ABSTRACT
PURPOSE: To determine the long-term patency of aortoiliac kissing stents and to identify predisposing factors for the development of in-stent restenosis (ISR). METHODS: A retrospective analysis was conducted of 105 patients (median age 60.9 years; 64 women) with symptomatic aortoiliac occlusive disease who had kissing stents implanted between 2001 and 2015. The indication for kissing stents was severe claudication in 91 (86.7%) patients and critical limb ischemia in 14 (13.3%). Lesions were TASC A in 52 (49.5%), B in 29 (27.6%), C in 4 (3.8%), and D in 20 (19%) patients. Twenty-five (23.8%) patients had heavily calcified lesions. In all, 210 stents were deployed [180 (85.7%) self-expanding and 30 (14.3%) balloon-expandable]. Follow-up included clinical evaluation, ankle-brachial index measurement, and duplex ultrasonography. RESULTS: The median follow-up was 45 months. The primary patency rates were 93%, 86%, and 77% at 12, 24, and 60 months, respectively. Significant ISR developed in 23 (21.9%) patients (12 unilateral and 11 bilateral). Univariate Cox regression analysis revealed older age [hazard ratio (HR) 0.5, 95% confidence interval (CI) 0.31 to 0.81, p=0.004] and larger aortic diameter (HR 0.42, 95% CI 0.25 to 0.7, p<0.001) to be variables favoring long-term patency, while a longer aortic stent segment (HR 1.56, 95% CI 1.16 to 2.09, p=0.003) and a larger discrepancy between the summed stent diameters and the aortic diameter (HR 1.64, 95% CI 1.01 to 2.65, p=0.043) were associated with ISR development. Multivariate analysis showed a longer aortic stent segment to be the only significant determinant of ISR (HR 1.44, 95% CI 1.02 to 2.01, p=0.035). CONCLUSION: The kissing stent technique can be performed with good long-term patency. Patients whose iliac stents protrude too far into the aorta need closer follow-up.
Subject(s)
Angioplasty, Balloon/adverse effects , Angioplasty, Balloon/instrumentation , Aortic Diseases/therapy , Arterial Occlusive Diseases/therapy , Iliac Artery , Intermittent Claudication/therapy , Ischemia/therapy , Stents , Aged , Aortic Diseases/diagnostic imaging , Aortic Diseases/physiopathology , Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/physiopathology , Critical Illness , Female , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/physiopathology , Intermittent Claudication/diagnostic imaging , Intermittent Claudication/physiopathology , Ischemia/diagnostic imaging , Ischemia/physiopathology , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Time Factors , Treatment Outcome , Vascular PatencyABSTRACT
During transcription cycles serine side chains in the carboxyl terminal domain (CTD) of the largest subunit of RNA polymerase II undergo dynamic phosphorylation-de-phosphorylation changes, and the modification status of the CTD serves as a signal for proteins involved in transcription and RNA maturation. We show here that the major CTD de-phosphorylating enzyme Fcp1 is expressed at high levels in germline cells of Drosophila. We used transgene constructs to modify the Fcp1 phosphatase level in Drosophila ovaries and found that high levels of Fcp1 are required for intensive gene expression in nurse cells. On the contrary, low Fcp1 levels might limit the rate of transcription. Fcp1 over-expression results in increased expression of microtubules in nurse cells. Our results show that tightly controlled high level Fcp1 expression in the nurse cells of Drosophila ovaries is required for proper egg maturation.
Subject(s)
Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Oogenesis/genetics , Oogenesis/physiology , Phosphoprotein Phosphatases/genetics , Phosphoprotein Phosphatases/metabolism , Animals , Animals, Genetically Modified , Base Sequence , DNA Primers/genetics , Drosophila melanogaster/cytology , Female , Gene Knockout Techniques , Genes, Insect , Ovary/cytology , Ovary/metabolism , RNA Polymerase I/genetics , RNA Polymerase II/chemistry , RNA Polymerase II/genetics , RNA Polymerase II/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Serine/chemistry , Transcription, GeneticABSTRACT
The reversible phosphorylation-dephosphorylation of RNA polymerase II (Pol II) large subunit carboxyl terminal domain (CTD) during transcription cycles in eukaryotic cells generates signals for the steps of RNA synthesis and maturation. The major phosphatase specific for CTD dephosphorylation from yeast to mammals is the TFIIF-interacting CTD-phosphatase, Fcp1. We report here on the in vivo analysis of Fcp1 function in Drosophila using transgenic lines in which the phosphatase production is misregulated. Fcp1 function is essential throughout Drosophila development and ectopic up- or downregulation of fcp1 results in lethality. The fly Fcp1 binds to specific regions of the polytene chromosomes at many sites colocalized with Pol II. In accord with the strong evolutional conservation of Fcp1: (1) the Xenopus fcp1 can substitute the fly fcp1 function, (2) similarly to its S. pombe homologue, Drosophila melanogaster (Dm)Fcp1 interacts with the RPB4 subunit of Pol II, and (3) transient expression of DmFcp1 has a negative effect on transcription in mammalian cells. The in vivo experimental system described here suggests that fly Fcp1 is associated with the transcription engaged Pol II and offers versatile possibilities for studying this evolutionary conserved essential enzyme.
