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Human concentrative nucleoside transporters (CNTs) are responsible for cellular uptake of ribonucleosides; however, although it is important to better characterize CNT-subtype specificity to understand the systemic disposition of deoxyribonucleosides (dNs) and their analogs, the involvement of CNTs in transporting dNs is not fully understood. In this study, using COS-7 cells that transiently expressed CNT1, CNT2, or CNT3, we investigated if CNTs could transport not only ribonucleosides but also dNs, i.e., 2'-deoxyadenosine (dAdo), 2'-deoxyguanosine (dGuo), and 2'-deoxycytidine (dCyd). The cellular uptake study demonstrated that dAdo and dGuo were taken up by CNT2 but not by CNT1. Although dCyd was taken up by CNT1, no significant uptake was detected in COS-7 cells expressing CNT2. Similarly, these dNs were transported by CNT3. The apparent K m values of their uptake were as follows: CNT1, K m ＝ 141 μM for dCyd; CNT2, K m ＝ 62.4 μM and 54.9 μM for dAdo and dGuo, respectively; CNT3, K m ＝ 14.7 μM and 34.4 μM for dGuo and dCyd, respectively. These results demonstrate that CNTs contribute not only to ribonucleoside transport but also to the transport of dNs. Moreover, our data indicated that CNT1 and CNT2 selectively transported pyrimidine and purine dNs, respectively, and CNT3 was shown to transport both pyrimidine and purine dNs., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Information on the growth rate of the diameter of the residual dissected supra-aortic trunk after surgical repair of type A aortic dissection is limited., Methods: We retrospectively reviewed 95 consecutive postsurgical patients with type A aortic dissection (acute, 91; chronic, 4) between 2005 and 2016 who were followed up with computed tomography. The diameter of the residual dissected supra-aortic trunk was measured by axial images and multiplanar reformatting, and the growth rate was calculated., Results: The mean age was 67.2 ± 12.8 years (range, 34-89 years). Forty-one brachiocephalic arteries (43%), 14 left common carotid arteries (15%), and 7 left subclavian arteries (10%) exhibited residual dissection. The diameter of the residual dissected branch with a patent false lumen (FL) gradually increased over time, whereas that with a thrombosed FL decreased and reached a plateau. The growth rate of brachiocephalic, left common carotid, and left subclavian arteries with a patent FL was 1.3 ± 1.2, 0.8 ± 0.3, and 0.6 ± 0.4 mm/y, respectively. One patient required surgical intervention for dilation of the brachiocephalic artery 8 years postoperatively. Multivariate analysis showed that male sex was an independent risk factor for a patent FL in the brachiocephalic artery (P = .0431; odds ratio, 2.04)., Conclusions: A residual dissected supra-aortic trunk with a thrombosed FL seems to be a benign condition. However, long-term follow-up is necessary for patients with a patent FL of residual dissected supra-aortic trunk, which might occasionally require surgical intervention., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients undergoing coronary artery bypass grafting seem to be older and have more comorbidity than patients in prior decades. We retrospectively assessed changes in the predicted mortality risk of patients who underwent coronary artery bypass surgery before and after the introduction of minimally invasive surgical techniques., Methods: Between 1993 and 2002, 345 consecutive patients underwent coronary bypass surgery at Osaka Prefectural General Hospital. Minimally invasive direct coronary artery bypass was introduced in 1997 and off-pump bypass in 1999. Patients were divided into two groups, based on the year of surgery (1993 to 1996 and 1997 to 2002), and mortality risk was assessed with the European System for Cardiac Operative Risk Evaluation (EuroSCORE)., Results: The in-hospital mortality was 3% overall (11 of 345), 8% during the early period (6 of 106), and 2% during the later period (5 of 239). Multiple regression analysis identified an emergent operation to be an independent predictor of in-hospital mortality (p = 0.035). Factors associated with higher scores were recent myocardial infarction (p = 0. 028), preoperative intraaortic balloon pumping (p = 0.026) and preoperative ventilation (p = 0.026), but not age. Scores were higher in the minimally invasive (6.5 +/- 3.6, p = 0.004) and off-pump (5.0 +/- 3.7, p = 0.04) groups than in the conventional bypass group (4.1 +/- 3.3). The arterial graft in coronary artery bypass graft group was significantly less than in off-pump coronary artery bypass group (0.8 +/- 0.8 vs 1.2 +/- 0.8, p = 0.0001). Despite the increasing risk scores, overall in-hospital mortality decreased., Conclusions: The EuroSCORE was useful for assessing changes in the risk profile of patients undergoing bypass surgery over the past decade. The decrease in in-hospital mortality despite the increased risk might reflect the introduction of less invasive coronary surgery in high-risk patients.

Background: Plasma levels of brain natriuretic peptide (BNP), a cardiac hormone secreted predominantly from the ventricle, are elevated in patients with myocardial infarction, hypertension, and dilated cardiomyopathy. In this study, we assessed the usefulness of measuring BNP to evaluate left ventricular function in patients with severe heart failure receiving mechanical circulatory support., Methods: Plasma BNP and creatine kinase (CK)-MB levels were measured serially in 8 consecutive patients with cardiogenic shock who received percutaneous cardiopulmonary support (PCPS) at Osaka Police Hospital from August 1999 to March 2000. Coronary artery bypass grafting or percutaneous transluminal coronary angioplasty was also performed in 5 patients during PCPS; in addition, 1 patient underwent insertion of a left ventricular venting catheter and implantation of a left ventricular assist system after PCPS., Results: Five patients were weaned from PCPS, and 3 died. In survivors, plasma BNP and CK-MB levels correlated positively and significantly (r = 0.968, p = 0.03). After PCPS was initiated, plasma BNP levels gradually decreased in survivors, but not in patients who died (p = 0.003)., Conclusions: These results suggest that plasma BNP levels accurately reflect myocardial damage in patients undergoing PCPS. A decrease in BNP might appear to indicate improved left ventricular function and predict successful weaning from mechanical support.

Background: Thoracic aneurysms involving the ascending aorta, arch, and descending aorta are usually approached in a series of operations. Here, we report our clinical experience with total arch replacement through a median sternotomy with or without left anterolateral thoracotomy, using a technique that preserves the anterior wall of the distal arch to avoid injuring the left recurrent and phrenic nerves., Methods: Between March 1999 and February 2001, 32 consecutive patients underwent total arch replacement through a median sternotomy alone (median group, n = 23) or in combination with a left anterolateral thoracotomy (LAT group, n = 9). In all cases, antegrade hypothermic selective cerebral perfusion was used in conjunction with mild hypothermic visceral perfusion (cool head-warm body perfusion)., Results: There were no in-hospital deaths and two late deaths. One patient in the median group had permanent neurological dysfunction postoperatively. There were no significant differences between the two groups in bypass time, cardiac ischemic time, respiratory assist time, beginning peroral intake, hospital stay, or postoperative respiratory function. The distal anastomosis level was significantly lower in the LAT group (thoracic vertebra level 7.1 +/- 1.5 vs 5.6 +/- 0.5, p = 0.0015)., Conclusions: Preservation of the anterior wall in the distal arch may decrease in-hospital mortality and perioperative neurological dysfunction after total arch replacement. Total arch replacement through a median sternotomy with left anterolateral thoracotomy allowed expeditious and extended replacement of the aorta without increasing postoperative respiratory complications.

Background: Few reports have assessed differences in the durability of mitral and tricuspid bioprostheses after simultaneous implantation of the same bioprosthesis in both positions. We investigated the long-term outcome after simultaneous mitral valve replacement (MVR) and tricuspid valve supraannular implantation (TVSI) with the Carpentier-Edwards bioprostheses in patients with severe tricuspid regurgitation and advanced mitral valve disease., Methods: Between 1982 and 1998, 37 patients in our hospital underwent MVR and TVSI with Carpentier-Edwards bioprostheses. The mean age of the patients was 55+/-11 years. The average postoperative follow-up was 7.9+/-4.5 years after surgery (range 0 to 14.6 years, 315.1 patient-years). The follow-up rate was 100%. We evaluated the actuarial survival rate, the actuarial freedom from structural valve deterioration (SVD) and reoperation, and postoperative complications., Results: The overall actuarial survival rate at 13 years after the operation was 69%+/-31%. The actuarial freedom from SVD and reoperation in the mitral and tricuspid positions were 78+/-22 and 100% and 70+/-30 and 90%+/-10% (p = 0.03), respectively. No patient had systemic or pulmonary thromboembolism, or complications associated with fatal arrhythmia., Conclusions: These results suggest that the bioprostheses in the tricuspid position yield significantly better long-term results than those in the mitral position after simultaneous MVR and TVSI.

Background: Tricuspid valve supra-annular implantation (TVSI) has been performed for adult patients with Ebstein's anomaly at our hospital for several decades. TVSI is characterized by reliable reduction of tricuspid annulus size without affecting the conduction system; by prevention of residual tricuspid regurgitation (RTR) through preservation of the native tricuspid valve; and by implantation of the bioprosthesis at a supra-annular site., Methods: Ten adult patients with Ebstein's anomaly underwent TVSI. The right ventricular diameter and residual tricuspid regurgitation were evaluated by echocardiography preoperatively, at discharge, 1 year after the operation, and over the long term (12.4 +/- 5.5 years). Actuarial survival rate, actuarial freedom from structural valve deterioration rate, and postoperative occurrence of arrhythmia were also evaluated., Results: The actuarial survival rate at 19 years was 76 +/- 15%. Tricuspid regurgitation disappeared in 8 patients just after operation. Right ventricular diameter was significantly smaller at discharge than preoperatively (63 +/- 11 vs 37 +/- 9, p < 0.01), and there were no significant differences between values at discharge and at follow-up. The actuarial freedom from structural valve deterioration rate and the reoperation rate were both 100%. There were no fatal complications related to arrhythmia or thromboembolism., Conclusions: TVSI is useful for adult patients with Ebstein's anomaly. The absence of complications related to fatal arrhythmia and thromboembolism, good durability of the bioprosthesis, and a simple operative procedure are merits of this therapy.

Background: It is still difficult to evaluate myocardial damage in the acute phase of reperfusion in cardiac operations. We investigated the clinical significance of human heart fatty acid-binding protein (HH-FABP) for detecting myocardial damage after cardiac operations earlier than creatine kinase MB isoform or troponin-T., Methods: Blood samples from 20 patients who underwent coronary artery bypass grafting were collected serially after reperfusion to measure serum levels of creatine kinase-MB, troponin-T, and HH-FABP., Results: Serum HH-FABP levels peaked earliest after reperfusion. In addition, the maximum serum HH-FABP level was predictable immediately after reperfusion. The maximum serum HH-FABP level correlated with the maximum serum creatine kinase-MB or troponin-T level, as well as with the aortic cross-clamp time or the maximum dose of catecholamines administered after reperfusion., Conclusions: Measurements of HH-FABP allow for earlier evaluation of myocardial damage in the acute phase of reperfusion. Human heart fatty acid-binding protein may be a useful indicator of myocardial damage after cardiac operations.

Background: Cardiopulmonary bypass (CPB) causes inflammatory reactions and abnormal responses of vascular resistance. Theoretically, the difference in the blood temperature during CPB may influence the degree of CPB-induced inflammatory reactions., Methods: To elucidate the effect of the perfusate temperature during CPB, serum levels of inflammatory cytokines, neutrophil elastase, complements, and vasoactive substances were measured in 18 patients undergoing elective coronary artery bypass grafting under tepid temperature (34 degrees C) and moderate hypothermia (28 degrees C). Respiratory index and systemic vascular resistance index during and after CPB and intubation time after postoperative course were also analyzed., Results: The patterns of the change in interleukin-8 and neutrophil elastase were significantly different between the two groups. The tepid group showed an earlier decrease in interleukin-8 and neutrophil elastase levels as compared with the hypothermic group. The prostaglandin E2 level just after CPB was significantly higher in the tepid group than in the hypothermic group. Systemic vascular resistance index and respiratory index and intubation time were significantly lower in the tepid group than in the hypothermic group., Conclusions: These results demonstrated that tepid CPB affected the inflammatory cytokine release and neutrophil activation compared with hypothermic CPB, resulting in the attenuation of respiratory dysfunction. This may suggest a beneficial effect of tepid temperature in CPB with possible attenuation of the postperfusion syndrome.

We analyzed a Japanese chick wingless mutant (Jwg) to know a molecular mechanism underlying wing development. We observed expression patterns of eleven marker genes to characterize the mutant. Expressions of dorsoventral (DV) and mesenchymal marker genes were intact in nascent Jwg limb buds. However, expression of Fgf8, a marker gene for the apical ectodermal ridge (AER), was delayed and shortly disappeared in the wing regressing AER. Later on, ventral expression of dorsal marker genes of Wnt7a and Lmx1 indicated that the wing bud without the AER became bi-dorsal. In addition, the posterior mesoderm became defective, as deduced from the impaired expression patterns of Sonic hedgehog (Shh), Msx1, and Prx1. We attempted to rescue a wing by implanting Fgf8-expressing cells into the Jwg wing bud. We found that FGF8 can rescue outgrowth of the wing bud by maintaining Shh expression. Thus, the Jwg gene seems to be involved in maintenance of the Fgf8 expression in the wing bud. Further, it is suggested that the AER is required for maintenance of the DV boundary and the polarizing activity of the established wing bud.

To elucidate what initiates formation of the limb, we have attempted to induce an additional limb from the flank of the chick embryo by infecting retrovirus or implanting cells. We report here that an additional limb can be formed from the flank when we implant fibroblast growth factor 4 (Fgf4)-expressing cells into the lateral plate mesoderm at the pre-limb bud stage. In a newly formed limb bud, expressions of both Sonic hedgehog and chick Fgf4, which are authentic morphogenetic signals from the zone of polarizing activity and the apical ectodermal ridge, respectively, are induced by the implanted cells. Thus, it is concluded that the competence for limb development is present along the flank of the chick embryo and that FGF4 applied ectopically at the pre-limb bud stage can alter the developmental fate of flank cells to become limb cells. The present experimental system will contribute to a further elucidation on how the limb is formed.

An assay method for serum cortisol, using precolumn sulphuric acid-ethanol fluorescence derivatization and reversed-phase liquid chromatography with a column-switching technique, has been developed. The crude precolumn fluorescence cortisol derivative was prepared by the addition of sulphuric acid to serum deproteinized with ethanol, and directly injected onto an octadecylsilane-bonded silica gel (ODS) precolumn for concentration and purification. After switching columns the samples were separated using an ODS analytical column and monitored fluorimetrically. When the pH of the mobile phase in the analytical separator decreased to 1.85, the emission wavelength of the cortisol derivative changed to 520 nm (excitation of 365 nm) and the fluorescence intensity increased. Among the sulphuric acid-ethanol derivatives of various steroids, cortisol, corticosterone and testosterone emitted fluorescence. However, their retention times differed from those of the cortisol derivatives (12.5 min). The detection limit of cortisol was 0.3 micrograms/dl (signal-to-noise ratio of 3). Use of the fully automated column-switching system contributed to good reproducibility and recovery.