• 【正常小鼠和那些早发性感光细胞营养不良的杂合子的视网膜中的循环GMP。】 复制标题 收藏 收藏
    DOI:10.1016/0014-4835(85)90094-6 复制DOI
    作者列表:Doshi M,Voaden MJ,Arden GB
    BACKGROUND & AIMS: :Cyclic GMP metabolism has been investigated in the retinas of mice that are heterozygous for a 'photoreceptor dystrophy' gene and have a lowered concentration of cGMP in their photoreceptor cells. The concentration of rhodopsin, retinal morphology and guanylate cyclase kinetics were normal. Cyclic GMP phosphodiesterase had a lowered affinity for cGMP. In accord with previous observations, chelation of exogenous calcium had no effect on cGMP levels in light-adapted retinas but increased them in dark-adapted tissue. The difference between cGMP concentrations in heterozygous and normal retinas in the dark was then eliminated. It was concluded that a modulator of cGMP phosphodiesterase activity is most likely to be causing the lowered steady-state level of cGMP in heterozygous retinas and that calcium is not involved.
    背景与目标: :已经对小鼠视网膜中的循环GMP代谢进行了研究,这些小鼠对于“感光器营养不良”基因是杂合的,并且其感光细胞中cGMP的浓度降低。视紫红质的浓度,视网膜形态和鸟苷酸环化酶动力学均正常。环状GMP磷酸二酯酶对cGMP的亲和力较低。与以前的观察结果一致,外源钙的螯合对光适应性视网膜中cGMP的含量没有影响,但在黑暗适应性组织中却增加了。然后消除了黑暗中杂合子和正常视网膜中cGMP浓度之间的差异。结论是,cGMP磷酸二酯酶活性的调节剂最有可能导致杂合性视网膜中cGMP的稳态水平降低,并且不涉及钙。
  • 【印度的四肢腰肌营养不良:综述。】 复制标题 收藏 收藏
    DOI:10.4103/aian.AIAN_81_17 复制DOI
    作者列表:Khadilkar SV,Faldu HD,Patil SB,Singh R
    BACKGROUND & AIMS: :Limb-girdle muscular dystrophies (LGMDs) are common in India. Information on LGMDs has been gradually evolving in the recent years. This information is scattered in case series and case studies. The aim of this study is to collate available Indian information on LGMDs and put it in perspective. PubMed search using keywords such as limb-girdle muscular dystrophies in India, sarcoglycanopathies, dysferlinopathy, calpainopathy, and GNE myopathy was carried out. The published information on LGMDs in Indian context suggests that dysferlinopathy, calpainopathy, sarcoglycanopathies, and other myopathies such as GNE myopathy are frequently seen in India. Besides these, anecdotal reports of many other forms are available, some with genetic support and others showing immunocytochemical defects. The genotypic information on LGMDs is gradually evolving and founder mutations have been detected in selected populations. Further multicenter studies are necessary to document the incidence and prevalence of these common conditions in India.
    背景与目标: :四肢肌营养不良症(LGMD)在印度很常见。近年来,有关LGMD的信息已逐渐发展。此信息分散在案例系列和案例研究中。这项研究的目的是整理有关LGMD的印度可用信息,并加以透视。使用关键词进行了PubMed搜索,例如印度的四肢肌肉营养不良,肌糖蛋白病,dysferlinopathy,钙蛋白酶病和GNE肌病。关于在印度背景下的LGMD的公开信息表明,在印度经常见到神经纤维异常,钙蛋白酶病,肌糖蛋白病和其他肌病,例如GNE肌病。除此之外,还有许多其他形式的轶事报道,其中一些具有遗传支持,而另一些则显示出免疫细胞化学缺陷。关于LGMD的基因型信息正在逐步发展,并且在选定的人群中发现了创始人突变。有必要进行进一步的多中心研究,以证明印度这些常见疾病的发生率和流行率。
  • 【将七个基因分配到围绕强直性营养不良基因区域的人类染色体19q的中部的不同区间。】 复制标题 收藏 收藏
    DOI:10.1159/000132946 复制DOI
    作者列表:Schonk D,van Dijk P,Riegmann P,Trapman J,Holm C,Willcocks TC,Sillekens P,van Venrooij W,Wimmer E,Geurts van Kessel A
    BACKGROUND & AIMS: :Hybridization studies using a panel of somatic cell hybrids with subchromosomal segments of 19q have localized the genes encoding hormone-sensitive lipase (LIPE), carcinoembryonic antigen (CEA), and small nuclear ribonucleoprotein polypeptide A (SNRPA) to various regions of 19q13.1; the cellular receptor for poliovirus sensitivity (PVS) to 19q13.2; and the genes coding for prostate-specific antigen (APS), human pancreatic kallikrein (KLK1), and small nuclear ribonucleoprotein 70-kD polypeptide (SNRP70) to 19q13.3----qter. Our results exclude several of these genes from being seriously considered as a candidate for the myotonic dystrophy gene on 19q.
    背景与目标: :使用一组具有19q染色体下染色体片段的体细胞杂种进行杂交研究,已将编码激素敏感性脂肪酶(LIPE),癌胚抗原(CEA)和小核糖核糖核蛋白多肽A(SNRPA)的基因定位于19q13.1的各个区域;脊髓灰质炎病毒对19q13.2的细胞受体(PVS);编码前列腺特异性抗原(APS),人胰激肽释放酶(KLK1)和小核核糖核蛋白70-kD多肽(SNRP70)的基因编码至19q13.3 ---- qter。我们的结果排除了其中几个基因被认为是19q上强直性营养不良基因的候选基因。
  • 【撤回:年龄依赖性肌肉营养不良症与mdx小鼠颅面形态的变化有关。】 复制标题 收藏 收藏
    DOI:10.1016/j.archoralbio.2013.07.002 复制DOI
    作者列表:Roderer B,Tsagkari E,Gredes T,Dominiak M,Gedrange T,Kunert-Keil C
    BACKGROUND & AIMS: :This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
    背景与目标: :本文已应作者和/或编辑的要求撤回。对于由此给您带来的任何不便,出版商深表歉意。完整的Elsevier物品提取政策可在http://www.elsevier.com/locate/withdrawalpolicy上找到。
  • 【Bestrophin-3(玻璃状黄斑营养不良2样3蛋白)对于血管平滑肌细胞中cGMP依赖性钙激活的氯化物传导至关重要。】 复制标题 收藏 收藏
    DOI:10.1161/CIRCRESAHA.108.178517 复制DOI
    作者列表:Matchkov VV,Larsen P,Bouzinova EV,Rojek A,Boedtkjer DM,Golubinskaya V,Pedersen FS,Aalkjaer C,Nilsson H
    BACKGROUND & AIMS: :Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small interfering RNA both in cultured cells and in vascular smooth muscle cells in vivo was associated with a significant reduction of the cGMP-dependent Ca(2+)-activated Cl(-) current, whereas the magnitude of the classic Ca(2+)-activated Cl(-) current was not affected. The majority of previous suggestions that bestrophins are a new Cl(-) channel family were based on heterologous expression in cell culture studies. Our present results demonstrate that at least 1 family member, bestrophin-3, is essential for a well-defined endogenous Ca(2+)-activated Cl(-) current in smooth muscles in the intact vascular wall.
    背景与目标: :尽管Ca(2)激活的Cl(-)电流的生物物理指纹(离子选择性,电压依赖性,动力学等)已被很好地建立,但它们的分子身份仍然存在争议。已经提出了几种分子候选物。但是,它们都没有被完全接受。我们最近表征了cGMP依赖性Ca(2)激活Cl(-)当前具有在平滑肌细胞中的独特特征。该新型电流已显示与“经典”(独立于cGMP的)Ca(2)激活的Cl(-)电流共存,并且具有不同于先前已知的Ca(2)激活的Cl(-)电流的特性。 。在这里,我们建议Bestrophin,最好的基因家族的产物,负责由cGMP依赖Ca(2)激活的Cl(-)电流,这取决于Bestrophins与cGMP的异源表达所产生的膜电流之间的相似性。依赖的Ca(2)激活的Cl(-)电流。这由cGMP依赖性Ca(2)激活的Cl(-)电流和Bestrophin-3(Best-3基因的产物)表达在不同平滑肌中的分布模式的相似性所支持。此外,在体内培养的细胞和血管平滑肌细胞中的小干扰RNA的Best-3基因表达的下调与cGMP依赖性Ca(2)激活的Cl(-)电流的显着降低有关,而的经典Ca(2)激活Cl(-)电流的大小不受影响。以前的大多数建议,即最佳动物生长素是一个新的Cl(-)通道家族,是基于细胞培养研究中的异源表达。我们目前的结果表明,至少1个家庭成员,Bestrophin-3,对于完整血管壁平滑肌中明确定义的内源性Ca(2)激活Cl(-)电流是必不可少的。
  • 【II型和III型脊髓性肌萎缩症的药物治疗。】 复制标题 收藏 收藏
    DOI:10.1002/14651858.CD006282.pub5 复制DOI
    作者列表:Wadman RI,van der Pol WL,Bosboom WM,Asselman FL,van den Berg LH,Iannaccone ST,Vrancken AF
    BACKGROUND & AIMS: BACKGROUND:Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron 1 (SMN1) gene on chromosome 5, or a heterozygous deletion in combination with a (point) mutation in the second SMN1 allele. This results in degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. This is an update of a review first published in 2009 and previously updated in 2011. OBJECTIVES:To evaluate if drug treatment is able to slow or arrest the disease progression of SMA types II and III, and to assess if such therapy can be given safely. SEARCH METHODS:We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and ISI Web of Science conference proceedings in October 2018. In October 2018, we also searched two trials registries to identify unpublished trials. SELECTION CRITERIA:We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a homozygous deletion or hemizygous deletion in combination with a point mutation in the second allele of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis. The primary outcome measure was change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full-time ventilation and adverse events attributable to treatment during the trial period. Treatment strategies involving SMN1-replacement with viral vectors are out of the scope of this review, but a summary is given in Appendix 1. Drug treatment for SMA type I is the topic of a separate Cochrane Review. DATA COLLECTION AND ANALYSIS:We followed standard Cochrane methodology. MAIN RESULTS:The review authors found 10 randomised, placebo-controlled trials of treatments for SMA types II and III for inclusion in this review, with 717 participants. We added four of the trials at this update. The trials investigated creatine (55 participants), gabapentin (84 participants), hydroxyurea (57 participants), nusinersen (126 participants), olesoxime (165 participants), phenylbutyrate (107 participants), somatotropin (20 participants), thyrotropin-releasing hormone (TRH) (nine participants), valproic acid (33 participants), and combination therapy with valproic acid and acetyl-L-carnitine (ALC) (61 participants). Treatment duration was from three to 24 months. None of the studies investigated the same treatment and none was completely free of bias. All studies had adequate blinding, sequence generation and reporting of primary outcomes. Based on moderate-certainty evidence, intrathecal nusinersen improved motor function (disability) in children with SMA type II, with a 3.7-point improvement in the nusinersen group on the Hammersmith Functional Motor Scale Expanded (HFMSE; range of possible scores 0 to 66), compared to a 1.9-point decline on the HFMSE in the sham procedure group (P < 0.01; n = 126). On all motor function scales used, higher scores indicate better function. Based on moderate-certainty evidence from two studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: creatine (median change 1 higher, 95% confidence interval (CI) -1 to 2; on the Gross Motor Function Measure (GMFM), scale 0 to 264; n = 40); and combination therapy with valproic acid and carnitine (mean difference (MD) 0.64, 95% CI -1.1 to 2.38; on the Modified Hammersmith Functional Motor Scale (MHFMS), scale 0 to 40; n = 61). Based on low-certainty evidence from other single studies, the following interventions had no clinically important effect on motor function scores in SMA types II or III (or both) in comparison to placebo: gabapentin (median change 0 in the gabapentin group and -2 in the placebo group on the SMA Functional Rating Scale (SMAFRS), scale 0 to 50; n = 66); hydroxyurea (MD -1.88, 95% CI -3.89 to 0.13 on the GMFM, scale 0 to 264; n = 57), phenylbutyrate (MD -0.13, 95% CI -0.84 to 0.58 on the Hammersmith Functional Motor Scale (HFMS) scale 0 to 40; n = 90) and monotherapy of valproic acid (MD 0.06, 95% CI -1.32 to 1.44 on SMAFRS, scale 0 to 50; n = 31). Very low-certainty evidence suggested that the following interventions had little or no effect on motor function: olesoxime (MD 2, 95% -0.25 to 4.25 on the Motor Function Measure (MFM) D1 + D2, scale 0 to 75; n = 160) and somatotropin (median change at 3 months 0.25 higher, 95% CI -1 to 2.5 on the HFMSE, scale 0 to 66; n = 19). One small TRH trial did not report effects on motor function and the certainty of evidence for other outcomes from this trial were low or very low. Results of nine completed trials investigating 4-aminopyridine, acetyl-L-carnitine, CK-2127107, hydroxyurea, pyridostigmine, riluzole, RO6885247/RG7800, salbutamol and valproic acid were awaited and not available for analysis at the time of writing. Various trials and studies investigating treatment strategies other than nusinersen (e.g. SMN2-augmentation by small molecules), are currently ongoing. AUTHORS' CONCLUSIONS:Nusinersen improves motor function in SMA type II, based on moderate-certainty evidence. Creatine, gabapentin, hydroxyurea, phenylbutyrate, valproic acid and the combination of valproic acid and ALC probably have no clinically important effect on motor function in SMA types II or III (or both) based on low-certainty evidence, and olesoxime and somatropin may also have little to no clinically important effect but evidence was of very low-certainty. One trial of TRH did not measure motor function.
    背景与目标: 背景:脊髓性肌萎缩症(SMA)是由5号染色体上的生存运动神经元1(SMN1)基因纯合缺失或与第二SMN1等位基因中的(点)突变相结合造成的杂合缺失所致。这导致前角细胞变性,从而导致进行性肌无力。 II型SMA儿童在没有支撑的情况下不会发展走路的能力,并且寿命会缩短,而III型SMA儿童会发展出走路的能力并具有正常的预期寿命。这是对2009年首次发布并于2011年更新的评论的更新。
    目的:评估药物治疗是否能够减缓或阻止II型和III型SMA的疾病进展,并评估这种治疗是否可以安全地进行。
    搜索方法:我们搜索了2018年10月的Cochrane神经肌肉专业注册簿,CENTRAL,MEDLINE,Embase和ISI Web of Science会议记录.2018年10月,我们还搜索了两个试验注册中心以识别未发表的试验。
    选择标准:我们寻求所有随机或半随机试验,以研究药物治疗II型和III型SMA的疗效。参加者必须满足临床标准,并通过基因分析确认SMN1基因第二等位基因(5q11.2-13.2)的点突变与纯合缺失或半合缺失相结合。主要结果指标是治疗开始后一年内的残疾评分变化。治疗开始后一年内的次要结局指标是肌肉力量变化,站立或行走能力,生活质量变化,从治疗开始到死亡或全时通气的时间以及在治疗期间可归因于治疗的不良事件试用期。涉及用病毒载体替代SMN1的治疗策略不在本评价的范围内,但附录1给出了摘要。I型SMA的药物治疗是另一项Cochrane评价的主题。
    数据收集和分析:我们遵循标准的Cochrane方法。
    主要结果:该评价的作者发现10项针对SMA II型和III型SMA的随机,安慰剂对照试验纳入了该评价,共有717名参与者。我们在此更新中添加了四个试验。该试验研究了肌酸(55名参与者),加巴喷丁(84名参与者),羟基脲(57名参与者),努森那森(126名参与者),奥索肟(165名参与者),苯丁酸(107名参与者),生长激素(20名参与者),促甲状腺激素释放激素( TRH)(9名参与者),丙戊酸(33名参与者),以及丙戊酸和乙酰基L-肉碱(ALC)的联合疗法(61名参与者)。治疗时间为3至24个月。没有一项研究调查相同的治疗方法,也没有完全没有偏倚。所有研究均具有足够的盲法,序列产生和主要结果的报告。根据中等程度的证据,鞘内注射Nusinersen可改善II型SMA儿童的运动功能(残疾),并且在Hammersmith功能运动量表扩展(HFMSE;可能评分范围为0至66)上,Nusinersen组改善了3.7点。相比,假手术组的HFMSE下降了1.9点(P <0.01; n = 126)。在所有使用的运动功能量表上,分数越高表示功能越好。根据两项研究的中度证据,与安慰剂相比,以下干预措施对SMA II型或III型(或两者)的运动功能评分均无临床重要影响:肌酸(中位数变化1较高,置信区间95%(CI) )-1到2;在总运动功能量度(GMFM)上,从0到264缩放; n = 40);丙戊酸和肉碱的联合疗法(平均差异(MD)0.64,95%CI -1.1至2.38;修改后的Hammersmith功能运动量表(MHFMS),量表0至40; n = 61)。根据来自其他单项研究的不确定性证据,与安慰剂相比,以下干预措施对SMA II型或III型(或两者)的运动功能评分均无临床重要影响:加巴喷丁(加巴喷丁组中位数变化0,-2在SMA功能评定量表(SMAFRS)上的安慰剂组中,量表为0到50; n = 66);羟基脲(GMFM的MD -1.88,95%CI -3.89至0.13,0至264比例; n = 57),丁酸苯酯(MD -0.13,95%CI -0.84至0.58在Hammersmith功能马达电子秤(HFMS)上0至40; n = 90)和丙戊酸的单药治疗(MDAF为0.06,SMAFRS上为95%CI -1.32至1.44,等级0至50; n = 31)。不确定性极低的证据表明,以下干预措施对运动功能的影响很小或没有影响:油酸肟酯(运动功能量度(MFM)D1 D2为MD 2,95%-0.25至4.25,等级0至75; n = 160)和生长激素(3个月时的中位数变化高0.25,HFMSE的95%CI -1至2.5,等级0至66; n = 19)。一项小型TRH试验未报告对运动功能的影响,该试验其他结果的证据确定性较低或非常低。尚待完成9个研究试验,涉及4-氨基吡啶,乙酰基-L-肉碱,CK-2127107,羟基脲,吡啶斯的明,利鲁唑,RO6885247 / RG7800,沙丁胺醇和丙戊酸的研究结果,在撰写本文时尚未提供分析结果。目前正在进行各种研究,以研究除Nusinersen以外的其他治疗策略(例如,SMN2-小分子增强)。
    作者的结论:Nusinersen可根据中度确定性证据改善II型SMA的运动功能。肌酐,加巴喷丁,羟基脲,苯丁酸,丙戊酸以及丙戊酸和ALC的组合可能基于低确定性证据对SMA II型或III型(或两者)的运动功能没有临床重要影响,并且油酸肟和生长激素也可能在临床上几乎没有影响,甚至没有,但是证据的准确性很低。 TRH的一项试验没有测量运动功能。
  • 【p.Ala546> Asp和p.Arg555> TGFBI基因的Trp突变及其在两个中国大型I型角膜营养不良家族中的临床表现。】 复制标题 收藏 收藏
    DOI:10.1089/gte.2008.0005 复制DOI
    作者列表:Yu P,Gu Y,Jin F,Hu R,Chen L,Yan X,Yang Y,Qi M
    BACKGROUND & AIMS: :The aim of this study was to conduct clinical, genetic, and molecular analysis of Chinese patients with granular corneal dystrophy type I (CDGG1). Two large unrelated Chinese families with CDGG1 were clinically and genetically evaluated. Molecular genetic analysis was performed on DNA extracted from peripheral blood. Exons 4, 11, 12, and 14 of the human transforming growth factor beta-induced gene (TGFBI, formerly designated BIGH3) were amplified by PCR, scanned for mutations using the single-strand conformation polymorphism method, and the mutations identified by nucleotide sequencing. One family segregated the p.Ala546 > Asp mutation, and the other family had a p.Arg555 > Trp mutation. These missense mutations were not found in 53 unrelated, healthy individuals analyzed as controls. Clinical and genetic evaluations revealed the variable severity, symmetry, and age of onset in visual impairment in these families for different mutations. Penetrance of visual impairment in these families was 100% and 75%, respectively. This study confirms that the p.Arg555 > Trp mutation is a frequent cause of CDGG1, and that the p.Ala546 > Asp mutation is also associated with this disease.
    背景与目标: :本研究的目的是对中国I型角膜颗粒性营养不良患者(CDGG1)进行临床,遗传和分子分析。临床和遗传学评估了两个与CDGG1无关的中国大家庭。对从外周血中提取的DNA进行了分子遗传分析。通过PCR扩增人类转化生长因子β诱导基因(TGFBI,以前称为BIGH3)的外显子4、11、12和14,使用单链构象多态性方法扫描突变,并通过核苷酸测序鉴定突变。一个家庭隔离了p.Ala546> Asp突变,另一家庭隔离了p.Arg555> Trp突变。在被分析为对照的53个不相关,健康的个体中未发现这些错义突变。临床和遗传学评估显示,这些家族中因不同突变而导致的视力障碍的严重程度,对称性和发病年龄各不相同。这些家庭的视觉障碍渗透率分别为100%和75%。这项研究证实p.Arg555> Trp突变是CDGG1的常见原因,并且p.Ala546> Asp突变也与此疾病有关。
  • 【[远端脊髓肌肉萎缩症1(DSMA1或SMARD1)]。】 复制标题 收藏 收藏
    DOI:10.1016/j.arcped.2008.07.014 复制DOI
    作者列表:Kaindl AM,Guenther UP,Rudnik-Schöneborn S,Varon R,Zerres K,Gressens P,Schuelke M,Hubner C,von Au K
    BACKGROUND & AIMS: :In this article, we review the clinical, neuropathological and genetic aspects of distal spinal-muscular atrophy 1 (DSMA1; MIM#604320), formerly designated as autosomal recessive spinal muscular atrophy with respiratory distress type 1 (SMARD1) and also known as distal hereditary-motor neuropathy type 6 (dHMN6 or HMN6).
    背景与目标: :在本文中,我们回顾了远端脊髓性肌肉萎缩症1(DSMA1; MIM#604320)的临床,神经病理学和遗传学方面,该疾病以前被称为常染色体隐性隐性脊髓性肌肉萎缩症,伴有呼吸窘迫1型(SMARD1),也被称为远端遗传性运动神经病6型(dHMN6或HMN6)。
  • 【1型强直性肌营养不良症的左室过度束缚。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:2001-06-01
    来源期刊:Herz
    DOI:10.1007/pl00002032 复制DOI
    作者列表:Finsterer J,Stöllberger C,Wegmann R,Jarius C,Janssen B
    BACKGROUND & AIMS: BACKGROUND:Left ventricular hypertrabeculation (LVHT) has not been described in myotonic dystrophy Type I (MD1) before. CASE REPORT:A 42-year-old man developed typical features of MD1 since 1992. Creatinekinase was slightly, but recurrently elevated. Needle electromyograms were myogenic and showed extensive spontaneous activity. Muscle biopsy was compatible with MDI. DNA analysis revealed a heterozygous 300 CTG-repeat expansion in the myotonic-dystrophy proteinkinase gene on chromosome 19q13.3. Cardiac history and clinical cardiologic examination were normal. On ECG, ST elevation and atrial flutter were found. The AECG was normal except for atrial flutter. Surprisingly, transthoracic echocardiography revealed LVHT, previously described only in Becker's muscular dystrophy, mitochondriopathies, and Barth syndrome. CONCLUSION:A rare cardiac manifestation of MD1 may be LVHT which alone has no therapeutic implication.
    背景与目标: 背景:以前在I型强直性肌营养不良症(MD1)中尚未描述左室超束(LVHT)。
    病例报告:自1992年以来,一名42岁的男性出现了MD1的典型特征。肌酸激酶轻微升高,但反复升高。针状肌电图是肌源性的,并显示出广泛的自发活动。肌肉活检与MDI兼容。 DNA分析显示,染色体19q13.3上的肌强直性营养不良蛋白激酶基因杂合了300个CTG重复序列。心脏病史和临床心脏检查均正常。在ECG上,发现ST抬高和房扑。除心房扑动外,AECG正常。出乎意料的是,经胸超声心动图显示LVHT,以前仅在贝克尔的肌营养不良症,线粒体病和Barth综合征中有所描述。
    结论:MDHT的一种罕见的心脏表现可能是LVHT,仅LVHT就没有治疗意义。
  • 【在癫痫和杜氏肌营养不良症中发现水通道的意义的优先事项。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Benga I
    BACKGROUND & AIMS: :In addition to the priority in the discovery of the first water channel protein in the red blood cell membrane the group of Gheorghe Benga in Cluj-Napoca, Romania, also has a world priority in the discovery of the implications of water channel proteins in epilepsy and Duchenne muscular dystrophy. This priority is briefly presented here. In 1977 Benga and Morariu reported a decreased water permeability of red blood cells in children with idiopathic epilepsy (cases selected by Ileana Benga). This investigation was performed as part of a program of research of hydroelectrolytic alterations in child epilepsy. On the other hand the group of Gheorghe Benga has reported a decreased water permeability of RBC in patients with Duchenne muscular dystrophy. These findings were interpreted as an expression of generalized membrane defects affecting water permeability in epilepsy and Duchenne muscular dystrophy. In recent years this idea was confirmed by reports indicating aquaporin abnormalities in the brain of epileptic patients and in the muscle of Duchenne muscular dystrophy patients.
    背景与目标: :除了优先发现红细胞膜中的第一个水通道蛋白外,罗马尼亚克卢日-纳波卡的Gheorghe Benga小组在发现水通道蛋白在癫痫中的意义方面也具有世界优先地位和杜氏肌营养不良症。在此简要介绍此优先级。 1977年,Benga和Morariu报告了特发性癫痫患儿(Ileana Benga选择的病例)中红细胞的透水性降低。这项研究是儿童癫痫中水电解改变研究计划的一部分。另一方面,Gheorghe Benga小组报告了Duchenne肌营养不良患者的RBC透水性降低。这些发现被解释为影响癫痫和杜氏肌营养不良症中透水性的广义膜缺损的表达。近年来,有报道表明癫痫患者的大脑和杜兴氏肌营养不良患者的肌肉中存在水通道蛋白异常,这一观点得到了证实。
  • 【在癫痫和杜氏肌营养不良症中发现水通道的意义的重点。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Obeid R,Herrmann W
    BACKGROUND & AIMS: :Folate and vitamin B12 are essential cofactors for the methionine/homocysteine cycle in the brain. These vitamins mediate the remethylation of homocysteine (HCY), which affects the production of the universal methyl donor, S-adenosylmethionine (SAM), in the brain among other organs. Acquired or inherited disorders in these metabolic pathways are associated with brain abnormalities and severe neurological symptoms that are mostly irreversible, even after providing the missing cofactors. This review discusses the relationship between brain and blood levels of key vitamins and metabolites related to one carbon metabolism.
    背景与目标: :叶酸和维生素B12是大脑中蛋氨酸/高半胱氨酸循环的重要辅助因子。这些维生素介导高半胱氨酸(HCY)的再甲基化,这会影响大脑其他器官中通用甲基供体S-腺苷甲硫氨酸(SAM)的产生。这些代谢途径中的获得性或遗传性疾病与脑部异常和严重的神经系统症状有关,即使提供了缺失的辅因子后,这些症状通常也是不可逆的。这篇评论讨论了大脑和血液中与一种碳代谢有关的关键维生素和代谢物的水平之间的关系。
  • 【患有终末心力衰竭的患者的皮肤和肌肉微循环,等待移植。】 复制标题 收藏 收藏
    DOI:10.3233/CH-2012-1599 复制DOI
    作者列表:Knaut M,Matschke K,Plötze K,Steinmann C,Mrowietz C,Jung F
    BACKGROUND & AIMS: :Heart failure patients are clinically characterized by extreme cardiomegaly, breathlessness, fluid retention and an early onset of fatigue. Studies have shown generalized restricted blood flow in those patients. Furthermore animal experiments proved an impaired blood flow and a diminished oxygen supply of the skeletal muscle in animals with chronic heart failure. Patients with chronic heart failure are limited to the extent of their ability to regulate their arterial pressure, especially in physical activity. It is however unclear in what way restriction of blood flow in the main arteries correlates with those in capillaries and to what extent. In this study it was examined the depth of capillary circulatory restriction as well as the disregulation of oxygen partial pressure in skeletal muscle in rest and stress conditions, in patients with terminal heart failure.
    背景与目标: 心力衰竭患者的临床特征是极端的心脏肥大,呼吸困难,体液retention留和疲劳的早期发作。研究表明,这些患者的血流普遍受限。此外,动物实验证明,患有慢性心力衰竭的动物的血流量受损,骨骼肌的氧气供应减少。患有慢性心力衰竭的患者被限制在调节其动脉压的能力范围内,特别是在体育锻炼中。然而,尚不清楚主要动脉中的血流限制与毛细血管中的血流以何种方式相关以及在何种程度上相关。在这项研究中,检查了患有终末心力衰竭的患者中毛细血管循环限制的深度,以及在休息和压力条件下骨骼肌中氧分压的失调。
  • 【脊柱肌肉萎缩的新兴疗法和挑战。】 复制标题 收藏 收藏
    DOI:10.1002/ana.24864 复制DOI
    作者列表:Farrar MA,Park SB,Vucic S,Carey KA,Turner BJ,Gillingwater TH,Swoboda KJ,Kiernan MC
    BACKGROUND & AIMS: :Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease with severity ranging from progressive infantile paralysis and premature death (type I) to limited motor neuron loss and normal life expectancy (type IV). Without disease-modifying therapies, the impact is profound for patients and their families. Improved understanding of the molecular basis of SMA, disease pathogenesis, natural history, and recognition of the impact of standardized care on outcomes has yielded progress toward the development of novel therapeutic strategies and are summarized. Therapeutic strategies in the pipeline are appraised, ranging from SMN1 gene replacement to modulation of SMN2 encoded transcripts, to neuroprotection, to an expanding repertoire of peripheral targets, including muscle. With the advent of preliminary trial data, it can be reasonably anticipated that the SMA treatment landscape will transform significantly. Advancement in presymptomatic diagnosis and screening programs will be critical, with pilot newborn screening studies underway to facilitate preclinical diagnosis. The development of disease-modifying therapies will necessitate monitoring programs to determine the long-term impact, careful evaluation of combined treatments, and further acceleration of improvements in supportive care. In advance of upcoming clinical trial results, we consider the challenges and controversies related to the implementation of novel therapies for all patients and set the scene as the field prepares to enter an era of novel therapies. Ann Neurol 2017;81:355-368.
    背景与目标: :脊髓性肌萎缩症(SMA)是一种遗传性神经退行性疾病,其严重程度从进行性婴儿瘫痪和过早死亡(I型)到有限的运动神经元丧失和正常预期寿命(IV型)不等。如果没有改善疾病的疗法,对患者及其家属的影响将是深远的。对SMA分子基础,疾病发病机制,自然病史以及对标准化治疗对预后的影响的认识得到了更好的理解,这为新型治疗策略的发展带来了进步,并对其进行了总结。评估中的治疗策略包括SMN1基因替换,SMN2编码转录物的调节,神经保护以及包括肌肉在内的周围靶标的扩展库。随着初步试验数据的出现,可以合理地预期SMA治疗前景将发生重大变化。症状前诊断和筛查计划的进展将至关重要,目前正在进行试点新生儿筛查研究以促进临床前诊断。疾病缓解疗法的发展将需要制定监测计划,以确定长期影响,对联合治疗进行认真评估,并进一步加速支持治疗的改善。在即将到来的临床试验结果公布之前,我们考虑了为所有患者实施新疗法带来的挑战和争议,并为该领域准备进入新疗法时代做好了准备。 Ann Neurol 2017; 81:355-368。
  • 【Myostatin阻滞剂可改善肢带型肌营养不良症2C小鼠模型的功能,但不能改善组织病理学。】 复制标题 收藏 收藏
    DOI:10.1002/mus.20920 复制DOI
    作者列表:Bogdanovich S,McNally EM,Khurana TS
    BACKGROUND & AIMS: :Myostatin is a negative regulator of skeletal muscle growth. Myostatin mutations and pharmacological strategies increase muscle mass in vivo, suggesting that myostatin blockade may prove useful in diseases characterized by muscle wasting, such as the muscular dystrophies. We subjected the gamma-sarcoglycan-deficient (Sgcg(-/-)) mouse model of limb-girdle muscular dystrophy (LGMD) 2C to antibody-mediated myostatin blockade in vivo. Myostatin inhibition led to increased fiber size, muscle mass, and absolute force. However, no clear improvement in muscle histopathology was evident, demonstrating discordance between physiological and histological improvement. These results and previous studies on the dyw/dyw mouse model of congenital muscular dystrophy and in the late-stage delta-sarcoglycan-deficient (Sgcd(-/-)) mouse model of LGMD2F document disease-specific limitations to therapeutic strategies based on myostatin blockade in the more severe mouse models of different muscular dystrophies.
    背景与目标: :肌生长抑制素是骨骼肌生长的负调节剂。肌肉生长抑制素的突变和药理学方法会增加体内肌肉的质量,这表明肌肉生长抑制素的阻断可能在以肌肉萎缩为特征的疾病(如肌肉营养不良)中被证明是有用的。我们经历了肢带肌肉萎缩症(LGMD)2C的γ-肌糖蛋白缺乏(Sgcg(-/-))小鼠模型体内抗体介导的肌生长抑制素阻断作用。抑制肌生长抑制素导致纤维大小,肌肉质量和绝对力增加。但是,肌肉组织病理学没有明显改善,表明生理和组织学改善之间不一致。这些结果和关于先天性肌营养不良的dyw / dyw小鼠模型以及LGMD2F的晚期δ-肌糖缺乏症(Sgcd(-/-))小鼠模型的先前研究记录了基于肌肉生长抑制素的疾病特异性治疗策略的局限性在不同肌肉营养不良的更严重的小鼠模型中具有阻断作用。
  • 【RCS大鼠视网膜营养不良基因的人类直系同源基因MERTK中的突变导致色素性视网膜炎。】 复制标题 收藏 收藏
    DOI:10.1038/81555 复制DOI
    作者列表:Gal A,Li Y,Thompson DA,Weir J,Orth U,Jacobson SG,Apfelstedt-Sylla E,Vollrath D
    BACKGROUND & AIMS: :Mutation of a receptor tyrosine kinase gene, Mertk, in the Royal College of Surgeons (RCS) rat results in defective phagocytosis of photoreceptor outer segments by the retinal pigment epithelium (RPE) and retinal degeneration. We screened the human orthologue, MERTK, located at 2q14.1 (ref. 10), in 328 DNA samples from individuals with various retinal dystrophies and found three mutations in three individuals with retinitis pigmentosa (RP). Our findings are the first conclusive evidence implicating the RPE phagocytosis pathway in human retinal disease.
    背景与目标: :在皇家外科医学院(RCS)大鼠中酪氨酸受体激酶基因Mertk的突变导致视网膜色素上皮(RPE)和视网膜变性导致光感受器外部节段的吞噬功能缺陷。我们在来自患有各种视网膜营养不良的个体的328个DNA样本中筛选了位于2q14.1(参考文献10)的人类直向同源基因MERTK,并在三个患有色素性视网膜炎(RP)的个体中发现了三个突变。我们的发现是人类视网膜疾病中涉及RPE吞噬途径的第一个确凿证据。

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