Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. We describe the severe form of nemaline myopathy diagnosed in two brothers who died at the age of 12 days and 9 months, due to respiratory insufficiency caused by severe muscle weakness. Polyhydramnios and weakness of foetal movements in the IIIrd trimester of pregnancy, as well as variable clinical severity were noted in both cases. Microscopically visible significant immaturity of muscle fibers was found in the skeletal muscle biopsy performed in one of the brothers. The diagnosis of nemaline myopathy was confirmed by the presence of nemaline bodies (rods) in sections stained using the Gomori trichrome method. Molecular studies of DNA isolated from blood leucocytes showed no mutation in the ACTA1 or the TPM3 genes. Linkage analysis with polymorphic markers did not rule out linkage to part of the NEB gene locus. Results of the clinical evaluation and the investigations performed in the family members confirm that it is essential to consider congenital myopathies in the differential diagnosis of neonatal and infantile hypotonia with respiratory insufficiency. Molecular verification of the clinical diagnosis is also important for genetic counselling of the families.
 ...
PMID:[Nemaline myopathy as a cause of neonatal hypotonia - with emphasis on personal experiences. Report of a family with two brothers affected]. 1964 53

In this study, we investigated the expression of the pathway, SRF-microRNA-1/microRNA-133a-Hand2, in the Wistar rat embryonic ventricular cardiomyocytes under conventional monolayer culture. The morphological observation of the cultured cardiomyocytes and the mRNA expression levels of three vital constituent proteins, MLC-2v, N-cadherin, and connexin43, demonstrated the immaturity of these cultured cells, which was featured by less myofibril density, immature sarcomeric structure, and significantly lower mRNA expression of the three constituent proteins than those in neonatal ventricular samples. More importantly, results in this study suggest that the change of SRF-microRNA-1/microRNA-133a-Hand2 pathway results into the attenuation of the Hand2 repression in cultured cardiomyocytes. These outcomes are valuable to understand the cellular state as embryonic cardiomyocytes to be in vitro model and might be useful for the assessment of engineered cardiac tissue and cardiac differentiation of stem cells.
...
PMID:Expression of microRNA-1, microRNA-133a and Hand2 protein in cultured embryonic rat cardiomyocytes. 2478 24

Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) have been extensively used for in vitro modeling of human cardiovascular disease, drug screening and pharmacotherapy, but little rigorous studies have been reported on their biophysical or Ca2+ signaling properties. There is also considerable concern as to the level of their maturity and whether they can serve as reliable models for adult human cardiac myocytes. Ultrastructural difference such as lack of t-tubular network, their polygonal shapes, disorganized sarcomeric myofilament, and their rhythmic automaticity, among others, have been cited as evidence for immaturity of hiPSC-CMs. In this review, we will deal with Ca2+ signaling, its regulation, and its stage of maturity as compared to the mammalian adult cardiomyocytes. We shall summarize the data on functional aspects of Ca2+signaling and its parameters that include: L-type calcium channel (Cav1.2), ICa-induced Ca2+release, CICR, and its parameters, cardiac Na/Ca exchanger (NCX1), the ryanodine receptors (RyR2), sarco-reticular Ca2+pump, SERCA2a/PLB, and the contribution of mitochondrial Ca2+ to hiPSC-CMs excitation-contraction (EC)-coupling as compared with adult mammalian cardiomyocytes. The comparative studies suggest that qualitatively hiPSC-CMs have similar Ca2+signaling properties as those of adult cardiomyocytes, but quantitative differences do exist. This review, we hope, will allow the readers to judge for themselves to what extent Ca2+signaling of hiPSC-CMs represents the adult form of this signaling pathway, and whether these cells can be used as good models of human cardiomyocytes.
 ...
PMID:Ca2+ signaling of human pluripotent stem cells-derived cardiomyocytes as compared to adult mammalian cardiomyocytes. 3258 8