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Biomedical subjects

A M Kelly

Publications and source records attributed to A M Kelly.

At least 127 records · Page 7Linked to original sources

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↗

Development of neuromuscular specialization.

This review outlines recent advances in understanding the program of muscle specialization during development and discusses some of the controls over this process. The scheme of fiber heterogeneity is laid down very early in myogenesis and, at least in the chicken, it appears to be intrinsically determined by the limb, independent of neuromuscular contact. In mature muscle, specialized fibers are usually intermingled in a mosaic. This results from the pattern of muscle assembly from primary and secondary generation cells as these distinct generations commonly express different phenotypes. The muscle develops in this way as secondary cells use the walls of primary myotubes as a scaffold to support their differentiation. This process may be regulated by transient expression of N CAMs. Myoblasts left after N CAMs are no longer expressed may become the satellite cells of mature muscle. In the rat, primary cells all initially express slow myosin, whereas most secondary cells are fast in phenotype. Post-partum, the initial plan of fiber specialization is modulated. In developing slow muscles many secondary generation fibers convert from a fast to a slow phenotype, whereas in developing fast muscles, primary slow fibers transform to a fast phenotype. Hormones, particularly thyroid hormone, play a significant role in this modification. The role of the nerve is less well understood.

Animals↗

PUVA therapy for psoriasis: choosing a suitable régime.

Three age- and sex-matched groups of 30 patients with chronic plaque psoriasis were treated by photochemotherapy (PUVA). Groups I and II received routine maintenance PUVA therapy at different intervals and Group III had no maintenance treatment. The remission time after the clearance treatment with PUVA is compared with the total cumulative dose of long wave ultraviolet light (UVA). A lower mean dose of UVA (51.0 +/- 1.7 joules/cm(2)) in Group III (no maintenance PUVA) achieved a comparable remission period to that after larger cumulative doses following routine maintenance therapy (87.8 +/- 4.9 and 77.0 +/- 4.1 joules/cm(2) in Groups I and II).

Adolescent↗

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↗

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↗

Letterer-Siwe disease: a study of thirteen cases over a 21 - year period.

In Northern Ireland, with a population of 1.5 million, thirteen cases of Letterer-Siwe disease have been diagnosed over the past 21 years. The average age of onset was 10.5 months. There was a 69% mortality with an average survival time from diagnosis to death of 3.3 months. Four children survived with no morbidity. All deaths were from pulmonary complications, but two cases with pulmonary infiltration responded to treatment with quadruple chemotherapy. There were no familial cases in this study.

Child, Preschool↗

Development of muscle fiber specialization in the rat hindlimb.

The appearance of fast and slow fiber types in the distal hindlimb of the rat was investigated using affinity-purified antibodies specific to adult fast and slow myosins, two-dimensional electrophoresis of myosin light chains, and electron microscope examination of developing muscle cells. As others have noted, muscle histogenesis is not synchronous; rather, a series of muscle fiber generations occurs, each generation forming along the walls of the previous generation. At the onset of myotube formation on the 15th d of gestation, the antimyosin antibodies do not distinguish among fibers. All fibers react strongly with antibody to fast myosin but not with antibody to slow myosin. The initiation of fiber type differentiation can be detected in the 17-d fetus by a gradual increase in the binding of antibody to slow myosin in the primary, but not the secondary, generation myotubes. Moreover, neuromuscular contacts at this crucial time are infrequent, primitive, and restricted predominantly, but not exclusively, to the primary generation cells, the same cells which begin to bind large amounts of antislow myosin at this time. With maturation, the primary generation cells decrease their binding of antifast myosin and become type I fibers. Secondary generation cells are initially all primitive type II fibers. In future fast muscles the secondary generation cells remain type II, while in future slow muscles most of the secondary generation cells eventually change to type I over a prolonged postnatal period. We conclude that the temporal sequence of muscle development is fundamentally important in determining the genetic expression of individual muscle cells.

Animals↗

Effect of electrical stimulation on diaphragmatic muscle used to enlarge right ventricle.

The effect of chronic electrical stimulation on muscle mass of pedicled diaphragmatic muscle grafts (DMGs) implanted into the right ventricle was studied in 21 dogs. Nineteen dogs, followed up to 70 days (mean, 34 days), were divided into three groups. In six dogs (control) the DMG was not stimulated. In six other dogs the DMG was stimulated at 50 stimuli/min with a fixed-rate unipolar pacemaker. In seven animals the graft was paced 1:1 with the dog's own rhythm with an R-wave synchronous pacemaker. Surface area of the DMG decreased 34% to 43% (P less than 0.05) in all dogs. DMG thickness increased in all dogs (P less than 0.05). The increase was 29% for control animals and 132% and 134% for the two paced groups. The volume of the DMG decreased 24% in the nonpaced animals but increased 29% and 51% in the two paced groups. Histologic studies showed some degree of muscle degeneration and atrophy in all grafts. However, morphometric studies showed relatively normal fiber diversity in paced grafts. Fiber size decreased in nonpaced grafts, indicating muscle atrophy. Perfusion studies with labeled microspheres and silicone injections demonstrated collateral circulation with the host ventricle as early as 28 days. However, total blood flow to DMGs implanted for 4 to 6 weeks averaged only 32% of the blood flow to normal ventricular myocardium. Chronic electrical stimulation of DMGs reduces muscle degeneration and atrophy and is associated with an increase in graft thickness and volume.

Animals↗

Why are fetal muscles slow?

Differentiating fast and slow mammalian muscles contract slowly at birth and increase their speed during the first few weeks of life. However, only small proportions of slow myosin light chains are found in early developing muscles and the fast type of light chains predominate. In addition, differentiating muscle contains unique, embryonic forms of myosin which may partially determine the early slow responses. The present study suggests additional reasons for these slow twitch times. Most skeletal muscles are initially formed from a small population of primary generation cells which are innervated by pioneering axons early in myogenesis. Subsequently, numerous secondary generation cells develop along the walls of primary myotubes, then separate and become independent units of contraction. Using affinity-purified antibodies to fast and slow myosin, it was found that most primary myotubes react with anti-slow myosin and are destined to become slow, Type I fibres. By contrast, secondary generation cells stain exclusively with anti-fast myosin and develop into Type II, fast fibres. We propose that primary myotubes constitute the fundamental motor units of the developing neuromuscular system and are responsible for early slow movements. Secondary generation cells become organized into large, fast motor units later in development, eclipsing the original slow response.

Animals↗

Investigation of pregnancy-related changes in red cell 2,3-diphosphoglycerate.

Significant gestational changes in red cell 2,3-DPG were found. No significant correlation was found between these pregnancy-related changes and alterations in the parameters of iron metabolism or red cell enzymes during the same gestational period. Possible reasons for the high concentration found at 21--24 weeks gestation are discussed.

Diphosphoglyceric Acids↗

Releasing factor tests in men with oligozoospermia.

FSH levels were assayed in 300 men attending with infertile marriages. From this number, releasing factor tests were carried out in 24 men with oligozoospermia and an initial FSH below our normal mean. In all of these cases there was a response to releasing factor. Isolated FSH deficiency is likely to be rare in adult men presenting with infertility and no previous endocrinological history.

Follicle Stimulating Hormone↗

Perisynaptic satellite cells in the developing and mature rat soleus muscle.

In mature rat soleus muscle it is shown that satellite cells are not evenly distributed over the surface of myofibers but are more numerous in the vicinity of the motor endplate. In this location they commonly lie close to the post synaptic membrane where they are termed perisynaptic satellite cells. In developing muscle several satellite cells may be seen close to the endplate and give the impression of limiting the spread of the axon over the myofiber. In addition these satellite cells make close plasmalemmal contact with Schwann cells and appear as a continuation of the Schwann sheath onto the surface of the myofiber.

Aging↗