Pirh2 (p53-induced RING-H2 domain protein, also known as Rchy1), is an E3 ubiquitin ligase involved in a negative-feedback loop with p53. Using NMR spectroscopy we show that Pirh2 is a unique cysteine-rich protein comprising three modular domains. The protein binds nine zinc ions using a variety of zinc coordination schemes including a RING domain and a novel left-handed β-spiral in which three zinc ions align three consecutive small β-sheets in an interleaved fashion. We demonstrate that Pirh2-p53 interaction is dependent on the C-terminal Zn-binding module of Pirh2 which binds to the tetramerization domain (TET) of p53. As a result, Pirh2 ubiquitylates preferably the tetrameric form of p53 in vitro and in vivo, suggesting that Pirh2 regulates protein turnover of the transcriptionally active form of p53 in the cell.
OBJECTIVES: Extended-arch techniques offer the potential to comprehensively treat acute type-A aortic dissection (ATAAD), but add surgical complexity compared to the standard hemiarch technique. This study describes both perioperative and mid-term outcomes following the introduction of an extended-arch technique for ATAAD. METHODS: Ours is a retrospective single-centre observational study of 95 consecutive patients with ATAAD from 2011 to 2016. The decision to perform extended-arch or hemiarch repair was individualized based on clinical and radiological features. Extended-arch repair was defined as replacement of the ascending aorta and arch with reimplantation of head vessels with or without distal endovascular extension. Clinical follow-up was 100% complete. Cross-sectional double-oblique measurements were performed for aortic remodelling analysis. RESULTS: Extended-arch (n = 28) and hemiarch (n = 67) repair resulted in a in-hospital mortality of 10% (n = 3) and 10%, (n = 7), and permanent neurological deficit rate of 7% and 12%, respectively. At a mean imaging follow-up duration of 2.7 ± 1.5 years, false lumen thrombosis was achieved in 57% and 9% of patients undergoing extended-arch and hemiarch repair, respectively. Rate of growth in the proximal descending aorta was 0.7 ± 2.3 mm/year in the extended-arch group vs 2.7 ± 3.9 mm/year in the hemiarch group. At a mean clinical follow-up time of 3.0 ± 1.6 years, open surgical aortic reoperation was 0% in the extended-arch group and 22% in the hemiarch group. CONCLUSIONS: Extended-arch repair of ATAAD can be introduced in the acute setting without increase in perioperative mortality or morbidity. At mid-term follow-up, extended-arch for ATAAD improves aortic remodelling and reduces the need for open surgical reoperation.
Purpose: Management of chylous ascites is poorly understood with no management guidelines. We retrospectively reviewed patients treated for chylous ascites at our institution to evaluate efficacy and safety of lipiodol lymphangiography and embolization. Materials and Methods: Seven patients underwent percutaneous interventional management of chylous ascites (average age 52.5 years, 3 female, 6 post-surgical, 1 pancreatitis) from 2012. All patients underwent lipiodol inguinal lymph node injection. Adjunctive glue embolization was performed if a leak was identified. Data were collected on the cause of chylous ascites, conservative management strategies, procedural details, and success. Results: All patients had chylous ascites refractory to conservative management. Preprocedure lymphoscintigraphy identified a retroperitoneal leak in 6 patients. Seven patients underwent 12 lymphangiogram procedures; 8 were performed at our institution. Lymphangiography identified a leak in 5 patients (71%). Success was achieved in 2 patients (28%) treated at our institution after glue embolization following cannulation of the leaking lymphatic channels and 1 patient (14%) after lymphangiography alone for an overall success rate of 43% (3/7). Two patients (29%) were successfully treated after one procedure. Two patients (29%) unsuccessfully treated at our institution were referred to a specialized center in the United States. No 30 day post procedural complications. Conclusions: In our experience, lymphangiography and embolization was a safe, relatively effective and minimally invasive method for treating medically refractory chylous ascites. Complex cases required referral to a specialized institution with resources unavailable at our tertiary care center.
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