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51.
Leo AB Joosten Erik Lubberts Monique MA Helsen Tore Saxne Christina JJ Coenen-de Roo Dick Heinegård Wim B van den Berg 《Arthritis research & therapy》1999,1(1):81-11
Destruction of cartilage and bone are hallmarks of human rheumatoid arthritis (RA), and controlling these erosive processes
is the most challenging objective in the treatment of RA. Systemic interleukin-4 treatment of established murine collagen-induced
arthritis suppressed disease activity and protected against cartilage and bone destruction. Reduced cartilage pathology was
confirmed by both decreased serum cartilage oligomeric matrix protein (COMP) and histological examination. In addition, radiological
analysis revealed that bone destruction was also partially prevented. Improved suppression of joint swelling was achieved
when interleukin-4 treatment was combined with low-dose prednisolone treatment. Interestingly, synergistic reduction of both
serum COMP and inflammatory parameters was noted when low-dose interleukin-4 was combined with prednisolone. Systemic treatment
with interleukin-4 appeared to be a protective therapy for cartilage and bone in arthritis, and in combination with prednisolone
at low dosages may offer an alternative therapy in RA. 相似文献
52.
Lonneke Smeding Jan Willem Kuiper Frans B Pl?tz Martin CJ Kneyber AB Johan Groeneveld 《Respiratory research》2013,14(1):92
Background
Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.Materials and methods
N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.Results
Instillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.Conclusions
Injurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity. 相似文献53.
Therien Denis AB Hou Renjie Lagugné-Labarthet François 《Plasmonics (Norwell, Mass.)》2020,15(2):507-515
Plasmonics - Nanostructured conductive surfaces have been exploited for a variety of applications in photonics and optical sensing due to the broad spectral tunability of the localized surface... 相似文献
54.
Sandra I Vieira Sandra Rebelo Hermann Esselmann Jens Wiltfang James Lah Rachel Lane Scott A Small Sam Gandy Edgar F da Cruz e Silva Odete AB da Cruz e Silva 《Molecular neurodegeneration》2010,5(1):1-21
Background
Retrograde transport of several transmembrane proteins from endosomes to the trans-Golgi network (TGN) occurs via Rab 5-containing endosomes, mediated by clathrin and the recently characterized retromer complex. This complex and one of its putative sorting receptor components, SorLA, were reported to be associated to late onset Alzheimer's disease (AD). The pathogenesis of this neurodegenerative disorder is still elusive, although accumulation of amyloidogenic Abeta is a hallmark. This peptide is generated from the sucessive β- and γ- secretase proteolysis of the Alzheimer's amyloid precursor protein (APP), events which are associated with endocytic pathway compartments. Therefore, APP targeting and time of residence in endosomes would be predicted to modulate Abeta levels. However, the formation of an APP- and retromer-containing protein complex with potential functions in retrieval of APP from the endosome to the TGN had, to date, not been demonstrated directly. Further, the motif(s) in APP that regulate its sorting to the TGN have not been characterized.Results
Through the use of APP-GFP constructs, we show that APP containing endocytic vesicles targeted for the TGN, are also immunoreactive for clathrin-, Rab 5- and VPS35. Further, they frequently generate protruding tubules near the TGN, supporting an association with a retromer-mediated pathway. Importantly, we show for the first time, that mimicking APP phosphorylation at S655, within the APP 653YTSI656 basolateral motif, enhances APP retrieval via a retromer-mediated process. The phosphomimetic APP S655E displays decreased APP lysosomal targeting, enhanced mature half-life, and decreased tendency towards Abeta production. VPS35 downregulation impairs the phosphorylation dependent APP retrieval to the TGN, and decreases APP half-life.Conclusions
We reported for the first time the importance of APP phosphorylation on S655 in regulating its retromer-mediated sorting to the TGN or lysosomes. Significantly, the data are consistent with known interactions involving the retromer, SorLA and APP. Further, these findings add to our understanding of APP targeting and potentially contribute to our knowledge of sporadic AD pathogenesis representing putative new targets for AD therapeutic strategies. 相似文献55.
Lucy Rutten Cecile Ribot Blanca Trejo-Aguilar Han AB Wösten Ronald P de Vries 《BMC microbiology》2009,9(1):166-7
Background
L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity. 相似文献56.
Radim Cegan Gabriel AB Marais Hana Kubekova Nicolas Blavet Alex Widmer Boris Vyskot Jaroslav Doležel Jan Šafář Roman Hobza 《BMC plant biology》2010,10(1):180
Background
The evolution of sex chromosomes is often accompanied by gene or chromosome rearrangements. Recently, the gene AP3 was characterized in the dioecious plant species Silene latifolia. It was suggested that this gene had been transferred from an autosome to the Y chromosome. 相似文献57.
Fanni Aspetsberger Matthias Zabel Timothy Ferdelman Ulrich Struck Andreas Mackensen Astrid Ahke Ursula Witte - Present address: University of Aberdeen Aberdeen AB TZ UK 《Marine Biology Research》2007,3(5):342-356
The benthic community in continental slope and deep-sea sediments of the Benguela Upwelling System was supplied with 13C-labelled organic matter (OM) of two different qualities using a benthic chamber lander. Freeze-dried cultures of Skeletonema costatum served as 'fresh' OM. 'Altered' OM of the same material had been additionally dialysed to remove low-molecular weight compounds. In order to investigate the benthic response pattern, mineralization of labelled OM, uptake by macrofauna and incorporation into bacteria were followed over 18-36 h. Total oxygen uptake was not affected beyond natural variation by the OM addition. Mineralization dominated the 13C-labelled phytodetritus processing, constituting 71-95% of the total processed OM. Bacterial incorporation of phytodetrital carbon exceeded macrofaunal uptake at all stations. Stations situated in a major centre of OM deposition showed phytodetritus processing rates on average twice as high as outside the depocentre. Phytodetritus processing was 1.5, 2.5 and 4.3 times higher for fresh than for altered OM at 605, 1019 and 1335 m water depth, respectively. Our observations clearly indicate the importance of OM quality on mineralization rates. 相似文献
58.
Ultrastructure of the sodium pump: Comparison of thin sectioning, negative staining, and freeze-fracture of purified, membrane-bound (Na+, K+)-ATPase 下载免费PDF全文
Purified (Na+, K+)-ATPase was studied by electron microscopy after thin sectioning, negative staining, and freeze-fracturing, particular emphasis being paid to the dimensions and frequencies of substructures in the membranes. Ultrathin sections show exclusively flat or cup-shaped membrane fragments which are triple-layered along much of their length and have diameters of 0.1-0.6 μm. Negative staining revealed a distinct substructure of particles with diameters between 30 and 50 A and with a frequency of 12,500 +/- 2,400 (SD) per μm(2). Comparisons with sizes of the protein components suggest that each surface particle contains as its major component one large catalytic chain with mol wt close to 100,000 and that two surface particles unite to form the unit of (Na+,K+)-ATPase which binds one molecule of ATP or ouabain. The further observations that the surface particles protrude from the membrane surface and are observed on both membrane surfaces in different patterns and degrees of clustering suggest that protein units span the membrane and are capable of lateral mobility. Freeze-fracturing shows intramembranous particles with diameters of 90-110 A and distributed on both concave and convex fracture faces with a frequency of 3,410 +/- 370 per μm(2) and 390 +/- 170 per μm(2), respectively. The larger diameters and three to fourfold smaller frequency of the intramembranous particles as compared to the surface particles seen after negative staining may reflect technical differences between methods, but it is more likely that the intramembranous particle is an oliogomer composed of two or even more of the protein units which form the surface particles. 相似文献
59.
Wanessa LF Tavares Gleidice E Lavalle Mariana S Figueiredo Aline G Souza Angelica C Bertagnolli Fernando AB Viana Paulo RO Paes Rubens A Carneiro Guilherme AO Cavalcanti Marilia M Melo Geovanni D Cassali 《Acta veterinaria Scandinavica》2010,52(1):1-6
Background
Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).Methods
This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).Results
Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).Conclusions
Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure. 相似文献60.
Jessica AB van Nies Celina Alves Audrey LS Radix-Bloemen Cécile Gaujoux-Viala Tom WJ Huizinga Johanna MW Hazes Elisabeth Brouwer Bruno Fautrel Annette HM van der Helm-van Mil 《Arthritis research & therapy》2015,17(1)
IntroductionMorning stiffness is assessed daily in the diagnostic process of arthralgia and arthritis, but large-scale studies on the discriminative ability are absent. This study explored the diagnostic value of morning stiffness in 5,202 arthralgia and arthritis patients and the prognostic value in early rheumatoid arthritis (RA).MethodsIn arthralgia patients referred to the Early Arthritis Recognition Clinics (EARC) of Leiden (n = 807) and Groningen (n = 481) or included in the Rotterdam Early Arthritis Cohort (REACH) study (n = 353), the associations (cross-sectional analyses) between morning stiffness and presence of arthritis at physical examination were studied. In early arthritis patients, included in the Leiden Early Arthritis Clinic (EAC) (n = 2,748) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n = 813), associations with fulfilling the 2010-RA criteria after one year were assessed. In 2010-RA patients included in the EAC (n = 1,140) and ESPOIR (n = 677), association with the long-term outcomes of disease-modifying antirheumatic drug (DMARD)-free sustained remission and radiological progression were determined. Morning stiffness was defined as a duration ≥60 minutes; sensitivity analyses were performed for other definitions.ResultsIn arthralgia, morning stiffness (≥60 minutes) associated with the presence of arthritis; Leiden EARC odds ratio (OR) 1.49 (95% CI 1.001 to 2.20), Groningen EARC OR 2.21 (1.33 to 3.69) and REACH OR 1.55 (0.97 to 2.47) but the areas under the receiver operating characteristic curve (AUCs) were low (0.52, 0.57, 0.54). In early arthritis, morning stiffness was associated with 2010-RA independent of other predictors (Leiden EAC OR 1.72 (95% CI 1.31 to 2.25, AUC 0.68), ESPOIR OR 1.68 (1.03 to 2.74, AUC 0.64)). Duration of ≥30 minutes provided optimal discrimination for RA in early arthritis. Morning stiffness was not associated with radiological progression or DMARD-free sustained remission.ConclusionsMorning stiffness in arthralgia and early arthritis is associated with arthritis and RA respectively. This supports the incorporation of morning stiffness in the diagnostic process.