Can CT predict the development of oroantral fistula in patients undergoing maxillary third molar removal?

PURPOSE: In maxillary wisdom tooth extraction, the necessity of CT is unknown. The purpose of this study was to investigate whether CT adding to orthopantomography is useful for predicting oroantral perforation during maxillary third molar extraction. METHODS: Various risk factors for oroantral perforation during maxillary third molar extraction were investigated by univariate and multivariate analyses. We analyzed those of all patients and the patients who underwent CT, respectively. The proximity of the roots to the maxillary sinus floor (root-sinus [RS] classification) and Archer classification were assessed using panoramic radiography. The number of roots and vertical relationship were assessed using CT. RESULTS: A total of 604 out of 3299 patients underwent CT adding to orthopantomography. In all cases, multivariate analyses except for CT findings showed that the RS classification type III/IV and the Archer classification Type B/C/D in panoramic findings were significantly correlated with oroantral perforation as radiological findings. In cases for which CT was performed, multivariate analyses showed that one root (OR 12.87) and the vertical relationship Type D (OR 5.63) in CT findings, besides the RS classification type III/IV (OR 4.47) in panoramic findings, were significantly related to oroantral perforation. CONCLUSION: The RS classification and the Archer classification in panoramic findings can predict the risk of oroantral perforation. The usefulness of CT adding to orthopantomography is limited. However, when the relationship between the upper wisdom tooth and maxillary sinus floor (RS classification) is unclear, to check whether the number of roots is one and the apex of one root is projecting into the maxillary sinus in CT findings, is useful for the prediction.

Degradation of p21Cip1 through anaphase-promoting complex/cyclosome and its activator Cdc20 (APC/CCdc20) ubiquitin ligase complex-mediated ubiquitylation is inhibited by cyclin-dependent kinase 2 in cardiomyocytes.

Cyclin-dependent kinase inhibitor p21Cip1 plays a crucial role in regulating cell cycle arrest and differentiation. It is known that p21Cip1 increases during terminal differentiation of cardiomyocytes, but its expression control and biological roles are not fully understood. Here, we show that the p21Cip1 protein is stabilized in cardiomyocytes after mitogenic stimulation, due to its increased CDK2 binding and inhibition of ubiquitylation. The APC/CCdc20 complex is shown to be an E3 ligase mediating ubiquitylation of p21Cip1 at the N terminus. CDK2, but not CDC2, suppressed the interaction of p21Cip1 with Cdc20, thereby leading to inhibition of anaphase-promoting complex/cyclosome and its activator Cdc20 (APC/CCdc20)-mediated p21Cip1 ubiquitylation. It was further demonstrated that p21Cip1 accumulation caused G2 arrest of cardiomyocytes that were forced to re-enter the cell cycle. Taken together, these data show that the stability of the p21Cip1 protein is actively regulated in terminally differentiated cardiomyocytes and plays a role in inhibiting their uncontrolled cell cycle progression. Our study provides a novel insight on the control of p21Cip1 by ubiquitin-mediated degradation and its implication in cell cycle arrest in terminal differentiation.

Differential regulation of cyclin D1 and D2 in protecting against cardiomyocyte proliferation.

Cardiomyocytes withdraw from cell cycle after terminal differentiation due in part to impaired nuclear import of cyclin D1. Thus, we have previously shown that expression of nuclear localization signal-tagged cyclin D1 (D1NLS) and cyclin-dependent kinase 4 promotes cardiomyocyte proliferation both in vitro and in vivo. Here we show that cyclin D2 fails to stimulate cell cycle in cardiomyocytes through a mechanism distinct from that of cyclin D1. We demonstrate that cyclin D2 can express in the nucleus much more efficiently than cyclin D1. Cyclin D2, however, was much less effective in activating CDK2 and cell proliferation than cyclin D1 when expressed transiently in the nucleus of cardiomyocytes using nuclear localization signals. Consistent with such an observation, CDK inhibitors p21(cip1) and p27(kip1) remained bound to CDK2 in cells expressing cyclin D2, whereas p21 and p27 were sequestered to cyclin D1 in cells expressing D1NLS. These data suggest that cyclin D2 has weaker affinities to the CDK inhibitors and therefore is less efficient in activating cell cycle than cyclin D1. According to such a notion, double knockdown of p21 and p27 in cells expressing D2NLS induced activation of CDK2/CDC2 and BrdU incorporation to levels similar to those in cells expressing D1NLS. Taken together, our data suggest that distinct mechanisms keep cyclin D1 and cyclin D2 from activating cell cycle in terminally differentiated cardiomyocytes.

Cardiomyocyte proliferation and protection against post-myocardial infarction heart failure by cyclin D1 and Skp2 ubiquitin ligase.

AIMS: Cyclins and other cell-cycle regulators have been used in several studies to regenerate cardiomyocytes in ischaemic heart failure. However, proliferation of cardiomyocytes induced by nuclear-targeted cyclin D1 (D1NLS) stops after one or two rounds of cell cycles due in part to accumulation of p27Kip1, an inhibitor of cyclin-dependent kinase (CDK). Thus, expression of S-phase kinase-associated protein 2 (Skp2), a negative regulator of p27Kip1, significantly enhances the effect of D1NLS and CDK4 on cardiomyocyte proliferation in vitro. Here, we examined whether Skp2 can also improve cardiomyocyte regeneration and post-ischaemic cardiac performance in vivo. METHODS AND RESULTS: Wistar rats underwent ischaemia/reperfusion injury by ligation of the coronary artery followed by injection of adenovirus vectors for D1NLS and CDK4 with or without Skp2. Enhanced proliferation of cardiomyocytes in the presence of Skp2 was demonstrated by increased expression of Ki67, a marker of proliferating cells (1.95% vs. 4.00%), and mitotic phosphorylated histone H3 (0.24% vs. 0.58%). Compared with rats that received only D1NLS and CDK4, expression of Skp2 improved left ventricular function as measured by the maximum and minimum rates of change in left ventricular pressure, the left ventricle end-diastolic pressure, left ventricle end-diastolic volume index, and the lung/body weight ratio. CONCLUSION: Expression of Skp2 enhanced the effect of D1NLS and CDK4 on the proliferation of cardiomyocytes and further contributed to improved post-ischaemic cardiac function. Skp2 might be a versatile tool to improve the effect of cyclins on post-ischaemic regeneration of cardiomyocytes in vivo.