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher

  8 / 205789 MEDLINE  
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[PMID]: 27796368
[Au] Autor:Wang X; Zhang J; Baylink DJ; Li CH; Watts DM; Xu Y; Qin X; Walter MH; Tang X
[Ad] Address:Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, California, USA.
[Ti] Title:Targeting Non-classical Myelin Epitopes to Treat Experimental Autoimmune Encephalomyelitis.
[So] Source:Sci Rep;6:36064, 2016 Oct 31.
[Is] ISSN:2045-2322
[Cp] Country of publication:England
[La] Language:ENG
[Ab] Abstract:Qa-1 epitopes, the peptides that bind to non-classical major histocompatibility complex Ib Qa-1 molecules and are recognized by Qa-1-restricted CD8(+) regulatory T (Treg) cells, have been identified in pathogenic autoimmune cells that attack myelin sheath in experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis [MS]). Additionally, immunization with such epitopes ameliorates the EAE. However, identification of such epitopes requires knowledge of the pathogenic autoimmune cells which are largely unknown in MS patients. Hence, we asked whether the CD8(+) Treg cells could directly target the myelin sheath to ameliorate EAE. To address this question, we analyzed Qa-1 epitopes in myelin oligodendrocyte glycoprotein (MOG that is a protein in myelin sheath). Here, we report identification of a MOG-specific Qa-1 epitope. Immunization with this epitope suppressed ongoing EAE, which was abrogated by CD8(+) T cell depletion. Additionally, the epitope immunization activated the epitope-specific CD8(+) T cells which specifically accumulated in the CNS-draining cervical lymph nodes. Finally, CD8(+) T cells primed by the epitope immunization transferred EAE suppression. Hence, this study reveals a novel regulatory mechanism mediated by the CD8(+) Treg cells. We propose that immunization with myelin-specific HLA-E epitopes (human homologues of Qa-1 epitopes) is a promising therapy for MS.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:In-Data-Review
[do] DOI:10.1038/srep36064

  9 / 205789 MEDLINE  
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[PMID]: 27796305
[Au] Autor:Tian F; Yang W; Mordes DA; Wang JY; Salameh JS; Mok J; Chew J; Sharma A; Leno-Duran E; Suzuki-Uematsu S; Suzuki N; Han SS; Lu FK; Ji M; Zhang R; Liu Y; Strominger J; Shneider NA; Petrucelli L; Xie XS; Eggan K
[Ad] Address:Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
[Ti] Title:Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging.
[So] Source:Nat Commun;7:13283, 2016 Oct 31.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:ENG
[Ab] Abstract:The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:In-Data-Review
[do] DOI:10.1038/ncomms13283

  10 / 205789 MEDLINE  
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[PMID]: 27796082
[Au] Autor:Kogan F; Fan AP; McWalter EJ; Oei EH; Quon A; Gold GE
[Ad] Address:Department of Radiology, Stanford University, Stanford, California, USA. fkogan@stanford.edu.
[Ti] Title:PET/MRI of metabolic activity in osteoarthritis: A feasibility study.
[So] Source:J Magn Reson Imaging;, 2016 Oct 31.
[Is] ISSN:1522-2586
[Cp] Country of publication:United States
[La] Language:ENG
[Ab] Abstract:PURPOSE: To evaluate positron emission tomography / magnetic resonance imaging (PET/MRI) knee imaging to detect and characterize osseous metabolic abnormalities and correlate PET radiotracer uptake with osseous abnormalities and cartilage degeneration observed on MRI. MATERIALS AND METHODS: Both knees of 22 subjects with knee pain or injury were scanned at one timepoint, without gadolinium, on a hybrid 3.0T PET-MRI system following injection of (18) F-fluoride or (18) F-fluorodeoxyglucose (FDG). A musculoskeletal radiologist identified volumes of interest (VOIs) around bone abnormalities on MR images and scored bone marrow lesions (BMLs) and osteophytes using a MOAKS scoring system. Cartilage appearance adjacent to bone abnormalities was graded with MRI-modified Outerbridge classifications. On PET standardized uptake values (SUV) maps, VOIs with SUV greater than 5 times the SUV in normal-appearing bone were identified as high-uptake VOI (VOIHigh ). Differences in (18) F-fluoride uptake between bone abnormalities, BML, and osteophyte grades and adjacent cartilage grades on MRI were identified using Mann-Whitney U-tests. RESULTS: SUVmax in all subchondral bone lesions (BML, osteophytes, sclerosis) was significantly higher than that of normal-appearing bone on MRI (P < 0.001 for all). Of the 172 high-uptake regions on (18) F-fluoride PET, 63 (37%) corresponded to normal-appearing subchondral bone on MRI. Furthermore, many small grade 1 osteophytes (40 of 82 [49%]), often described as the earliest signs of osteoarthritis (OA), did not show high uptake. Lastly, PET SUVmax in subchondral bone adjacent to grade 0 cartilage was significantly lower compared to that of grades 1-2 (P < 0.05) and grades 3-4 cartilage (P < 0.001). CONCLUSION: PET/MRI can simultaneously assess multiple early metabolic and morphologic markers of knee OA across multiple tissues in the joint. Our findings suggest that PET/MR may detect metabolic abnormalities in subchondral bone, which appear normal on MRI. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2016.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1610
[Cu] Class update date: 161031
[Lr] Last revision date:161031
[St] Status:Publisher
[do] DOI:10.1002/jmri.25529


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