Evaluation of repair activity by quantification of ribonucleotides in the genome

Ribonucleotides incorporated in the genome are a source of endogenous DNA damage and also serve as signals for repair. Although recent advances of ribonucleotide detection by sequencing, the balance between incorporation and repair of ribonucleotides has not been elucidated. Here, we describe a competitive sequencing method, Ribonucleotide Scanning Quantification sequencing (RiSQ-seq), which enables absolute quantification of misincorporated ribonucleotides throughout the genome by background normalization and standard adjustment within a single sample. RiSQ-seq analysis of cells harboring wild-type DNA polymerases revealed that ribonucleotides were incorporated nonuniformly in the genome with a 3′-shifted distribution and preference for GC sequences. Although ribonucleotide profiles in wild-type and repair-deficient mutant strains showed a similar pattern, direct comparison of distinct ribonucleotide levels in the strains by RiSQ-seq enabled evaluation of ribonucleotide excision repair activity at base resolution and revealed the strand bias of repair. The distinct preferences of ribonucleotide incorporation and repair create vulnerable regions associated with indel hotspots, suggesting that repair at sites of ribonucleotide misincorporation serves to maintain genome integrity and that RiSQ-seq can provide an estimate of indel risk.     

The safety and efficacy of systemic versus catheter-based therapies: application of a prognostic model by a pulmonary embolism response team

Journal of Thrombosis and Thrombolysis - The decision by pulmonary embolism response teams (PERTs) to utilize anticoagulation (AC) with or without systemic thrombolysis (ST) or catheter-directed...     

Surgical treatment of coarctation of the aorta and interrupted aortic arch

From December, 1984, through April, 1987, ten infants with coarctation of the aorta and six with interrupted aortic arch underwent staged repair of aorta and other cardiac lesions. Simultaneous pulmonary artery banding was performed in six of 8 patients with ventricular septal defect (VSD) and in all of seven patients with complex cardiac lesions. With first operation, there were no operative deaths and two late deaths. Eight of 14 survivors underwent total correction of associated lesions at three to 17 months after initial operation. VSD was closed in five patients with one operative death. One patient required pulmonary artery debanding alone because of decrease of VSD size. The Damus-Kaye-Stansel operation was performed successfully in one patient with Taussig-Bing anomaly and the Jatene operation was done in one with transposition of the great arteries. Based on these results, we prefer staged repair with pulmonary artery banding for coarctation or interruption of the aorta associated with complex cardiac lesions.     

A successful case of localized aortic dissection associated with bicuspid aortic valve

It is known that bicuspid aortic valve is a risk factor of aortic dissection in Europe and America, but there is no report of the case in Japan. A 47-year-old male teacher of senior high school had an abrupt onset of chest pain. Aortogram showed localized dissection of the ascending aorta and moderate degree of aortic regurgitation. Cold cardioplegic arrest with moderate systemic hypothermia was used under cardiopulmonary bypass. The aortic valve was bicuspid and localized transverse intimal dissection was also found above left-sided commissure. As both cusps were soft and not degenerative, mattress sutures were used to support the prolapsed cusps against the outer aortic wall. The ascending aorta was replaced with a prosthetic vascular graft. Postoperative clinical course was uneventful and he is doing well two years after the surgery. The bicuspid aortic valve and aortic dissection were also discussed.     

Primary tissue failure of the freestyle stentless aortic root bioprosthesis

We present a case of early tissue failure of the Medtronic Freestyle stentless bioprosthesis used in the aortic position which led to reoperation 27 months after implantation. Almost one half of the left coronary cusp of the prosthetic valve had torn away along the annulus. The tear started from the left-non coronary commissure and reached the midpoint of the base of the left coronary cusp. The prosthetic valve was easily excised and replaced with a new mechanical valve. There was no sign of calcification or vegetation in the excised valve. The cause of the valve dysfunction was thought to be primary tissue failure. Long-term function of the Freestyle stentless valve should be carefully followed up.     

Kay's mitral valve repair for mitral regurgitation due to ruptured chordae tendineae--clinical and hemodynamic observations

Kay's mitral valve repair was performed in six consecutive patients with symptomatic mitral regurgitation due to ruptured chordae tendineae of the posterior leaflet. All patients including one with mild residual murmur showed a marked decrease in the heart size and significant clinical improvement. Postoperative hemodynamic studies, performed in four patients, showed restoration of normal or near-normal dynamics. The medium-term follow-up, 15 to 30 months after the operation, revealed continuing asymptomatic states in all. The function of the repaired valves was significantly better than that of the Hancock mitral bioprostheses. The advantages of this procedure compared with mitral valve replacement for the same condition were stressed.     

Influence of perfusion pressure on oxygen supply and demand in beating empty hypertrophied dog hearts

As cardiopulmonary bypass is frequently accompanied by hypotension, the effect of varying perfusion pressure (30, 60, and 90 mm Hg) on the adequacy and distribution of coronary flow was studied under conditions of a normothermic beating empty state, of normal and hypertrophied hearts of 20 mongrel dogs, using the radioactive microsphere technique. In the normal hearts, 30 mmHg caused a 47% (P < 0.005 to prebypass) reduction of left ventricular coronary flow but did not change flow distribution (ENDO/EPI flow ratio: 1.01); increasing mean perfusion pressure from 30 to 90 mm Hg did not alter the oxygen consumption but did increase the coronary flow and decrease the oxygen extraction ratio. In the hypertrophied hearts, 30 and 60 mm Hg perfusion pressures resulted in a redistribution of flow away from the subendocardium (ENDO/EPI flow ratio: 0.82 and 0.87, respectively, P < 0.02 to prebypass). An increase in perfusion pressure from 30 to 60 mm Hg resulted in a significant increase in oxygen uptake (4.0 vs 5.6 cc/100 g/min, respectively, P < 0.02). An increased perfusion pressure of 90 mmHg resulted in a sufficient subendocardial flow and an augmentation of the oxygen uptake. These results indicate that subendocardial underperfusion occurs in the beating empty hypertrophied heart, under conditions of lower perfusion pressures (30 and 60 mm Hg), but that such can be improved by increasing the perfusion pressure to 90 mmHg. In contrast, the subendocardial underperfusion does not occur with a perfusion pressure of 30 mm Hg in normal hearts.