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31.
32.
H?Bukulmez AL?Matthews CM?Sullivan C?Chen MJ?Kraay RC?Elston RW?Moskowitz VM?Goldberg ML?WarmanEmail author 《Arthritis research & therapy》2005,8(1):R25
In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA),
we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family
histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses
to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis
of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing
total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We
compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings
of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the
siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age
and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to
identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with
hip OA than in those with knee OA. 相似文献
33.
The restriction enzyme TaqI digests 0.2% of the genomic DNA from the
grasshopper Caledia captiva to a family of sequences 168 bp in length
(length of consensus sequence). The sequence variation of this "Taq family"
of repeat units was examined among four races from C. captiva to assay the
pattern of evolution within this highly repeated DNA. The Taq-family
repeats are located in C-banded heterochromatin on at least one member of
each homologous pair of chromosomes; the locations range from centromeric
to telomeric. Thirty-nine cloned repeats isolated from two population 1A
individuals along with 11 clones from seven populations taken from three of
the races demonstrated sequence variation at 72 positions. Pairwise
comparisons of the cloned repeats, both within an individual and between
different races, indicate that levels of intraspecific divergence, as
measured by reproductive incompatibility, do not correlate with sequence
divergence among the 168-bp repeats. A number of subsequences within the
repeat remain unchanged among all 50 clones; the longest of these is 18 bp.
That the same 18-bp subsequence is present in all clones examined is a
finding that departs significantly (P less than 0.01) from what would be
expected to occur at random. Two other cloned repeats, from a
reproductively isolated race of C. captiva, have sequences that show 56%
identity with this 18-bp conserved region. An analysis showed that the
frequency of occurrence of an RsaI recognition site within the 168- bp
repeat in the entire Taq family agreed with that found in the cloned
sequences. These data, along with a partial sequence for the entire Taq
family obtained by sequencing uncloned repeats, suggest that the consensus
sequence from the cloned copies is representative of this highly repeated
family and is not a biased sample resulting from the cloning procedure. The
18-bp conserved sequence is part of a 42-bp sequence that possesses dyad
symmetry typical of protein-binding sites. We speculate that this may be
significant in the evolution of the Taq family of sequences.
相似文献
34.
Marie-Lise?Blondot Loic?Dragin Hichem?Lahouassa Florence?Margottin-GoguetEmail author 《Retrovirology》2014,11(1):117
Vpr is one of the most enigmatic viral auxiliary proteins of HIV. During the past twenty years, several activities have been ascribed to this viral protein, but one, its ability to mediate cell cycle arrest at the G2 to M transition has been the most extensively studied. Nonetheless, the genuine role of Vpr and its pathophysiological relevance in the viral life cycle have remained mysterious. Recent work by Laguette et al. (Cell 156:134-145, 2014) provides important insight into the molecular mechanism of Vpr-mediated G2 arrest. This study highlights for the first time how Vpr recruits the SLX4 endonuclease complex and how Vpr-induced inappropriate activation of this complex leads to G2 arrest. Here, we will discuss these findings in the light of previous work to show how they change the view of Vpr’s mechanism of action. We will also discuss how these findings open new questions towards the understanding of the biological function of Vpr regarding innate immune sensing. 相似文献
35.
Intercalation of proflavine and a platinum derivative of proflavine into double-helical Poly(A) 下载免费PDF全文
The equilibria and kinetics of the interactions of proflavine (PR) and its platinum-containing derivative [PtCl(tmen)(2)HNC(13)H(7)(NHCH(2)CH(2))(2)](+) (PRPt) with double-stranded poly(A) have been investigated by spectrophotometry and Joule temperature-jump relaxation at ionic strength 0.1 M, 25 degrees C, and pH 5.2. Spectrophotometric measurements indicate that base-dye interactions are prevailing. T-jump experiments with polarized light showed that effects due to field-induced alignment could be neglected. Both of the investigated systems display two relaxation effects. The kinetic features of the reaction are discussed in terms of a two-step series mechanism in which a precursor complex DS(I) is formed in the fast step, which is then converted to a final complex in the slow step. The rate constants of the fast step are k(1) = (2.5 +/- 0.4) x 10(6) M(-1) s(-1), k(-1) = (2.4 +/- 0.1) x 10(3) s(-1) for poly(A)-PR and k(1) = (2.3 +/- 0.1) x 10(6) M(-1) s(-1), k(-1) = (1.6 +/- 0.2) x 10(3) s(-1) for poly(A)-PRPt. The rate constants for the slow step are k(2) = (4.5 +/- 0.5) x 10(2) s(-1), k(-2) = (1.7 +/- 0.1) x 10(2) s(-1) for poly(A)-PR and k(2) = 9.7 +/- 1.2 s(-1), k(-2) = 10.6 +/- 0.2 s(-1) for poly(A)-PRPt. Spectrophotometric measurements yield for the equilibrium constants and site size the values K = (4.5 +/- 0.1) x 10(3) M(-1), n = 1.3 +/- 0.5 for poly(A)-PR and K = (2.9 +/- 0.1) x 10(3) M(-1), n = 2.3 +/- 0.6 for poly(A)-PRPt. The values of k(1) are similar and lower than expected for diffusion-limited reactions. The values of k(-1) are similar as well. It is suggested that the formation of DS(I) involves only the proflavine residues in both systems. In contrast, the values of k(2) and k(-2) in poly(A)-PRPt are much lower than in poly(A)-PR. The results suggest that in the complex DS(II) of poly(A)-PRPt both proflavine and platinum residues are intercalated. In addition, a very slow process was detected and ascribed to the covalent binding of Pt(II) to the adenine. 相似文献
36.
Daniel R Getts Meghann T Getts Derrick P McCarthy Emily ML Chastain Stephen D Miller 《MABS-AUSTIN》2010,2(6):682-694
The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account.Key words: immunogenicity, human anti-mouse antibody, cytokine release syndrome 相似文献
37.
Josimari M DeSantana Kamilla ML da Cruz Kathleen A Sluka 《Arthritis research & therapy》2013,15(6):222
Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles. 相似文献
38.
One of the cellular defenses against virus infection is the silencing of viral gene expression. There is evidence that at
least two gene-silencing mechanisms are used against the human immuno-deficiency virus (HIV). Paradoxically, this cellular
defense mechanism contributes to viral latency and persistence, and we review here the relationship of viral latency to gene-silencing
mechanisms. 相似文献
39.
40.
D. Mercanti A. Angelini MT. Ciotti ML. Eboli C. Galli L. Battistini D. Merlo P. Calissano 《Cytotechnology》1993,11(Z1):S117-S119
The neurite outgrowth and adhesion complex (NOAC), isolated from rabbit sera has been dissociated in its major components by reverse-phase chromatography in HPLC by using a C18 column. SDS-PAGE analisys of the active fractions revealed the presence of three major bands of approximately 100, 70 and 50 kDa. Studies on the biological activity of NOAC were carried out on rat cerebellar granule cells. NOAC-cultured cells exhibit a marked resistance to excitotoxic stimuli carried by glutamate. 相似文献