Level IV. Therapeutic retrospective study.

Although elbow dislocations are common orthopaedic lesions, vascular complications remain rare. We report the cases of three patients who presented with a rupture of the brachial artery after closed posterior dislocation, which is even more uncommon. Arteriograms were performed in all cases because of the persistent absence of pulses at the wrist after emergency reduction. In each patient, the treatment consisted of the insertion of reversed end-to-end saphenous bridges. None of them presented mid-term vascular complications (mean follow-up, 17 months). Brachial artery disruption can result from closed posterior elbow dislocation and responds well to vascular repair.

Telomerase catalytic subunit (hTERT) has been shown to play a critical role not only in telomere homeostasis but also in cellular survival, DNA repair, and genetic stability. In a previous study, we described that tumor necrosis factor-␣ (TNF␣) induced in the leukemic KG1 cells a senescence state characterized by decreased hTERT activity followed by prolonged growth arrest, increased ␤-galactosidase activity, telomere shortening, and major chromosomal instability. Interestingly, granulocyte-macrophage colony-stimulating factor (GM-CSF) abrogated all these events. In the present study, we show for the first time that TNF␣ acts by inhibiting the hTERT gene in both normal CD34 ؉ cells and fresh leukemic cells. Using KG1 cells as a representative cellular model, we show that TNF␣ induced sphingomyelin hydrolysis, ceramide production, and c-Jun N-terminal kinase (JNK) activation, all of which are critical components of TNF␣ signaling, resulting in hTERT gene inhibition. Moreover, we provide evidence that the protective effect of GM-CSF is related to its capacity to interfere with both ceramide generation and ceramide signaling. IntroductionTelomerase is a large ribonucleoprotein complex containing 2 major subunits contributing to enzymatic activity: a RNA component (hTR) that serves as a template for the polymerase activity of the enzyme and a catalytic subunit with reverse transcriptase activity (hTERT). Previous studies have documented that hTERT represents the rate-limiting step in telomerase function. 1 For this reason, and because this enzyme has been found to play an essential role in the regulation of telomere elongation and cellular protection, hTERT regulation has been the subject of intense investigation in recent years. From these studies, it appears that hTERT is tightly regulated both at transcriptional and posttranscriptional levels. For example, the cloning and characterization of the hTERT 5Ј gene regulatory elements have identified more than 20 transcription factor binding sites acting as activators or repressors (for a review, see Poole et al 2 ).Despite increasing knowledge about hTERT transcription regulation, much less is known about which type of internal or external stimuli could interfere with hTERT gene regulation. Recent studies have described that, in epithelial cells, oncogenes, such as Her2/Neu, 3 growth factors, such as epidermal growth factor (EGF), 4 or steroids 5 could activate hTERT at the transcriptional level. In contrast, transforming growth factor-␤ (TGF␤) acts as a repressor of hTERT gene transcription in a variety of cellular models. [6][7][8] In a previous study, we described that, in leukemic myeloid KG1 cells, tumor necrosis factor-␣ (TNF␣) induced premature senescence, characterized by cellular growth arrest, increased ␤-galactosidase activity, reduced hTERT activity, telomeric disturbances (shortening, losses, fusions), and intense chromosomal instability. 9 Moreover, increased ␤-galactosidase activity was also found in normal CD34 ϩ as well as in fresh acute myeloid leuk...

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