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91.
Manon JM van Oosten Radboud JEM Dolhain Jan W Koper Elisabeth FC van Rossum Marieke Emonts Khik H Han Jacques MGW Wouters Johanne MW Hazes Steven WJ Lamberts Richard A Feelders 《Arthritis research & therapy》2010,12(4):R159
Introduction
The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9β are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity. 相似文献92.
Mohamed M Thabet Thomas WJ Huizinga Désirée M van der Heijde Annette HM van der Helm-van Mil 《Arthritis research & therapy》2009,11(5):R155
Introduction
Undifferentiated arthritis (UA) has a variable disease course; 40 to 50% of UA patients remit spontaneously, while 30% develop rheumatoid arthritis (RA). Identifying the UA patients who will develop RA is essential to initiate early disease-modifying anti-rheumatic drug (DMARD) therapy. Although the presence of bone erosions at baseline is predictive for a severe destructive disease course in RA, the prognostic importance of erosive joints for disease outcome in UA is unknown. This study evaluates the predictive value of erosive joints for the disease outcome in UA as measured by RA development and disease persistency. 相似文献93.
94.
William J. Bodell 《Mutation research》1990,233(1-2):203-210
The induction of sister-chromatid exchanges (SCEs) and cytotoxicity in 9L cells treated with monofunctional and bifunctional alkylating agents has been investigated. Three classes of monofunctional and bifunctional agents were studied: nitrosoureas, mustards and epoxides. Independent of class the bifunctional agents were 55–630-fold more effective at inducing SCEs and 300–2400-fold more effective at inducing cellular cytotoxicity than the corresponding monofunctional agents. Comparing the induction of SCEs and cytotoxicity by these agents showed that these two cellular responses to DNA damage are highly correlated. The extent of DNA alkylation in cells treated with 1-ethyl-1-nitrosourea (ENU) or 1-(2-chloro-ethyl)-1-nitrosourea (CNU) was similar indicating that the increased effectiveness of CNU to induce SCEs and cytotoxicity was not due to increased DNA alkylation. Molecular dosimetry calculations indicate that for CNU and ENU treatment of 9L cells there are 116 and 8500 alkylations per SCE induced and 2.6 × 104 and 4.6 × 106 alkylations at the dose required to reduce survival of 9L cells by 90%. Comparison of the DNA alkylation products produced by CNU and ENU treatment of 9L cells suggests that the formation of the intrastrand crosslink N7-bis(guanyl)ethane the interstrand crosslink 1-(3-deoxycytidyl)-2-(1-deoxyguanosinyl)ethane by CNU is responsible for the increased effectiveness of CNU treatment at both induction of SCEs and cytotoxicity. 相似文献
95.
Sema Nickbakhsh Louise Matthews Paul R Bessell Stuart WJ Reid Rowland R Kao 《BMC veterinary research》2011,7(1):1-16
Background
The United Kingdom (UK) government has been recording the births, deaths, and movements of cattle for the last decade. Despite reservations about the accuracy of these data, they represent a large and valuable body of information about the demographics of the UK cattle herd and its contact structure. In this article, a range of demographic data about UK cattle, and particularly their movements, are presented, as well as yearly trends in the patterns of movements.Results
A clear seasonal pattern is evident in the number of movements of cattle, as are the reductions in movement volume due to foot and mouth disease outbreaks in 2001 and 2007. The distribution of ages of cattle at their time of death is multimodal, and the impact of the over thirty months rule is marked. Most movements occur between agricultural holdings, markets, and slaughterhouses, and there is a non-random pattern to the types of holdings movements occur between. Most animals move only a short distance and a few times in their life. Most movements between any given pair of holdings only occurred once in the last 10 years, but about a third occurred between 2 and 10 times in that period. There is no clear trend to movement patterns in the UK since 2002.Conclusions
Despite a substantial number of regulatory interventions during the last decade, movement patterns show no clear trend since 2002. The observed patterns in the repeatability of movements, the types of holdings involved in movements, the distances and frequencies of cattle movements, and the batch sizes involved give an insight into the structure of the UK cattle industry, and could act as the basis for a predictive model of livestock movements in the UK. 相似文献96.
We examined the phylogenetic relationships of 16 northern species of the
aplocheiloid genus Rivulus inhabiting the Caribbean, Central America, and
South America. A total of 714 base pairs per taxon were sequenced from two
segments of the mitochondrial genome, 12S rRNA and cytochrome b. Both
parsimony and neighbor-joining analyses suggest an ancient vicariant origin
of the Greater Antillean taxa, in addition to a quite recent dispersal of
species into the Lesser Antilles from the South American mainland. Combined
analyses support the monophyly of the northern South American assemblage as
the sister group of a Central American/Columbian biota. However, the
monophyly of the Central American biota remains uncertain. Divergence
estimates for the Central American taxa are calibrated from the Last
Cretaceous separation of the proto-Antilles from the Americas. These data
suggest that the extant Central American taxa represent the descendants of
at least two separate invasions during the Cenozoic, prior to the closing
of the Panamanian isthmus. Times are consistent with the extensive evidence
for reptilian and mammalian exchange throughout the Cenozoic.
相似文献
97.
A computational method is presented for characterizing residue usage, i.e.,
site-specific residue frequencies, in aligned protein sequences. The method
obtains frequency estimates that maximize the likelihood of the sequences
in a simple model for sequence evolution, given a tree or a set of
candidate trees computed by other methods. These maximum- likelihood
frequencies constitute a profile of the sequences, and thus the method
offers a rigorous alternative to sequence weighting for constructing such a
profile. The ability of this method to discard misleading phylogenetic
effects allows the biochemical propensities of different positions in a
sequence to be more clearly observed and interpreted.
相似文献
98.
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.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0616-3) contains supplementary material, which is available to authorized users. 相似文献99.
Combined isometric, concentric, and eccentric resistance exercise prevents unloading-induced muscle atrophy in rats. 总被引:1,自引:0,他引:1
G R Adams F Haddad P W Bodell P D Tran K M Baldwin 《Journal of applied physiology》2007,103(5):1644-1654
Previously, we reported that an isometric resistance training program that was effective in stimulating muscle hypertrophy in ambulatory rats could not completely prevent muscle atrophy during unloading (Haddad F, Adams GR, Bodell PW, Baldwin KM. J Appl Physiol 100: 433-441, 2006). These results indicated that preventing muscle atrophy does not appear to be simply a function of providing an anabolic stimulus. The present study was undertaken to determine if resistance training, with increased volume (3-s contractions) and incorporating both static and dynamic components, would be effective in preventing unloading-induced muscle atrophy. Rats were exposed to 5 days of muscle unloading via tail suspension. During that time one leg received electrically stimulated resistance exercise (RE) that included an isometric, concentric, and eccentric phase. The results of this study indicate that this combined-mode RE provided an anabolic stimulus sufficient to maintain the mass and myofibril content of the trained but not the contralateral medial gastrocnemius (MG) muscle. Relative to the contralateral MG, the RE stimulus increased the amount of total RNA (indicative of translational capacity) as well as the mRNA for several anabolic/myogenic markers such as insulin-like growth factor-I, myogenin, myoferlin, and procollagen III-alpha-1 and decreased that of myostatin, a negative regulator of muscle size. The combined-mode RE protocol also increased the activity of anabolic signaling intermediates such as p70S6 kinase. These results indicate that a combination of static- and dynamic-mode RE of sufficient volume provides an effective stimulus to stimulate anabolic/myogenic mechanisms to counter the initial stages of unloading-induced muscle atrophy. 相似文献
100.
Marije B Overdijk Sandra Verploegen Marijn B?gels Marjolein van Egmond Jeroen J Lammerts van Bueren Tuna Mutis Richard WJ Groen Esther Breij Anton CM Martens Wim K Bleeker Paul WHI Parren 《MABS-AUSTIN》2015,7(2):311-320
Daratumumab (DARA) is a human CD38-specific IgG1 antibody that is in clinical development for the treatment of multiple myeloma (MM). The potential for IgG1 antibodies to induce macrophage-mediated phagocytosis, in combination with the known presence of macrophages in the tumor microenvironment in MM and other hematological tumors, led us to investigate the contribution of antibody-dependent, macrophage-mediated phagocytosis to DARA''s mechanism of action. Live cell imaging revealed that DARA efficiently induced macrophage-mediated phagocytosis, in which individual macrophages rapidly and sequentially engulfed multiple tumor cells. DARA-dependent phagocytosis by mouse and human macrophages was also observed in an in vitro flow cytometry assay, using a range of MM and Burkitt''s lymphoma cell lines. Phagocytosis contributed to DARA''s anti-tumor activity in vivo, in both a subcutaneous and an intravenous leukemic xenograft mouse model. Finally, DARA was shown to induce macrophage-mediated phagocytosis of MM cells isolated from 11 of 12 MM patients that showed variable levels of CD38 expression. In summary, we demonstrate that phagocytosis is a fast, potent and clinically relevant mechanism of action that may contribute to the therapeutic activity of DARA in multiple myeloma and potentially other hematological tumors. 相似文献