Maintenance of genome integrity is critical for both faithful propagation of genetic information and prevention of mutagenesis induced by various DNA damage events. Here we report cold-inducible RNA-binding protein (CIRBP) as a newly identified key regulator in DNA double-strand break (DSB) repair. On DNA damage, CIRBP temporarily accumulates at the damaged regions and is poly(ADP ribosyl)ated by poly(ADP ribose) polymerase-1 (PARP-1). Its dissociation from the sites of damage may depend on its phosphorylation status as mediated by phosphatidylinositol 3-kinase-related kinases. In the absence of CIRBP, cells showed reduced γH2AX, Rad51, and 53BP1 foci formation. Moreover, CIRBP-depleted cells exhibited impaired homologous recombination, impaired nonhomologous end-joining, increased micronuclei formation, and higher sensitivity to gamma irradiation, demonstrating the active involvement of CIRBP in DSB repair. Furthermore, CIRBP depleted cells exhibited defects in DNA damage-induced chromatin association of the MRN complex (Mre11, Rad50, and NBS1) and ATM kinase. CIRBP depletion also reduced phosphorylation of a variety of ATM substrate proteins and thus impaired the DNA damage response. Taken together, these results reveal a previously unrecognized role for CIRBP in DSB repair.
Although considered a minimally invasive procedure, percutaneous vertebroplasty with polymethylmethacrylate is not risk free. Intractable neurologic complications can occur if it is not performed by experienced physicians under appropriate indications and cautionary safeguards.
Inducing a DNA damage response in tumor cells ex vivo creates an immunogenic live-cell adjuvant.
BackgroundThe purpose of the study is to retrospectively review the clinical outcome of our study population of middle-aged RA patients who had suffered extensor-tendon rupture. We reported the outcome of autogenous palmaris tendon grafting of multiple extensor tendons at wrist level in 14 middle-aged rheumatoid patients.MethodsBetween Feb. 2000 to Feb. 2004, thirty-six ruptured wrist level extensor tendons were reconstructed in fourteen rheumatoid patients (11 women and three men) using autogenous palmaris longus tendon as a free interposition graft. In each case, the evaluation was based on both subjective and objective criteria, including the range of MCP joint flexion after surgery, the extension lag at the metacarpophalangeal joint before and after surgery, and the ability of the patient to work.Results and DiscussionThe average of follow-up was 54.1 months (range, 40 to 72 months). The average range of MCP joint flexion after reconstruction was 66°. The extension lag at the metacarpophalangeal joint significantly improved from a preoperative mean of 38° (range, 25°–60°) to a postoperative mean of 16° (range, 0°–30°). Subjectively all patients were satisfied with the clinical results, and achieved a return to their level of ability before tendon rupture. We found good functional results in our series of interposition grafting using palmaris longus to reconstruct extensor tendon defects in the rheumatoid patients.ConclusionReconstruction for multiple tendon ruptures is a salvage procedure that is often associated with extensor lag and impairment of overall function. Early aggressive treatment of extensor tendon reconstruction using autogenous palmaris longus tendon as a free interposition graft in the rheumatoid wrist is another viable option to achieve good clinical functional result.
Background:Short-segment fixation alone to treat thoracolumbar burst fractures is common but it has a 20-50% incidence of implant failure and rekyphosis. A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture. This article is to evaluate the longterm results of short-segment fixation with TpBA for treatment of thoracolumbar burst fractures.Materials and Methods:Patients included in the study had a single-level burst fracture involving T11-L2 and no distraction or rotation element with limited neurological deficit. Patients in the control group (n = 42) were treated with short-segment posterior instrumentation alone, whereas patients in the augmented group (n = 90) were treated with a titanium spacer designed for transpedicle body reconstruction. The followup was 48-101 months. The radiographic and clinical results were evaluated and compared by Student's t test and Fisher's exact test.Results:The blood loss, operation time and hospitalization were similar in both the groups. The immediate postoperative anterior vertebral restoration rate of the augmented group was similar to that of the control group (97.6% ± 2.4% vs. 96.6% ± 3.2%). The final anterior vertebral restoration was greater in the augmented group than in the control group (93.3% ± 3.4% vs. 62.5% ± 11.2%). Immediate postoperative kyphotic angles were not significantly different between the groups (3.0° ± 1.8° vs. 5.1° ± 2.3°). The final kyphotic angles were less in the augmented group than the control group (7.3° ± 3.5° vs. 20.1° ± 5.4°). The augmented group had less (P < 0.001) implant failure [0% (n=0) vs. 23.8% (n=10)] for the control group) and more patients (P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group [90.0% (n=81) vs. 66.7% (n=28)]. All patients in the augmented group and 39 (92.8%) patients in the control group experienced neurological recovery to Frankel Grade E. Three patients in the control group had improvement to Frankel Grade D from Frankel Grade C, but later had deterioration to Frankel Grade C because of loosening and dislodgement of the implant.Conclusion:Posterior body reconstruction with TpBA can maintain kyphosis correction and vertebral restoration, prevent implant failure and lead to better clinical results.
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