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The DNA-dependent protein kinase (DNA-PK) is composed of a large catalytic subunit of approximately 470 kDa (DNA-PKcs) and the DNA-binding protein, Ku. Absence of DNA-PK activity confers sensitivity to x-rays and defects in both DNA double-strand break repair and V(D)J recombination. However the precise function of DNA-PK in DNA double-strand break repair is not known. Here we show, using electrophoretic mobility shift assays, that polypeptides in a fraction purified from human cells interact with DNA-PK and stabilize the formation of a complex containing DNA-PKcs-Ku and DNA. Five polypeptides in this fraction have been identified by amino-terminal sequence analysis and/or immunoblotting. These proteins are NF90 and NF45, which are the 90- and 45-kDa subunits of a protein known to bind specifically to the antigen receptor response element of the interleukin 2 promoter, and the alpha, beta, and gamma subunits of eukaryotic translation initiation factor eIF-2. We also show that NF90, NF45, and eIF-2 beta are substrates for DNA-PK in vitro. In addition, recombinant NF90 promotes formation of a complex between DNA-PKcs, Ku, and DNA, and antibodies to recombinant NF90 or recombinant NF45 immunoprecipitate DNA-PKcs in vitro. Together, our data suggest that NF90, in complex with NF45, interacts with DNA-PKcs and Ku on DNA and that NF90 and NF45 may be important for the function of DNA-PK.

We have reviewed 16 cases of soft tissue sarcomas of the upper limb treated with wide excision of the tumour and immediate soft tissue reconstruction by means of a microvascular flap. 9 patients were males, 7 females; age ranged from 12 to 74 years. All the patients had been referred to us after previous failed or inadequate excisions. All the tumours were high-grade malignancies in an extracompartmental location (stade IIB according to Enneking). Histopathologic diagnosis was: synovial-sarcoma in 11 cases; fibrosarcoma in 2 cases; malignant fibrous histiocytoma in 1 case, soft tissue osteosarcoma in 1 case, epitheloid sarcoma in 1 case. The site of the tumour was the hand in 2 cases, the wrist in 6 cases, the forearm in 5 cases and the elbow in 3 cases. The free flaps used for soft tissue reconstructions were the latissimus dorsi in 6 cases, the dorsalis pedis in 2 cases, the lateral arm flap in 2 cases, the serratus in 1 case, the gracilis in 1 case. The island flaps were the radial forearm flap in 1 case, the posterior interosseous flap in 1 case, the cubital flap in 1 case. 14 cases required immediate associated reconstructive procedures such as tendon transfers or grafts (5 cases), vascularized or non vascularized bone grafts (4 cases), articular allografts (1 case), ligament reconstruction (1 case), nerve grafts (2 cases). Brachytherapy was associated to microsurgical reconstruction in the last 6 cases of this group. The catheters were charged with the radioisotope 5 days after surgery. No complications were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Iron deficiency (ID) is a known co-morbidity and a potential therapeutic target in heart failure. Whether ID is frequent also in ST-segment elevation acute myocardial infarction (STEMI) patients and is associated with worse in-hospital outcomes has never been evaluated. Methods: We defined ID as a serum ferritin < 100 μg/L or transferrin saturation < 20% at hospital admission. We assessed the association between ID and the primary endpoint (a composite of in-hospital mortality and Killip class ≥ 3). We explored the potential association between ID, circulating cell-free mitochondrial DNA (mtDNA), and cardiac magnetic resonance (CMR) parameters. Results: Four-hundred-twenty STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were included. Of them, 237 (56%) had ID. They had significantly higher admission high-sensitivity troponin and mtDNA levels as compared to non-ID patients (145 ± 35 vs. 231 ± 66 ng/L, P < 0.001; 917 [404–1748] vs. 1368 [908–4260] copies/μL; P < 0.003, respectively). A lower incidence of the primary endpoint (10% vs. 18%, P = 0.01) was observed in ID patients (adjusted OR 0.50 [95% CI 0.27–0.93]; P = 0.02). At CMR (n = 192), ID patients had a similar infarct size (21 ± 18 vs. 21 ± 19 g; P = 0.95), but a higher myocardial salvage index (0.56 ± 0.30 vs. 0.43 ± 0.27; P = 0.002), and a smaller microvascular obstruction extent (3.6 ± 2.2 vs. 6.9 ± 3.9 g; P < 0.001). Conclusions: Iron deficiency is frequent in STEMI patients, it is coupled with mitochondrial injury, and, paradoxically, with a better in-hospital outcome. This unexpected clinical result seems to be associated with a smaller myocardial reperfusion injury. The mechanisms underlying our findings and their potential clinical implications warrant further investigation.