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1.

001-es BibID:BIBFORM043609
Első szerző:Albert Réka
Cím:Cultivation and characterization of cornea limbal epithelial stem cells on lens capsule in animal material-free medium / Réka Albert, Zoltán Veréb, Krisztián Csomós, Morten C. Moe, Erik O. Johnsen, Ole Kristoffer Olstad, Bjørn Nicolaissen, Éva Rajnavölgyi, László Fésüs, András Berta, Goran Petrovski
Dátum:2012
ISSN:1932-6203
Megjegyzések:A simple, reproducible, animal-material free method for cultivating and characterizing cornea limbal epithelial stem cells (LESCs) on human lens capsule (LC) was developed for future clinical transplantation. The limbal tissue explants (2 ? 2 ? 0.25 mm) were harvested from 77 cadavers and expanded ex vivo on either cell culture plates or LC in medium containing human serum as the only growth supplement. Cell outgrowth at the edge of the explants was observed within 24 hours of cultivation and achieved viable outgrowth (>97% viability as measured by MTT assay and flow cytometry) within two weeks. The outgrowing cells were examined by genome-wide microarray including markers of stemness (p63?, ABCG2, CK19, Vimentin and Integrin ?9), proliferation (Ki-67), limbal epithelial cells (CK 8/18 and 14) and differentiated cornea epithelial cells (CK 3 and 12). Immunostaining revealed the non-hematopoietic, -endothelial and -mesenchymal stem cell phenotype of the LESCs and the localization of specific markers in situ. Cell adhesion molecules, integrins and lectin-based surface carbohydrate profiling showed a specific pattern on these cells, while colony-formation assay confirmed their clonal potency. The LESCs expressed a specific surface marker fingerprint (CD117/c-kit, CXCR4, CD144/VE-Cadherin, CD146/MCAM, CD166/ALCAM, and surface carbohydrates: WGA, ConA, RCA, PNA and AIL) which can be used for better localization of the limbal stem cell niche. In summary, we report a novel method combining the use of a medium with human serum as the only growth supplement with LC for cultivating, characterizing and expanding cornea LESCs from cadavers or alternatively from autologous donors for possible treatment of LESC deficiency.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Limbal epithelial stem cell
egyetemen (Magyarországon) készült közlemény
Megjelenés:PLoS One. - 7 : 10 (2012), p. e47187. -
További szerzők:Veréb Zoltán (1980-) (immunológus, mikrobiológus, molekuláris biológus) Csomós Krisztián (1981-) (molekuláris biológus) Moe, Morten C. Johnsen, Erik O. Olstad, Ole Kristoffer Nicolaissen, Bjorn Rajnavölgyi Éva (1950-) (immunológus) Fésüs László (1947-) (orvos biokémikus) Berta András (1955-) (szemész, gyermekszemész) Petrovski, Goran (1975-) (orvos)
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2.

001-es BibID:BIBFORM068528
035-os BibID:(cikkazonosító)e0177003 (WOS)000400648500113 (Scopus)85019125377
Első szerző:Csutak Adrienne (szemész)
Cím:Plasminogen Activator Activity in Tears of Pregnant Women / Adrienne Csutak, Zita Steiber, József Tőzsér, Attila Jakab, András Berta, David M. Silver
Dátum:2017
ISSN:1932-6203
Megjegyzések:Purpose: Plasminogen activator activity (PAA) in tears of pregnant women wasinvestigated at various gestation times to assess the availability of plasminogenactivator for aiding potential corneal wound healing processes during pregnancy.Methods: PAA was measured by a spectrophotometric method. The analysis used 91tear samples from pregnant and non-pregnant women, supplemented with 10additional tear PAA measurements from non-pregnant women obtained in a previousstudy.Results: Tear levels of PAA in pregnant women formed a bimodal distribution. Eitherthe tear PAA level was zero or non-zero during pregnancy. When non-zero, the tearPAA level was dissociated from gestation time and not different than non-pregnant andpost-pregnant levels.The frequency of occurrence of zero level tear PAA increasedwith gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women inthe first, second and third trimester,respectively.Conclusions:Overall, of the tear samples taken from women during pregnancy, a totalof 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAAvalues throughout gestation equivalent to non-pregnant tear PAA values, suggestinglocal control of the source of PAA in tears. Given the importance of the plasminogenactivator system in tears to wound healing in the cornea, and the high occurrence ofzero tear PAA in our sample of pregnant women, elective corneal surgery would becontraindicated. If corneal surgery is nevertheless necessary, the tear PAA level wouldbe worth checking and patients with low level should be closely observed during thepostoperative period
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
gestation
human tears
plasminogen activator activity
pregnancy
proteolysis
tear enzymes
Megjelenés:Plos One. - 12 : 5 (2017), p. 1-10. -
További szerzők:Steiber Zita (1977-) (orvos, szemész) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Jakab Attila (1964-) (szülész-nőgyógyász, endokrinológus) Berta András (1955-) (szemész, gyermekszemész) Silver, David M.
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3.

001-es BibID:BIBFORM064300
035-os BibID:(cikkazonosító)e0158000 (WOS)000378212400066 (Scopus)84976863903
Első szerző:Kalló Gergő (molekuláris biológus)
Cím:Changes in the chemical barrier composition of tears in Alzheimer's disease reveal potential tear diagnostic biomarkers / Gergő Kalló, Miklós Emri, Zsófia Varga, Bernadett Ujhelyi, József Tőzsér, Adrienne Csutak, Éva Csősz
Dátum:2016
ISSN:1932-6203
Megjegyzések:Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, with increasing prevalence affecting millions of people worldwide. Currently, only autopsy is able to confirm the diagnosis with a 100 % certainty, therefore, biomarkers from body fluids obtained by non-invasive means provide an attractive alternative for the diagnosis of Alzheimer`s disease. Global changes of the protein profile were examined by quantitative proteomics; firstly, electrophoresis and LC-MS/MS were used, thereafter, SRM-based targeted proteomics method was developed and applied to examine quantitative changes of tear proteins.Alterations in the tear flow rate, total tear protein concentration and composition of the chemical barrier specific to AD were demonstrated, and the combination of lipocalin-1, dermcidin, lysozyme-C and lacritin was shown to be a potential biomarker, with an 81 % sensitivity and 77 % specificity.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
chemical barrier
Alzheimer's disease
tear
proteomics
biomarker
quantitative mass spectrometry
SRM
Megjelenés:Plos One. - 11 : 6 (2016), p. 1-14. -
További szerzők:Emri Miklós (1962-) (fizikus) Varga Zsófia (1970-) (pszichiáter) Ujhelyi Bernadett (1981-) (szemész) Tőzsér József (1959-) (molekuláris biológus, biokémikus, vegyész) Csutak Adrienne (1971-) (szemész) Csősz Éva (1977-) (biokémikus, molekuláris biológus)
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Proteomika, Szemészet Kutatócsoport
TÁMOP 4.2.4.A/2-11-1-2012-0001
TÁMOP
TÁMOP-4.2.2.D-15/1/KONV-2015-0016
TÁMOP
TÁMOP-4.2.2.B-15/1/KONV-2015-0001
TÁMOP
National Brain Research Program KTIA_13_NAP-A-II/3 ME
Egyéb
Astellas Pharma Ltd. Fellowship
Egyéb
Lajos Szodoray Postdoctoral Fellowship
Egyéb
Janos Bolyai Postdoctoral Fellowship
Egyéb
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4.

001-es BibID:BIBFORM048756
Első szerző:Kolozsvári Bence Lajos (szemész)
Cím:Alterations of Tear Mediators in Patients with Keratoconus after Corneal Crosslinking Associate with Corneal Changes / Bence Lajos Kolozsvári, András Berta, Goran Petrovski, Kata Miháltz, Péter Gogolák, Éva Rajnavölgyi, Ziad Hassan, Péter Széles, Mariann Fodor
Dátum:2013
ISSN:1932-6203
Megjegyzések:Keratoconus (KC) is the most common primary corneal ectatic disease which has considerable importance in public health. Corneal collagen crosslinking (CXL) is a procedure to mitigate progression of KC and reduce demand for corneal transplantation. Although studies have proven the efficacy of CXL regarding corneal shape, none have investigated the effects of CXL on tear biomarkers which are useful tools to understand molecular mechanisms behind CXL. Our purpose was to determine the effect of CXL on tear mediators in patients with KC and analyze associations with corneal changes. Tear samples were collected pre-CXL from 26 eyes of 23 patients and during a 12-month follow-up. The mediators' concentration was measured by Cytometric Bead Array technology. Corneal topography parameters measured by Scheimpflug Camera included: Thinnest-corneal-thickness (ThCT), keratometry values (K1, K2), Radii-Minimum (Rmin), Keratoconus-Index (KI), Center-KI (CKI), Index-of-Height Asymmetry (IHA) and Index-of-Surface Variance (ISV). At baseline, KI was correlated negatively with chemokine (C-C motif) ligand 5 (CCL5) (p=0.015) and matrix metalloproteinase (MMP)-13 (p=0.007). At day 4, interleukin (IL)-6 and IL-8 increased, while IL-13, IL-17A, interferon (IFN)-?, CCL5, MMP-13, epidermal growth factor (EGF), nerve growth factor (NGF) and plasminogen activator inhibitor (PAI-1) decreased significantly compared to pre-CXL concentrations (p?0.02). At 6 months tissue plasminogen activator (t-PA) increased (p=0.02), while at 12 months Rmin increased (p?0.004), and IL-6 and CXCL8 (p=0.005 and p=0.047) as well as K1, ISV and KI decreased. After 6 months CKI and ISV showed significant associations with IL-17A; CKI with IL-13 and ThCT with IL-13 (p?0.02), while at 12 months there were reverse associations between ThCT and IL-6, IL-13, INF?, CCL5 and PAI-1 (p?0.02). Alterations of mediators in tear fluid after CXL associate with topographic changes highlight the fact that many mediators are involved in the complex mechanisms after CXL. Further studies on biomarkers to investigate the efficacy of CXL are needed.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
corneal ectatic disease
Keratoconus
Corneal collagen crosslinking
Megjelenés:Plos One. - 8 : 10 (2013), p. e76333-. -
További szerzők:Berta András (1955-) (szemész, gyermekszemész) Petrovski, Goran (1975-) (orvos) Miháltz Kata Gogolák Péter (1968-) (biológus, immunológus) Rajnavölgyi Éva (1950-) (immunológus) Hassan, Ziad (1962-) (szemész) Széles Péter Fodor Mariann (1975-) (szemész)
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5.

001-es BibID:BIBFORM042063
Első szerző:Losonczy Gergely (szemész)
Cím:Effect of the Gas6 c.834+7G>A Polymorphism and the Interaction of Known Risk Factors on AMD Pathogenesis in Hungarian Patients / Gergely Losonczy, Attila Vajas, Lili Takács, Erika Dzsudzsák, Ágnes Fekete, Éva Márhoffer, László Kardos, Éva Ajzner, Begoña Hurtado, Pablo Garcia de Frutos, András Berta, István Balogh
Dátum:2012
Megjegyzések:Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD. We searched for genetic interactions and for differences in dry and wet AMD etiology. We enrolled 213 patients with exudative, 67 patients with dry AMD and 106 age and ethnically matched controls. Altogether 12 polymorphisms in Apolipoprotein E, complement factor H, complement factor I, complement component 3, blood coagulation factor XIII, HTRA1, LOC387715, Gas6 and MerTK genes were tested. No association was found between either the exudative or the dry form and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. Gas6 c.834+7G>A polymorphism was found to be significantly protective irrespective of other genotypes, reducing the odds of wet type AMD by a half (OR = 0.50, 95%CI: 0.26-0.97, p = 0.04). Multiple regression models revealed an interesting genetic interaction in the dry AMD subgroup. In the absence of C3 risk allele, mutant genotypes of both CFH and HTRA1 behaved as strongly significant risk factors (OR = 7.96, 95%CI: 2.39 = 26.50, p = 0.0007, and OR = 36.02, 95%CI: 3.30-393.02, p = 0.0033, respectively), but reduced to neutrality otherwise. The risk allele of C3 was observed to carry a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only, in which case it was associated with a near-five-fold relative increase in the odds of dry type AMD (OR = 4.93, 95%CI: 1.98-12.25, p = 0.0006). Our results suggest a protective role of Gas6 c.834+7G>A polymorphism in exudative AMD development. In addition, novel genetic interactions were revealed between CFH, HTRA1 and C3 polymorphisms that might contribute to the pathogenesis of dry AMD.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:PLoS One. - 7 : 11 (2012), p. e50181. -
További szerzők:Vajas Attila (1973-) (szemész) Takács Lili (1969-) (szemész) Dzsudzsák Erika Fekete Ágnes Márhoffer Éva Kardos László (1970-) (megelőző orvostan és népegészségtan szakorvos) Ajzner Éva (1968-) (laboratóriumi szakorvos) Hurtado, Begona de Frutos, Pablo Garcia Berta András (1955-) (szemész, gyermekszemész) Balogh István (1972-) (molekuláris biológus, genetikus)
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6.

001-es BibID:BIBFORM063542
035-os BibID:(cikkazonosító)e0153186 (WOS)000374131200058 (Scopus)84963717840
Első szerző:Pásztor Dorottya (szemész)
Cím:Tear Mediators in Corneal Ectatic Disorders / Pásztor Dorottya, Kolozsvári Bence Lajos, Csutak Adrienne, Berta András, Hassan Ziad, Ujhelyi Bernadett, Gogolák Péter, Fodor Mariann
Dátum:2016
ISSN:1932-6203
Megjegyzések:Purpose To compare the concentrations of 11 tear mediators in order to reveal the biochemical difference between pellucid marginal degeneration (PMD) and keratoconus (KC).MethodsWe have designed a cross-sectional study in which patients with corneal ectasia based on slit-lamp biomicroscopy and Pentacam HR (keratometry values (K1, K2, Kmax), astigmatism, minimal radius of curvature (Rmin), corneal thickness (Apex and Min), indices (surfacevariation, vertical asymmetry, keratoconus, central keratoconus, height asymmetry and decentration)) were enrolled. Eyes of keratoconic patients were similar to the PMD patients in age and severity (K2, Kmax and Rmin). Non-stimulated tear samples were collected from nine eyes of seven PMD patients, 55 eyes of 55 KC patients and 24 eyes of 24 healthy controls. The mediators' (interleukin -6, -10, chemokine ligand 5, -8, -10, matrix metalloproteinase (MMP) -9, -13, tissue inhibitor of metalloproteinases (TIMP)-1, tissue plasminogen activator, plasminogen activator inhibitor, nerve growth factor) concentrations were measured using Cytometric Bead Array.ResultsMMP-9 was the only mediator which presented relevant variances between the two patient groups (p = 0.005). The ratios of MMP-9 and TIMP-1 were 2.45, 0.40 and 0.23 in PMD, KC and the controls, respectively.ConclusionAs far as we are aware, this is the first study that aims to reveal the biochemical differences between PMD and KC. Further studies of biomarkers to investigate the precise role of these mediators need to be defined, and it is important to confirm the observed changes in a larger study to gain further insights into the molecular alterations in PMD.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Plos One. - 11 : 4 (2016), p. 1-14. -
További szerzők:Kolozsvári Bence Lajos (1977-) (szemész) Csutak Adrienne (1971-) (szemész) Berta András (1955-) (szemész, gyermekszemész) Hassan, Ziad (1962-) (szemész) Ujhelyi Bernadett (1981-) (szemész) Gogolák Péter (1968-) (biológus, immunológus) Fodor Mariann (1975-) (szemész)
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7.

001-es BibID:BIBFORM059238
Első szerző:Viiri, Johanna
Cím:Autophagy Activation Clears ELAVL1/HuR-Mediated Accumulation of SQSTM1/p62 during Proteasomal Inhibition in Human Retinal Pigment Epithelial Cells / Johanna Viiri, Marialaura Amadio, Nicoletta Marchesi, Juha M. T. Hyttinen, Niko Kivinen, Reijo Sironen, Kirsi Rilla, Saeed Akhtar, Alessandro Provenzani, Vito Giuseppe D'Agostino, Stefano Govoni, Alessia Pascale, Hansjurgen Agostini, Goran Petrovski, Antero Salminen, Kai Kaarniranta
Dátum:2013
ISSN:1932-6203
Megjegyzések:Age-related macular degeneration (AMD) is the most common reason of visual impairment in the elderly in the Western countries. The degeneration of retinal pigment epithelial cells (RPE) causes secondarily adverse effects on neural retina leading to visual loss. The aging characteristics of the RPE involve lysosomal accumulation of lipofuscin and extracellular protein aggregates called "drusen". Molecular mechanisms behind protein aggregations are weakly understood. There is intriguing evidence suggesting that protein SQSTM1/p62, together with autophagy, has a role in the pathology of different degenerative diseases. It appears that SQSTM1/p62 is a connecting link between autophagy and proteasome mediated proteolysis, and expressed strongly under the exposure to various oxidative stimuli and proteasomal inhibition. ELAVL1/HuR protein is a post-transcriptional factor, which acts mainly as a positive regulator of gene expression by binding to specific mRNAs whose corresponding proteins are fundamental for key cellular functions. We here show that, under proteasomal inhibitor MG-132, ELAVL1/HuR is up-regulated at both mRNA and protein levels, and that this protein binds and post-transcriptionally regulates SQSTM1/p62 mRNA in ARPE-19 cell line. Furthermore, we observed that proteasomal inhibition caused accumulation of SQSTM1/p62 bound irreversibly to perinuclear protein aggregates. The addition of the AMPK activator AICAR was pro-survival and promoted cleansing by autophagy of the former complex, but not of the ELAVL1/HuR accumulation, indeed suggesting that SQSTM1/p62 is decreased through autophagy-mediated degradation, while ELAVL1/HuR through the proteasomal pathway. Interestingly, when compared to human controls, AMD donor samples show strong SQSTM1/p62 rather than ELAVL1/HuR accumulation in the drusen rich macular area suggesting impaired autophagy in the pathology of AMD.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Apoptosis
autophagic cell death
cell staining
Cytoplasm
Immunoprecipitation
macular degeneration
messenger RNA
proteasomes
Megjelenés:Plos One. - 8 : 7 (2013), p. e69563-. -
További szerzők:Amadio, Marialaura Marchesi, Nicoletta Hyttinen, Juha M. T. Kivinen, Niko Sironen, Reijo Rilla, Kirsi Akhtar, Saeed (1949-) (molekuláris biológus) Provenzani, Alessandro D'Agostino, Vito Giuseppe Govoni, Stefano Pascale, Alessia Agostini, Hansjurgen Petrovski, Goran (1975-) (orvos) Salminen, Antero Kaarniranta, Kai (1972-) (szemész szakorvos)
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