PubMed Health⌕ Search

Biomedical subjects

G E Lyons

Publications and source records attributed to G E Lyons.

60 records · Page 4Linked to original sources
PubMed1988

Hormonal control of myosin heavy chain genes during development of skeletal muscles.

A pattern of myosin heavy chain (MHC) switching is a hallmark of developing muscles. Factors responsible for these changes in gene expression include endogenous signals, motoneurons and hormones, especially thyroid hormones. After perturbing the innervation and/or thyroid hormone levels we have examined the neonatal-IIb MHC transition during rat development. First, denervation does not qualitatively affect the transition at either the transcriptional or translational level. Second, hypothyroidism prevents the appearance of IIb MHC and its mRNA in the innervated limb; in the denervated hypothyroid limb IIb MHC is synthesized at moderately high levels. Third, hyperthyroidism causes a precocious increase in IIb MHC in both innervated and denervated muscles. These results suggest that the transition from neonatal to adult IIb myosin synthesis is endogenously programmed during development, but is closely orchestrated by the changing neuronal and hormonal status of the animal. Thyroid hormone may exert its influence by effects both on the muscle fibre and on the developing motoneuron. In the guinea-pig the temporalis muscle is sexually dimorphic: it contains a fast-red MHC in the female but a fast-white MHC in the male. This dimorphism has been shown to be mediated by testosterone, since the castrated male synthesizes the fast-red MHC while the testosterone-supplemented female contains the fast-white MHC. During development male and female muscles initially synthesize the fast-red isoform. The male switches to the fast-white form at puberty.

Animals↗
PubMed1986

Testosterone-induced changes in contractile protein isoforms in the sexually dimorphic temporalis muscle of the guinea pig.

The guinea pig temporalis muscle is sexually dimorphic, classified histochemically as a fast-red muscle in the female, but as a fast-white muscle in the adult male. Since this sexual difference in metabolic properties is related to plasma testosterone levels, we asked if testosterone also affected the contractile protein isoforms. In the newborn guinea pig, both male and female temporalis muscles contained a fast-red isoform of the myosin heavy chain and approximately equal amounts of alpha- and beta-tropomyosins. At puberty, the male began to replace the fast-red isoform with a fast-white isoform of the heavy chain and by 120 days the muscle contained predominantly the fast-white myosin heavy chain. This transition in myosins in the male was accompanied by a shift to greater than 90% alpha-tropomyosin. No changes in myosins or tropomyosins were observed in the female. The changes in the male could be reversed by castration and could be mimicked in the female by the injection of testosterone. Although these same myosins and tropomyosins could be detected in other fast-twitch muscles, postpartum transitions in contractile protein isoforms in those muscles were testosterone-insensitive, and no sexual dimorphism of these proteins was seen in other muscles.

Animals↗
PubMed1983

Thyroidal and neural control of myosin transitions during development of rat fast and slow muscles.

Experiments with developing euthyroid, hypothyroid and hyperthyroid rats show that the transition from neonatal to adult fast myosin is orchestrated by thyroid hormones acting directly upon fast muscle cells. Denervation studies reveal the switch from neonatal to adult fast myosin synthesis is independent of the motoneuron. However the synthesis of slow myosin during development is critically dependent on innervation.

Animals↗
PubMed1983

Myosin transitions in developing fast and slow muscles of the rat hindlimb.

Myosin isozymes from the slow soleus and fast EDL muscles of the rat hindlimb were analyzed by pyrophosphate gel electrophoresis, by peptide mapping of heavy chains, and by antibody staining. At the earliest stage examined, 20 days gestation, distinctions between the developing fast and slow muscles were seen by all these criteria; all fibers in the distal hindlimb reacted strongly with antibody to adult fast myosin. Some fibers also reacted with antibody to adult slow myosin; these fibers had a precise, axial distribution in the hindlimb. This pattern of staining which includes the entire soleus, foreshadows the adult distribution of slow fibers and may indicate that the specific pattern of innervation of the limb is already determined. In the early developing soleus there are four fetal and neonatal isozymes plus two isozymes present in equal proportions in the 'slow' area of the pyrophosphate gel. The mobility of these two slow isozymes decreases with maturity and the slowest moving isozyme gradually becomes the dominant species. Thus early diversity between the soleus and EDL is expressed by myosins which are distinct from the mature isozymes. The relative proportion of slow isozymes significantly increases with development and as this occurs the fetal and neonatal isozymes are progressively eliminated. Transiently at least one mature fast isozyme appears in the soleus. This is present at 15 days postpartum and probably correlates with the population of fast, type II fibers, which comprise 50% of this muscle cell population at 15 days. The EDL contained three fetal and neonatal isozymes and only one slow isozyme which does not change in mobility with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Down syndrome congenital heart disease: a narrowed region and a candidate gene.

PURPOSE: Down syndrome (DS) is a major cause of congenital heart disease (CHD) and the most frequent known cause of atrioventricular septal defects (AVSDs). Molecular studies of rare individuals with CHD and partial duplications of chromosome 21 established a candidate region that included D21S55 through the telomere. We now report human molecular and cardiac data that narrow the DS-CHD region, excluding two candidate regions, and propose DSCAM (Down syndrome cell adhesion molecule) as a candidate gene. METHODS: A panel of 19 individuals with partial trisomy 21 was evaluated using quantitative Southern blot dosage analysis and fluorescence in situ hybridization (FISH) with subsets of 32 BACs spanning the region defined by D21S16 (21q11.2) through the telomere. These BACs span the molecular markers D21S55, ERG, ETS2, MX1/2, collagen XVIII and collagen VI A1/A2. Fourteen individuals are duplicated for the candidate region, of whom eight (57%) have the characteristic spectrum of DS-CHD. RESULTS: Combining the results from these eight individuals suggests the candidate region for DS-CHD is demarcated by D21S3 (defined by ventricular septal defect), through PFKL (defined by tetralogy of Fallot). CONCLUSIONS: These data suggest that the presence of three copies of gene(s) from the region is sufficient for the production of subsets of DS-CHD. This region does not include genes located near D21S55, previously proposed as a "DS critical region," or the genes encoding collagens VI and XVIII. Of the potential gene candidates in the narrowed DS-CHD region, DSCAM is notable in that it encodes a cell adhesion molecule, spans more than 840 kb of the candidate region, and is expressed in the heart during cardiac development. Given these properties, we propose DSCAM as a candidate for DS-CHD.

Blotting, Southern↗