排序方式: 共有11条查询结果,搜索用时 14 毫秒
1.
Magdaline Costa Koula Sourris Sue Mei Lim Qing C. Yu Claire E. Hirst Helena C. Parkington Vanta J. Jokubaitis Anthony E. Dear Hong B. Liu Suzanne J. Micallef Kathy Koutsis Andrew G. Elefanty Edouard G. Stanley 《Stem cell research》2013,10(1):103-117
The limited availability of human vascular endothelial cells (ECs) hampers research into EC function whilst the lack of precisely defined culture conditions for this cell type presents problems for addressing basic questions surrounding EC physiology. We aimed to generate endothelial progenitors from human pluripotent stem cells to facilitate the study of human EC physiology, using a defined serum-free protocol. Human embryonic stem cells (hESC-ECs) differentiated under serum-free conditions generated CD34+KDR+ endothelial progenitor cells after 6 days that could be further expanded in the presence of vascular endothelial growth factor (VEGF). The resultant EC population expressed CD31 and TIE2/TEK, took up acetylated low-density lipoprotein (LDL) and up-regulated expression of ICAM-1, PAI-1 and ET-1 following treatment with TNFα. Immunofluorescence studies indicated that a key mediator of vascular tone, endothelial nitric oxide synthase (eNOS), was localised to a perinuclear compartment of hESC-ECs, in contrast with the pan-cellular distribution of this enzyme within human umbilical vein ECs (HUVECs). Further investigation revealed that that the serum-associated lipids, lysophosphatidic acid (LPA) and platelet activating factor (PAF), were the key molecules that affected eNOS localisation in hESC-ECs cultures. These studies illustrate the feasibility of EC generation from hESCs and the utility of these cells for investigating environmental cues that impact on EC phenotype. We have demonstrated a hitherto unrecognized role for LPA and PAF in the regulation of eNOS subcellular localization. 相似文献
2.
Ricardas Radisauskas Vilija Malinauskiene Egle Milinaviciene Daina Kranciukaite-Butylkiniene Abdonas Tamosiunas Gailute Bernotiene Dalia Luksiene Zemyna Milasauskiene Diana Sopagiene Daiva Rastenyte 《PloS one》2016,11(4)
BackgroundThere is a lack of reliable epidemiological data on longitudinal trends in stroke attack rates, incidence, and mortality in the countries of the Baltic region.AimsThe aim of the present study was to explore the longitudinal trends of stroke in middle-aged urban population of Lithuania during the period of 1986 through 2012.MethodsAll stroke events in the studied population were ascertained and validated according to the standardized criteria outlined by the WHO MONICA Project. The study included all patients in Kaunas (Lithuania) city aged 25 to 64 years who experienced a stroke between 1986 and 2012. Estimates of time-trends of the annual percentage change in stroke attack rates, incidence of stroke, and mortality from this condition were made by applying the Joinpoint regression analysis.ResultsDuring the study period, 9,992 stroke events were registered. The overall proportion of recurrent events was 25.7%. Overall, 18.9% of the events (20.0% in men, and 17.4% in women) were fatal within 28 days. During the period of 1986 to 2012, a flat trend in the incidence of stroke was observed among both male and female middle-aged inhabitants of Kaunas city, while attack rates were increasing due to the increase in recurrent strokes. Both mortality and 28-day case fatality of stroke declined significantly over the study period in both sexes.ConclusionsAn increase both in the incidence and recurrence of stroke among middle-aged men residing in Kaunas city and in the recurrence of stroke among women denotes the inefficiency of measures applied both for primary and secondary prevention of stroke in Lithuania. The revision of current prevention strategies and the introduction of new ones are of paramount importance in order to fight the epidemic of stroke. 相似文献
3.
C Meyniel T Spelman VG Jokubaitis M Trojano G Izquierdo F Grand'Maison C Oreja-Guevara C Boz A Lugaresi M Girard P Grammond G Iuliano M Fiol JA Cabrera-Gomez R Fernandez-Bolanos G Giuliani J Lechner-Scott E Cristiano J Herbert T Petkovska-Boskova R Bergamaschi V van Pesch F Moore N Vella M Slee V Santiago M Barnett E Havrdova C Young CA Sirbu M Tanner M Rutherford H Butzkueven;MSBasis Study Group 《PloS one》2012,7(6):e38661
4.
Vilija G. Jokubaitis Tim Spelman Jeannette Lechner-Scott Michael Barnett Cameron Shaw Steve Vucic Danny Liew Helmut Butzkueven Mark Slee 《PloS one》2013,8(3)
Objective
To prospectively characterise treatment persistence and predictors of treatment discontinuation in an Australian relapsing-remitting multiple sclerosis (RRMS) population.Methods
Tertiary MS treatment centres participating in the MSBase registry prospectively assessed treatment utilisation, persistence, predictors of treatment discontinuation and switch rates. Multivariable survival analyses were used to compare treatment persistence between drugs and to identify predictors of treatment discontinuation.Results
1113 RRMS patients were studied. Patients persisted on their first disease-modifying therapy (DMT) for a median of 2.5 years. Treatment persistence on GA was shorter than on all IFNβ products (p<0.03). Younger age at treatment initiation and higher EDSS were predictive of DMT discontinuation. Patients persisted on subsequent DMTs, for 2.3 years. Patients receiving natalizumab (NAT) as a subsequent DMT persisted longer on treatment than those on IFNβ or GA (p<0.000). The primary reason for treatment discontinuation for any drug class was poor tolerability. Annualised switch or cessation rates were 9.5–12.5% for individual IFNβ products, 11.6% for GA and 4.4% for NAT.Conclusion
This multicentre MS cohort study is the first to directly compare treatment persistence on IFNβ and GA to NAT. We report that treatment persistence in our Australian RRMS population is short, although patients receiving IFNβ as a first DMT persisted longer on treatment than those on GA. Additionally, patients receiving NAT as a subsequent DMT were more likely to persist on treatment than those switched to IFNβ or GA. EDSS and age at DMT initiation were predictive of DMT discontinuation. Treatment intolerance was the principal reason for treatment cessation. 相似文献5.
Espinosa A Oke V Elfving A Nyberg F Covacu R Wahren-Herlenius M 《Experimental cell research》2008,314(20):3605-3613
Patients with the systemic autoimmune diseases Sjögrens's syndrome and systemic lupus erythematosus often have autoantibodies against the intracellular protein Ro52. Ro52 is an E3 ligase dependent on the ubiquitin conjugation enzymes UBE2D1 and UBE2E1. While Ro52 and UBE2D1 are cytoplasmic proteins, UBE2E1 is localized to the nucleus. Here, we investigate how domains of human Ro52 regulate its intracellular localization. By expressing fluorescently labeled Ro52 and Ro52 mutants in HeLa cells, an intact coiled-coil domain was found to be necessary for the cytoplasmic localization of Ro52. The amino acids 381-470 of the B30.2 region were essential for translocation into the nucleus. Furthermore, after exposure of HeLa cells to the inflammatory mediator nitric oxide (NO), Ro52 translocated to the nucleus. A nuclear localization of Ro52 in inflamed tissue expressing inducible NO synthetase (iNOS) from cutaneous lupus patients was observed by immunohistochemistry and verified in NO-treated cultures of patient-derived primary keratinocytes. Our results show that the localization of Ro52 is regulated by endogenous sequences, and that nuclear translocation is induced by an inflammatory mediator. This suggests that Ro52 has both cytoplasmic and nuclear substrates, and that Ro52 mediates ubiquitination through UBE2D1 in the cytoplasm and through UBE2E1 in the nucleus. 相似文献
6.
Abdonas Tamosiunas Ricardas Radisauskas Jurate Klumbiene Gailute Bernotiene Janina Petkeviciene Dalia Luksiene Dalia Virviciute Vilija Malinauskiene Olga Vikhireva Vilius Grabauskas 《PloS one》2015,10(12)
Aim
To evaluate the additional prognostic value of family history for the estimation of cardiovascular (CVD) mortality risk in middle-aged urban Lithuanian men.Methods
The association between family history of CVD and the risk of CVD mortality was examined in a population-based cohort of 6,098 men enrolled during 1972–1974 and 1976–1980 in Kaunas, Lithuania. After up to 40 years of follow-up, 2,272 deaths from CVD and 1,482 deaths from coronary heart disease (CHD) were identified. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HR) for CVD and CHD mortality.Results
After adjustment for traditional CVD risk factors, the HR for CVD mortality was 1.24 (95% CI 1.09–1.42) and for CHD mortality 1.20 (1.02–1.42) in men with first-degree relatives having a history of myocardial infarction (MI), compared to men without positive family history. A significant effect on the risk of CVD and CHD mortality was also observed for the family history of sudden cardiac death and any CVD. Addition of family history of MI, sudden death, and any CVD to traditional CVD risk factors demonstrated modest improvement in the performance of Cox models for CVD and CHD mortality.Conclusions
Family history of CVD is associated with a risk of CVD and CHD mortality significantly and independently of other risk factors in a middle-aged male population. Addition of family history to traditional CVD risk factors improves the prediction of CVD mortality and could be used for identification of high-risk individuals. 相似文献7.
Melissa M. Gresle Estella Alexandrou Qizhu Wu Gary Egan Vilija Jokubaitis Margaret Ayers Anna Jonas William Doherty Anna Friedhuber Gerry Shaw Michael Sendtner Ben Emery Trevor Kilpatrick Helmut Butzkueven 《PloS one》2012,7(10)
Leukemia inhibitory factor (LIF) and Ciliary Neurotrophic factor (CNTF) are members of the interleukin-6 family of cytokines, defined by use of the gp130 molecule as an obligate receptor. In the murine experimental autoimmune encephalomyelitis (EAE) model, antagonism of LIF and genetic deletion of CNTF worsen disease. The potential mechanism of action of these cytokines in EAE is complex, as gp130 is expressed by all neural cells, and could involve immuno-modulation, reduction of oligodendrocyte injury, neuronal protection, or a combination of these actions. In this study we aim to investigate whether the beneficial effects of CNTF/LIF signalling in EAE are associated with axonal protection; and whether this requires signalling through oligodendrocytes. We induced MOG35–55 EAE in CNTF, LIF and double knockout mice. On a CNTF null background, LIF knockout was associated with increased EAE severity (EAE grade 2.1±0.14 vs 2.6±0.19; P<0.05). These mice also showed increased axonal damage relative to LIF heterozygous mice, as indicated by decreased optic nerve parallel diffusivity on MRI (1540±207 µm2−/s vs 1310±175 µm2−/s; P<0.05), and optic nerve (−12.5%) and spinal cord (−16%) axon densities; and increased serum neurofilament-H levels (2.5 fold increase). No differences in inflammatory cell numbers or peripheral auto-immune T-cell priming were evident. Oligodendrocyte-targeted gp130 knockout mice showed that disruption of CNTF/LIF signalling in these cells has no effect on acute EAE severity. These studies demonstrate that endogenous CNTF and LIF act centrally to protect axons from acute inflammatory destruction via an oligodendrocyte-independent mechanism. 相似文献
8.
Abdonas?TamosiunasEmail author Migle?Baceviciene Regina?Reklaitiene Ricardas?Radisauskas Kristina?Jureniene Adelina?Azaraviciene Dalia?Luksiene Vilija?Malinauskiene Evelina?Daugeliene Laura?Sapranaviciute-Zabazlajeva 《BMC neurology》2012,12(1):149
Background
The purpose of this study was to examine associations between cardiovascular risk factors and cognitive ability in middle aged and elderly Lithuanian urban population.Methods
Data from the survey performed in the framework of the HAPIEE (Health, Alcohol, Psychosocial Factors in Eastern Europe) study were presented. A random sample of 7,087 individuals aged 45–72 years was screened in 2006–2008.Results
The scores of immediate recall and delayed verbal recall, cognitive speed and attention were significantly lower in men than in women; yet numerical ability scores were higher in men. Significant associations between lowered cognitive functions and previous stroke (in male OR?=?2.52; 95% CI?=?1.75-3.64; in female OR?=?2.45; 95% CI?=?1.75, 3.64) as well as ischemic heart disease history (among male OR?=?1.28; 95% CI?=?1.03-1.60) have been determined. Higher level of physical activity in leisure time (among female OR?=?1.32; 95% CI?=?1.03-1.69), poor self-rated health (among male OR?=?1.57; 95% CI?=?1.15-2.14) and poor quality of life (in male OR?=?1.67; 95% CI?=?1.07-2.61; in female OR?=?2.81; 95% CI?=?1.92-4.11) were related to lowered cognitive function.Conclusions
The findings of the study suggest that associations between cardiovascular risk factors and lowered cognitive function among healthy middle-aged and elderly adults strongly depend on gender.9.
Makoto Tanaka Vanta Jokubaitis Colin Wood Yi Wang Nathalie Brouard Martin Pera Milton Hearn Paul Simmons Naoki Nakayama 《Stem cell research》2009,3(2-3):126-141
WNT and bone morphogenetic protein (BMP) signaling are known to stimulate hemogenesis from pluripotent embryonic stem (ES) cells. However, osteochondrogenic mesoderm was generated effectively when BMP signaling is kept to a low level, while WNT signaling was strongly activated. When mesoderm specification from ES cells was exogenous factor dependent, WNT3a addition supported the generation of cardiomyogenic cells expressing lateral plate/extraembryonic mesoderm genes, and this process involved endogenous BMP activities. Exogenous BMP4 showed a similar effect that depended on endogenous WNT activities. However, neither factor induced robust chondrogenic activity. In support, ES cell differentiation in the presence of either WNT3a or BMP4 was associated with elevated levels of both Bmp and Wnt mRNAs, which appeared to provide sufficient levels of active BMPs and WNTs to promote the nonchondrogenic mesoderm specification. The osteochondrogenic mesoderm expressed PDGFRα, which also expressed genes that mark somite and rostral presomitic mesoderm. A strong WNT signaling was required for generating the mesodermal progeny, while approximately 50- to 100-fold lower concentration of WNT3a was sufficient for specifying axial mes(end)oderm. Thus, depending on the dose and cofactor (BMP), WNT signaling stimulates the generation of different biological activities and specification of different types of mesodermal progeny from ES cells. 相似文献
10.
Feng Xu Juozas J. Kulys Kyle Duke Kaichang Li Kastis Krikstopaitis Heinz-Josef W. Deussen Eric Abbate Vilija Galinyte Palle Schneider 《Applied microbiology》2000,66(5):2052-2056
1-Hydroxybenzotriazole, violuric acid, and N-hydroxyacetanilide are three N-OH compounds capable of mediating a range of laccase-catalyzed biotransformations, such as paper pulp delignification and degradation of polycyclic hydrocarbons. The mechanism of their enzymatic oxidation was studied with seven fungal laccases. The oxidation had a bell-shaped pH-activity profile with an optimal pH ranging from 4 to 7. The oxidation rate was found to be dependent on the redox potential difference between the N-OH substrate and laccase. A laccase with a higher redox potential or an N-OH compound with a lower redox potential tended to have a higher oxidation rate. Similar to the enzymatic oxidation of phenols, phenoxazines, phenothiazines, and other redox-active compounds, an “outer-sphere” type of single-electron transfer from the substrate to laccase and proton release are speculated to be involved in the rate-limiting step for N-OH oxidation. 相似文献