Role of troponin T in disease

Several striated muscle myopathies have been directly linked to mutations in contractile and associated proteins. Troponin T (TnT) is one of the three subunits that form troponin (Tn) which together with tropomyosin is responsible for the regulation of striated muscle contraction. All three subunits of cardiac Tn as well as tropomyosin have been associated with hypertrophic cardiomyopathy (HCM). However, TnT accounts for most of the mutations that cause HCM in these regulatory proteins. To date 30 mutations have been identified in the cardiac TnT (CTnT) gene that results in familial HCM (FHC). The CTnT gene has also been associated with familial dilated cardiomyopathy (DCM). CTnT deficiency is lethal due to impaired cardiac development. A recessive nonsense mutation in the gene encoding slow skeletal TnT has been associated with an unusual, severe form of nemaline myopathy among the Old Order Amish. How each mutation leads to the diverse clinical symptoms associated with FHC, DCM or nemaline myopathy is unclear. However, the use of animal model systems, in particular transgenic mice, has significantly increased our knowledge of normal and myopathic muscle physiology. In this review, we focus on the role of TnT in muscle physiology and disease. (Mol Cell Biochem 263: 115–129, 2004)     

Malignant arrhythmia in apical ballooning syndrome: risk factors and outcomes

Objectives

We sought to determine the frequency and outcomes with symptomatic arrhythmia in patients with apical ballooning syndrome (ABS).

Methods

A retrospective review of the Mayo Clinic Angiography database was conducted to identify patients who met the Mayo criteria for ABS. Patients with documented arrhythmias formed the study group, and 31 randomly selected patients with ABS but without arrhythmia formed the control group.

Results

Out of 105 patients identified with ABS, 6 (5.7%) women aged 69 +/- 9 years experienced significant arrhythmia (ventricular fibrillation, asystole), 2 patients died, and 1 required permanent pacemaker implantation. When compared with controls, the study group showed no significant difference with respect to ECG characteristics (QT, QRS duration or axis) except for R-R interval variability (see comments below) (30.6±6 vs 14.5±17 p = 0.0004), QTc, and P-R interval. Patients without arrhythmia were more likely to be on beta-blocker therapy than the study population (33% vs 80.6% p = 0.02).

Conclusion

Life-threatening arrhythmia is uncommon (5.7%) with ABS despite marked, structural abnormalities. When arrhythmias do occur, the outcome is poor. Prominent variability in R-R intervals appears to be predictive of significant arrhythmias in ABS. The role of beta-blocker therapy in preventing arrhythmia with ABS requires further investigation.     

ACE I/D polymorphism in Indian patients with hypertrophic cardiomyopathy and dilated cardiomyopathy

Aim The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). Methods and results A total of 174 patients diagnosed with cardiomyopathy (118 with HCM, 51 with DCM, and 5 with RCM) and 164 ethnically, age- and gender-matched controls were included in the study. ACE I/D genotyping was performed by PCR. In total, 25.86% of the patients were in New York Heart Association (NYHA) class III and IV at presentation. A total of 67.24% patients had dyspnea, 56.89% had angina pectoris, and 25.28% of the patients had at least one event of syncope. Frequency of occurrence of the disease was more in male patients compared to female patients (P < 0.05). After adjustment for age, sex, body mass index (BMI), and smoking habit, the prevalence of ACE DD genotype, and ACE ‘D’ allele was significantly higher in patients as compared to controls and was associated with increased risk (DD: OR 2.11, 95% CI 1.27–3.52, P < 0.05; ‘D’: OR 1.91, 95% CI 1.08–3.35, P < 0.05). The mean septal thickness was higher for DD and ID genotypes (20.40 ± 3.73 mm and 21.82 ± 5.35 mm, respectively) when compared with II genotype (18.63 ± 6.69 mm) in HCM patients, however, the differences were not significant statistically (P > 0.05). The DCM patients with ID genotype showed significantly decreased left ventricular ejection fraction (LVEF) at enrolment (26.50 ± 8.04%) (P = 0.04). Conclusion Our results suggest that D allele of ACE I/D polymorphism significantly influences the HCM and DCM phenotypes.     

Acetaldehyde addition throughout the growth phase alleviates the phenotypic effect of zinc deficiency in Saccharomyces cerevisiae

During experiments to determine the effects of exogenously added acetaldehyde on pure cultures of various yeast strains, we discovered that an early acetaldehyde perfusion during the growth phase allowed several yeasts to partially overcome the phenotypic effects of zinc depletion during alcoholic fermentation. We, therefore, performed genome-wide expression and proteomic analysis on an industrial Saccharomyces cerevisiae yeast strain (VL1) growing in zinc-replete or zinc-depleted conditions in the presence of perfused acetaldehyde to identify molecular markers of this effect. Zinc depletion severely affects ethanol production and therefore nicotinamide adenine dinucleotide (NAD) regeneration, although we observed partial compensation by the upregulation of the poorly efficient Fe-dependent Adh4p in our conditions. A coordinate metabolic response was indeed observed in response to the early acetaldehyde perfusion, and particularly of the lower part of glycolysis, leading to the cellular replenishment of NAD cofactor. These various findings suggest that acetaldehyde exchange between strains may inhibit the growth of some yeast strains while encouraging the growth of others. This phenomenon could be particularly important for understanding the ecology of colonization of complex fermentation media by S. cerevisiae after elimination of non-Saccharomyces yeasts.     

致心律失常性右室心肌病患者的诱导性多能干细胞系的建立

目的：建立致心律失常性右室心肌病（ARVC）患者特异性的诱导性多能干细胞（iPSCs）,为研究ARVC发病机制提供研究模型。方法：培养来源于ARVC患者皮肤成纤维细胞,并进行突变位点测序鉴定。通过仙台病毒转导入外源性多能转录因子,将ARVC患者皮肤细胞诱导为iPSCs,结合免疫荧光法,实时荧光定量PCR,以及体内外三胚层形成实验对iPS细胞全能型进行鉴定。通过调控Wnt信号通路诱导iPS细胞定向分化为心肌细胞。结果：ARVC患者来源的iPSCs显示碱性磷酸酶阳性,多能性相关基因高表达,胚胎干细胞标志物Oct4,SSEA4,TRA-1-81阳性。体外悬浮培养形成的拟胚体以及体内畸胎瘤形成实验均显示ARVC-iPSCs具有向3个胚层分化能力。经过体外心肌定向,ARVC-iPSC可诱导产生自主节律性搏动细胞团,免疫荧光显示cTnT阳性。结论：本研究使用仙台病毒,建立了无插入型ARVC患者特异的诱导性多能干细胞系,该细胞系具有多能分化特性,并可定向分化为心肌细胞,为研究ARVC的致病因素和药物筛选提供宝贵的实验模型。     

扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义

目的:探究扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义。方法:收集2012年3月至2016年3月我院收治的90例扩张型心肌病慢性心力衰竭患者,将患者按照NYHA心功能分级分为A组(II级)20例、B组(III级)38例、C组(IV级)32例。比较各组患者的血浆脑力钠肽(BNP)以及超声心动图相关指标,包括左心室射血分数(LVEF)、左心房内径(LA)、左室舒张末期内径(LVEDD)以及左室收缩末期内径(LVESD),分析血浆BNP与NYHA分级和超声心动图相关指标的相关性,以及比较血浆BNP和LVEF在慢性心力衰竭病情程度中的能力。结果:C组患者的血浆BNP浓度显著高于A组和B组(P0.05),而B组患者的血浆BNP浓度显著高于A组,比较差异具有统计学意义(P0.05)。心脏超声检测发现,C组患者的LA显著高于A组(P0.05),而LVEF、LVEDD及LVESD比较差异无统计学意义(P0.05)。血浆BNP与NYHA分级呈正相关关系,但与LVEDD、LVESD、LVEF、LA无明显相关关系(P0.05)。血浆BNP对评价心力衰竭患者病情程度呈现出较强的能力(受试者工作特征曲线下面积=0.902,P0.001)。血浆BNP=523.5 pg/mL为中重度心力衰竭患者的诊断最佳值。LVEF对评价心力衰竭患者病情程度无明显能力(受试者工作特征曲线下面积=0.392,P=0.276)。结论:血浆BNP浓度对扩张型心肌病慢性心力衰竭患者的诊断、筛查以及心功能分级具有重要的临床意义。     

儿童不明原因扩张型心肌病左室射血分数恢复的影响因素分析

目的:探讨儿童不明原因扩张型心肌病(DCM)左室射血分数(LVEF)恢复的影响因素。方法:回顾性分析2010年1月至2014年12月在我院住院治疗的不明原因DCM患儿的临床资料,对所有患者随访16月后,根据二维超声心动图(UCG)中LVEF值,分为LVEF恢复组、未恢复组和死亡组,比较各组之间各相关检测指标的差异。结果:大选194例患者男性113例。恢复组45例(23.20%),末恢复组65例(33.51%),死亡组84例(43.29%)。恢复组发病年龄≤2岁者患者比例明显高于未恢复组与死亡组(P均0.05)。初诊时,恢复组左室舒张末期内径(LVDD)明显小于未恢复组与死亡组AVEF明显高于未恢复组与死亡组(P均0.05)。恢复组二尖瓣轻度反流的患者明显多于未恢复组及死亡组(P均0.05)。恢复组室性心律失常者比例明显少于未恢复组及死亡组(P0.05)。恢复组患者无心肌延迟强化现象,末恢复组延迟强化占5.41%,死亡组占21.74%。恢复组LVEF恢复正常的中位时间8.0月,同时有LVDD恢复正常者11例。多因素分析发现年龄2.0岁(OR=17.064,95%C13.494-83.171,P=0.000)、心功能Ⅲ-Ⅳ级(OR=17.711,95%CI2.229-140.704,P=0.007)、MR中重度反流(OR=3.762,95%CI1.209-11.706,P=0.022)是LVEF不能恢复正常的独立危险因素。结论:年龄2.0岁、心功能Ⅲ-Ⅳ级、二尖瓣中重度反流是不利于儿童不明原因扩张型心肌病患儿LVEF恢复的独立危险因素。     

Infantile dilated cardiomyopathy in Portuguese water dogs: Correlation of the autosomal recessive trait with low plasma taurine at infancy

Summary. Infantile dilated cardiomyopathy (IDCM) in Portuguese water dogs (PWD) involves an autosomal recessive trait. Based on our previous studies we have tested the hypothesis that this disorder may be correlated with taurine deficiency. The plasma taurine levels of 249 puppies from 36 litters obtained from breeders at six and nine weeks of age, an early stage when usually the clinical symptoms are not manifested, were analyzed. Additional samples were collected from sixteen puppies that we raised from four litters. These litters were born to a dam that had low plasma taurine as a puppy and two known carrier sires. From the random samples obtained from the breeders, forty-eight pups from fourteen litters and twenty-nine pups from seven litters had low plasma taurine at least at one and at two time points, respectively. Also several puppies showing low plasma taurine died due to IDCM. Furthermore, from the sixteen pups we raised, fifteen had at least low taurine level at one and seven had at two time points. Considered together, these results strongly support the view that IDCM in PWD is associated with abnormal taurine metabolism that leads to low plasma taurine at early stages before the clinical symptoms appear.     

Characterization of a wine-like beverage obtained from sugarcane juice

Two yeasts (Saccharomyces cerevisiae and Saccharomyces cerevisiae var ellipsoideus)were tested for their ability to ferment sugarcane (Saccharum officinarum) juice. In order to do this, time course studies of volatile, fixed, and total acidity, pH, alcohol, total sugars and °Bx were performed and the presence of methanol was tested. The fermentation studies were carried out at 25, 28 and 30 °C and the juice was inoculated with 1 and 5% (v/v) suspensions of both yeasts containing 1 × 10⁸ cells ml⁻¹. Time course studies indicated a similar fermentative pattern at the three temperatures evaluated, hence 25 °C was chosen as the cheapest alternative. The size of the inoculum made no difference in the fermentation. Analyses of the sugarcane juice wine showed the following results: pH, 3.2; alcohol, 10 °GL; total solids, 16.5 g l⁻¹; ash, 1.4 g l⁻¹; total acidity, 5.4 g l⁻¹; volatile acidity, 0.12 g l⁻¹; fixed acidity, 5.3 g l⁻¹ and no methanol was detected. Two additional products were obtained after adding passion fruit juice and roselle (Hibiscus sabdarifa Linn) concentrates. The fruit-flavoured wines were significantly preferred (P ≤ 0.05) over the plain product. These results indicated that the elaboration of wine-like beverages is a good alternative use for sugarcane.