吴茱萸碱诱导人黑色素瘤A375-S2细胞的两种死亡机制吴茱萸碱诱导人黑色素瘤A375-S2细胞的两种死亡机制

目的研究吴茱萸碱诱导A375-S2细胞死亡机制。方法MTT法测定吴茱萸碱对A375-S2的细胞毒作用。通过倒置光显微镜，荧光染色， DNA电泳观察细胞形态学变化。应用流式细胞分析技术研究药物对细胞周期的影响。结果吴茱萸碱明显抑制A375-S2生长，在24 h前可诱导A375-S2凋亡，亚二倍体峰出现，caspase蛋白酶被激活， 24 h后启动坏死途径，caspase蛋白酶抑制剂不能抑制细胞死亡。结论吴茱萸碱诱导A375-S2死亡时早期启动了caspase依赖性的非经典凋亡途径，后期则启动了坏死途径。     

Short sleep duration and long spells of driving are associated with the occurrence of Japanese drivers’ rear‐end collisions and single‐car accidents

Sleepiness and fatigue are important risk factors for traffic accidents. However, the relation between the accident type and lack of sleep as well as spells of driving has not been examined sufficiently. This study aimed to clarify that short sleep duration and long spells of driving are more associated with rear‐end collisions and single‐car accidents as compared with accidents of other types in cases of people who cause accidents. After removing drunken driving as a cause of accidents, 1772 parties involved in accidents were questioned. The quantities of rear‐end collisions and single‐car accidents were, respectively, 240 and 293. Logistic regression analysis showed that short nocturnal sleep (<6 h) and 10‐min increments of spells of driving were significantly associated not only with rear‐end collisions but also with single‐car accidents as compared with accidents of other types. Furthermore, younger age (≤25 years old) and nighttime (21:00–06:00 h) driving were significantly associated with single‐car accidents as compared with accidents of other types. To prevent such accidents, countermeasures must be considered in light of the characteristics of drivers involved in each type of accident described above.     

Maximum Ventricular Dyssynchrony Predicts Clinical Improvement and Reverse Remodeling during Cardiac Resynchronization Therapy

Background: Tissue synchronization imaging (TSI) and tissue tracking imaging (TTI) might facilitate the evaluation of ventricular dyssynchrony.
Methods: In 22 patients, TSI and TTI were performed before and <1 month after onset of cardiac resynchronization therapy (CRT). With TSI guidance, maximum left ventricular (LV) intraventricular conduction delay (IVCDmax) was the greatest difference in time-to-peak velocity between septum and lateral wall. IVCD between the basal septum and lateral wall (IVCDbase) was also measured. Using TTI, the mean peak myocardial displacement of the basal septal and lateral walls (PMDbase), and the temporal coefficient of variation of the PMD in six LV regions (CV-PMDLV) were measured. The patients were divided into responders (whose LV end-systolic volume decreased by ≥15% during a 27 ± 9 months follow-up) and nonresponders.
Results: Before CRT, IVCDbase was similar in both groups, and remained unchanged within the 1st month of CRT in both groups. However, before CRT, IVCDmax was greater in responders than in nonresponders (P < 0.05), and decreased only in the responders during CRT (P < 0.05). No significant difference was observed in PMDbase or CV-PMDLV between the two groups, before or during CRT.
Conclusions: TSI was useful to measure IVCDmax. A greater IVCDmax before CRT that decreased shortly after onset of CRT may predict long-term clinical improvement in CRT recipients.     

Ablation of Idiopathic Ventricular Tachycardia in Two Separate Regions of the Outflow Tract: Prevalence and Electrocardiographic Characteristics

Few studies have clarified the prevalence and characteristics of idiopathic outflow tachycardia (OT-VT) with an altered QRS morphology after radiofrequency catheter ablation (RFCA), requiring additional RFCA applications at a different portion of the outflow tract (OT) to abolish the OT-VT. Among 344 patients (97 VTs and 247 premature ventricular contractions), 12 (3.5%; VTs-7, PVCs-5; 6 women) had dynamic QRS morphology changes following the RFCA, requiring additional RFCA applications at a different portion to abolish the OT-VT. In 8 of 12 patients (67%), this phenomenon occurred following RFCA at right (RVOT; n = 7) or left ventricular (LVOT; n = 1) endocardial sites of the OT: The second OT-VT was consistently associated with an increase in the R-wave amplitude in the inferior leads, and in five it was finally abolished by RFCA at the left sinus of Valsalva (LSV). Conversely, in four patients (33%), the second OT-VT appeared after RFCA at the LSV: two required additional RFCA applications at the LVOT to abolish the second OT-VT, and one at the RVOT, and all were associated with a decrease in the R-wave amplitude in the inferior leads. This kind of dynamic QRS morphology change was often observed when RFCA was applied to either the first or second OT-VT at a right or left ventricular endocardial site, with the other site being the LSV. A detailed continuous observation of the QRS morphology, especially of the R-wave in the inferior leads, is important for identifying changes in the QRS morphology during RFCA .     

Prevalence and Characteristics of Left Atrial Tachycardia Following Left Atrial Catheter Ablation

Background: Left atrial tachycardia (AT) is a complication of left atrial catheter ablation (LACA) of atrial fibrillation (AF). However, its prevalence and characteristics have not been sufficiently clarified.
Methods: We divided 121 patients who underwent LACA into 2 groups based on the results of AT occurrence after LACA (follow-up period; 12 ± 7 months): an AT+ group and AT– group.
Results: New-onset left AT occurred in 30 patients (25%) 31 ± 51 days after LACA. Among the 26 patients with an early onset of AT, 4 underwent a second ablation for AT, and 21 became free of AT within 6 months without a repeat ablation procedure. Among the 4 patients with a late onset of AT (>2 months after the LACA), the tachycardia remitted without a repeat ablation procedure in a single patient within 6 months. Among 71 patients who underwent LACA with additional ablation lines, 22 (31%) developed new-onset left AT. Among 50 patients who underwent LACA alone, 8 (16%) developed new-onset left AT (P = 0.02).
Conclusions: New-onset left AT is a frequent complication of LACA for AF, especially in men and in patients with a low left ventricular ejection fraction. Early (<2 months) onset AT does not require a repeat ablation because it often represents a transient phenomenon and disappears spontaneously.     

Fetal Atrioventricular Block and Postpartum Augmentative QT Prolongation in a Patient With Long‐QT Syndrome With KCNQ1 Mutation

2:1 AV Block in KCNQ1. The case of a 32‐year‐old pregnant woman, who had had several syncopal episodes during swimming and running at 9 and 10 years of age and whose fetus had 2:1 AV block, is presented. The mother and baby had the same heterozygous single nucleotide substitution in KCNQ1 at T587M. After 27 weeks of gestation, the fetal 2:1 AV block disappeared, and 1:1 AV conduction resumed, with a fetal heart rate of 110–120 beats/min. The maternal electrocardiogram revealed a normal QTc interval (433 ms) without ST‐T abnormalities at gestational week 23, but the QTc was 490 and 531 ms at 1 and 2 months postpartum, with biphasic T waves in leads V2 and V3. This case is the first report of fetal 2:1 AV block with KCNQ1 mutation (T587M) and unmasked maternal QT prolongation in the postpartum period. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1170‐1173)     

吴茱萸碱诱导A375-S2细胞死亡过程中对ERK激酶的调控

目的:对比吴茱萸碱与化疗药物对A375-S2细胞的细胞毒活性,并且研究PKC及ERK激酶在吴茱萸碱诱导A375-S2细胞死亡中的作用。 方法: MTT法,Western印迹法。 结果:虽吴茱萸碱对A375-S2细胞毒作用比化疗药物放线菌素D、顺铂和5-氟尿嘧啶弱,但对药物撤除后细胞继续增殖能力的影响远胜于3种化疗药物。低浓度(10 μg/L) 佛波酯 (PMA) 引起的PKC的激活可部分抑制吴茱萸碱引起的细胞死亡,PKC及ERK抑制剂可逆转这种作用,而且吴茱萸碱减少了ERK蛋白表达,并降低了ERK的磷酸化水平。结论: 吴茱萸碱对A375-S2细胞的细胞毒作用即使在药物撤除后仍对细胞继续增殖能力产生抑制作用。吴茱萸碱可通过减少ERK及磷酸化ERK的蛋白表达而阻断ERK激酶对细胞的保护作用。     

Inactivation of Vesicular Stomatitis Virus by Serum from Patients with Hepatocellular Carcinoma

Vesicular stomatitis virus was inactivated by serum from tenpatients with hepatocellular carcinoma more strongly than bythe serum of ten healthy adults. This action of human serumwas also observed in an infant, a child, a patient with agammaglobulinemia(Bruton type) and the cord blood of three babies (lacking IgM).Serum samples treated with zymosan and by heating at 56°Cfor 30 min lost this ability only partially, although complementaction in the same samples was completely inactivated.     

紫草素诱导A375-S2细胞凋亡的分子机制研究

目的　研究紫草素诱导人黑色素瘤A375 S2细胞凋亡的分子机制。方法　MTT法、Hoechst33258荧光染色、DNA片段化分析、Westernblot、流式细胞分析以及caspase活力分析等。结果　10μmol·L-1紫草素可明显地抑制A375 S2细胞的生长,其半数有效抑制浓度IC50为 (10 9±1 8)μmol·L-1。10μmol·L-1紫草素可诱导A375 S2细胞凋亡,并经历了caspase 9和caspase 3的激活。紫草素促进p53蛋白的积聚,Bax蛋白表达的上调和Bcl xL蛋白表达的下调,进而导致细胞色素C的释放,致使细胞凋亡。紫草素可使细胞周期停止在G1 期。结论　紫草素可诱导A375 S2细胞周期停止在G1 期,其诱导细胞凋亡的途径经过p53介导的Bax和caspase 9的激活。