Alan M Kelly

Alan M Kelly
  • University of Pennsylvania

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73
Publications
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6,364
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Current institution
University of Pennsylvania

Publications

Publications (73)
Article
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Reducing food wastage is one of the key strategies to combat hunger and sustainably feed the world. We present a comprehensive analysis of available data, despite uncertainties due to data limitation, indicating that the U.S. loses at least 150 million metric tonnes (MMT) of food between farm and fork annually, of which about 70MMT is edible food l...
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Article
To characterize trends in gender, employment, starting salaries, and educational debt of graduates of US veterinary medical schools and colleges from 1988 to 2007. Meta-analysis. Sample Population-Veterinary medical graduates from 26 or 27 of 27 US veterinary schools and colleges from 1988 through 2007. Data were obtained from surveys published in...
Article
The veterinary profession is presently challenged with developing and maintaining on-farm biosecurity protocols to protect the nation's food supply from acts of bioterrorism, from the growing threat of foreign animal diseases, and from multidrug resistance among pathogenic organisms. This challenge comes at a time when the supply of food animal vet...
Article
The chicken c-ski gene expresses at least three alternatively spliced messages. Transgenic mice expressing proteins from cDNA corresponding to two of these messages (FB27 and FB29) under the control of a murine sarcoma virus (MSV) long terminal repeat (LTR) express the transgene in skeletal muscle and develop a muscular phenotype. Both a biological...
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Full-text available
Three main fiber types (one slow [type I] and two fast [type IIA and IIB] can be distinguished using conventional actomyosin ATPase (AM-ATPase) histochemistry after acidic pretreatment in mature pig skeletal muscle. We report the isolation, characterization, and identification of four adult 3'-untranslated regions corresponding to types I, IIA, IIB...
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Unlike the random distribution of fiber types seen in skeletal muscles of most mammals, pig muscle exhibits a rosette pattern consisting of islets of slow fibers surrounded by concentric circles of type IIA and IIB fibers. Within each islet of slow fibers, one of the central fibers is a primary myofiber, whereas all others are secondary fibers. The...
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The expression of a ski transgene in the bind leg muscles of mice follows a spatial and temporal pattern reminiscent of the pattern of myogenic development. Anterior muscles, which are formed earliest during development, are also the first muscles to express ski mRNA. Muscles derived from the posterior muscle group, formed later during development,...
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Using a monoclonal antibody specific to the neonatal myosin heavy chain, we have cloned the full-length heavy chain cDNA from an 18-week human fetal cDNA library. Ribonuclease protection assays were used to survey a human muscle collection ranging from 11 weeks gestation to 16 years. Expression of the RNA encoded by this cDNA was observed at 20 and...
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Full-text available
The control of c-ski transgene expression and muscle hypertrophy have been investigated in transgenic mice. In adult animals, the level of transgene expression is linked to the specialized phenotype of individual muscles, high levels occur in fast muscles and significantly lower levels in muscles with high metabolic activity (diaphragm, soleus). Th...
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Recent work indicates that upper airway dilator muscles of individuals with obstructive sleep apnea syndrome (OSAS) demonstrate an increased level of activity during wakefulness compared with normal subjects. In addition, massive bursts of pharyngeal dilator activity are associated with the termination of upper airway occlusive events during sleep....
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The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice...
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The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the presen...
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The effect of thyroid status on the expression of cytochrome c oxidase (CYTOX) and the activities of citrate synthase (CS) and phosphofructokinase (PFK) were examined in chronically stimulated (10 Hz; 35 days) and contralateral, nonstimulated rat tibialis anterior muscle of hypothyroid, hyperthyroid, and euthyroid animals. Stimulation increased CYT...
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Myoblast transfer has emerged as a promising treatment for inherited myopathies such as Duchenne muscular dystrophy (DMD). Further development of the technique's therapeutic potential requires an experimental system in which issues of graft rejection can be clearly discriminated from those related to myoblast biology. Here we report the development...
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Although the association between hypothyroidism and obstructive sleep apnea is well established, the effect of thyroid hormone deficiency on contractile proteins in pharyngeal dilator muscles responsible for maintaining upper airway patency is unknown. In the present study, the effects of hypothyroidism on myosin heavy chain (MHC) expression were e...
Article
We have examined the histogenesis of the diaphragm and extensor digitorum muscle in rat embryos, with the aim of defining differences in developmental patterns that can be related to the functional requirements of these muscles during and after development. Patterns of interactions between myotubes and other cells, and frequency of gap junctions ar...
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Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm...
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Full-text available
Progressive changes in myosin isozyme expression and in energy-generating enzyme activities were followed in the diaphragm and, for comparison, in axial and appendicular muscles of rats from 18 d gestation to maturity. Native myosins were characterized by pyrophosphate gel electrophoresis. Myosin heavy-chain (MHC) isozymes were measured with ELISA...
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The present study examines the developmental accumulation of slow myosin heavy chain in the extensor digitorum longus, soleus and plantaris muscles of rats after early post-natal imposition of mechanical overload by removal of synergistic muscles. The proportions of slow and fast myosin heavy chain were measured in each muscle by ELISA. Fibres expr...
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Although chronic severe asthma is characterized by increased smooth muscle mass in the airways, the physiological stimuli that promote airway smooth muscle (ASM) proliferation (hyperplasia) or increase ASM protein expression (hypertrophy) are unknown. We examined the effects of histamine, an autocoid associated with airway hyperresponsiveness, on p...
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Full-text available
We have created several lines of mice that contain a truncated chicken c-ski cDNA linked to an MSV LTR promoter. Adult mice from three independent lines show large increases in skeletal muscle. All three lines of mice express high levels of c-ski mRNA and protein in skeletal muscle. All other tissues examined show little or no expression of the c-s...
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This study investigates effects of chronic low frequency stimulation (CLFS) on myosin heavy (MHC) and light chain (MLC) expression in fast-twitch muscles in hypothyroid, euthyroid, and hyperthyroid rats. The changes at both the mRNA and protein level indicated antagonistic effects of thyroid hormone and CLFS: under euthyroid conditions, CLFS mainly...
Article
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We have isolated a single 6021-nucleotide cDNA fragment encoding the full length of the myosin heavy chain (MHC) isoform initially expressed in developing human limb muscle. The corresponding transcript is expressed in fetal, but not adult, human muscle, and the corresponding gene maps to human chromosome 17. Comparison of the full length nucleotid...
Article
A series of cDNA fragments encoding immunodetectable portions of the human slow/beta, neonatal, and embryonic isoforms of myosin heavy chain (MHC) were isolated from a human fetal muscle cDNA expression library. A 6 kb fragment isolated on a secondary screen represents the first cloned cDNA encoding a full-length vertebrate MHC (the human embryonic...
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A 3.6 kilobase cDNA clone coding for the human embryonic myosin heavy chain has been isolated and characterized from an expression library prepared from human fetal skeletal muscle. The derived amino acid sequence for the entire rod part of myosin shows 97% sequence homology between human and rat and a striking interspecies sequence conservation am...
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Individual fibers of prospective fast (extensor digitorum longus; EDL) and slow (soleus) muscles of rats have been analyzed to determine the profiles of key energy-generating enzymes at successive stages of postnatal development. Mean activities of lactate dehydrogenase (LDH) and adenylokinase (AK), 2 enzymes associated with contractile function, a...
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Using a variety of techniques, we have demonstrated the presence of at least two fibre types inLimulus median telson levator muscle. By light and electron microscopy, large (21 56 μm2 mean cross-sectional area) fibres have A-bands of 4.1 μm, one-half I bands of 2.15 μm and Z lines ⩽ 0.5 μm in width. Few mitochondria are found in these fibres, which...
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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 de...
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Full-text available
Through S1 nuclease mapping using a specific cDNA probe, we demonstrate that the slow myosin heavy-chain (MHC) gene, characteristic of adult soleus, is expressed in bulk hind limb muscle obtained from the 18-d rat fetus. We support these results by use of a monoclonal antibody (mAb) which is highly specific to the adult slow MHC. Immunoblots of MHC...
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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 gu...
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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...
Article
We describe the construction of a densitometer based on a TV camera linked to an IBM personal computer (PC)1 1 Abbreviations used: PC, personal computer; OD, optical density. using commercially available components. We discuss some of the problems of accurate quantitative densitometry using low-cost video systems, and describe the manner in which a...
Article
Like most contractile proteins, the myosin molecule exists in a number of polymorphic forms which show specificity among muscles (365, 366) and among muscle fibers (367, 368) with different physiological and metabolic properties. For example, fast and slow twitch fibers contain both different myosin heavy chain and myosin light chain complements; a...
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The present study outlines the changes in contractile proteins which occur during sexual differentiation of the guinea pig temporalis muscle. This is an androgen sensitive muscle, which in the female progresses from a fetal phenotype to a muscle rich in IIa fibers, and in the male, undergoes a further switch to an almost pure IIb fiber phenotype. W...
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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...
Article
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 th...
Article
Eight canine right hemidiaphragms were electrically stimulated at 2Hz (N = 3) and 10 Hz (N = 5) for up to 135 days. ATPase histochemical studies showed nearly total transformation of type II fast twitch fatigable muscle fibers to type I slow twitch fatigue resistant muscle fibers. The thickness and vascular perfusion of the stimulated muscle increa...
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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...
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Full-text available
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 synchronou...
Article
The distribution of t tubules in neonatal rat soleus and EDL muscles has been investigated by light and electron microscopy using a modification of the “black reaction in Golgi.” It is shown that the t system is more complete than previously recognized. Longitudinal tubules permeate the fiber between all myofibrils. Transverse elements regularly cr...
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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...
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This study demonstrates a significantly lower incidence of satellite cells in the fast twitch extensor digitorum longus muscle (EDL) than in the slow twitch soleus muscles both in developing and mature rats. This distinction appears early in myogenesis, before histochemical differentiation is evident in the two muscles. Correlated with the differen...
Article
The histochemical ATPase activity and the myosin light chains of a rat fast muscle (extensor digitorum longus, EDL) and a rat slow muscle (soleus) during development have been investigated. Both muscles initially synthesize fast myosin light chains and show the intense histochemical ATPase activity characteristic of adult fast muscle fibers. After...
Article
Specialised, internal membrane junctions are described on the walls of plasma-lemmal invaginations within single chick cardiac muscle cells in vitro. These internal junctions occur most frequently within single cells isolated from neighbouring cells. They include desmosomes and intercalated discs at various stages of differentiation. Internal membr...
Article
Specialised, internal membrane junctions are described on the walls of plasma-lemmal invaginations within single chick cardiac muscle cells in vitro. These internal junctions occur most frequently within single cells isolated from neighbouring cells. They include desmosomes and intercalated discs at various stages of differentiation. Internal membr...
Article
Isolated cardiac muscle cells grown in vitro have been studied with respect to their ability to contract spontaneously and maintain myofibrillar organisation during division. These cells do not round up to undergo mitosis; division is achieved by the cell pinching itself in two in a selected area. This adaptation minimises disturbance to cell attac...
Article
Neurogenic atrophy is described in biopsy specimens of laryngeal muscles in 7 large breed dogs. Signs shown by the dogs were similar but varied in degree of severity; most had a rough bark and stridorous respiration of several mths' duration which progressed to obstructive dyspnoea and, in some cases, to glottic obstruction with collapse on exertio...
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Full-text available
An electron microscope study has been made of the distribution of membrane couplings between the sarcoplasmic reticulum (SR) and either the plasmalemma or the T tubules in fetal and neonatal rat intercostal muscle. Within primitive muscle cells at 12 days of gestation, the SR forms both simple and specialized membrane junctions with the plasmalemma...
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Intercostal muscle from fetal and newborn rats was examined with the electron microscope. At 16 days' gestation, the developing muscle was composed of primary generations of myotubes, many of which were clustered together in groups. Within these groups, the membranes of neighboring myotubes were interconnected by specialized junctions, including ti...
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Full-text available
The fine structure of the developing neuromuscular junction of rat intercostal muscle has been studied from 16 days in utero to 10 days postpartum. At 16 days, neuromuscular relations consist of close membrane apposition between clusters of axons and groups of myotubes. Focal electron-opaque membrane specializations more intimately connect axon and...

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