Value of fetal skeletal radiographs in the diagnosis of fetal death

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Bourliere-Najean, B.; Russel, A.S.; Petit, P.; Devred, P. [Department of Pediatric Radiology, CHU Timone, 264 rue St. Pierre, 13385 Marseille cedex 5 (France); Panuel, M. [Department of Radiology, Hopital Nord, chemin Bourrelys, 13915 Marseille cedex 20 (France); Piercecchi-Marti, M.D.; Fredouille, C. [Department of Pathology, CHU Timone, 264 rue St. Pierre, 13385 Marseille cedex 5 (France); Sigaudy, S.; Philip, N. [Department of Genetics, CHU Timone, 264 rue St. Pierre, 13385 Marseille cedex 5 (France)

2003-05-01

The aim of this study was to assess the value of fetal skeletal radiographs in determining the etiology of fetal death. A total of 1193 post-mortem fetal skeletal radiographs were analysed. Fetuses were classified into one of three groups (group I: abnormality diagnosed during pregnancy; group II: maternal pathology; group III: spontaneous abortion of pregnancy, IIIa before 26 weeks of gestation (WG), IIIb after 26 weeks of gestation). Face, supine and lateral skeletal views were performed. Skeletal abnormalities were detected in 33.9% of the fetuses, including 22.7% with minor abnormalities (abnormal rib number, no nasal bone ossification, amesophalangia or P2 hypoplasia of the fifth digit) and 14.5% with major abnormalities (other skeletal abnormalities). Among the fetuses with major abnormalities, 98.8% came from group I, 2.9% came from group II, 2.3% came from group IIIa and none came from group IIIb. Fetal skeletal radiographs are not useful in fetuses arising from spontaneous abortion of pregnancy without abnormality on ultrasound screening, abnormality clinical examination or in fetuses with prenatal diagnosis of chromosomal abnormality. This practice is valuable only if there is a multidisciplinary team, with all the participants (pathologists, radiologists, geneticists) knowledgeable about fetal pathology. In the absence of this multidisciplinary approach, it is easier to X-ray all fetuses to avoid misdiagnosis and the important consequences for genetic counselling. (orig.)

An atlas of normal skeletal scintigraphy

International Nuclear Information System (INIS)

Flanagan, J.J.; Maisey, M.N.

1985-01-01

This atlas was compiled to provide the neophyte as well as the experienced radiologist and the nuclear medicine physician with a reference on normal skeletal scintigraphy as an aid in distinguishing normal variations in skeletal uptake from abnormal findings. Each skeletal scintigraph is labeled, and utilizing an identical scale, a relevant skeletal photograph and radiograph are placed adjacent to the scintigraph

Brain and bone abnormalities of thanatophoric dwarfism.

Science.gov (United States)

Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa

2009-01-01

The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.

Growth of limb muscle is dependent on skeletal-derived Indian hedgehog

OpenAIRE

Bren-Mattison, Yvette; Hausburg, Melissa; Olwin, Bradley B.

2011-01-01

During embryogenesis, muscle and bone develop in close temporal and spatial proximity. We show that Indian Hedgehog, a bone-derived signaling molecule, participates in growth of skeletal muscle. In Ihh−/− embryos, skeletal muscle development appears abnormal at embryonic day 14.5 and at later ages through embryonic day 20.5, dramatic losses of hindlimb muscle occur. To further examine the role of Ihh in myogenesis, we manipulated Ihh expression in the developing chick hindlimb. Reduction of I...

Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension.

Science.gov (United States)

Malenfant, Simon; Potus, François; Fournier, Frédéric; Breuils-Bonnet, Sandra; Pflieger, Aude; Bourassa, Sylvie; Tremblay, Ève; Nehmé, Benjamin; Droit, Arnaud; Bonnet, Sébastien; Provencher, Steeve

2015-05-01

Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles.

Skeletal abnormalities in fetuses with Down's syndrome: a radiographic post-mortem study

International Nuclear Information System (INIS)

Stempfle, N.; Brisse, H.; Huten, Y.; Fredouille, C.; Nessmann, C.

1999-01-01

Objective. To evaluate skeletal abnormalities on post-mortem radiographs of fetuses with Down's syndrome. Materials and methods. Biometrical and morphological criteria, which are used for US prenatal detection of trisomy 21, were assessed. Limb long bones, biparietal diameter (BPD)/occipito-frontal diameter (OFD) ratio, ossification of nasal bones and appearance of the middle phalanx of the fifth digit (P2) in 60 fetuses with Down's syndrome were analysed and compared with 82 normal fetuses matched for gestational age (GA) from 15 to 40 weeks' gestation (WG). Results. We observed reduced growth velocity of limb long bones during the third trimester in both groups, but the reduction was more pronounced in the trisomic group. Brachycephaly was found as early as 15 WG in Down's syndrome and continued throughout gestation (sensitivity 0.28, specificity 1). Ossification of the nasal bones, which can be detected in normal fetuses from 14 WG, was absent in one quarter of trisomic fetuses, regardless of GA. The middle phalanx of the fifth digit was evaluated by comparison with the distal phalanx (P3) of the same digit. We found that P2 was not ossified in 11/31 trisomic fetuses before 23 WG, and was either not ossified or hypoplastic in 17/29 cases after 24 WG (sensitivity 0.56, specificity 1). Conclusions. Three key skeletal signs were present in trisomic fetuses: brachycephaly, absence of nasal bone ossification, and hypoplasia of the middle phalanx of the fifth digit. All these signs are appropriate to prenatal US screening. When present, they fully justify determination of the fetal karyotype by amniocentesis. (orig.)

Histone Deacetylases in Bone Development and Skeletal Disorders

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Bradley, Elizabeth W.; Carpio, Lomeli R.; van Wijnen, Andre J.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.

2015-01-01

Histone deacetylases (Hdacs) are conserved enzymes that remove acetyl groups from lysine side chains in histones and other proteins. Eleven of the 18 Hdacs encoded by the human and mouse genomes depend on Zn2+ for enzymatic activity, while the other 7, the sirtuins (Sirts), require NAD2+. Collectively, Hdacs and Sirts regulate numerous cellular and mitochondrial processes including gene transcription, DNA repair, protein stability, cytoskeletal dynamics, and signaling pathways to affect both development and aging. Of clinical relevance, Hdacs inhibitors are United States Food and Drug Administration-approved cancer therapeutics and are candidate therapies for other common diseases including arthritis, diabetes, epilepsy, heart disease, HIV infection, neurodegeneration, and numerous aging-related disorders. Hdacs and Sirts influence skeletal development, maintenance of mineral density and bone strength by affecting intramembranous and endochondral ossification, as well as bone resorption. With few exceptions, inhibition of Hdac or Sirt activity though either loss-of-function mutations or prolonged chemical inhibition has negative and/or toxic effects on skeletal development and bone mineral density. Specifically, Hdac/Sirt suppression causes abnormalities in physiological development such as craniofacial dimorphisms, short stature, and bone fragility that are associated with several human syndromes or diseases. In contrast, activation of Sirts may protect the skeleton from aging and immobilization-related bone loss. This knowledge may prolong healthspan and prevent adverse events caused by epigenetic therapies that are entering the clinical realm at an unprecedented rate. In this review, we summarize the general properties of Hdacs/Sirts and the research that has revealed their essential functions in bone forming cells (e.g., osteoblasts and chondrocytes) and bone resorbing osteoclasts. Finally, we offer predictions on future research in this area and the utility of

Gamma-ray-induced dominant mutations that cause skeletal abnormalities in mice

International Nuclear Information System (INIS)

Selby, P.B.; Selby, P.R.

1977-01-01

Male mice were exposed to 100 R + 500 R γ-rays (60 R/min) with a 24-h fractionation interval. Skeletons of F 1 sons were examined for abnormalities, and, if any were found, the skeletons of their descendants were also examined. Of 2646 sons from treated spermatogonia, 37, or 1.4%, were diagnosed as carriers of autosomal dominant mutations affecting the skeleton, 31 by breeding tests, and six by other criteria for identifying mutations in F 1 's having no progeny. Many mutations caused a large number of anomalies in different regions of the skeleton. Most regions of the skeleton were affected by at least one mutation, and the mutations had incomplete penetrance for some or all of their effects. Three of the mutations affected skeletal size only. If certain assumptions are made, these skeletal data can be used to derive an estimate of induced genetic damage from dominant mutations affecting all parts of the body. When applied to man, the resultant risk estimate is not inconsistent with that made for dominant and irregularly inherited diseases by the BEIR Committee, by use of the doubling-dose method. Since most of the mutations can be characterized as models of irregularly inherited conditions in man, the data directly relate to the controversy over the relative importance of mutation pressure and balanced selection in maintaining man's large burden of irregularly inherited disease. Contrary to a recent hypothesis by H.B. Newcombe that man's large burden of irregularly inherited disease is maintained almost exclusively by balanced selection, these results suggest that at least an important fraction of the irregularly inherited conditions are maintained by mutation pressure. Therefore, this finding does not support the major changes in the estimate of genetic hazard to man that would be required on the basis of Newcombe's hypothesis

Role of skeletal muscle in lung development.

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Baguma-Nibasheka, Mark; Gugic, Dijana; Saraga-Babic, Mirna; Kablar, Boris

2012-07-01

Skeletal (striated) muscle is one of the four basic tissue types, together with the epithelium, connective and nervous tissues. Lungs, on the other hand, develop from the foregut and among various cell types contain smooth, but not skeletal muscle. Therefore, during earlier stages of development, it is unlikely that skeletal muscle and lung depend on each other. However, during the later stages of development, respiratory muscle, primarily the diaphragm and the intercostal muscles, execute so called fetal breathing-like movements (FBMs), that are essential for lung growth and cell differentiation. In fact, the absence of FBMs results in pulmonary hypoplasia, the most common cause of death in the first week of human neonatal life. Most knowledge on this topic arises from in vivo experiments on larger animals and from various in vitro experiments. In the current era of mouse mutagenesis and functional genomics, it was our goal to develop a mouse model for pulmonary hypoplasia. We employed various genetically engineered mice lacking different groups of respiratory muscles or lacking all the skeletal muscle and established the criteria for pulmonary hypoplasia in mice, and therefore established a mouse model for this disease. We followed up this discovery with systematic subtractive microarray analysis approach and revealed novel functions in lung development and disease for several molecules. We believe that our approach combines elements of both in vivo and in vitro approaches and allows us to study the function of a series of molecules in the context of lung development and disease and, simultaneously, in the context of lung's dependence on skeletal muscle-executed FBMs.

Longitudinal study of the effects of chronic hypothyroidism on skeletal muscle in dogs.

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Rossmeisl, John H; Duncan, Robert B; Inzana, Karen D; Panciera, David L; Shelton, G Diane

2009-07-01

To study the effects of experimentally induced hypothyroidism on skeletal muscle and characterize any observed myopathic abnormalities in dogs. 9 female, adult mixed-breed dogs; 6 with hypothyroidism induced with irradiation with 131 iodine and 3 untreated control dogs. Clinical examinations were performed monthly. Electromyographic examinations; measurement of plasma creatine kinase, alanine aminotransferase, aspartate aminotransferase, lactate, and lactate dehydrogenase isoenzyme activities; and skeletal muscle morphologic-morphometric examinations were performed prior to and every 6 months for 18 months after induction of hypothyroidism. Baseline, 6-month, and 18-month assessments of plasma, urine, and skeletal muscle carnitine concentrations were also performed. Hypothyroid dogs developed electromyographic and morphologic evidence of myopathy by 6 months after treatment, which persisted throughout the study, although these changes were subclinical at all times. Hypothyroid myopathy was associated with significant increases in plasma creatine kinase, aspartate aminotransferase, and lactate dehydrogenase 5 isoenzyme activities and was characterized by nemaline rod inclusions, substantial and progressive predominance of type I myofibers, decrease in mean type II fiber area, subsarcolemmal accumulations of abnormal mitochondria, and myofiber degeneration. Chronic hypothyroidism was associated with substantial depletion in skeletal muscle free carnitine. Chronic, experimentally induced hypothyroidism resulted in substantial but subclinical phenotypic myopathic changes indicative of altered muscle energy metabolism and depletion of skeletal muscle carnitine. These abnormalities may contribute to nonspecific clinical signs, such as lethargy and exercise intolerance, often reported in hypothyroid dogs.

Skeletal injuries in small mammals: a multispecies assessment of prevalence and location

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Stephens, Ryan B.; Burke, Christopher B.; Woodman, Neal; Poland, Lily B.; Rowe, Rebecca J.

2018-01-01

Wild mammals are known to survive injuries that result in skeletal abnormalities. Quantifying and comparing skeletal injuries among species can provide insight into the factors that cause skeletal injuries and enable survival following an injury. We documented the prevalence and location of structural bone abnormalities in a community of 7 small mammal species inhabiting the White Mountains of New Hampshire. These species differ in locomotion type and levels of intraspecific aggression. Overall, the majority of injuries were to the ribs or caudal vertebrae. Incidence of skeletal injuries was highest in older animals, indicating that injuries accumulate over a lifetime. Compared to species with ambulatory locomotion, those with more specialized (semi-fossorial, saltatorial, and scansorial) locomotion exhibited fewer skeletal abnormalities in the arms and legs, which we hypothesize is a result of a lesser ability to survive limb injuries. Patterns of skeletal injuries in shrews (Soricidae) were consistent with intraspecific aggression, particularly in males, whereas skeletal injuries in rodents (Rodentia) were more likely accidental or resulting from interactions with predators. Our results demonstrate that both the incidence and pattern of skeletal injuries vary by species and suggest that the ability of an individual to survive a specific skeletal injury depends on its severity and location as well as the locomotor mode of the species involved.

Study of muscular skeletal apparatus’s functional state of junior sportsmen-power lifters, who have backbone verterbral abnormalities

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V.R. Ilmatov

2015-10-01

Full Text Available Purpose: determination of abnormalities and disorders of muscular skeletal apparatuses’ status of power lifters, who have vertebral abnormalities of backbone. Material: 58 junior sportsmen participated in the research. 36 sportsmen were the main group of the research and had vertebral disorders in backbone. For posture testing visual examination was used. Backbone mobility was tested with goniometry method. Flat feet were registered with plantography method. Results: we determined posture abnormalities in sagittal and frontal planes; feet flat, limited maximal movements in thoracic and lumbar spines. It was determined that the most limited were rotational movements and backbone unbending. The next were side bents. These limitations were accompanied by pain syndrome. These observations indirectly confirmed theory of direct interaction of backbone structures with nervous structures. It is also a confirmation of vertebral abnormalities’ presence in junior sportsmen. Conclusions: it was found that in junior sportsmen - power lifters with backbone pathologies in 100% of cases symptoms are determined by local limitations of backbone mobility with pain syndrome. In 35% of cases they are accompanied by posture’s disorders and feet flat. Orientation and methodic of rehabilitation of such sportsmen have been determined.

Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome.

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Oud, Machteld M; Tuijnenburg, Paul; Hempel, Maja; van Vlies, Naomi; Ren, Zemin; Ferdinandusse, Sacha; Jansen, Machiel H; Santer, René; Johannsen, Jessika; Bacchelli, Chiara; Alders, Marielle; Li, Rui; Davies, Rosalind; Dupuis, Lucie; Cale, Catherine M; Wanders, Ronald J A; Pals, Steven T; Ocaka, Louise; James, Chela; Müller, Ingo; Lehmberg, Kai; Strom, Tim; Engels, Hartmut; Williams, Hywel J; Beales, Phil; Roepman, Ronald; Dias, Patricia; Brunner, Han G; Cobben, Jan-Maarten; Hall, Christine; Hartley, Taila; Le Quesne Stabej, Polona; Mendoza-Londono, Roberto; Davies, E Graham; de Sousa, Sérgio B; Lessel, Davor; Arts, Heleen H; Kuijpers, Taco W

2017-02-02

EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs). By whole-exome sequencing, we identified homozygous missense mutations c.1382C>T, c.1537C>T, c.1970A>G, and c.2008T>G in EXTL3 in nine affected individuals from five unrelated families. Notably, we found the identical homozygous missense mutation c.1382C>T (p.Pro461Leu) in four affected individuals from two unrelated families. Affected individuals presented with variable skeletal abnormalities and neurodevelopmental defects. Severe combined immunodeficiency (SCID) with a complete absence of T cells was observed in three families. EXTL3 was most abundant in hematopoietic stem cells and early progenitor T cells, which is in line with a SCID phenotype at the level of early T cell development in the thymus. To provide further support for the hypothesis that mutations in EXTL3 cause a neuro-immuno-skeletal dysplasia syndrome, and to gain insight into the pathogenesis of the disorder, we analyzed the localization of EXTL3 in fibroblasts derived from affected individuals and determined glycosaminoglycan concentrations in these cells as well as in urine and blood. We observed abnormal glycosaminoglycan concentrations and increased concentrations of the non-sulfated chondroitin disaccharide D0a0 and the disaccharide D0a4 in serum and urine of all analyzed affected individuals. In summary, we show that biallelic mutations in EXTL3 disturb glycosaminoglycan synthesis and thus lead to a recognizable syndrome characterized by variable expression of skeletal, neurological, and immunological abnormalities. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Multiple congenital skeletal malformations in a lamb associated with ...

African Journals Online (AJOL)

Other malformations included patella absence, resulting in bowing of both fore and hind limbs with poorly developed muscles associated with these skeletal structure. Dystocia was believed to be a result of fetal monstrosity resulting in abnormal posture. The cause of the congenital malformations was not obvious ...

[Size of lower jaw as an early indicator of skeletal class III development].

Science.gov (United States)

Stojanović, Zdenka; Nikodijević, Angelina; Udovicić, Bozidar; Milić, Jasmina; Nikolić, Predrag

2008-08-01

Malocclusion of skeletal class III is a complex abnormality, with a characteristic sagital position of the lower jaw in front of the upper one. A higher level of prognatism of the lower jaw in relation to the upper one can be the consequence of its excessive length. The aim of this study was to find the differences in the length of the lower jaw in the children with skeletal class III and the children with normal sagital interjaw relation (skeletal class I) in the period of mixed dentition. After clinical and x-ray diagnostics, profile tele-x-rays of the head were analyzed in 60 examinees with mixed dentition, aged from 6 to 12 years. The examinees were divided into two groups: group 1--the children with skeletal class III and group 2--the children with skeletal class I. The length of the lower jaw, upper jaw and cranial base were measured. The proportional relations between the lengths measured within each group were established and the level of difference in the lengths measured and their proportions between the groups were estimated. No significant difference between the groups was found in the body length, ramus and the total length of the lower jaw. Proportional relation between the body length and the length of the lower jaw ramus and proportional relation between the forward cranial base and the lower jaw body were not significantly different. A significant difference was found in proportional relations of the total length of the lower jaw with the total lengths of cranial base and the upper jaw and proportional relation of the length of the lower and upper jaw body. Of all the analyzed parameters, the following were selected as the early indicators of the development of skeletal class III on the lower jaw: greater total length of the lower jaw, proportional to the total lengths of cranial base and theupper jaw, as well as greater length of the lower jaw body, proportional to the length of the upper jaw body.

Radiology of postnatal skeletal development. Pt. 7

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Ogden, J.A.; Phillips, S.B.

1983-02-01

Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence.

Radiology of postnatal skeletal development. Pt. 7

International Nuclear Information System (INIS)

Ogden, J.A.; Phillips, S.B.

1983-01-01

Twenty-four pairs of scapulae from fetal specimens and 35 pairs of scapulae from postnatal cadavers ranging in age from full-term neonates to 14 years, were studied morphologically and roentgenographically. Air-cartilage interfacing was used to demonstrate both the osseous and cartilaginous contours. When the entire chondro-osseous dimensions, rather than just the osseous dimensions, were measured, the scapula had a height-width ratio ranging from 1.36 to 1.52 (average 1.44) during most of fetal development. The exceptions were three stillborns with camptomelic, thanatophoric, and achondrogenic dwarfism in which the ratio averaged 0.6. At no time during fetal development was the glenoid cavity convex; it always had a concave articular surface. However, the osseous subchrondral countour was often flat or slightly convex. In the postnatal period the height-width ratio averaged 1.49. The ratio remained virtually unchanged throughout skeletal growth and maturation. In a patient with unilateral Sprengel's deformity the ratio for the normal side was 1.5, while the abnormal was 1.0. The cartilaginous glenoid cavity was always concave during postnatal development, even in the specimens with major structural deformities, although the subchondral osseous contour was usually flat or convex during the first few years of postnatal development. Ossification of the coracoid process began with the development of a primary center at three to four months. A bipolar physis was present between the primary coracoid center and the primary scapular center until late adolescence. (orig.)

Radiology of postnatal skeletal development. Pt. 6

International Nuclear Information System (INIS)

McCarthy, S.M.; Ogden, J.A.; Yale Univ., New Haven, CT; Yale Univ., New Haven, CT

1982-01-01

Thirty-six pairs of proximal radioulnar and elbow units from cadavers and prepared skeletons ranging in age from full-term neonates to fourteen years, were studied morphologically and roentgenographically. Air/cartilage interfacing was used to demonstrate the osseous and cartilaginous portions of the developing epiphyses. These roentgenographic aspects are discussed and illustrated to provide a reference index. The skeletal development is outlined with regard to the diagnosis of several traumatic skeletal diseases as dislocation of elbow or radial head. Moteggia fracture dislocation and Nursemaid's elbow. (orig./WU)

Pelvic radiograph in skeletal dysplasias: An approach

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Manisha Jana

2017-01-01

Full Text Available The bony pelvis is constituted by the ilium, ischium, pubis, and sacrum. The pelvic radiograph is an important component of the skeletal survey performed in suspected skeletal dysplasia. Most of the common skeletal dysplasias have either minor or major radiological abnormalities; hence, knowledge of the normal radiological appearance of bony pelvis is vital for recognizing the early signs of various skeletal dysplasias. This article discusses many common and some uncommon radiological findings on pelvic radiographs along with the specific dysplasia in which they are seen; common differential diagnostic considerations are also discussed.

Peripheral endocannabinoids regulate skeletal muscle development and maintenance

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Dongjiao Zhao

2010-12-01

Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

Proteomics analysis of human skeletal muscle reveals novel abnormalities in obesity and type 2 diabetes

DEFF Research Database (Denmark)

Hwang, Hyonson; Bowen, Benjamin P; Lefort, Natalie

2010-01-01

changes involving the use of proteomics was used here. RESEARCH DESIGN AND METHODS: Muscle biopsies were obtained basally from lean, obese, and type 2 diabetic volunteers (n = 8 each); glucose clamps were used to assess insulin sensitivity. Muscle protein was subjected to mass spectrometry......OBJECTIVE : Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Studies of insulin resistance usually are highly focused. However, approaches that give a more global picture of abnormalities in insulin resistance are useful in pointing out new......-based quantification using normalized spectral abundance factors. RESULTS: Of 1,218 proteins assigned, 400 were present in at least half of all subjects. Of these, 92 were altered by a factor of 2 in insulin resistance, and of those, 15 were significantly increased or decreased by ANOVA (P

Epigenetic Control of Skeletal Development by the Histone Methyltransferase Ezh2*

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Dudakovic, Amel; Camilleri, Emily T.; Xu, Fuhua; Riester, Scott M.; McGee-Lawrence, Meghan E.; Bradley, Elizabeth W.; Paradise, Christopher R.; Lewallen, Eric A.; Thaler, Roman; Deyle, David R.; Larson, A. Noelle; Lewallen, David G.; Dietz, Allan B.; Stein, Gary S.; Montecino, Martin A.; Westendorf, Jennifer J.; van Wijnen, Andre J.

2015-01-01

Epigenetic control of gene expression is critical for normal fetal development. However, chromatin-related mechanisms that activate bone-specific programs during osteogenesis have remained underexplored. Therefore, we investigated the expression profiles of a large cohort of epigenetic regulators (>300) during osteogenic differentiation of human mesenchymal cells derived from the stromal vascular fraction of adipose tissue (AMSCs). Molecular analyses establish that the polycomb group protein EZH2 (enhancer of zeste homolog 2) is down-regulated during osteoblastic differentiation of AMSCs. Chemical inhibitor and siRNA knockdown studies show that EZH2, a histone methyltransferase that catalyzes trimethylation of histone 3 lysine 27 (H3K27me3), suppresses osteogenic differentiation. Blocking EZH2 activity promotes osteoblast differentiation and suppresses adipogenic differentiation of AMSCs. High throughput RNA sequence (mRNASeq) analysis reveals that EZH2 inhibition stimulates cell cycle inhibitory proteins and enhances the production of extracellular matrix proteins. Conditional genetic loss of Ezh2 in uncommitted mesenchymal cells (Prrx1-Cre) results in multiple defects in skeletal patterning and bone formation, including shortened forelimbs, craniosynostosis, and clinodactyly. Histological analysis and mRNASeq profiling suggest that these effects are attributable to growth plate abnormalities and premature cranial suture closure because of precocious maturation of osteoblasts. We conclude that the epigenetic activity of EZH2 is required for skeletal patterning and development, but EZH2 expression declines during terminal osteoblast differentiation and matrix production. PMID:26424790

Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

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Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

2011-09-01

Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

Suspected fetal skeletal malformations or bone diseases: how to explore

International Nuclear Information System (INIS)

Cassart, Marie

2010-01-01

Skeletal dysplasias are a heterogeneous and complex group of conditions that affect bone growth and development and result in various anomalies in shape and size of the skeleton. Although US has proved reliable for the prenatal detection of skeletal abnormalities, the precise diagnosis of a dysplasia is often difficult to make before birth (especially in the absence of a familial history) due to their various phenotypic presentations, the variability in the time at which they manifest and often, the lack of precise molecular diagnosis. In addition to the accuracy of the antenatal diagnosis, it is very important to establish a prognosis. This is a clinically relevant issue as skeletal dysplasias may be associated with severe disability and may even be lethal. We will therefore describe the respective role of two-dimensional (2-D) US, three-dimensional (3-D) US and CT in the antenatal assessment of skeletal malformations. (orig.)

Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome?

International Nuclear Information System (INIS)

Nishimura, G.; Haga, Yoshihiko; Aoki, Katsuhiko; Hasegawa, Tomoko

1998-01-01

A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome. (orig.)

Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome.

Science.gov (United States)

Iqbal, Zafar; Cejudo-Martin, Pilar; de Brouwer, Arjan; van der Zwaag, Bert; Ruiz-Lozano, Pilar; Scimia, M Cecilia; Lindsey, James D; Weinreb, Robert; Albrecht, Beate; Megarbane, Andre; Alanay, Yasemin; Ben-Neriah, Ziva; Amenduni, Mariangela; Artuso, Rosangela; Veltman, Joris A; van Beusekom, Ellen; Oudakker, Astrid; Millán, José Luis; Hennekam, Raoul; Hamel, Ben; Courtneidge, Sara A; van Bokhoven, Hans

2010-02-12

Frank-Ter Haar syndrome (FTHS), also known as Ter Haar syndrome, is an autosomal-recessive disorder characterized by skeletal, cardiovascular, and eye abnormalities, such as increased intraocular pressure, prominent eyes, and hypertelorism. We have conducted homozygosity mapping on patients representing 12 FTHS families. A locus on chromosome 5q35.1 was identified for which patients from nine families shared homozygosity. For one family, a homozygous deletion mapped exactly to the smallest region of overlapping homozygosity, which contains a single gene, SH3PXD2B. This gene encodes the TKS4 protein, a phox homology (PX) and Src homology 3 (SH3) domain-containing adaptor protein and Src substrate. This protein was recently shown to be involved in the formation of actin-rich membrane protrusions called podosomes or invadopodia, which coordinate pericellular proteolysis with cell migration. Mice lacking Tks4 also showed pronounced skeletal, eye, and cardiac abnormalities and phenocopied the majority of the defects associated with FTHS. These findings establish a role for TKS4 in FTHS and embryonic development. Mutation analysis revealed five different homozygous mutations in SH3PXD2B in seven FTHS families. No SH3PXD2B mutations were detected in six other FTHS families, demonstrating the genetic heterogeneity of this condition. Interestingly however, dermal fibroblasts from one of the individuals without an SH3PXD2B mutation nevertheless expressed lower levels of the TKS4 protein, suggesting a common mechanism underlying disease causation. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Phenotypic characterization of miR-92a-/- mice reveals an important function of miR-92a in skeletal development.

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Daniela Penzkofer

Full Text Available MicroRNAs (miRNAs, miRs emerged as key regulators of gene expression. Germline hemizygous deletion of the gene that encodes the miR-17∼92 miRNA cluster was associated with microcephaly, short stature and digital abnormalities in humans. Mice deficient for the miR-17∼92 cluster phenocopy several features such as growth and skeletal development defects and exhibit impaired B cell development. However, the individual contribution of miR-17∼92 cluster members to this phenotype is unknown. Here we show that germline deletion of miR-92a in mice is not affecting heart development and does not reduce circulating or bone marrow-derived hematopoietic cells, but induces skeletal defects. MiR-92a-/- mice are born at a reduced Mendelian ratio, but surviving mice are viable and fertile. However, body weight of miR-92a-/- mice was reduced during embryonic and postnatal development and adulthood. A significantly reduced body and skull length was observed in miR-92a-/- mice compared to wild type littermates. µCT analysis revealed that the length of the 5th mesophalanx to 5th metacarpal bone of the forelimbs was significantly reduced, but bones of the hindlimbs were not altered. Bone density was not affected. These findings demonstrate that deletion of miR-92a is sufficient to induce a developmental skeletal defect.

Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome?

Energy Technology Data Exchange (ETDEWEB)

Nishimura, G. [Department of Radiology, Dokkyo University School of Medicine (Japan); Haga, Yoshihiko [Department of Orthopaedics, Shizuoka Children`s Hospital, Shizuoka (Japan); Aoki, Katsuhiko [Department of Radiology, Shizuoka Children`s Hospital, Shizuoka (Japan); Hasegawa, Tomoko [Division of Clinical Genetics, Shizuoka Children`s Hospital, Shizuoka (Japan)

1998-12-01

A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome. (orig.) With 4 figs., 8 refs.

Skeletal changes in congenital fibrinogen abnormalities

Energy Technology Data Exchange (ETDEWEB)

Lagier, R.; Bouvier, C.A.; van Strijthem, N.

1980-01-01

We report anatomico-radiologic study of humerus, femur, and tibia from a case of total congenital afibrinogenemia. Juxtatrabecular hemorrhages occur mainly in metaphyses and seem to be related to normal lines of stress. They may lead to the formation of intraosseous cysts and to a remodelling of bone trabeculae. The radiologic lesions in a second case, diagnosed as congenital dysfibrinogenemia, are similar to those found in Case 1 (femoral trabeculae remodelling) but also resemble some alterations described in hemophilia (pseudotumor of the right iliac bone). Anatomic study of the lesions in Case 2 was not possible. The significance of these observations could be better defined by a more extended skeletal study (radiologic and when feasible anatomic) of patients with congenital clotting defects and especially with inherited disorders of the fibrinogen molecule. It would also be worthwhile investigating manifest or latent hemostatic disorders (particularly at the fibrinogen level) in patients with solitary or aneurysmal bone cysts, and even with bone infarct or unexplained trabecular remodelling.

The significance of measuring serum IGF1, IGFBP3 and OST for the judgement of abnormal skeletal development and therapeutic monitoring in precocious children

International Nuclear Information System (INIS)

Ji Zhiying; Zhao Ruifang; Lv Xiaomei; Gu Fanlei; Cai Depei

2004-01-01

monitoring on delaying skeletal maturity and ameliorating skeletal development that to re-examine the change of serum IGF 1 and OST at regular intervals during treatment course

Role of skeletal muscle in ear development.

Science.gov (United States)

Rot, Irena; Baguma-Nibasheka, Mark; Costain, Willard J; Hong, Paul; Tafra, Robert; Mardesic-Brakus, Snjezana; Mrduljas-Djujic, Natasa; Saraga-Babic, Mirna; Kablar, Boris

2017-10-01

The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants' cristae was further used here to identify a profile of genes specific to the lacking cell type. Microarrays followed by a detailed consultation of web-accessible mouse databases allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have associated inner ear abnormalities. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X-linked deafness in humans. Our current study suggests an epigenetic role that mechanical, and potentially other, stimuli originating from muscle, play in organogenesis, and offers an approach to finding novel genes responsible for altered inner ear phenotypes.

Radiological and orthopedic abnormalities in Satoyoshi syndrome

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Haymon, M.L. [Children`s Hospital, New Orleans, LA (United States). Dept. of Radiology; Willis, R.B. [Children`s Hospital, New Orleans, LA (United States). Dept. of Orthopedics; Ehlayel, M.S. [Div. of Genetics, Dept. of Pediatrics, Louisiana State Univ. Medical Center, Orleans, LA (United States)]|[Louisiana State Medical Center, New Orleans, LA (United States). Center for Molecular and Human Genetics; Lacassie, Y. [Div. of Genetics, Dept. of Pediatrics, Louisiana State Univ. Medical Center, Orleans, LA (United States)]|[Louisiana State Medical Center, New Orleans, LA (United States). Center for Molecular and Human Genetics]|[Children`s Hospital, New Orleans, LA (United States). Dept. of Pediatrics

1997-05-01

Satoyoshi syndrome is a are disorder on unknown etiology characterized by progressive, painful intermittent muscle spasms, serve skeletal abnormalities mimicking a skeletal dyplasia, malabsorption, alopecia, and amenorrhea. We further report on a 20{sup 1}/{sub 2}-year-old Caucasian woman whith characteristic manifestation of the syndrome. Since the establishment of the diagnostic 1 year ago, she has been treated with prednisone with good response. However, treatment of the multiple deformities and fractures has been difficult and challenging. The early recognition and treatment of this disorder is of utmost importance, as the skeletal deformities and fractures seem to be secondary to the muscular spasms, as suggested by Satoyoshi.

Radiological and orthopedic abnormalities in Satoyoshi syndrome

International Nuclear Information System (INIS)

Haymon, M.L.; Willis, R.B.; Ehlayel, M.S.; Louisiana State Medical Center, New Orleans, LA; Lacassie, Y.; Louisiana State Medical Center, New Orleans, LA; Children's Hospital, New Orleans, LA

1997-01-01

Satoyoshi syndrome is a are disorder on unknown etiology characterized by progressive, painful intermittent muscle spasms, serve skeletal abnormalities mimicking a skeletal dyplasia, malabsorption, alopecia, and amenorrhea. We further report on a 20 1 / 2 -year-old Caucasian woman whith characteristic manifestation of the syndrome. Since the establishment of the diagnostic 1 year ago, she has been treated with prednisone with good response. However, treatment of the multiple deformities and fractures has been difficult and challenging. The early recognition and treatment of this disorder is of utmost importance, as the skeletal deformities and fractures seem to be secondary to the muscular spasms, as suggested by Satoyoshi

Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

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Maide Ö. Raeker

2011-01-01

Full Text Available During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues.

Obscurin Depletion Impairs Organization of Skeletal Muscle in Developing Zebrafish Embryos

Science.gov (United States)

Raeker, Maide Ö.; Russell, Mark W.

2011-01-01

During development, skeletal myoblasts differentiate into myocytes and skeletal myotubes with mature contractile structures that are precisely oriented with respect to surrounding cells and tissues. Establishment of this highly ordered structure requires reciprocal interactions between the differentiating myocytes and the surrounding extracellular matrix to form correctly positioned and well-organized attachments from the skeletal muscle to the bony skeleton. Using the developing zebrafish embryo as a model, we examined the relationship between new myofibril assembly and the organization of the membrane domains involved in cell-extracellular matrix interactions. We determined that depletion of obscurin, a giant muscle protein, resulted in irregular cell morphology and disturbed extracellular matrix organization during skeletal muscle development. The resulting impairment of myocyte organization was associated with disturbance of the internal architecture of the myocyte suggesting that obscurin participates in organizing the internal structure of the myocyte and translating those structural cues to surrounding cells and tissues. PMID:22190853

US of the hips in skeletal dysplasias and chromosomal aberrations

International Nuclear Information System (INIS)

Langer, R.; Langer, M.F.J.; Zwicker, C.

1987-01-01

Since January 1984 all newborns and infants with skeletal dysplasias and chromosomal aberrations were investigated by hip US, in addition to plain x-ray surveys. The authors observed one chondroectodermal dysplasia, one congenital spondyloepiphysial dysplasia, one cleidocranial dysplasia, one fibrochondrogenesis, two diastrophic dysplasias, and eight trisomies. The abnormalities of the hip joints could be demonstrated, and were compared with the findings on plain films. Especially skeletal dysplasias with abundant presence of cartilage were well visible. The newborn with trisomies showed normal hip joints. In the authors' opinion, all newborns with skeletal dysplasias should be investigated by hip sonography, in addition to skeletal radiography

Relative Skeletal Muscle Mass Is Associated with Development of Metabolic Syndrome

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Byung Sam Park

2013-12-01

Full Text Available BackgroundVisceral adiposity is related to insulin resistance. Skeletal muscle plays a central role in insulin-mediated glucose disposal; however, little is known about the association between muscle mass and metabolic syndrome (MS. This study is to clarify the clinical role of skeletal muscle mass in development of MS.MethodsA total of 1,042 subjects were enrolled. Subjects with prior MS and chronic diseases were excluded. After 24 months, development of MS was assessed using NCEP-ATP III criteria. Skeletal muscle mass (SMM; kg, body fat mass (BFM; kg, and visceral fat area (VFA; cm2 were obtained from bioelectrical analysis. Then, the following values were calculated as follows: percent of SMM (SMM%; %: SMM (kg/weight (kg, skeletal muscle index (SMI; kg/m2: SMM (kg/height (m2, skeletal muscle to body fat ratio (MFR: SMM (kg/BFM (kg, and skeletal muscle to visceral fat ratio (SVR; kg/cm2: SMM (kg/VFA (cm2.ResultsAmong 838 subjects, 88 (10.5% were newly diagnosed with MS. Development of MS increased according to increasing quintiles of BMI, SMM, VFA, and SMI, but was negatively associated with SMM%, MFR, and SVR. VFA was positively associated with high waist circumference (WC, high blood pressure (BP, dysglycemia, and high triglyceride (TG. In contrast, MFR was negatively associated with high WC, high BP, dysglycemia, and high TG. SVR was negatively associated with all components of MS.ConclusionRelative SMM ratio to body composition, rather than absolute mass, may play a critical role in development of MS and could be used as a strong predictor.

FXIIIA and TGF-beta over-expression produces normal musculo-skeletal phenotype in TG2-/- mice.

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Tarantino, U; Oliva, F; Taurisano, G; Orlandi, A; Pietroni, V; Candi, E; Melino, G; Maffulli, N

2009-04-01

Transglutaminase (TGs) enzymes and proteins crosslinking have for long time been implicated in the formation of hard tissue development, matrix maturation and mineralization. Among the TGs family members, in the context of connective tissue formation, TG2 and Factor XIII are expressed in cartilage by hypertrophic chondrocytes. Here, we analyse the morphological consequences of TG2 deficiency, during the development of skeletal elements. When TG2 is absent, there are not gross abnormalities in the development of the skeletal system, probably from compensatory mechanisms resulting in increased expression of FXIIIA and TGF-beta 1. In vivo other TGs may be involved in promoting chondrocytes and osteoblast differentiation and matrix mineralisation.

Skeletal MR imaging: Correlation with skeletal scintigraphy

International Nuclear Information System (INIS)

Colletti, P.M.; Raval, J.K.; Ford, P.V.; Benson, R.C.; Kerr, R.M.; Boswell, W.D.; Siegel, M.E.; Ralls, P.W.

1987-01-01

Skeletal MR images bone marrow while skeletal scintigraphy uses bone metabolism to demonstrate abnormalities. The purpose of this paper is to correlate these MR and scintigraphic findings. T1 and T2 MR images at 0.5 T were correlated with planar bone scintigraphy (RN) using Tc-99m MDP in 56 patients. Of 23 cases with suspected spinal metastases, 19 were positive by MR imaging, 16 by RN. Individual lesions were shown better by MR imaging in five and by RN in two. These two cases had scoliosis, a potential difficulty with MR imaging. In 14 cases of suspected avascular necrosis (AVN), MR imaging was positive in 13 while RN was positive in ten. One negative case by RN had bilateral AVN by MR imaging. Four skull lesions shown easily by RN were seen only in retrospect on MR images. MR imaging is advantageous in evaluating bones with predominant marrow such as vertebrae or the femoral head, while RN is superior in areas primarily composed of cortical bone such as the skull

Thyroid Hormone Receptor α Mutation Causes a Severe and Thyroxine-Resistant Skeletal Dysplasia in Female Mice

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Bassett, J. H. Duncan; Boyde, Alan; Zikmund, Tomas; Evans, Holly; Croucher, Peter I.; Zhu, Xuguang; Park, Jeong Won

2014-01-01

A new genetic disorder has been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio and variable degrees of intellectual deficit and constipation but exhibit a consistently severe skeletal dysplasia. In an attempt to improve developmental delay and alleviate symptoms of hypothyroidism, patients are receiving varying doses and durations of T4 treatment, but responses have been inconsistent so far. Thra1PV/+ mice express a similar potent dominant-negative mutant TRα1 to affected individuals, and thus represent an excellent disease model. We hypothesized that Thra1PV/+ mice could be used to predict the skeletal outcome of human THRA mutations and determine whether prolonged treatment with a supraphysiological dose of T4 ameliorates the skeletal abnormalities. Adult female Thra1PV/+ mice had short stature, grossly abnormal bone morphology but normal bone strength despite high bone mass. Although T4 treatment suppressed TSH secretion, it had no effect on skeletal maturation, linear growth, or bone mineralization, thus demonstrating profound tissue resistance to thyroid hormone. Despite this, prolonged T4 treatment abnormally increased bone stiffness and strength, suggesting the potential for detrimental consequences in the long term. Our studies establish that TRα1 has an essential role in the developing and adult skeleton and predict that patients with different THRA mutations will display variable responses to T4 treatment, which depend on the severity of the causative mutation. PMID:24914936

Growth of Limb Muscle is Dependent on Skeletal-Derived Indian Hedgehog

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Bren-Mattison, Yvette; Hausburg, Melissa; Olwin, Bradley B.

2011-01-01

During embryogenesis, muscle and bone develop in close temporal and spatial proximity. We show that Indian Hedgehog, a bone-derived signaling molecule, participates in growth of skeletal muscle. In Ihh−/− embryos, skeletal muscle development appears abnormal at embryonic day 14.5 and at later ages through embryonic day 20.5, dramatic losses of hindlimb muscle occur. To further examine the role of Ihh in myogenesis, we manipulated Ihh expression in the developing chick hindlimb. Reduction of Ihh in chicken embryo hindlimbs reduced skeletal muscle mass similar to that seen in Ihh−/− mouse embryos. The reduction in muscle mass appears to be a direct effect of Ihh since ectopic expression of Ihh by RCAS retroviral infection of chicken embryo hindlimbs restores muscle mass. These effects are independent of bone length, and occur when Shh is not expressed, suggesting Ihh acts directly on fetal myoblasts to regulate secondary myogenesis. Loss of muscle mass in Ihh null mouse embryos is accompanied by a dramatic increase in myoblast apoptosis accompanied by a loss of p21 protein. Our data suggest that Ihh promotes fetal myoblast survival during their differentiation into secondary myofibers by maintaining p21 protein levels. PMID:21683695

Skeletal and reticuloendothelial imaging in osteopetrosis: case report

International Nuclear Information System (INIS)

Park, H.M.; Lambertus, J.

1977-01-01

Skeletal and reticuloendothelial images, using Tc-99m HEDP and Tc-99m sulfur colloid, respectively, were obtained from two adult patients with osteopetrosis. Skeletal images demonstrated increased activity in multiple fracture sites, in mandibular osteomyelitis, in ends of splayed long bones adjacent to joints, and in the epiphyseal ends of short tubular bones. The remainder of the skeleton involved with osteopetrosis showed no generalized increased uptake of Tc-99m HEDP. These findings indicate that metabolic activity in this disease is abnormally increased in the usual areas of bone growth but appears normal elsewhere. Reticuloendothelial imaging showed an almost total lack of activity in the axial and peripheral skeletal marrow space. Anemia, however, was only moderate in these patients. Skeletal scintigraphy may be useful to evaluate the presence and extent of the frequent complications of osteopetrosis, namely fractures and osteomyelitis

Expression of Pannexin 1 and Pannexin 3 during skeletal muscle development, regeneration, and Duchenne muscular dystrophy.

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Pham, Tammy L; St-Pierre, Marie-Eve; Ravel-Chapuis, Aymeric; Parks, Tara E C; Langlois, Stéphanie; Penuela, Silvia; Jasmin, Bernard J; Cowan, Kyle N

2018-05-10

Pannexin 1 (Panx1) and Pannexin 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well as myoblast proliferation and differentiation in vitro. However, their expression patterns during skeletal muscle development and regeneration had yet to be investigated. Here, we show that Panx1 levels increase during skeletal muscle development becoming highly expressed together with Panx3 in adult skeletal muscle. In adult mice, Panx1 and Panx3 were differentially expressed in fast- and slow-twitch muscles. We also report that Panx1/PANX1 and Panx3/PANX3 are co-expressed in mouse and human satellite cells, which play crucial roles in skeletal muscle regeneration. Interestingly, Panx1 and Panx3 levels were modulated in muscle degeneration/regeneration, similar to the pattern seen during skeletal muscle development. As Duchenne muscular dystrophy is characterized by skeletal muscle degeneration and impaired regeneration, we next used mild and severe mouse models of this disease and found a significant dysregulation of Panx1 and Panx3 levels in dystrophic skeletal muscles. Together, our results are the first demonstration that Panx1 and Panx3 are differentially expressed amongst skeletal muscle types with their levels being highly modulated during skeletal muscle development, regeneration, and dystrophy. These findings suggest that Panx1 and Panx3 channels may play important and distinct roles in healthy and diseased skeletal muscles. © 2018 Wiley Periodicals, Inc.

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population

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Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and l...

Fetal chromosome abnormalities and congenital malformations: an ...

African Journals Online (AJOL)

The results also showed that Multiple congenital anomalies (MCA) represented among 42.2%, congenital malformation of CNS represents 26.6%, congenital malformation of the skeletal system 20%, congenital polycystic kidney 8.8% and pyloric stenosis in 2.2%. Among the 21 women with abnormal karyotype of amniotic ...

Rickets and/or scurvy-like skeletal lesions in Cooley's anemia

International Nuclear Information System (INIS)

Orzincolo, C.; De Sanctis, V.; Vullo, C.; Castaldi, G.; Scutellari, P.N.; Ciaccio, C.

1990-01-01

Recently, a new type of skeletal lesions has been described in Cooley's anemia as a possible complication secondary to therapy. In 12 children affected with thalassemia major, who received an intensive transfusional regiment combined with continuous iron chelation therapy (desferoxamine-B: 50-80 mg/kg/day), some radiological abnormalities of the long bones were observed similar to those described in rickets and scurvy. These rickets and/or scurvy-like lesions had never been reported before the introduction of high-dose desferoxamine therapy. The pathogenesis of these lesions is uncertain, but the toxic effect of desferoxamine probably plays an important role in their development. The association of growth retardation and rickets and/or scurvy-like skeletal lesions in Cooley's anemia patients may be used as a valuable clinical criterion in long-term chelation management

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

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Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

2014-08-01

The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

Skeletal Manifestations of Scurvy: A Case Report from Dubai

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Shahryar Noordin

2012-01-01

Full Text Available Introduction. Nutritional deficiencies are rarely reported in developed countries. We report a child of Pakistani origin brought up in Dubai who developed skeletal manifestations of scurvy due to peculiar dietary habits. Case Presentation. A 4.5 year old boy presented with pain and swelling of multiple joints for three months and inability to walk for two months. Dietary history was significant for exclusive meat intake for the preceding two years. On examination the child’s height and weight were below the 5th percentile for his age. He was pale and tachycardic. There was significant swelling and tenderness over the wrist, knee and ankle joints, along with painful restriction of motion. Basic blood workup was unremarkable except for anemia. However, X-rays showed delayed bone age, severe osteopenia of the long bones, epiphyseal separation, cortical thinning and dense zone of provisional calcification, suggesting a radiological diagnosis of scurvy. The child was started on vitamin C replacement therapy. Over the following two months, the pain and swelling substantially reduced and the child became able to walk. Repeat X-rays showed improvement in the bony abnormalities. Conclusion. Although scurvy is not a very commonly encountered entity in the modern era, inappropriate dietary intake can lead to skeletal abnormalities which may be confused with rickets. A high index of suspicion is thus required for prompt diagnosis of scurvy in patients with bone and joint symptoms.

Skeletal blood flow: implications for bone-scan interpretation

International Nuclear Information System (INIS)

Charkes, N.D.

1980-01-01

The dispersion of the skeleton throughout the body and its complex vascular anatomy require indirect methods for the measurement of skeletal blood flow. The results of one such method, compartmental analysis of skeletal tracer kinetics, are presented. The assumptions underlying the models were tested in animals and found to be in agreement with experimental observations. Based upon the models and the experimental results, inferences concerning bone-scan interpretation can be drawn: decreased cardiac output produces low-contrast (technically poor) scans; decreased skeletal flow produces photon-deficient lesions; increase of cardiac output or of generalized systemic blood flow is undetectable 1 to 2 h after dose; increased local skeletal blood flow results from disturbance of the bone microvasculature and can occur from neurologic (sympatholytic) disorders or in association with focal abnormalities that also incite the formation of reactive bone (e.g., metastasis, fracture, etc.). Mathematical solutions of tracer kinetic data thus become relevant to bone-scan interpretation

Whole Body MR Imaging Versus 99mTC-Methylene Diphosphonate Scintigraphy in Detection of Skeletal Metastases

International Nuclear Information System (INIS)

SALEM, H.T.M.

2009-01-01

The introduction of new chemotherapy protocols, which include both marrow and stem cell transplantation, has increased the demand for accurate and early detection of skeletal metastases, particularly metastases to marrow (Eustace et al., 1997). All existing methods of detection skeletal metastases have limitations. Metastases to bone only become apparent on radiographs after the loss of more than 50% of the bone mineral content at the site of the disease. Although CT allows earlier detection of cortical destruction by imaging in contiguous tomographic slices, its ability to detect early deposits in marrow is limited (Gold et al., 1990). The use of bone scintigraphy in the assessment of skeletal abnormalities is based on increased sensitivity in detecting abnormalities before other diagnostic imaging techniques. The pitfall of bone scintigraphy is its lack of specificity. There must be close correlation of scintigraphic findings with those of other imaging modalities (Nadel et al., 2001). The high spatial resolution and excellent soft-tissue contrast make MR imaging an ideal tool for the detection of osseous lesions. The limited field of view must be considered a major limitation of conventional MR imaging. Furthermore MR imaging approaches were limited by long acquisition times. Development in MR imaging, such as the development of turbo sequences, have led to renewed interest in MR imaging as a potential whole body screening tool (Johnson et al., 1997 and Lauenstein et al., 2004).

Best practices in peri-operative management of patients with skeletal dysplasias.

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White, Klane K; Bompadre, Viviana; Goldberg, Michael J; Bober, Michael B; Cho, Tae-Joon; Hoover-Fong, Julie E; Irving, Melita; Mackenzie, William G; Kamps, Shawn E; Raggio, Cathleen; Redding, Gregory J; Spencer, Samantha S; Savarirayan, Ravi; Theroux, Mary C

2017-10-01

Patients with skeletal dysplasia frequently require surgery. This patient population has an increased risk for peri-operative complications related to the anatomy of their upper airway, abnormalities of tracheal-bronchial morphology and function; deformity of their chest wall; abnormal mobility of their upper cervical spine; and associated issues with general health and body habitus. Utilizing evidence analysis and expert opinion, this study aims to describe best practices regarding the peri-operative management of patients with skeletal dysplasia. A panel of 13 multidisciplinary international experts participated in a Delphi process that included a thorough literature review; a list of 22 possible care recommendations; two rounds of anonymous voting; and a face to face meeting. Those recommendations with more than 80% agreement were considered as consensual. Consensus was reached to support 19 recommendations for best pre-operative management of patients with skeletal dysplasia. These recommendations include pre-operative pulmonary, polysomnography; cardiac, and neurological evaluations; imaging of the cervical spine; and anesthetic management of patients with a difficult airway for intubation and extubation. The goals of this consensus based best practice guideline are to provide a minimum of standardized care, reduce perioperative complications, and improve clinical outcomes for patients with skeletal dysplasia. © 2017 Wiley Periodicals, Inc.

Prenatal diagnosis of sirenomelia by two-dimensional and three-dimensional skeletal imaging ultrasound.

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Liu, Rong; Chen, Xin-lin; Yang, Xiao-hong; Ma, Hui-jing

2015-12-01

This study sought to evaluate the contribution of two-dimensional ultrasound (2D-US) and three-dimensional skeletal imaging ultrasound (3D-SUIS) in the prenatal diagnosis of sirenomelia. Between September 2010 and April 2014, a prospective study was conducted in a single referral center using 3D-SUIS performed after 2D-US in 10 cases of sirenomelia. Diagnostic accuracy and detailed findings were compared with postnatal three-dimensional helical computed tomography (3D-HCT), radiological findings and autopsy. Pregnancy was terminated in all 10 sirenomelia cases, including 9 singletons and 1 conjoined twin pregnancy, for a total of 5 males and 5 females. These cases of sirenomelia were determined by autopsy and/or chromosomal examination. Initial 2D-US showed that there were 10 cases of oligohydramnios, bilateral renal agenesis, bladder agenesis, single umbilical artery, fusion of the lower limbs and spinal abnormalities; 8 cases of dipus or monopus; 2 cases of apus; and 8 cases of cardiac abnormalities. Subsequent 3D-SUIS showed that there were 9 cases of scoliosis, 10 cases of sacrococcygeal vertebra dysplasia, 3 cases of hemivertebra, 1 case of vertebral fusion, 3 cases of spina bifida, and 5 cases of rib abnormalities. 3D-SUIS identified significantly more skeletal abnormalities than did 2D-US, and its accuracy was 79.5% (70/88) compared with 3D-HCT and radiography. 3D-SUIS seems to be a useful complementary method to 2D-US and may improve the accuracy of identifying prenatal skeletal abnormalities related to sirenomelia.

Study on the abnormalities in sperm and gene mutation induced by retention of 147Pm in testis

International Nuclear Information System (INIS)

Zhu Shoupeng; Lun Mingyue; Yang Shuqin

1990-05-01

The purpose of the present study is to ascertain 147 Pm retention in testis and its radiogenotoxicological effects of gene mutation through varying radioactivities of internal exposure. Especially the accumulation of 147 Pm in testis induces the dominant lethal, dominant skeletal mutation and abnormalities in sperm. Studies indicated that the cumulative absorption dose in testis increases as the internal exposure of 147 Pm increases. The internal exposure of 147 Pm can destroy the genetic materials and raise the rates of dominant lethal and dominant mutation of skeletal abnormalities in the offspring. The relationship between the rate of dominant skeletal mutation (B) and accumulated radioactivities of 147 Pm (D) in testis can be described by a linear equation that is B 20.68 + 35.48 D. The relationship between abnormalities of the sperm and the cumulative dose from 147 Pm in testis can be expressed by the following equation: S = 10.8705 D 0.5224 + 3.1768

Global pathway analysis using DNA microarrays in skeletal muscle of women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Skov, Vibe

2007-01-01

(study 1), to investigate whether pioglitazone therapy could reverse abnormalities in the transcriptional profile of muscle associated with insulin resistance in skeletal muscle of obese PCOS patients (study 2), and to develop a microarray platform for global gene expression profiling (study 3). In study...... comparable to other commercial and custom made microarrays and is a cost-effective alternative especially in larger epidemiological studies....

Skeletal coccidioidomycosis: imaging findings in 19 patients

International Nuclear Information System (INIS)

Zeppa, M.A.; Greenspan, A.; McGahan, J.P.; Laorr, A.; Steinbach, L.S.

1996-01-01

The objective of this study was to describe the distribution and radiologic appearance of skeletal coccidioidomycosis in 19 documented cases. Medical records of 19 patients with clinically confirmed skeletal occidioidomycosis were retrospectively reviewed. The patients were studied with plain radiography, skeletal scintigraphy and MRI. Multiple lesions were seen in 11 of 19 patients (58%). Of a total of 46 lesions, 27 (59%) were described as punched-out lytic, 10 (22%) as permeative/destructive, and 9 (17%) as involving a joint and/or disk space. Lesions were identified in almost every bone (with the exception of the facial bones, ulna, carpus, and fibula) and were most commonly found in the axial skeleton (20 of 46; 43%). Plain radiographs are effective in the initial evaluation of bones and joints, scintigraphic studies can identify disseminated disease, and CT and MRI are effective in determining soft tissue involvement and spinal abnormalities. (orig./MG)

Insights into skeletal muscle development and applications in regenerative medicine.

Science.gov (United States)

Tran, T; Andersen, R; Sherman, S P; Pyle, A D

2013-01-01

Embryonic and postnatal development of skeletal muscle entails highly regulated processes whose complexity continues to be deconstructed. One key stage of development is the satellite cell, whose niche is composed of multiple cell types that eventually contribute to terminally differentiated myotubes. Understanding these developmental processes will ultimately facilitate treatments of myopathies such as Duchenne muscular dystrophy (DMD), a disease characterized by compromised cell membrane structure, resulting in severe muscle wasting. One theoretical approach is to use pluripotent stem cells in a therapeutic setting to help replace degenerated muscle tissue. This chapter discusses key myogenic developmental stages and their regulatory pathways; artificial myogenic induction in pluripotent stem cells; advantages and disadvantages of DMD animal models; and therapeutic approaches targeting DMD. Furthermore, skeletal muscle serves as an excellent paradigm for understanding general cell fate decisions throughout development. Copyright © 2013 Elsevier Inc. All rights reserved.

Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system.

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Saitoh, Yurika; Ohno, Nobuhiko; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

2017-12-01

We previously demonstrated that a membrane skeletal molecular complex, 4.1G-membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice. When suspended by the tail, aged 4.1G -/- mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G -/- mice was slower than that in wild-type mice. Using electron microscopy, 4.1G -/- mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G -/- sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.

Transcriptional profiling identifies differentially expressed genes in developing turkey skeletal muscle

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Velleman Sandra G

2011-03-01

Full Text Available Abstract Background Skeletal muscle growth and development from embryo to adult consists of a series of carefully regulated changes in gene expression. Understanding these developmental changes in agriculturally important species is essential to the production of high quality meat products. For example, consumer demand for lean, inexpensive meat products has driven the turkey industry to unprecedented production through intensive genetic selection. However, achievements of increased body weight and muscle mass have been countered by an increased incidence of myopathies and meat quality defects. In a previous study, we developed and validated a turkey skeletal muscle-specific microarray as a tool for functional genomics studies. The goals of the current study were to utilize this microarray to elucidate functional pathways of genes responsible for key events in turkey skeletal muscle development and to compare differences in gene expression between two genetic lines of turkeys. To achieve these goals, skeletal muscle samples were collected at three critical stages in muscle development: 18d embryo (hyperplasia, 1d post-hatch (shift from myoblast-mediated growth to satellite cell-modulated growth by hypertrophy, and 16wk (market age from two genetic lines: a randombred control line (RBC2 maintained without selection pressure, and a line (F selected from the RBC2 line for increased 16wk body weight. Array hybridizations were performed in two experiments: Experiment 1 directly compared the developmental stages within genetic line, while Experiment 2 directly compared the two lines within each developmental stage. Results A total of 3474 genes were differentially expressed (false discovery rate; FDR Conclusions The current study identified gene pathways and uncovered novel genes important in turkey muscle growth and development. Future experiments will focus further on several of these candidate genes and the expression and mechanism of action of

Endochondral gigantism: a newly recognized skeletal dysplasia with pre- and postnatal overgrowth and endocrine abnormalities.

Science.gov (United States)

Schmidt, Heinrich; Kammer, Birgit; Grasser, Monika; Enders, Angelika; Rost, Imma; Kiess, Wieland

2007-08-15

We report on a 3-year-old male, born at 34 weeks of gestation, with marked pre- and postnatal overgrowth, birth weight of 6,600 g, length of 61 cm, and head circumference of 38.5 cm. A striking phenotype was recorded at birth, which became more evident during the follow-up period. He had macrobrachycephaly, facial abnormalities, small thoracic cage, long trunk, deformed spine, rhizomelia, large hands and feets, absent subcutaneous fat, small umbilical hernia, inguinal hernias, and large joints with mild contractures. Hypoglycemic episodes and obstructive apnea complicated the neonatal period. During follow-up, overgrowth continued with a height of 146 cm (+11.65 SDS) and a weight of 39 kg (BMI 18.3 kg/m(2)) at 3.5 years. Endocrinological work-up disclosed extremely low levels of growth hormone, insulin-like growth factors, and insulin. What makes our patient unique is the association of marked prenatal overgrowth; unusual phenotype; skeletal dysplasia caused by accelerated endochondral ossification resulting in cartilage hyperplasia of the skull base and spine, and postnatal gigantism; and complete absence of subcutaneous fat. Other well-known overgrowth syndromes were excluded. We hypothesize that autocrine/paracrine growth factors could be the cause of excessive endochondral ossification. Alternately, activating mutations in transcription factors involved in both growth and endocrine/metabolic homeostasis could be responsible for this unusual phenotype. (c) 2007 Wiley-Liss, Inc.

Study on the abnormalities in sperm and gene mutation induced by retention of {sup 147}Pm in testis

Energy Technology Data Exchange (ETDEWEB)

Shoupeng, Zhu; Mingyue, Lun; Shuqin, Yang [Suzhou Medical Coll., JS (China)

1990-05-01

The purpose of the present study is to ascertain {sup 147}Pm retention in testis and its radiogenotoxicological effects of gene mutation through varying radioactivities of internal exposure. Especially the accumulation of {sup 147}Pm in testis induces the dominant lethal, dominant skeletal mutation and abnormalities in sperm. Studies indicated that the cumulative absorption dose in testis increases as the internal exposure of {sup 147}Pm increases. The internal exposure of {sup 147}Pm can destroy the genetic materials and raise the rates of dominant lethal and dominant mutation of skeletal abnormalities in the offspring. The relationship between the rate of dominant skeletal mutation (B) and accumulated radioactivities of {sup 147}Pm (D) in testis can be described by a linear equation that is B 20.68 + 35.48 D. The relationship between abnormalities of the sperm and the cumulative dose from {sup 147}Pm in testis can be expressed by the following equation: S = 10.8705 D{sup 0.5224} + 3.1768.

Fibulin-4 E57K Knock-in Mice Recapitulate Cutaneous, Vascular and Skeletal Defects of Recessive Cutis Laxa 1B with both Elastic Fiber and Collagen Fibril Abnormalities.

Science.gov (United States)

Igoucheva, Olga; Alexeev, Vitali; Halabi, Carmen M; Adams, Sheila M; Stoilov, Ivan; Sasaki, Takako; Arita, Machiko; Donahue, Adele; Mecham, Robert P; Birk, David E; Chu, Mon-Li

2015-08-28

Fibulin-4 is an extracellular matrix protein essential for elastic fiber formation. Frameshift and missense mutations in the fibulin-4 gene (EFEMP2/FBLN4) cause autosomal recessive cutis laxa (ARCL) 1B, characterized by loose skin, aortic aneurysm, arterial tortuosity, lung emphysema, and skeletal abnormalities. Homozygous missense mutations in FBLN4 are a prevalent cause of ARCL 1B. Here we generated a knock-in mouse strain bearing a recurrent fibulin-4 E57K homozygous missense mutation. The mutant mice survived into adulthood and displayed abnormalities in multiple organ systems, including loose skin, bent forelimb, aortic aneurysm, tortuous artery, and pulmonary emphysema. Biochemical studies of dermal fibroblasts showed that fibulin-4 E57K mutant protein was produced but was prone to dimer formation and inefficiently secreted, thereby triggering an endoplasmic reticulum stress response. Immunohistochemistry detected a low level of fibulin-4 E57K protein in the knock-in skin along with altered expression of selected elastic fiber components. Processing of a precursor to mature lysyl oxidase, an enzyme involved in cross-linking of elastin and collagen, was compromised. The knock-in skin had a reduced level of desmosine, an elastin-specific cross-link compound, and ultrastructurally abnormal elastic fibers. Surprisingly, structurally aberrant collagen fibrils and altered organization into fibers were characteristics of the knock-in dermis and forelimb tendons. Type I collagen extracted from the knock-in skin had decreased amounts of covalent intermolecular cross-links, which could contribute to the collagen fibril abnormalities. Our studies provide the first evidence that fibulin-4 plays a role in regulating collagen fibril assembly and offer a preclinical platform for developing treatments for ARCL 1B. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Pseudoachondroplasia in a child: The role of anthropometric measurements and skeletal imaging in differential diagnosis

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Radwa Gamal, MSc

2017-03-01

Full Text Available Pseudoachondroplasia is a rare osteochondrodysplasia characterized by disproportionate short stature and limb deformity. Diagnostic accuracy is based on a detailed evaluation of the radioclinical features. We report a boy with pseudoachondroplasia. We aim to underscore why is accurate delineation of the pattern of radioclinical skeletal abnormalities in pseudoachondroplasia a weighty part of diagnosis. Furthermore, we aim to highlight the main clinical and skeletal imaging features of skeletal dysplasias that overlap with pseudoachondroplasia using clinical cases evaluated in our institution. The findings affirm that anthropometric measurements and skeletal radiography are important contributors to the differential diagnosis and classification of disproportionate growth.

PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

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Leone Teresa C

2005-01-01

Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

Directory of Open Access Journals (Sweden)

Teresa C Leone

2005-04-01

Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

Weight-adjusted lean body mass and calf circumference are protective against obesity-associated insulin resistance and metabolic abnormalities.

Science.gov (United States)

Takamura, Toshinari; Kita, Yuki; Nakagen, Masatoshi; Sakurai, Masaru; Isobe, Yuki; Takeshita, Yumie; Kawai, Kohzo; Urabe, Takeshi; Kaneko, Shuichi

2017-07-01

To test the hypothesis that preserved muscle mass is protective against obesity-associated insulin resistance and metabolic abnormalities, we analyzed the relationship of lean body mass and computed tomography-assessed sectional areas of specific skeletal muscles with insulin resistance and metabolic abnormalities in a healthy cohort. A total of 195 subjects without diabetes who had completed a medical examination were included in this study. Various anthropometric indices such as circumferences of the arm, waist, hip, thigh, and calf were measured. Body composition (fat and lean body mass) was determined by bioelectrical impedance analysis. Sectional areas of specific skeletal muscles (iliopsoas, erector spinae, gluteus, femoris, and rectus abdominis muscles) were measured using computed tomography. Fat and lean body mass were significantly correlated with metabolic abnormalities and insulin resistance indices. When adjusted by weight, relationships of fat and lean body mass with metabolic parameters were mirror images of each other. The weight-adjusted lean body mass negatively correlated with systolic and diastolic blood pressures; fasting plasma glucose, HbA1c, alanine aminotransferase, and triglyceride, and insulin levels; and hepatic insulin resistance indices, and positively correlated with HDL-cholesterol levels and muscle insulin sensitivity indices. Compared with weight-adjusted lean body mass, weight-adjusted sectional areas of specific skeletal muscles showed similar, but not as strong, correlations with metabolic parameters. Among anthropometric measures, the calf circumference best reflected lean body mass, and weight-adjusted calf circumference negatively correlated with metabolic abnormalities and insulin resistance indices. Weight-adjusted lean body mass and skeletal muscle area are protective against weight-associated insulin resistance and metabolic abnormalities. The calf circumference reflects lean body mass and may be useful as a protective

The expression of myosin genes in developing skeletal muscle in the mouse embryo

International Nuclear Information System (INIS)

Lyons, G.E.; Ontell, M.; Cox, R.; Sassoon, D.; Buckingham, M.

1990-01-01

Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta-cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and acculumation

Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

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Yang, Lin; Xia, Liangping; Wang, Yan; He, Shasha; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Hong, Shaodong; Chen, Yong

2017-09-06

The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P system (P skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

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Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

2015-01-01

Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean Population.

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Eun Jin Woo

Full Text Available Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements

OpenAIRE

Akiyama, Ryutaro; Kawakami, Hiroko; Wong, Julia; Oishi, Isao; Nishinakamura, Ryuichi; Kawakami, Yasuhiko

2015-01-01

The limb skeletal elements that have unique morphology and distinct locations are developed from limb progenitors, derived from the lateral plate mesoderm. These skeletal elements arise during limb development. In this study, we show genetic evidence that function of Sall4 is essential prior to limb outgrowth for development of the anterior-proximal skeletal elements. Furthermore, genetic interaction between Sall4 and Gli3 is upstream of establishing Shh (Sonic hedgehog) expression, and there...

Weight-adjusted lean body mass and calf circumference are protective against obesity-associated insulin resistance and metabolic abnormalities

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Toshinari Takamura

2017-07-01

Interpretation: Weight-adjusted lean body mass and skeletal muscle area are protective against weight-associated insulin resistance and metabolic abnormalities. The calf circumference reflects lean body mass and may be useful as a protective marker against obesity-associated metabolic abnormalities.

Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements.

Science.gov (United States)

Akiyama, Ryutaro; Kawakami, Hiroko; Wong, Julia; Oishi, Isao; Nishinakamura, Ryuichi; Kawakami, Yasuhiko

2015-04-21

Limb skeletal elements originate from the limb progenitor cells, which undergo expansion and patterning to develop each skeletal element. Posterior-distal skeletal elements, such as the ulna/fibula and posterior digits develop in a Sonic hedgehog (Shh)-dependent manner. However, it is poorly understood how anterior-proximal elements, such as the humerus/femur, the radius/tibia and the anterior digits, are developed. Here we show that the zinc finger factors Sall4 and Gli3 cooperate for proper development of the anterior-proximal skeletal elements and also function upstream of Shh-dependent posterior skeletal element development. Conditional inactivation of Sall4 in the mesoderm before limb outgrowth caused severe defects in the anterior-proximal skeletal elements in the hindlimb. We found that Gli3 expression is reduced in Sall4 mutant hindlimbs, but not in forelimbs. This reduction caused posteriorization of nascent hindlimb buds, which is correlated with a loss of anterior digits. In proximal development, Sall4 integrates Gli3 and the Plzf-Hox system, in addition to proliferative expansion of cells in the mesenchymal core of nascent hindlimb buds. Whereas forelimbs developed normally in Sall4 mutants, further genetic analysis identified that the Sall4-Gli3 system is a common regulator of the early limb progenitor cells in both forelimbs and hindlimbs. The Sall4-Gli3 system also functions upstream of the Shh-expressing ZPA and the Fgf8-expressing AER in fore- and hindlimbs. Therefore, our study identified a critical role of the Sall4-Gli3 system at the early steps of limb development for proper development of the appendicular skeletal elements.

MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

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Shi, Lei; Zhou, Bo; Li, Pinghua; Schinckel, Allan P; Liang, Tingting; Wang, Han; Li, Huizhi; Fu, Lingling; Chu, Qingpo; Huang, Ruihua

2015-09-01

MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development. In a previous study we observed that miR-128 was highly expressed in skeletal muscle. However, its function in regulating skeletal muscle development is not clear. Our hypothesis was that miR-128 is involved in the regulation of the proliferation and differentiation of skeletal myoblasts. In this study, through bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding domain sequence (CDS) region, resulting in down-regulating of myostatin post-transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12 myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had completely opposite effects. In addition, ectopic miR-128 regulated the expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and 7. Furthermore, an inverse relationship was found between the expression of miR-128 and MSTN protein expression in vivo and in vitro. Taken together, these results reveal that there is a novel pathway in skeletal muscle development in which miR-128 regulates myostatin at CDS region to inhibit proliferation but promote differentiation of myoblast cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

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Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

2006-12-01

Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P intrauterine growth restriction

Osseous abnormalities and CT findings in stueve-wiedemann-syndrome (SWS)

International Nuclear Information System (INIS)

Langer, R.; Al-Gazali, L.; Haas, D.; Raupp, P.; Varady, E.

2004-01-01

Purpose: analysis of typical conventional radiological and CT findings in our group of patients with the rare skeletal dysplasia Stueve-Wiedemann-Syndrome (SWS) and comparison with published data. Materials and methods: in 16 newborns with clinically dysmorphic features, dwarfism, and bowed limbs, radiographs of the chest and skeleton were obtained for classification of the underlying skeletal dysplasia. For the first time, computed tomography was performed for further investigation of midface hypoplasia. The early diagnosis of SWS could be made by correlation of the radiological and clinical findings. For evaluation of progression, follow-up radiological examinations of the skeleton were performed in four children surviving infancy. Results: clinically, the newborns with SWS showed dwarfisms, midface hypoplasia, bowed extremities with contractures and had severe problems with respiration, feeding, and swallowing as well as episodes of hyperthermia. Skeletal radiographs revealed bowing of the long tubular bones, most pronounced at the lower extremities. Additional findings were internal triangular cortical diaphyseal thickening at the concave side of the bowing, wide metaphyses with abnormal trabecular pattern and radiolucencies. Four patients survived infancy. Clinically, they suffered from recurrent aspiration pneumonia and recurrent episodes of hyperthermia as well as form cutaneous and mucosal infections. The follow-up radiographs showed progressive bowing of the long tubular bones as well as progressive metaphyseal decalcification. Conclusions: skeletal abnormalities in SWS are so characteristic that an early post partum diagnosis can be made. However, a close cooperation between radiologists, clinicians, and geneticists is required for correlation of clinical and radiological findings. The few cases that survive infancy have progressing orthopaedic problems. (orig.) [de

HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy

Science.gov (United States)

Smeets, Cleo J. L. M.; Franklin, Sophie A.; Bondulich, Marie K.; Jolinon, Nelly; Muller, Thomas; Ahmed, Mhoriam; Dick, James R. T.; Piotrowska, Izabela; Greensmith, Linda; Smolenski, Ryszard T.; Bates, Gillian P.

2015-01-01

Skeletal muscle remodelling and contractile dysfunction occur through both acute and chronic disease processes. These include the accumulation of insoluble aggregates of misfolded amyloid proteins that is a pathological feature of Huntington’s disease (HD). While HD has been described primarily as a neurological disease, HD patients’ exhibit pronounced skeletal muscle atrophy. Given that huntingtin is a ubiquitously expressed protein, skeletal muscle fibres may be at risk of a cell autonomous HD-related dysfunction. However the mechanism leading to skeletal muscle abnormalities in the clinical and pre-clinical HD settings remains unknown. To unravel this mechanism, we employed the R6/2 transgenic and HdhQ150 knock-in mouse models of HD. We found that symptomatic animals developed a progressive impairment of the contractile characteristics of the hind limb muscles tibialis anterior (TA) and extensor digitorum longus (EDL), accompanied by a significant loss of motor units in the EDL. In symptomatic animals, these pronounced functional changes were accompanied by an aberrant deregulation of contractile protein transcripts and their up-stream transcriptional regulators. In addition, HD mouse models develop a significant reduction in muscle force, possibly as a result of a deterioration in energy metabolism and decreased oxidation that is accompanied by the re-expression of the HDAC4-DACH2-myogenin axis. These results show that muscle dysfunction is a key pathological feature of HD. PMID:25748626

Orthognathic Surgery for the Correction of Severe Skeletal Class III Malocclusion.

Science.gov (United States)

Kafle, D; Upadhayaya, C; Chaurasia, N; Agarwal, A

2016-01-01

Skeletal Malocclusions results from the abnormal position of maxilla and mandible in relation with cranial base. These types of malocclusion are commonly treated by orthodontic teeth movement known as camouflage orthodontics. However severe skeletal malocclusions cannot be treated by orthodontics alone. Such cases need surgical intervention to align the position of the jaw along with orthodontic correction. This procedure is commonly known as Orthognathic Surgery. Orthognathic Surgery dates back to early eighteenth century but became popular on mid twentieth century. Though the prevalence of skeletal malocclusion is more than 1% the treatment facility was not available in Nepal till 2012. Here we present a case of Skeletal Class III malocclusion treated at Dhulikhel Hospital, Kathmandu University Hospital. For this case, double jaw surgery was performed by le-Fort I osteotomy and Bilateral Sagital Split Osteotomy. Orthognathic surgery has been routinely performed at this centre since then.

Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

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Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

2017-01-01

Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

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Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: population affinities and pathological abnormalities.

Science.gov (United States)

Jacob, T; Indriati, E; Soejono, R P; Hsü, K; Frayer, D W; Eckhardt, R B; Kuperavage, A J; Thorne, A; Henneberg, M

2006-09-05

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose that LB1 is drawn from an earlier pygmy H. sapiens population but individually shows signs of a developmental abnormality, including microcephaly. Additional mandibular and postcranial remains from the site share small body size but not microcephaly.

[Amyoplasia congenita: a serious congenital abnormality with a relatively favorable prognosis

NARCIS (Netherlands)

Petru, R.; Verrips, A.; Ravenswaaij-Arts, C.M.A. van

2002-01-01

After an uneventful pregnancy a girl was born with serious joint contractures and several fractures of the long bones. The family history was negative for congenital abnormalities. Based on the distinct clinical presentation the diagnosis was 'amyoplasia', which is a partial aplasia of skeletal

FDG-PET/CT in Skeletal Muscle: Pitfalls and Pathologies.

Science.gov (United States)

Parida, Girish Kumar; Roy, Shambo Guha; Kumar, Rakesh

2017-07-01

FDG-PET/CT is an integral part of modern-day practice of medicine. By detecting increased cellular metabolism, FDG-PET/CT can help us detect infection, inflammatory disorders, or tumors, and also help us in prognostication of patients. However, one of the most important challenges is to correctly differentiate the abnormal uptake that is potentially pathologic from the physiological uptake. So while interpreting a PET/CT, one must be aware of normal biodistribution and different physiological variants of FDG uptake. Skeletal muscles constitute a large part of our body mass and one of the major users of glucose. Naturally, they are often the site of increased FDG uptake in a PET study. We as a nuclear medicine physician must be aware of all the pitfalls of increased skeletal muscle uptake to differentiate between physiological and pathologic causes. In this review, we have discussed the different causes and patterns of physiological FDG uptake in skeletal muscles. This knowledge of normal physiological variants of FDG uptake in the skeletal muscles is essential for differentiating pathologic uptake from the physiological ones. Also, we reviewed the role of FDG-PET/CT in various benign and malignant diseases involving skeletal muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

Science.gov (United States)

Sabharwal, Rasna; Chapleau, Mark W

2014-04-01

New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

Emerging new tools to study and treat muscle pathologies: genetics and molecular mechanisms underlying skeletal muscle development, regeneration, and disease.

Science.gov (United States)

Crist, Colin

2017-01-01

Skeletal muscle is the most abundant tissue in our body, is responsible for generating the force required for movement, and is also an important thermogenic organ. Skeletal muscle is an enigmatic tissue because while on the one hand, skeletal muscle regeneration after injury is arguably one of the best-studied stem cell-dependent regenerative processes, on the other hand, skeletal muscle is still subject to many degenerative disorders with few therapeutic options in the clinic. It is important to develop new regenerative medicine-based therapies for skeletal muscle. Future therapeutic strategies should take advantage of rapidly developing technologies enabling the differentiation of skeletal muscle from human pluripotent stem cells, along with precise genome editing, which will go hand in hand with a steady and focused approach to understanding underlying mechanisms of skeletal muscle development, regeneration, and disease. In this review, I focus on highlighting the recent advances that particularly have relied on developmental and molecular biology approaches to understanding muscle development and stem cell function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Skeletal development in Acropora palmata (Lamarck 1816): a scanning electron microscope (SEM) comparison demonstrating similar mechanisms of skeletal extension in axial versus encrusting growth

Science.gov (United States)

Gladfelter, E. H.

2007-12-01

Many Acropora palmata colonies consist of an encrusting basal portion and erect branches. Linear growth of the skeleton results in extension along the substrate (encrusting growth), lengthening of branches (axial growth) and thickening of branches and crust (radial growth). Scanning Electron Microscopy is used to compare the mechanisms of skeletal extension between encrusting growth and axial growth. In encrusting growth, the distal margin of the skeleton lacks corallites (which develop about 1 mm from the edge); in contrast, in axial growth, axial corallites along the branch tip form the distal portion of the skeleton. In both locations, the distal margin of the skeleton consists of a lattice-like structure composed of rods that extend from the body of the skeleton and bars that connect these rods. An actively extending skeleton is characterized by sharply pointed rods and partially developed bars. Distal growth of rods (and formation of bars) is effected by the formation of new sclerodermites. Each sclerodermite begins with the deposition of fusiform crystals (that range in length from 1 to 5 μm). These provide a surface for nucleation and growth of spherulitic tufts, clusters of short (<1 μm long) aragonite needles. The needles that are oriented perpendicular to the axis of the skeletal element (rod or bar), and perpendicular to the overlying calicoblastic epithelium, continue extension to appear on the surface of the skeleton as 10-15 μm wide bundles (of needle tips) called fasciculi. However, some crusts that abut competitors for space have a different morphology of skeletal elements (rods and bars). The distal edge of these crusts terminates in blunt coalescing rods, and bars that are fully formed. Absence of fusiform crystals, lack of sharply pointed rods and bars, and full development of sclerodermites characterize a skeletal region that has ceased, perhaps only temporarily, skeletal extension.

The Effect of Neonatal Gene Therapy on Skeletal Manifestations in Mucopolysaccharidosis VII Dogs after a Decade

Science.gov (United States)

Xing, Elizabeth M.; Knox, Van W.; O'Donnell, Patricia A.; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

2013-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. PMID:23628461

Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.

Science.gov (United States)

Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu; Khademhosseini, Ali

2014-10-01

Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.

Inadequate Dietary Phosphorus Levels Cause Skeletal Anomalies and Alter Osteocalcin Gene Expression in Zebrafish

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Juliana M. Costa

2018-01-01

Full Text Available Phosphorus (P is an essential mineral for the development and maintenance of the vertebrate skeletal system. Modulation of P levels is believed to influence metabolism and the physiological responses of gene expression. In this study, we investigated the influence of dietary P on skeletal deformities and osteocalcin gene expression in zebrafish (Danio rerio, and sought to determine appropriate levels in a diet. We analyzed a total of 450 zebrafish within 31 days of hatching. Animals were distributed in a completely randomized experimental design that consisted of five replications. After an eight-week experiment, fish were diaphanized to evaluate cranial and spinal bone deformities. Increases in dietary phosphorus were inversely proportional to the occurrence of partial spine fusions, the absence of spine fusions, absence of parallelism between spines, intervertebral spacing, vertebral compression, scoliosis, lordosis, ankylosis, fin caudal insertion, and craniofacial deformities. Additionally, osteocalcin expression was inversely correlated to P levels, suggesting a physiological recovery response for bone mineralization deficiency. Our data showed that dietary P concentration was a critical factor in the occurrence of zebrafish skeletal abnormalities. We concluded that 1.55% P in the diet significantly reduces the appearance of skeletal deformities and favors adequate bone mineralization through the adjustment of osteocalcin expression.

The skeletal deformity in response of dietary phosphorus and calcium level in the Caspian roach (Rutilus rutilus caspicus larvae

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Sohrab Ahmadivand

2013-05-01

Full Text Available Skeletal deformities are a common problem in fish hatcheries and commercial farms that affect growth, development and survival as well as the market value of the final product. Among the nutritional components, phosphorus (P and calcium (Ca are of special interest as they are directly involved in the development and maintenance of the skeletal system. Hence, the present study was carried out to investigate the effects of dietary P and Ca on the skeletal deformity, growth and carcass composition the Caspian roach (Rutilus rutilus caspicus larvae. In this study, six semi-purified diets were formulated. The diets A, B, C, D and E were supplemented with 0.0, 0.4, 0.8, 1.2 and 1.6% available P supplied as a 1:1mixture of NaH2Po4/KH2Po4. These five diets were supplemented with 1% Ca, supplied as CaCo3. Diets F was Ca-free and supplemented with 0.8% available P served as control level of P. Each diet was randomly assigned to triplicate groups of fish, and each group was stocked with 30 larvae and fed three times a day for 60 days. At the end experiment, there was no significant effect of dietary P (0 to 1.6% or Ca (0 or 1% supplementation on growth performance such as weight gain and FCR, carcass moisture, P and Ca. However, a significant difference found between treatments in carcass ash. Analysis of length, height and area of vertebrae in two regions of the vertebral column showed no significant difference between the dietary treatments. The skeletal abnormalities were highest incidence in the Caspian roach fed with a low P. Kyphosis placement of vertebrae was the most frequent abnormality.

Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

2007-01-01

Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism......, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle...... of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative...

SKELETAL MORPHOLOGY OF THE FORELIMB OF MYRMECOPHAGA TRIDACTYLA.

Science.gov (United States)

Sesoko, Natália Ferreira; Rahal, Sheila Canevese; Bortolini, Zara; de Souza, Lívia Pasini; Vulcano, Luiz Carlos; Monteiro, Frederico Ozanan Barros; Teixeira, Carlos Roberto

2015-12-01

Anteater forelimbs are morphologically adapted to obtain food and to provide defense and locomotion. Four species are known, but there are few anatomical studies presenting the morphologic features of each species. The aim of this study was to describe the skeletal morphology of the giant anteater (Myrmecophaga tridactyla) forelimb. Pictures and schematic drawings of six cadavers were created to show the bone morphology. In addition, radiographs and computed tomographs were obtained. The skeletal structure of the forelimb had several notable anatomical features. The scapula had two spines, with apparent differences between infant and adult animals. The humerus had a pectoral ridge, a pectoral tubercle, and a pronounced medial epicondyle that represent the origins of muscles important for fossorial activity. The radius had cranial, lateral, and caudal ridges that became more prominent in older animals, and the distal condyle joint provided enhanced support of the dorsal articulation for the manus. Knowledge of the bone morphology of the forelimb generates a better understanding of giant anteater habits and helps in the diagnosis of skeletal abnormalities and in the routine medical assessment of this species.

Guidelines for genetic skeletal dysplasias for pediatricians

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Sung Yoon Cho

2015-12-01

Full Text Available Skeletal dysplasia (SD is a kind of heterogeneous genetic disorder characterized by abnormal growth, development, differentiation, and maintenance of the bone and cartilage. The patients with SD most likely to be seen by a pediatrician or orthopedic surgeon are those who present with short stature in childhood. Because each category has so many diseases, classification is important to understand SD better. In order to diagnose a SD accurately, clinical and radiographic findings should be evaluated in detail. In addition, genetic diagnosis of SD is important because there are so various SDs with complex phenotypes. To reach an exact diagnosis of SDs, cooperative approach by a clinician, a radiologist and a geneticist is important. This review aims to provide an outline of the diagnostic approach for children with disproportional short stature.

Kabuki Syndrome: a case report with severe ocular abnormalities

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Flavio Mac Cord Medina

2013-10-01

Full Text Available Kabuki syndrome is a rare congenital anomaly, characterized by five fundamental features, the "Pentad of Niikawa": dysmorphic facies, skeletal anomalies, dermatoglyphic abnormalities, mild to moderate mental retardation and postnatal growth deficiency. Patients present characteristic external ocular features, nonetheless they may also present significant ocular abnormalities. We report a case of a brazilian child diagnosed with Kabuki syndrome, addressing the clinical features observed, with emphasis on the ocular manifestations. This case highlights the existence of this syndrome and all of its complexity. The identification of preventable causes of loss of vision underlines the value of detailed ophthalmologic examination of Kabuki syndrome patients.

The principles of the pattern recognition of skeletal structures

International Nuclear Information System (INIS)

Motto, J.A.

2006-01-01

Request of the skeletal system form a lage proportion of plain film radiographic examinations. A sound knowledge of normal radiographic appearances is vital if abnormal patterns are to be recognized.The ABCS, SPACED and SASNOES methods of applying pattern recognition to plain radiographers of bones and joints will be presented in an attempt to make pattern recognition and offer an opinion constitutes role extension of radiographers

Magnetic resonance findings in skeletal muscle tears

International Nuclear Information System (INIS)

De Smet, A.A.

1993-01-01

Magnetic resonance (MR) images of skeletal muscle tears can clearly delineate the severity of muscle injury. Although MR imaging is seldom necessary in patients with acute musle trauma, it can be helpful in deciding on clinical management. The two major MR findings in acute muscle tears are deformity of the muscle and the presence of abnormal signal reflecting hemorrhage and edema. In acute tears, methemoglobin within the extravascular blood causes high-signal areas on both T1- and T2-weighted images. With partial tears, the blood may dissect in a distinctive linear pattern along the muscle bundles and fibers. As healing begins, the muscle signal diminishes, first on the T1-weighted images and then on the T2-weighted images. When there is residual abnormal signal on images obtained more than several months after the injury, it is presumed to represent hemorrhage from recurrent tears. In patients with a questionable history of a remote injury, the clinical presentation may be that of persistent pain or a soft tissue mass. In these cases MR imaging may identify the cause of the pain and can exclude a neoplasm by proving that the mass is a hypertrophied or retracted musle. Thus, MR imaging has a limited, but occasionally important role in selected patients with skeletal muscle tears. (orig.)

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Science.gov (United States)

Vasques, Gabriela A; Funari, Mariana F A; Ferreira, Frederico M; Aza-Carmona, Miriam; Sentchordi-Montané, Lucia; Barraza-García, Jimena; Lerario, Antonio M; Yamamoto, Guilherme L; Naslavsky, Michel S; Duarte, Yeda A O; Bertola, Debora R; Heath, Karen E; Jorge, Alexander A L

2018-02-01

Genetic evaluation has been recognized as an important tool to elucidate the causes of growth disorders. To investigate the cause of short stature and to determine the phenotype of patients with IHH mutations, including the response to recombinant human growth hormone (rhGH) therapy. We studied 17 families with autosomal-dominant short stature by using whole exome sequencing and screened IHH defects in 290 patients with growth disorders. Molecular analyses were performed to evaluate the potential impact of N-terminal IHH variants. We identified 10 pathogenic or possibly pathogenic variants in IHH, an important regulator of endochondral ossification. Molecular analyses revealed a smaller potential energy of mutated IHH molecules. The allele frequency of rare, predicted to be deleterious IHH variants found in short-stature samples (1.6%) was higher than that observed in two control cohorts (0.017% and 0.08%; P IHH variants segregate with short stature in a dominant inheritance pattern. Affected individuals typically manifest mild disproportional short stature with a frequent finding of shortening of the middle phalanx of the fifth finger. None of them have classic features of brachydactyly type A1, which was previously associated with IHH mutations. Five patients heterozygous for IHH variants had a good response to rhGH therapy. The mean change in height standard deviation score in 1 year was 0.6. Our study demonstrated the association of pathogenic variants in IHH with short stature with nonspecific skeletal abnormalities and established a frequent cause of growth disorder, with a preliminary good response to rhGH. Copyright © 2017 Endocrine Society

Unusual facies, arthrogryposis, advanced skeletal maturation and unique bone changes. A new congenital malformation syndrome

Energy Technology Data Exchange (ETDEWEB)

Jequier, S.; Kozlowski, K.

1987-07-01

Two strikingly similar infant siblings showed the following pattern of anomalies: unusual cranio-facial appearance, arthrogryposis, advanced bone age of the hips and unique skeletal X-ray abnormalities. They represent a previously unrecognised, fatal malformation syndrome.

Applying Next Generation Sequencing to Skeletal Development and Disease

OpenAIRE

Bowen, Margot Elizabeth

2013-01-01

Next Generation Sequencing (NGS) technologies have dramatically increased the throughput and lowered the cost of DNA sequencing. In this thesis, I apply these technologies to unresolved questions in skeletal development and disease. Firstly, I use targeted re-sequencing of genomic DNA to identify the genetic cause of the cartilage tumor syndrome, metachondromatosis (MC). I show that the majority of MC patients carry heterozygous loss-of-function mutations in the PTPN11 gene, which encodes a p...

The Ptch1DL mouse: a new model to study lambdoid craniosynostosis and basal cell nevus syndrome associated skeletal defects

OpenAIRE

Feng, Weiguo; Choi, Irene; Clouthier, David E.; Niswander, Lee; Williams, Trevor

2013-01-01

Mouse models provide valuable opportunities for probing the underlying pathology of human birth defects. Employing an ENU-based screen for recessive mutations affecting craniofacial anatomy we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture. Further analysis revealed skeletal defects related to the pathology of basal cell nevus syndrome (BCNS) including de...

Increase in relative skeletal muscle mass over time and its inverse association with metabolic syndrome development: a 7-year retrospective cohort study.

Science.gov (United States)

Kim, Gyuri; Lee, Seung-Eun; Jun, Ji Eun; Lee, You-Bin; Ahn, Jiyeon; Bae, Ji Cheol; Jin, Sang-Man; Hur, Kyu Yeon; Jee, Jae Hwan; Lee, Moon-Kyu; Kim, Jae Hyeon

2018-02-05

Skeletal muscle mass was negatively associated with metabolic syndrome prevalence in previous cross-sectional studies. The aim of this study was to investigate the impact of baseline skeletal muscle mass and changes in skeletal muscle mass over time on the development of metabolic syndrome in a large population-based 7-year cohort study. A total of 14,830 and 11,639 individuals who underwent health examinations at the Health Promotion Center at Samsung Medical Center, Seoul, Korea were included in the analyses of baseline skeletal muscle mass and those changes from baseline over 1 year, respectively. Skeletal muscle mass was estimated by bioelectrical impedance analysis and was presented as a skeletal muscle mass index (SMI), a body weight-adjusted appendicular skeletal muscle mass value. Using Cox regression models, hazard ratio for developing metabolic syndrome associated with SMI values at baseline or changes of SMI over a year was analyzed. During 7 years of follow-up, 20.1% of subjects developed metabolic syndrome. Compared to the lowest sex-specific SMI tertile at baseline, the highest sex-specific SMI tertile showed a significant inverse association with metabolic syndrome risk (adjusted hazard ratio [AHR] = 0.61, 95% confidence interval [CI] 0.54-0.68). Furthermore, compared with SMI changes metabolic syndrome development were 0.87 (95% CI 0.78-0.97) for 0-1% changes and 0.67 (0.56-0.79) for > 1% changes in SMI over 1 year after additionally adjusting for baseline SMI and glycometabolic parameters. An increase in relative skeletal muscle mass over time has a potential preventive effect on developing metabolic syndrome, independently of baseline skeletal muscle mass and glycometabolic parameters.

MicroRNA transcriptome profiles during swine skeletal muscle development

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Sonstegard Tad S

2009-02-01

Full Text Available Abstract Background MicroRNA (miR are a class of small RNAs that regulate gene expression by inhibiting translation of protein encoding transcripts. To evaluate the role of miR in skeletal muscle of swine, global microRNA abundance was measured at specific developmental stages including proliferating satellite cells, three stages of fetal growth, day-old neonate, and the adult. Results Twelve potential novel miR were detected that did not match previously reported sequences. In addition, a number of miR previously reported to be expressed in mammalian muscle were detected, having a variety of abundance patterns through muscle development. Muscle-specific miR-206 was nearly absent in proliferating satellite cells in culture, but was the highest abundant miR at other time points evaluated. In addition, miR-1 was moderately abundant throughout developmental stages with highest abundance in the adult. In contrast, miR-133 was moderately abundant in adult muscle and either not detectable or lowly abundant throughout fetal and neonate development. Changes in abundance of ubiquitously expressed miR were also observed. MiR-432 abundance was highest at the earliest stage of fetal development tested (60 day-old fetus and decreased throughout development to the adult. Conversely, miR-24 and miR-27 exhibited greatest abundance in proliferating satellite cells and the adult, while abundance of miR-368, miR-376, and miR-423-5p was greatest in the neonate. Conclusion These data present a complete set of transcriptome profiles to evaluate miR abundance at specific stages of skeletal muscle growth in swine. Identification of these miR provides an initial group of miR that may play a vital role in muscle development and growth.

Pygmoid Australomelanesian Homo sapiens skeletal remains from Liang Bua, Flores: Population affinities and pathological abnormalities

OpenAIRE

Jacob, T.; Indriati, E.; Soejono, R. P.; Hsü, K.; Frayer, D. W.; Eckhardt, R. B.; Kuperavage, A. J.; Thorne, A.; Henneberg, M.

2006-01-01

Liang Bua 1 (LB1) exhibits marked craniofacial and postcranial asymmetries and other indicators of abnormal growth and development. Anomalies aside, 140 cranial features place LB1 within modern human ranges of variation, resembling Australomelanesian populations. Mandibular and dental features of LB1 and LB6/1 either show no substantial deviation from modern Homo sapiens or share features (receding chins and rotated premolars) with Rampasasa pygmies now living near Liang Bua Cave. We propose ...

Foetal radiography for suspected skeletal dysplasia: technique, normal appearances, diagnostic approach

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Calder, Alistair D. [Great Ormond Street Hospital for Children NHS Foundation Trust, Radiology Department, London (United Kingdom); Offiah, Amaka C. [Sheffield Children' s NHS Foundation Trust, Academic Unit of Child Health, Sheffield (United Kingdom)

2015-04-01

Despite advances in antenatal imaging and genetic techniques, post-delivery post-mortem foetal radiography remains the key investigation in accurate diagnosis of skeletal dysplasia manifesting in the foetus. Foetal radiography is best performed using pathology-specimen radiography equipment and is often carried out in the pathology department without involvement of the radiology unit. However, paediatric radiologists may be asked to interpret post-mortem foetal radiographs when an abnormality is suspected. Many foetal radiographs are carried out before 20 weeks' gestation, and the interpreting radiologist needs to be familiar with the range of normal post-mortem foetal appearances at different gestational ages, as well as the appearances of some of the more commonly presenting skeletal dysplasias, and will benefit from a systematic approach when assessing more challenging cases. In this pictorial essay, we illustrate various normal post-mortem foetal radiographic appearances, give examples of commonly occurring skeletal dysplasias, and describe an approach to establishing more difficult diagnoses. (orig.)

Foetal radiography for suspected skeletal dysplasia: technique, normal appearances, diagnostic approach

International Nuclear Information System (INIS)

Calder, Alistair D.; Offiah, Amaka C.

2015-01-01

Despite advances in antenatal imaging and genetic techniques, post-delivery post-mortem foetal radiography remains the key investigation in accurate diagnosis of skeletal dysplasia manifesting in the foetus. Foetal radiography is best performed using pathology-specimen radiography equipment and is often carried out in the pathology department without involvement of the radiology unit. However, paediatric radiologists may be asked to interpret post-mortem foetal radiographs when an abnormality is suspected. Many foetal radiographs are carried out before 20 weeks' gestation, and the interpreting radiologist needs to be familiar with the range of normal post-mortem foetal appearances at different gestational ages, as well as the appearances of some of the more commonly presenting skeletal dysplasias, and will benefit from a systematic approach when assessing more challenging cases. In this pictorial essay, we illustrate various normal post-mortem foetal radiographic appearances, give examples of commonly occurring skeletal dysplasias, and describe an approach to establishing more difficult diagnoses. (orig.)

Skeletal muscle performance and ageing.

Science.gov (United States)

Tieland, Michael; Trouwborst, Inez; Clark, Brian C

2018-02-01

The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co-morbidity, and premature death. An important cause of physical limitations is the age-related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation-contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Proteomic profiling of non-obese type 2 diabetic skeletal muscle

OpenAIRE

Mullen, Edel; Ohlendieck, Kay

2010-01-01

Abnormal glucose handling has emerged as a major clinical problem in millions of diabetic patients worldwide. Insulin resistance affects especially one of the main target organs of this hormone, the skeletal musculature, making impaired glucose metabolism in contractile fibres a major feature of type 2 diabetes. High levels of circulating free fatty acids, an increased intramyocellular lipid content, impaired insulin-mediated glucose uptake, diminished mitochondrial functioning and an overall...

Wnt Signaling in Skeletal Muscle Development and Regeneration.

Science.gov (United States)

Girardi, Francesco; Le Grand, Fabien

2018-01-01

Wnt is a family of signaling molecules involved in embryogenesis, adult tissue repair, and cancer. They activate canonical and noncanonical Wnt signaling cascades in target cells. Several studies, within the last decades, showed that several Wnt ligands are involved in myogenesis and both canonical and noncanonical Wnt pathways regulate muscle formation and the maintenance of adult tissue homeostasis. In this review, we provide a comprehensive overview of the roles of Wnt signaling during muscle development and an updated description of Wnt functions during muscle repair. Lastly, we discuss the crosstalk between Wnt and TGFβ signaling pathways in skeletal muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

Passive stiffness of rat skeletal muscle undernourished during fetal development

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Ana Elisa Toscano

2010-01-01

Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

Development and validation of an n-dodecane skeletal mechanism for spray combustion applications

KAUST Repository

Luo, Zhaoyu

2014-03-04

n-Dodecane is a promising surrogate fuel for diesel engine study because its physicochemical properties are similar to those of the practical diesel fuels. In the present study, a skeletal mechanism for n-dodecane with 105 species and 420 reactions was developed for spray combustion simulations. The reduction starts from the most recent detailed mechanism for n-alkanes consisting of 2755 species and 11,173 reactions developed by the Lawrence Livermore National Laboratory. An algorithm combining direct relation graph with expert knowledge (DRGX) and sensitivity analysis was employed for the present skeletal reduction. The skeletal mechanism was first extensively validated in 0-D and 1-D combustion systems, including auto-ignition, jet stirred reactor (JSR), laminar premixed flame and counter flow diffusion flame. Then it was coupled with well-established spray models and further validated in 3-D turbulent spray combustion simulations under engine-like conditions. These simulations were compared with the recent experiments with n-dodecane as a surrogate for diesel fuels. It can be seen that combustion characteristics such as ignition delay and flame lift-off length were well captured by the skeletal mechanism, particularly under conditions with high ambient temperatures. Simulations also captured the transient flame development phenomenon fairly well. The results further show that ignition delay may not be the only factor controlling the stabilisation of the present flames since a good match in ignition delay does not necessarily result in improved flame lift-off length prediction. The work of Zhaoyu Luo, Sibendu Som, Max Plomer, William J. Pitz, Douglas E. Longman and Tianfeng Lu was authored as part of their official duties as Employees of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law. S. Mani Sarathy hereby waives his right to

Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis.

Science.gov (United States)

Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J

2011-12-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.

Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle

DEFF Research Database (Denmark)

Højlund, Kurt; Beck-Nielsen, Henning

2006-01-01

Insulin resistance in skeletal muscle is a major hallmark of type 2 diabetes and an early detectable abnormality in the development of this disease. The cellular mechanisms of insulin resistance include impaired insulin-mediated muscle glycogen synthesis and increased intramyocellular lipid content......, whereas impaired insulin activation of muscle glycogen synthase represents a consistent, molecular defect found in both type 2 diabetic and high-risk individuals. Despite several studies of the insulin signaling pathway believed to mediate dephosphorylation and hence activation of glycogen synthase......, the molecular mechanisms responsible for this defect remain unknown. Recently, the use of phospho-specific antibodies in human diabetic muscle has revealed hyperphosphorylation of glycogen synthase at sites not regulated by the classical insulin signaling pathway. In addition, novel approaches such as gene...

Cell death induced by gamma irradiation of developing skeletal muscle

International Nuclear Information System (INIS)

Olive, M.; Blanco, R.; Rivera, R.; Cinos, C.; Ferrer, I.

1995-01-01

Newborn Sprague-Dawley rats were exposed to a single dose of 2 Gy gamma rays and killed from 6 h to 5 d later. Increased numbers of dying cells, characterised by their extreme chromatin condensation and often nuclear fragmentation were seen in skeletal muscle 6 h after irradiation. Dying cells decreased to nearly normal values 48 h later. In situ labelling of nuclear DNA fragmentation identified individual cells bearing fragmented DNA. The effects of gamma rays were suppressed following cycloheximide i.p. at a dose of 1 μg/g body weight given at the time of irradiation. Taken together, the present morphological and pharmacological results suggest that gamma ray induced cell death in skeletal muscle is apoptotic, and that the process is associated with protein synthesis. Finally, proliferating cell nuclear antigen-immunoreactive cells, which were abundant in control rats, decreased in number 48 h after irradiation. However, a marked increase significantly above normal age values was observed at the 5th day, thus suggesting that regeneration occurs following irradiation-induced cell death in developing muscle. (author)

Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

Science.gov (United States)

Mitchell, Jere H

2017-06-01

During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

Proteomic Analysis of Chicken Skeletal Muscle during Embryonic Development

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Hongjia Ouyang

2017-05-01

Full Text Available Embryonic growth and development of skeletal muscle is a major determinant of muscle mass, and has a significant effect on meat production in chicken. To assess the protein expression profiles during embryonic skeletal muscle development, we performed a proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ in leg muscle tissues of female Xinghua chicken at embryonic age (E 11, E16, and 1-day post hatch (D1. We identified 3,240 proteins in chicken embryonic muscle and 491 of them were differentially expressed (fold change ≥ 1.5 or ≤ 0.666 and p < 0.05. There were 19 up- and 32 down-regulated proteins in E11 vs. E16 group, 238 up- and 227 down-regulated proteins in E11 vs. D1 group, and 13 up- and 5 down-regulated proteins in E16 vs. D1 group. Protein interaction network analyses indicated that these differentially expressed proteins were mainly involved in the pathway of protein synthesis, muscle contraction, and oxidative phosphorylation. Integrative analysis of proteome and our previous transcriptome data found 189 differentially expressed proteins that correlated with their mRNA level. The interactions between these proteins were also involved in muscle contraction and oxidative phosphorylation pathways. The lncRNA-protein interaction network found four proteins DMD, MYL3, TNNI2, and TNNT3 that are all involved in muscle contraction and may be lncRNA regulated. These results provide several candidate genes for further investigation into the molecular mechanisms of chicken embryonic muscle development, and enable us to better understanding their regulation networks and biochemical pathways.

Development of diagnostic process for abnormal conditions of Ulchin units 1 and 2

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Choi, Hyun Soo; Kwak, Jeong Keun; Yun, Jung Hyun; Kim, Jong Hyun [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

2012-10-15

Diagnosis of abnormal conditions during operation is one of difficult tasks to nuclear power plant operators. Operators may have trouble in handling abnormal conditions due to various reasons such as 1) many alarms (around 2,000 alarms in the Ulchin units 1 and 2 each) and multi alarms occurrences, 2) the same alarms occurrences in different abnormal conditions, and 3) a number of Abnormal Operating Procedures (AOPs). For these reasons, the first diagnosis on abnormal conditions largely relies on operator's experiences and pattern recognition. Then, this difficulty may be highlighted for inexperienced operators. This paper suggests an approach to develop the optimal diagnostic process for appropriate selection of AOPs by using the Elimination by Aspect (EBA) method. The EBA method uses a heuristic followed by decision makers during a process of sequential choice and which constitutes a good balance between the cost of a decision and its quality. At each stage of decision, the individuals eliminate all the options not having an expected given attribute, until only one option remains. This approach is applied to steam generator level control system abnormal procedure for Ulchin units 1 and 2. The result indicates that the EBA method is applicable to the development of optimal process on diagnosis of abnormal conditions.

Loss of ATRX in chondrocytes has minimal effects on skeletal development.

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Lauren A Solomon

Full Text Available BACKGROUND: Mutations in the human ATRX gene cause developmental defects, including skeletal deformities and dwarfism. ATRX encodes a chromatin remodeling protein, however the role of ATRX in skeletal development is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: We induced Atrx deletion in mouse cartilage using the Cre-loxP system, with Cre expression driven by the collagen II (Col2a1 promoter. Growth rate, body size and weight, and long bone length did not differ in Atrx(Col2cre mice compared to control littermates. Histological analyses of the growth plate did not reveal any differences between control and mutant mice. Expression patterns of Sox9, a transcription factor required for cartilage morphogenesis, and p57, a marker of cell cycle arrest and hypertrophic chondrocyte differentiation, was unaffected. However, loss of ATRX in cartilage led to a delay in the ossification of the hips in some mice. We also observed hindlimb polydactily in one out of 61 mutants. CONCLUSIONS/SIGNIFICANCE: These findings indicate that ATRX is not directly required for development or growth of cartilage in the mouse, suggesting that the short stature in ATR-X patients is caused by defects in cartilage-extrinsic mechanisms.

Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

International Nuclear Information System (INIS)

Perna, A.F.; Smogorzewski, M.; Massry, S.G.

1988-01-01

Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

Human age estimation combining third molar and skeletal development.

Science.gov (United States)

Thevissen, P W; Kaur, J; Willems, G

2012-03-01

The wide prediction intervals obtained with age estimation methods based on third molar development could be reduced by combining these dental observations with age-related skeletal information. Therefore, on cephalometric radiographs, the most accurate age-estimating skeletal variable and related registration method were searched and added to a regression model, with age as response and third molar stages as explanatory variable. In a pilot set up on a dataset of 496 (283 M; 213 F) cephalometric radiographs, the techniques of Baccetti et al. (2005) (BA), Seedat et al. (2005) (SE), Caldas et al. (2007) and Rai et al. (2008) (RA) were verified. In the main study, data from 460 (208 F, 224 M) individuals in an age range between 3 and 26 years, for which at the same day an orthopantogram and a cephalogram were taken, were collected. On the orthopantomograms, the left third molar development was registered using the scoring system described by Gleiser and Hunt (1955) and modified by Köhler (1994) (GH). On the cephalograms, cervical vertebrae development was registered according to the BA and SE techniques. A regression model, with age as response and the GH scores as explanatory variable, was fitted to the data. Next, information of BA, SE and BA + SE was, respectively, added to this model. From all obtained models, the determination coefficients and the root mean squared errors were calculated. Inclusion of information from cephalograms based on the BA, as well as the SE, technique improved the amount of explained variance in age acquired from panoramic radiographs using the GH technique with 48%. Inclusion of cephalometric BA + SE information marginally improved the previous result (+1%). The RMSE decreased with 1.93, 1.85 and 2.03 years by adding, respectively, BA, SE and BA + SE information to the GH model. The SE technique allows clinically the fastest and easiest registration of the degree of development of the cervical vertebrae. Therefore, the choice of

Aberrant mitochondrial homeostasis in the skeletal muscle of sedentary older adults.

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Adeel Safdar

Full Text Available The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; female symbol = male symbol. We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging.

Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study.

Science.gov (United States)

Al-Sarraj, Safa; King, Andrew; Cleveland, Matt; Pradat, Pierre-François; Corse, Andrea; Rothstein, Jeffrey D; Leigh, Peter Nigel; Abila, Bams; Bates, Stewart; Wurthner, Jens; Meininger, Vincent

2014-12-14

Amyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and subsequent denervation atrophy of skeletal muscle. A comprehensive examination of muscle pathology from a cohort of clinically confirmed ALS patients, including an investigation of inflammation, complement activation, and deposition of abnormal proteins in order to compare them with findings from an age-matched, control group. 31 muscle biopsies from clinically confirmed ALS patients and 20 normal controls underwent a comprehensive protocol of histochemical and immunohistochemical stains, including HLA-ABC, C5b-9, p62, and TDP-43. Neurogenic changes were confirmed in 30/31 ALS cases. In one case, no neurogenic changes could be detected. Muscle fibre necrosis was seen in 5/31 cases and chronic mononuclear inflammatory cell infiltration in 5/31 (2 of them overlapped with those showing muscle necrosis). In four biopsies there was an increase in the proportion of cytochrome oxidase (COX) negative fibres (2-3%). p62 faintly stained cytoplasmic bodies in eight cases and none were immunoreactive to TDP-43. This large series of muscle biopsies from patients with ALS demonstrates neurogenic atrophy is a nearly uniform finding and that mild mitochondrial abnormalities and low-grade inflammation can be seen and do not rule out the diagnosis of ALS. These findings could lend support to the notion that ALS is a complex and heterogeneous disorder.

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system.

Science.gov (United States)

Gutch, Manish; Philip, Rajeev; Philip, Renjit; Toms, Ajit; Saran, Sanjay; Gupta, K K

2013-10-01

Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis.

Science.gov (United States)

Kumar, Avinash; Davuluri, Gangarao; Silva, Rafaella Nascimento E; Engelen, Marielle P K J; Ten Have, Gabrie A M; Prayson, Richard; Deutz, Nicolaas E P; Dasarathy, Srinivasan

2017-06-01

Sarcopenia or skeletal muscle loss is a frequent, potentially reversible complication in cirrhosis that adversely affects clinical outcomes. Hyperammonemia is a consistent abnormality in cirrhosis that results in impaired skeletal muscle protein synthesis and breakdown (proteostasis). Despite the availability of effective ammonia-lowering therapies, whether lowering ammonia restores proteostasis and increases muscle mass is unknown. Myotube diameter, protein synthesis, and molecular responses in C2C12 murine myotubes to withdrawal of ammonium acetate following 24-hour exposure to 10 mM ammonium acetate were complemented by in vivo studies in the hyperammonemic portacaval anastomosis rat and sham-operated, pair-fed Sprague-Dawley rats treated with ammonia-lowering therapy by l-ornithine l-aspartate and rifaximin orally for 4 weeks. We observed reduced myotube diameter, impaired protein synthesis, and increased autophagy flux in response to hyperammonemia, which were partially reversed following 24-hour and 48-hour withdrawal of ammonium acetate. Consistently, 4 weeks of ammonia-lowering therapy resulted in significant lowering of blood and skeletal muscle ammonia, increase in lean body mass, improved grip strength, higher skeletal muscle mass and diameter, and an increase in type 2 fibers in treated compared to untreated portacaval anastomosis rats. The increased skeletal muscle myostatin expression, reduced mammalian target of rapamycin complex 1 function, and hyperammonemic stress response including autophagy markers normally found in portacaval anastomosis rats were reversed by treatment with ammonia-lowering therapy. Despite significant improvement, molecular and functional readouts were not completely reversed by ammonia-lowering measures. Ammonia-lowering therapy results in improvement in skeletal muscle phenotype and function and molecular perturbations of hyperammonemia; these preclinical studies complement previous studies on ammonia-induced skeletal muscle

Skeletal Stem Cells: Origins, Functions and Uncertainties.

Science.gov (United States)

Mohamed, Fatma F; Franceschi, Renny T

2017-12-01

The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes

Science.gov (United States)

White, Jennifer; Barro, Marietta V.; Makarenkova, Helen P.; Sanger, Joseph W.; Sanger, Jean M.

2014-01-01

It is important to understand how muscle forms normally in order to understand muscle diseases that result in abnormal muscle formation. Although the structure of myofibrils is well understood, the process through which the myofibril components form organized contractile units is not clear. Based on the staining of muscle proteins in avian embryonic cardiomyocytes, we previously proposed that myofibrils formation occurred in steps that began with premyofibrils followed by nascent myofibrils and ending with mature myofibrils. The purpose of this study was to determine whether the premyofibril model of myofibrillogenesis developed from studies developed from studies in avian cardiomyocytes was supported by our current studies of myofibril assembly in mouse skeletal muscle. Emphasis was on establishing how the key sarcomeric proteins, F-actin, non-muscle myosin II, muscle myosin II, and α-actinin were organized in the three stages of myofibril assembly. The results also test previous reports that non-muscle myosins II A and B are components of the Z-Bands of mature myofibrils, data that are inconsistent with the premyofibril model. We have also determined that in mouse muscle cells, telethonin is a late assembling protein that is present only in the Z-Bands of mature myofibrils. This result of using specific telethonin antibodies supports the approach of using YFP-tagged proteins to determine where and when these YFP-sarcomeric fusion proteins are localized. The data presented in this study on cultures of primary mouse skeletal myocytes are consistent with the premyofibril model of myofibrillogenesis previously proposed for both avian cardiac and skeletal muscle cells. PMID:25125171

Skeletal Muscle Insulin Resistance in Endocrine Disease

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Melpomeni Peppa

2010-01-01

Full Text Available We summarize the existing literature data concerning the involvement of skeletal muscle (SM in whole body glucose homeostasis and the contribution of SM insulin resistance (IR to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS, adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

Radiological diagnosis of skeletal metastases

International Nuclear Information System (INIS)

Soederlund, V.

1996-01-01

The clinical management of patients with skeletal metastases puts new demands on imaging. The radiological imaging in screening for skeletal metastases entails detection, metastatic site description and radiologically guided biopsy for morphological typing and diagnosis. Regarding sensitivity and the ease in performing surveys of the whole skeleton, radionuclide bone scintigraphy still is the first choice in routine follow-up of asymptomatic patients with metastatic disease of the skeleton. A negative scan has to be re-evaluated with other findings, with emphasis on the possibility of a false-negative result. Screening for metastases in patients with local symptoms or pain is best accomplished by a combination of radiography and MRI. Water-weighted sequences are superior in sensitivity and in detection of metastases. Standard spin-echo sequences on the other hand are superior in metastatic site description and in detection of intraspinal metastases. MRI is helpful in differentiating between malignant disease, infection, benign vertebral collapse, insufficiency fracture after radiation therapy, degenerative vertebral disease and benign skeletal lesions. About 30% of patients with known cancer have benign causes of radiographic abnormalities. Most of these are related to degenerative diseases and are often easily diagnosed. However, due to overlap in MRI characteristics, bone biopsy sometimes is essential for differentiating between malignant and nonmalignant lesions. Performing bone biopsy and aspiration cytology by radiologist and cytologist in co-operation has proven highly accurate in diagnosing bone lesions. The procedure involves low risk to the patient and provides a morphological diagnosis. Once a suspected metastatic lesion is detected, irrespective of modality, the morphological diagnosis determines the appropriate work-up imaging with respect to the therapy alternatives. (orig./VHE)

Quantitative skeletal scintiscanning

International Nuclear Information System (INIS)

Haushofer, R.

1982-01-01

330 patients were examined by skeletal scintiscanning with sup(99m)Tc pyrophosphate and sup(99m)methylene diphosphonate in the years between 1977 and 1979. Course control examinations were carried out in 12 patients. The collective of patients presented with primary skeletal tumours, metastases, inflammatory and degenerative skeletal diseases. Bone scintiscanning combined with the ''region of interest'' technique was found to be an objective and reproducible technique for quantitative measurement of skeletal radioactivity concentrations. The validity of nuclear skeletal examinations can thus be enhanced as far as diagnosis, course control, and differential diagnosis are concerned. Quantitative skeletal scintiscanning by means of the ''region of interest'' technique has opened up a new era in skeletal diagnosis by nuclear methods. (orig./MG) [de

Primary skeletal muscle cells cultured on gelatin bead microcarriers develop structural and biochemical features characteristic of adult skeletal muscle.

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Kubis, Hans-Peter; Scheibe, Renate J; Decker, Brigitte; Hufendiek, Karsten; Hanke, Nina; Gros, Gerolf; Meissner, Joachim D

2016-04-01

A primary skeletal muscle cell culture, in which myoblasts derived from newborn rabbit hindlimb muscles grow on gelatin bead microcarriers in suspension and differentiate into myotubes, has been established previously. In the course of differentiation and beginning spontaneous contractions, these multinucleated myotubes do not detach from their support. Here, we describe the development of the primary myotubes with respect to their ultrastructural differentiation. Scanning electron microscopy reveals that myotubes not only grow around the surface of one carrier bead but also attach themselves to neighboring carriers, forming bridges between carriers. Transmission electron microscopy demonstrates highly ordered myofibrils, T-tubules, and sarcoplasmic reticulum. The functionality of the contractile apparatus is evidenced by contractile activity that occurs spontaneously or can be elicited by electrostimulation. Creatine kinase activity increases steadily until day 20 of culture. Regarding the expression of isoforms of myosin heavy chains (MHC), we could demonstrate that from day 16 on, no non-adult MHC isoform mRNAs are present. Instead, on day 28 the myotubes express predominantly adult fast MHCIId/x mRNA and protein. This MHC pattern resembles that of fast muscles of adult rabbits. In contrast, primary myotubes grown on matrigel-covered culture dishes express substantial amounts of non-adult MHC protein even on day 21. To conclude, primary myotubes grown on microcarriers in their later stages exhibit many features of adult skeletal muscle and characteristics of fast type II fibers. Thus, the culture represents an excellent model of adult fast skeletal muscle, for example, when investigating molecular mechanisms of fast-to-slow fiber-type transformation. © 2015 International Federation for Cell Biology.

Management of skeletal Class III malocclusion with reverse pull headgear in a growing individual

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Ambreen Afzal

2016-01-01

Full Text Available Skeletal Class III malocclusion is considered to be one of the most difficult orthodontic problems to treat. This malocclusion is associated with the retrognathic maxilla or prognathic mandible or sometimes a combination of both. The treatment of such cases requires an integrated approach and a comprehensive treatment plan including growth modification, dental camouflage, or orthognathic surgery. In a growing patient, orthopedic correction of skeletal Class III malocclusion with the help of a reverse pull headgear is crucial as it can reduce the chances of further surgical treatment to correct the skeletal discrepancy. This case report describes the management of skeletal Class III malocclusion in a 12-year-old female child with a retrognathic maxilla. The patient did not have any other genetic abnormality or significant known comorbidity. The treatment plan involved fixed orthodontic appliance therapy in combination with a reverse pull headgear for an orthopedic effect. This treatment was continued for 3 years, and well-aligned dental arches with a positive over jet were achieved at the conclusion of treatment. Using facemask therapy in conjunction with fixed orthodontic appliances has been a successful treatment option in growing children. Treatment should be carried out as early as possible to correct the skeletal discrepancy nonsurgically and achieve better results.

A contemporary Colombian skeletal reference collection: A resource for the development of population specific standards.

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Sanabria-Medina, Cesar; González-Colmenares, Gretel; Restrepo, Hadaluz Osorio; Rodríguez, Juan Manuel Guerrero

2016-09-01

Several authors who have discussed human variability and its impact on the forensic identification of bodies pose the need for regional studies documenting the global variation of the attributes analyzed osteological characteristics that aid in establishing biological profile (sex, ancestry, biological age and height). This is primarily accomplished by studying documented human skeletal collections in order to investigate secular trends in skeletal development and aging, among others in the Colombian population. The purpose of this paper is to disclose the details of the new "Contemporary Colombian Skeletal Reference Collection" that currently comprises 600 identified skeletons of both sexes, who died between 2005 and 2008; and which contain information about their cause of death. This collection has infinite potential for research, open to the national and international community, and still has pending opportunities to address a variety of topics such as studies on osteopathology, bone trauma and taphonomic studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

T wave abnormalities, high body mass index, current smoking and high lipoprotein (a levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

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Sundstrom Johan

2006-03-01

Full Text Available Abstract Background Most studies on risk factors for development of coronary heart disease (CHD have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17, high lipoprotein (a levels, high body mass index (BMI and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a levels may be a stronger risk factor for silent myocardial infarction (MI compared to clinically recognized MI.

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system

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Manish Gutch

2013-01-01

Full Text Available Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

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Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

2016-04-01

In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

Spop promotes skeletal development and homeostasis by positively regulating Ihh signaling.

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Cai, Hongchen; Liu, Aimin

2016-12-20

Indian Hedgehog (Ihh) regulates chondrocyte and osteoblast differentiation through the Glioma-associated oncogene homolog (Gli) transcription factors. Previous in vitro studies suggested that Speckle-type POZ protein (Spop), part of the Cullin-3 (Cul3) ubiquitin ligase complex, targets Gli2 and Gli3 for degradation and negatively regulates Hedgehog (Hh) signaling. In this study, we found defects in chondrocyte and osteoblast differentiation in Spop-null mutant mice. Strikingly, both the full-length and repressor forms of Gli3, but not Gli2, were up-regulated in Spop mutants, and Ihh target genes Patched 1 (Ptch1) and parathyroid hormone-like peptide (Pthlh) were down-regulated, indicating compromised Hh signaling. Consistent with this finding, reducing Gli3 dosage greatly rescued the Spop mutant skeletal defects. We further show that Spop directly targets the Gli3 repressor for ubiquitination and degradation. Finally, we demonstrate in a conditional mutant that loss of Spop results in brachydactyly and osteopenia, which can be rescued by reducing the dosage of Gli3. In summary, Spop is an important positive regulator of Ihh signaling and skeletal development.

Induced skeletal mutations

International Nuclear Information System (INIS)

Selby, P.B.

1979-01-01

This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

KAUST Repository

Conti, Antonio

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS\\'s pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V.

Comparison of skeletal scintigraphy and radiology for showing the osseous manifestations of generalised mastocytosis

Energy Technology Data Exchange (ETDEWEB)

Bieler, E.U.; Wohlenberg, H.; Utech, C.

1985-05-01

Bone scans and skeletal X-rays of eight patients with systemic mastocytosis were reviewed. Mast cell infiltration of bone marrow had been proven histologically in every patient. Bone scan and roentgenographic findings are not specific for the disease and do not correlate well in some patients. A generalized increase of uptake was noted in two patients, a generalized decrease of skeletal activity with poor delineation of bony structures was observed in others. A circumscribed increase of activity was observed in some patients, only one patient had a normal bone scan. Roentgenographic examination revealed diffuse sclerosis of trabecular bone in three patients, osteoporosis with collaps of multiple vertebral bodies in three patients, and no abnormalities in two patients.

Assessment of mandibular growth by skeletal scintigraphy

International Nuclear Information System (INIS)

Kaban, L.B.; Cisneros, G.J.; Heyman, S.; Treves, S.

1982-01-01

Accurate assessment of facial skeletal growth remains a major problem in craniomaxillofacial surgery. Current methods include: (1) comparisons of chronologic age with growth histories of the patient and the family, (2) hand-wrist radiographs compared with a standard, and (3) serial cephalometric radiographs. Uptake of technetium-99m methylene diphosphonate into bone is a reflection of current metabolic activity and blood flow. Therefore, scintigraphy with this radiopharmaceutical might serve as a good method of assessing skeletal growth. Thirty-four patients, ranging in age from 15 months to 22 years, who were undergoing skeletal scintigrams for acute pathologic conditions of the extremities, were used to develop standards of uptake based on age and skeletal maturation. The results indicate that skeletal scintigraphy may be useful in evaluation of mandibular growth

Determinants of relative skeletal maturity in South African children.

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Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

2012-01-01

The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (pdetermining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle function

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Gallagher, Thomas L.; Arribere, Joshua A.; Geurts, Paul A.; Exner, Cameron R. T.; McDonald, Kent L.; Dill, Kariena K.; Marr, Henry L.; Adkar, Shaunak S.; Garnett, Aaron T.; Amacher, Sharon L.; Conboy, John G.

2012-01-01

Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos was strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle function. PMID:21925157

Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions.

Science.gov (United States)

Gallagher, Thomas L; Arribere, Joshua A; Geurts, Paul A; Exner, Cameron R T; McDonald, Kent L; Dill, Kariena K; Marr, Henry L; Adkar, Shaunak S; Garnett, Aaron T; Amacher, Sharon L; Conboy, John G

2011-11-15

Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos were strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle functions. Published by Elsevier Inc.

A unified anatomy ontology of the vertebrate skeletal system.

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Wasila M Dahdul

Full Text Available The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO, to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish and multispecies (teleost, amphibian vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages, and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO, Gene Ontology (GO, Uberon, and Cell Ontology (CL, and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A unified anatomy ontology of the vertebrate skeletal system.

Science.gov (United States)

Dahdul, Wasila M; Balhoff, James P; Blackburn, David C; Diehl, Alexander D; Haendel, Melissa A; Hall, Brian K; Lapp, Hilmar; Lundberg, John G; Mungall, Christopher J; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E; Vickaryous, Matthew K; Westerfield, Monte; Mabee, Paula M

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A Unified Anatomy Ontology of the Vertebrate Skeletal System

Science.gov (United States)

Dahdul, Wasila M.; Balhoff, James P.; Blackburn, David C.; Diehl, Alexander D.; Haendel, Melissa A.; Hall, Brian K.; Lapp, Hilmar; Lundberg, John G.; Mungall, Christopher J.; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E.; Vickaryous, Matthew K.; Westerfield, Monte; Mabee, Paula M.

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity. PMID:23251424

Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients

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Ákos Tényi

2018-02-01

Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD patients often show skeletal muscle dysfunction that has a prominent negative impact on prognosis. The study aims to further explore underlying mechanisms of skeletal muscle dysfunction as a characteristic systemic effect of COPD, potentially modifiable with preventive interventions (i.e. muscle training. The research analyzes network module associated pathways and evaluates the findings using independent measurements. Methods We characterized the transcriptionally active network modules of interacting proteins in the vastus lateralis of COPD patients (n = 15, FEV1 46 ± 12% pred, age 68 ± 7 years and healthy sedentary controls (n = 12, age 65 ± 9  years, at rest and after an 8-week endurance training program. Network modules were functionally evaluated using experimental data derived from the same study groups. Results At baseline, we identified four COPD specific network modules indicating abnormalities in creatinine metabolism, calcium homeostasis, oxidative stress and inflammatory responses, showing statistically significant associations with exercise capacity (VO2 peak, Watts peak, BODE index and blood lactate levels (P < 0.05 each, but not with lung function (FEV1. Training-induced network modules displayed marked differences between COPD and controls. Healthy subjects specific training adaptations were significantly associated with cell bioenergetics (P < 0.05 which, in turn, showed strong relationships with training-induced plasma metabolomic changes; whereas, effects of training in COPD were constrained to muscle remodeling. Conclusion In summary, altered muscle bioenergetics appears as the most striking finding, potentially driving other abnormal skeletal muscle responses. Trial registration The study was based on a retrospectively registered trial (May 2017, ClinicalTrials.gov identifier: NCT03169270

Phenotypic characterization of skeletal abnormalities of osteopotentia mutant mice by micro-CT: a descriptive approach with emphasis on reconstruction techniques

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Roemer, Frank W. [Department of Radiology, Klinikum Augsburg, Augsburg (Germany); Boston University School of Medicine, Quantitative Imaging Center, Boston, MA (United States); University of California, San Francisco, Osteoporosis and Arthritis Research Group, San Francisco, CA (United States); Boston University Medical Center, Department of Radiology, Boston, MA (United States); Mohr, Andreas [University of California, San Francisco, Osteoporosis and Arthritis Research Group, San Francisco, CA (United States); Sligo General Hospital, Department of Radiology, Sligo (Ireland); Guermazi, Ali [Boston University School of Medicine, Quantitative Imaging Center, Boston, MA (United States); University of California, San Francisco, Osteoporosis and Arthritis Research Group, San Francisco, CA (United States); Jiang, Yebin [University of California, San Francisco, Osteoporosis and Arthritis Research Group, San Francisco, CA (United States); University of Michigan Medical School, Osteoporosis and Arthritis Laboratory, Musculoskeletal Division, Department of Radiology, Ann Arbor, MI (United States); Schlechtweg, Philipp [University of Erlangen, Department of Radiology, Erlangen (Germany); Genant, Harry K. [University of California, San Francisco, Osteoporosis and Arthritis Research Group, San Francisco, CA (United States); CCBR-SYNARC, Inc., San Francisco, CA (United States); Sohaskey, Michael L. [University of California, Berkeley, Department of Molecular and Cell Biology and Center for Integrative Genomics, Berkeley, CA (United States)

2011-08-15

The novel protein osteopotentia (Opt) has recently been described as an essential regulator of postnatal osteoblast maturation and might possibly be responsible for some of the rarer types of osteogenesis imperfecta. Our aim was the evaluation of micro CT for the qualitative morphological assessment of skeletal abnormalities of Osteopotentia-mutant mice in comparison to radiography and histology. Four homozygous mice with insertional mutations in the Opt gene and three wild-type controls were examined ex vivo using radiography and micro-CT. Two of the homozygous animals were evaluated histologically (trichrome reagent). For the micro-CT evaluation three-dimensional (3D) surface reconstructions and two-dimensional (2D) multiplanar reformations (MPRs) were applied. The Opt-homozygous mice exhibited severe growth. The radiographic examinations showed osteopenia and fractures with hypertrophic callus formation and pseudarthroses of the forelimbs and ribs. Micro-CT confirmed these findings and was able to demonstrate additional fractures especially at smaller bones such as the metacarpals and phalanges. Additional characterization and superior delineation of cortices and fracture fragments was achieved by 2D MPRs. Histological correlation verified several of these imaging findings. Micro-CT is able to screen Opt-mutant mice for osseous pathologies and furthermore characterize these anomalies. The modality seems superior to conventional radiography, but is not able to demonstrate cellular pathology. However, histology is destructive and more time- and material-consuming than micro-CT. Additional information may be gathered by 2D MPRs. (orig.)

Phenotypic characterization of skeletal abnormalities of osteopotentia mutant mice by micro-CT: a descriptive approach with emphasis on reconstruction techniques

International Nuclear Information System (INIS)

Roemer, Frank W.; Mohr, Andreas; Guermazi, Ali; Jiang, Yebin; Schlechtweg, Philipp; Genant, Harry K.; Sohaskey, Michael L.

2011-01-01

The novel protein osteopotentia (Opt) has recently been described as an essential regulator of postnatal osteoblast maturation and might possibly be responsible for some of the rarer types of osteogenesis imperfecta. Our aim was the evaluation of micro CT for the qualitative morphological assessment of skeletal abnormalities of Osteopotentia-mutant mice in comparison to radiography and histology. Four homozygous mice with insertional mutations in the Opt gene and three wild-type controls were examined ex vivo using radiography and micro-CT. Two of the homozygous animals were evaluated histologically (trichrome reagent). For the micro-CT evaluation three-dimensional (3D) surface reconstructions and two-dimensional (2D) multiplanar reformations (MPRs) were applied. The Opt-homozygous mice exhibited severe growth. The radiographic examinations showed osteopenia and fractures with hypertrophic callus formation and pseudarthroses of the forelimbs and ribs. Micro-CT confirmed these findings and was able to demonstrate additional fractures especially at smaller bones such as the metacarpals and phalanges. Additional characterization and superior delineation of cortices and fracture fragments was achieved by 2D MPRs. Histological correlation verified several of these imaging findings. Micro-CT is able to screen Opt-mutant mice for osseous pathologies and furthermore characterize these anomalies. The modality seems superior to conventional radiography, but is not able to demonstrate cellular pathology. However, histology is destructive and more time- and material-consuming than micro-CT. Additional information may be gathered by 2D MPRs. (orig.)

Development and validation of an n-dodecane skeletal mechanism for spray combustion applications

KAUST Repository

Luo, Zhaoyu; Som, Sibendu K.; Sarathy, Mani; Plomer, Max; Pitz, William J.; Longman, Douglas E.; Lu, Tianfeng

2014-01-01

relation graph with expert knowledge (DRGX) and sensitivity analysis was employed for the present skeletal reduction. The skeletal mechanism was first extensively validated in 0-D and 1-D combustion systems, including auto-ignition, jet stirred reactor (JSR

Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice.

Science.gov (United States)

Kahr, Walter H A; Lo, Richard W; Li, Ling; Pluthero, Fred G; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E; Weyrich, Andrew S; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L

2013-11-07

Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2(-/-) platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte survival, development, and platelet production.

Emotion processes in normal and abnormal development and preventive intervention.

Science.gov (United States)

Izard, Carroll E; Fine, Sarah; Mostow, Allison; Trentacosta, Christopher; Campbell, Jan

2002-01-01

We present an analysis of the role of emotions in normal and abnormal development and preventive intervention. The conceptual framework stems from three tenets of differential emotions theory (DET). These principles concern the constructs of emotion utilization; intersystem connections among modular emotion systems, cognition, and action; and the organizational and motivational functions of discrete emotions. Particular emotions and patterns of emotions function differentially in different periods of development and in influencing the cognition and behavior associated with different forms of psychopathology. Established prevention programs have not emphasized the concept of emotion as motivation. It is even more critical that they have generally neglected the idea of modulating emotions, not simply to achieve self-regulation, but also to utilize their inherently adaptive functions as a means of facilitating the development of social competence and preventing psychopathology. The paper includes a brief description of a theory-based prevention program and suggestions for complementary targeted interventions to address specific externalizing and internalizing problems. In the final section, we describe ways in which emotion-centered preventions can provide excellent opportunities for research on the development of normal and abnormal behavior.

Pathogenesis of Insulin Resistance in Skeletal Muscle

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Muhammad A. Abdul-Ghani

2010-01-01

Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

Impact of upper airway abnormalities on the success and adherence to mandibular advancement device treatment in patients with Obstructive Sleep Apnea Syndrome.

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Prescinotto, Renato; Haddad, Fernanda Louise Martinho; Fukuchi, Ilana; Gregório, Luiz Carlos; Cunali, Paulo Afonso; Tufik, Sérgio; Bittencourt, Lia Rita Azeredo

2015-01-01

The mandibular advancement device (MAD) is a option to treat patients with Obstructive Sleep Apnea Syndrome (OSAS). To assess the influence of upper airway abnormalities on the success of and adherence to MAD in patients with OSAS. Prospective study with 30 patients with mild to moderate OSAS and indications for MAD. The protocol included questionnaires addressing sleep and nasal complaints, polysomnography, and upper airway assessment. The analyzed parameters of patients who showed therapeutic success and failure and those who exhibited good and poor treatment adherence were compared. 28 patients completed the protocol; 64.3% responded successfully to treatment with MAD, and 60.7% exhibited good adherence to treatment. Factors associated with greater success rates were younger age (p=0.02), smaller cervical circumference (p=0.05), and lower AHI at baseline (p=0.05). There was a predominance of patients without nasal abnormalities among patients treated successfully compared to those with treatment failure (p=0.04), which was not observed in relation to adherence. Neither pharyngeal nor facial skeletal abnormalities were significantly associated with either therapeutic success or adherence. MAD treatment success was significantly lower among patients with nasal abnormalities; however, treatment adherence was not influenced by the presence of upper airway or facial skeletal abnormalities. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle.

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Glenn C Rowe

Full Text Available Exercise confers numerous health benefits, many of which are thought to stem from exercise-induced mitochondrial biogenesis (EIMB in skeletal muscle. The transcriptional coactivator PGC-1α, a potent regulator of metabolism in numerous tissues, is widely believed to be required for EIMB. We show here that this is not the case. Mice engineered to lack PGC-1α specifically in skeletal muscle (Myo-PGC-1αKO mice retained intact EIMB. The exercise capacity of these mice was comparable to littermate controls. Induction of metabolic genes after 2 weeks of in-cage voluntary wheel running was intact. Electron microscopy revealed no gross abnormalities in mitochondria, and the mitochondrial biogenic response to endurance exercise was as robust in Myo-PGC-1αKO mice as in wildtype mice. The induction of enzymatic activity of the electron transport chain by exercise was likewise unperturbed in Myo-PGC-1αKO mice. These data demonstrate that PGC-1α is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle, in sharp contrast to the prevalent assumption in the field.

Proteomic profiling of non-obese type 2 diabetic skeletal muscle.

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Mullen, Edel; Ohlendieck, Kay

2010-03-01

Abnormal glucose handling has emerged as a major clinical problem in millions of diabetic patients worldwide. Insulin resistance affects especially one of the main target organs of this hormone, the skeletal musculature, making impaired glucose metabolism in contractile fibres a major feature of type 2 diabetes. High levels of circulating free fatty acids, an increased intramyocellular lipid content, impaired insulin-mediated glucose uptake, diminished mitochondrial functioning and an overall weakened metabolic flexibility are pathobiochemical hallmarks of diabetic skeletal muscles. In order to increase our cellular understanding of the molecular mechanisms that underlie this complex diabetes-associated skeletal muscle pathology, we initiated herein a mass spectrometry-based proteomic analysis of skeletal muscle preparations from the non-obese Goto-Kakizaki rat model of type 2 diabetes. Following staining of high-resolution two-dimensional gels with colloidal Coomassie Blue, 929 protein spots were detected, whereby 21 proteins showed a moderate differential expression pattern. Decreased proteins included carbonic anhydrase, 3-hydroxyisobutyrate dehydrogenase and enolase. Increased proteins were identified as monoglyceride lipase, adenylate kinase, Cu/Zn superoxide dismutase, phosphoglucomutase, aldolase, isocitrate dehydrogenase, cytochrome c oxidase, small heat shock Hsp27/B1, actin and 3-mercaptopyruvate sulfurtransferase. These proteomic findings suggest that the diabetic phenotype is associated with a generally perturbed protein expression pattern, affecting especially glucose, fatty acid, nucleotide and amino acid metabolism, as well as the contractile apparatus, the cellular stress response, the anti-oxidant defense system and detoxification mechanisms. The altered expression levels of distinct skeletal muscle proteins, as documented in this study, might be helpful for the future establishment of a comprehensive biomarker signature of type 2 diabetes

Study of some abnormalities of ovule development to seed in Pistacia vera L.

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Najmeh Hosseini

2014-05-01

Full Text Available Seed production in some crops like pistachio is limited by some abnormalities in ovule development stages. In this study, the ovule developmental stages as well as abnormalities of these stages were investigated. Pistacia vera ovule is single, fullynucellate, monotegumental and converse (anatrope and is set in an ovary with basic placement and the Polygonum type embryo sac is organized in it one week after complete dehiscence. After pollination and fertilization of egg cell, after 6 weeks of complete dehiscence, the pericarpe was grown to final size and even the lignifications of endocarpe started but the zygote cell was in a dormant state and in 6-8 weeks after complete dehiscence the zygote cell division along an increase in endosperm division occured so that cotyledonary embryo was formed in 10-12 weeks after complete dehiscence and the cotyledons attained their final size in 3 weesks after that, namely 15 weeks after complete dehiscence and at this time, the seedless and filled fruits were completely distinguished. During the ovule development stages, some abnormalities were observed such as lack of embryo sac formation, embryo sac degeneration, small and abnormal embryo sac formation, vascular band collapse inside the funicule, presence of zygote without endosperm and presence of endosperm without zygote, and these abnormalities caused lack of enough ovule growth and seedless or semiseedless fruit formation in pistachio.

Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

International Nuclear Information System (INIS)

He Chengyong; Zuo Zhenghong; Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin; Wang Chonggang

2011-01-01

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

Effects of benzo(a)pyrene on the skeletal development of Sebastiscus marmoratus embryos and the molecular mechanism involved

Energy Technology Data Exchange (ETDEWEB)

He Chengyong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Zuo Zhenghong [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China); Shi Xiao; Li Ruixia; Chen Donglei; Huang Xin; Chen Yixin [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); Wang Chonggang, E-mail: cgwang@xmu.edu.cn [Key Laboratory of Ministry of Education for Subtropical Wetland Ecosystem Research, School of Life Sciences, Xiamen University, Xiamen (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen (China)

2011-01-25

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants, which have been known to be carcinogenic and teratogenic. However, the skeletal development toxicity of PAHs and the mechanism involved remain unclear. In fishes, the neurocranial and craniofacial skeleton develop as cartilage. The signaling molecules of hedgehog (Hh) family play crucial roles in regulating skeletal development. In the present study, rockfish (Sebastiscus marmoratus) embryos were exposed to benzo(a)pyrene (BaP) for 7 days at environmental levels (0.05, 0.5 and 5 nmol/L) which resulted in craniofacial skeleton deformities. BaP exposure reduced the cell proliferation activity in the craniofacial skeleton as detected by quantitative PCR and in situ hybridization. The expression of Sonic hedgehog (Shh), rather than Indian hedgehog (Ihh), was down-regulated in the craniofacial skeleton in the 0.5 and 5 nmol/L groups. Consistent with the Shh results, the expression of Ptch1 and Gli2 was decreased by BaP exposure and BMP4 was presented on changes in the 0.5 and 5 nmol/L groups. These results suggested that BaP could impair the expression and function of Shh signaling pathway, perturbing the proliferation of chondrocytes and so disturbing craniofacial skeletal development.

Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients.

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Conti, Antonio; Riva, Nilo; Pesca, Mariasabina; Iannaccone, Sandro; Cannistraci, Carlo V; Corbo, Massimo; Previtali, Stefano C; Quattrini, Angelo; Alessio, Massimo

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek diagnostic markers, we analyzed skeletal muscle biopsies with the differential expression proteomic approach. We studied skeletal muscle biopsies from healthy controls (CN), sporadic ALS (sALS), motor neuropathies (MN) and myopathies (M). Pre-eminently among several differentially expressed proteins, Myosin binding protein H (MyBP-H) expression in ALS samples was anomalously high. MyBP-H is a component of the thick filaments of the skeletal muscle and has strong affinity for myosin, but its function is still unclear. High MyBP-H expression level was associated with abnormal expression of Rho kinase 2 (ROCK2), LIM domain kinase 1 (LIMK1) and cofilin2, that might affect the actin-myosin interaction. We propose that MyBP-H expression level serves, as a putative biomarker in the skeletal muscle, to discriminate ALS from motor neuropathies, and that it signals the onset of dysregulation in actin-myosin interaction; this in turn might contribute to the pathogenesis of ALS. © 2013 Elsevier B.V. All rights reserved.

Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from mdx mice.

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Divet, Alexandra; Huchet-Cadiou, Corinne

2002-08-01

The aim of the present study was to establish whether alterations in sarcoplasmic reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic reticulum and contractile proteins of fast- and slow-twitch muscles were therefore investigated in chemically skinned fibres isolated from the extensor digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4 and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by the Ca(2+) release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca(2+) quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of the contractile apparatus was not significantly different. These results indicate that mdx hindlimb muscles are affected differently by the disease process and suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca(2+) homeostasis.

Redox Control of Skeletal Muscle Regeneration.

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Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

2017-08-10

Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

Development of a skeletal multi-component fuel reaction mechanism based on decoupling methodology

International Nuclear Information System (INIS)

Mohan, Balaji; Tay, Kun Lin; Yang, Wenming; Chua, Kian Jon

2015-01-01

Highlights: • A compact multi-component skeletal reaction mechanism was developed. • Combined bio-diesel and PRF mechanism was proposed. • The mechanism consists of 68 species and 183 reactions. • Well validated against ignition delay times, flame speed and engine results. - Abstract: A new coupled bio-diesel surrogate and primary reference fuel (PRF) oxidation skeletal mechanism has been developed. The bio-diesel surrogate sub-mechanism consists of oxidation sub-mechanisms of Methyl decanoate (MD), Methyl 9-decenoate (MD9D) and n-Heptane fuel components. The MD and MD9D are chosen to represent the saturated and unsaturated methyl esters respectively in bio-diesel fuels. Then, a reduced iso-Octane oxidation sub-mechanism is added to the bio-diesel surrogate sub-mechanism. Then, all the sub-mechanisms are integrated to a reduced C_2–C_3 mechanism, detailed H_2/CO/C_1 mechanism and reduced NO_x mechanism based on decoupling methodology. The final mechanism consisted of 68 species and 183 reactions. The mechanism was well validated with shock-tube ignition delay times, laminar flame speed and 3D engine simulations.

Comparison of radiographic and radionuclide skeletal surveys in battered children

International Nuclear Information System (INIS)

Pickett, W.J.; Faleski, E.J.; Chacko, A.; Jarrett, R.V.

1983-01-01

A review of 13 cases of suspected child abuse in which radionuclide (RN) scans, radiographic skeletal surveys, and sufficient follow-up were available showed that the RN scans were insensitive, even though fractures were more than 48 hours old at the time of the scan. Frequently missed lesions included skull and extremity fractures. Furthermore, soft tissue and visceral abnormalities that were identified on radiographic examination went undetected on RN scan. We conclude that, although the RN scan may augment the radiographic examination, it should not be used alone to screen for the battered child

The effect of exercise on skeletal muscle fibre type distribution in obesity: From cellular levels to clinical application.

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Pattanakuhar, Sintip; Pongchaidecha, Anchalee; Chattipakorn, Nipon; Chattipakorn, Siriporn C

Skeletal muscles play important roles in metabolism, energy expenditure, physical strength, and locomotive activity. Skeletal muscle fibre types in the body are heterogeneous. They can be classified as oxidative types and glycolytic types with oxidative-type are fatigue-resistant and use oxidative metabolism, while fibres with glycolytic-type are fatigue-sensitive and prefer glycolytic metabolism. Several studies demonstrated that an obese condition with abnormal metabolic parameters has been negatively correlated with the distribution of oxidative-type skeletal muscle fibres, but positively associated with that of glycolytic-type muscle fibres. However, some studies demonstrated otherwise. In addition, several studies demonstrated that an exercise training programme caused the redistribution of oxidative-type skeletal muscle fibres in obesity. In contrast, some studies showed inconsistent findings. Therefore, the present review comprehensively summarizes and discusses those consistent and inconsistent findings from clinical studies, regarding the association among the distribution of skeletal muscle fibre types, obese condition, and exercise training programmes. Furthermore, the possible underlying mechanisms and clinical application of the alterations in muscle fibre type following obesity are presented and discussed. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

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Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

2012-01-01

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process. PMID:22279050

A new take on an old story: chick limb organ culture for skeletal niche development and regenerative medicine evaluation

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EL Smith

2013-09-01

Full Text Available Scientific research and progress, particularly in the drug discovery and regenerative medicine fields, is typically dependent on suitable animal models to develop new and improved clinical therapies for injuries and diseases. In vivo model systems are frequently utilised, but these models are expensive, highly complex and pose a number of ethical considerations leading to the development and use of a number of alternative ex vivo model systems. The ex vivo embryonic chick long bone and limb bud models have been utilised in the scientific research field as a model to understand skeletal development for over eighty years. The rapid development of avian skeletal tissues, coupled with the ease of experimental manipulation, availability of genome sequence and the presence of multiple cell and tissue types has seen such model systems gain significant research interest in the last few years in the tissue engineering field. The models have been explored both as systems for understanding the developmental bone niche and as potential testing tools for tissue engineering strategies for bone repair and regeneration. This review details the evolution of the chick limb organ culture system and presents recent innovative developments and emerging techniques and technologies applied to these models that are aiding our understanding of skeletal developmental and regenerative medicine research and application.

Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

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Lisa Vu, MD

2014-01-01

Full Text Available Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus.

Skeletal muscle stem cells from animals I. Basic cell biology

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Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

Dentofacial transverse development in Koreans according to skeletal maturation: A cross-sectional study.

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Hwang, Soonshin; Noh, Yoonjeong; Choi, Yoon Jeong; Chung, Chooryung; Lee, Hye Sun; Kim, Kyung-Ho

2018-01-01

The aim of this study was to establish the normative data of dentofacial transverse dimensions according to the skeletal maturation stage in Korean adolescents with good occlusion, assess gender differences and determine correlations between transverse variables. A total of 577 Korean subjects between ages 7 to 19 years and exhibiting skeletal Class I occlusion were categorized by skeletal maturation index (SMI) of Fishman using hand-wrist radiographs. Dentofacial transverse dimensions were assessed using posteroanterior cephalograms. Independent two-sample t -tests were used to analyze differences between genders. Pearson correlation coefficient was used to determine the correlation between transverse measurements. Dentofacial transverse norms relevant to skeletal maturation stages were established. The average maxillomandibular width difference and ratio at growth completion was 22.16 mm and 77.01% for males; 23.70 mm and 74.06% for females, respectively. Males had greater facial, maxillary and mandibular widths compared to females at every SMI stage. The maxillary and mandibular intermolar widths showed the strongest correlation for both sexes (r = 0.826 for males, r = 0.725 for females). Dentofacial transverse norms of Korean adolescents were established according to developmental stage. All dentofacial widths were greater in males at growth completion. Maxillary and mandibular intermolar widths were strongly correlated. This study may serve as a guideline for the assessment of dentofacial transverse growth according to skeletal maturation stage in Korean adolescents with good occlusion.

Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

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Bárez-López, Soledad; Bosch-García, Daniel; Gómez-Andrés, David; Pulido-Valdeolivas, Irene; Montero-Pedrazuela, Ana; Obregon, Maria Jesus; Guadaño-Ferraz, Ana

2014-01-01

Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms. This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed. The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

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Soledad Bárez-López

Full Text Available BACKGROUND: Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4 but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2. To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO did not find gross neurological alterations, possibly due to compensatory mechanisms. AIM: This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. RESULTS: Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice. No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction and skeletal muscle (33% reduction, but not in the cerebellum where other deiodinase (type 1 is expressed. CONCLUSIONS: The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.

New prognostic factors and scoring system for patients with skeletal metastasis.

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Katagiri, Hirohisa; Okada, Rieko; Takagi, Tatsuya; Takahashi, Mitsuru; Murata, Hideki; Harada, Hideyuki; Nishimura, Tetsuo; Asakura, Hirofumi; Ogawa, Hirofumi

2014-10-01

The aim of this study was to update a previous scoring system for patients with skeletal metastases, that was proposed by Katagiri et al. in 2005, by introducing a new factor (laboratory data) and analyzing a new patient cohort. Between January 2005 and January 2008, we treated 808 patients with symptomatic skeletal metastases. They were prospectively registered regardless of their treatments, and the last follow-up evaluation was performed in 2012. There were 441 male and 367 female patients with a median age of 64 years. Of these patients, 749 were treated nonsurgically while the remaining 59 underwent surgery for skeletal metastasis. A multivariate analysis was conducted using the Cox proportional hazards model. We identified six significant prognostic factors for survival, namely, the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy, and multiple skeletal metastases. The first three factors had a larger impact than the remaining three. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27% at 6 months, and only 6% at 1 year. In contrast, patients with a prognostic score of ≤3 had a survival rate of 91% at 1 year, and 78% at 2 years. Comparing the revised system with the previous one, there was a significantly lower number of wrongly predicted patients using the revised system. This revised scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than the previous system and may be useful for selecting an optimal treatment. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

pitx2 Deficiency results in abnormal ocular and craniofacial development in zebrafish.

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Yi Liu

Full Text Available Human PITX2 mutations are associated with Axenfeld-Rieger syndrome, an autosomal-dominant developmental disorder that involves ocular anterior segment defects, dental hypoplasia, craniofacial dysmorphism and umbilical abnormalities. Characterization of the PITX2 pathway and identification of the mechanisms underlying the anomalies associated with PITX2 deficiency is important for better understanding of normal development and disease; studies of pitx2 function in animal models can facilitate these analyses. A knockdown of pitx2 in zebrafish was generated using a morpholino that targeted all known alternative transcripts of the pitx2 gene; morphant embryos generated with the pitx2(ex4/5 splicing-blocking oligomer produced abnormal transcripts predicted to encode truncated pitx2 proteins lacking the third (recognition helix of the DNA-binding homeodomain. The morphological phenotype of pitx2(ex4/5 morphants included small head and eyes, jaw abnormalities and pericardial edema; lethality was observed at ∼6-8-dpf. Cartilage staining revealed a reduction in size and an abnormal shape/position of the elements of the mandibular and hyoid pharyngeal arches; the ceratobranchial arches were also decreased in size. Histological and marker analyses of the misshapen eyes of the pitx2(ex4/5 morphants identified anterior segment dysgenesis and disordered hyaloid vasculature. In summary, we demonstrate that pitx2 is essential for proper eye and craniofacial development in zebrafish and, therefore, that PITX2/pitx2 function is conserved in vertebrates.

A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development

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Bidwell Christopher A

2010-06-01

Full Text Available Abstract Background The developmental transition between the late fetus and a newborn animal is associated with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels. We tested the hypothesis that this developmental transition is associated with large coordinated changes in the transcription of skeletal muscle genes. Results Using an ovine model, transcriptional profiling was performed on Longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development and two postnatal time points, one approximately 3 days postpartum and a second at 3 months of age. The developmental time course was dominated by large changes in expression of 2,471 genes during the interval between late fetal development (120 d fetal development and 1-3 days postpartum. Analysis of the functions of genes that were uniquely up-regulated in this interval showed strong enrichment for oxidative metabolism and the tricarboxylic acid cycle indicating enhanced mitochondrial activity. Histological examination of tissues from these developmental time points directly confirmed a marked increase in mitochondrial activity between the late fetal and early postnatal samples. The promoters of genes that were up-regulated during this fetal to neonatal transition were enriched for estrogen receptor 1 and estrogen related receptor alpha cis-regulatory motifs. The genes down-regulated during this interval highlighted de-emphasis of an array of functions including Wnt signaling, cell adhesion and differentiation. There were also changes in gene expression prior to this late fetal - postnatal transition and between the two postnatal time points. The former genes were enriched for functions involving the extracellular matrix and immune

The skeletal system

NARCIS (Netherlands)

Nikkels, PGJ

2015-01-01

Skeletal dysplasias are a group of disorders with a disturbance in development and/or growth of cartilage and/or bone. Epiphysis, metaphysis, and diaphysis of long bones are affected in a generalized manner with or without involvement of membranous bone of the skull. A dysostosis affects one or some

Computed tomographic findings of skeletal muscles in amyotrophic lateral sclerosis (ALS)

International Nuclear Information System (INIS)

Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirobumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya

1989-01-01

We evaluated the Computed Tomographic (CT) findings of skeletal muscles in 12 cases of amyotrophic lateral sclerosis (ALS), 1 case of spinal progressive muscular atrophy (SPMA), and 1 case of Kugelberg-Welander disease. CT examination was performed in the neck, shoulders, abdomen, pelvis, thighs, and lower legs, 15 muscles were selected for evaluation. The following muscles tended to be affected: m. transversospinalis (12 cases were abnormal), m. deltoideus (10), m. subscapularis (10), m. infraspinatus (10), mm. dorsi (12), hamstring muscles (14), m. tibialis anterior (14), and m. triceps surae (14). On the contrary, the following muscles tended to be preserved: m. sternocleidomastoideus (only 7 cases were abnormal), m. psoas major (7), m. gluteus maximus (7), m. rectus femoris (7), m. sartorius (7) and m. gracilis (6). The distribution of the muscles affected showed neither proximal nor distal dominancy. As the disease advanced, however, all the muscles became affected without any severity. CT findings of skeletal muscles in ALS were characterized by muscle atrophy and fat infiltration, which showed a patchy, linear, or moth-eaten appearance. In mildly affected cases, there was muscle atrophy without internal architectual changes. In moderately affected cases, muscle atrophy advanced and internal architectural changes (patchy, linear, and moth-eaten fat infiltration) became evident. In most advanced cases, every muscle showed a ragged appearance because of severe muscle atrophy and internal architectural changes. These findings were well distinguished from those of SPMA, which resembled the CT pattern of primary muscle diseases. (author)

Computed tomographic findings of skeletal muscles in amyotrophic lateral sclerosis (ALS)

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirobumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya (Kitano Hospital, Osaka (Japan))

1989-04-01

We evaluated the Computed Tomographic (CT) findings of skeletal muscles in 12 cases of amyotrophic lateral sclerosis (ALS), 1 case of spinal progressive muscular atrophy (SPMA), and 1 case of Kugelberg-Welander disease. CT examination was performed in the neck, shoulders, abdomen, pelvis, thighs, and lower legs, 15 muscles were selected for evaluation. The following muscles tended to be affected: m. transversospinalis (12 cases were abnormal), m. deltoideus (10), m. subscapularis (10), m. infraspinatus (10), mm. dorsi (12), hamstring muscles (14), m. tibialis anterior (14), and m. triceps surae (14). On the contrary, the following muscles tended to be preserved: m. sternocleidomastoideus (only 7 cases were abnormal), m. psoas major (7), m. gluteus maximus (7), m. rectus femoris (7), m. sartorius (7) and m. gracilis (6). The distribution of the muscles affected showed neither proximal nor distal dominancy. As the disease advanced, however, all the muscles became affected without any severity. CT findings of skeletal muscles in ALS were characterized by muscle atrophy and fat infiltration, which showed a patchy, linear, or moth-eaten appearance. In mildly affected cases, there was muscle atrophy without internal architectual changes. In moderately affected cases, muscle atrophy advanced and internal architectural changes (patchy, linear, and moth-eaten fat infiltration) became evident. In most advanced cases, every muscle showed a ragged appearance because of severe muscle atrophy and internal architectural changes. These findings were well distinguished from those of SPMA, which resembled the CT pattern of primary muscle diseases. (author).

The diagnosis of skeletal dysplasias: a multidisciplinary approach

International Nuclear Information System (INIS)

Mortier, Geert R.

2001-01-01

Skeletal dysplasias are heritable connective tissue disorders affecting skeletal morphogenesis and development. They represent a heterogeneous group of genetic disorders with more than 200 different entities being delineated to date. Because of this diversity, the diagnosis of a skeletal dysplasia is usually based on a combination of clinical, radiographic, morphologic, and, in some instances, biochemical and molecular studies. Tremendous advances have been made in the elucidation of the genetic defect of several of these conditions over the past 10 years. This progress has provided us with more insights into the genes controlling normal skeletal development. It also has opened new diagnostic perspectives. For several disorders, identification of the causal gene allows us now to confirm with a molecular test the diagnosis postulated on the basis of clinical, radiographic and/or morphologic studies. It also enables us to establish the diagnosis early in pregnancy. An accurate diagnosis is not only important for proper management of the affected individual but also the cornerstone for adequate genetic counseling

The diagnosis of skeletal dysplasias: a multidisciplinary approach

Energy Technology Data Exchange (ETDEWEB)

Mortier, Geert R. E-mail: geert.mortier@rug.ac.be

2001-12-01

Skeletal dysplasias are heritable connective tissue disorders affecting skeletal morphogenesis and development. They represent a heterogeneous group of genetic disorders with more than 200 different entities being delineated to date. Because of this diversity, the diagnosis of a skeletal dysplasia is usually based on a combination of clinical, radiographic, morphologic, and, in some instances, biochemical and molecular studies. Tremendous advances have been made in the elucidation of the genetic defect of several of these conditions over the past 10 years. This progress has provided us with more insights into the genes controlling normal skeletal development. It also has opened new diagnostic perspectives. For several disorders, identification of the causal gene allows us now to confirm with a molecular test the diagnosis postulated on the basis of clinical, radiographic and/or morphologic studies. It also enables us to establish the diagnosis early in pregnancy. An accurate diagnosis is not only important for proper management of the affected individual but also the cornerstone for adequate genetic counseling.

Is skeletal anchorage changing the limit of orthodontics?

DEFF Research Database (Denmark)

Melsen, Birte

2007-01-01

The limits for orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied; not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... and can be loaded immediately. The course will be addressed the following topics: Are the mini-implants replacing conventional anchorage? Why are orthodontic mini-implants necessary? The development of the skeletal anchorage systems The biological basis for the skeletal anchorage systems...... The characteristics of the different skeletal anchorage systems The insertion procedure The indications for the use of orthodontic mini-implants Treatment planning in relation to the use of mini-implants Case presentations...

mTOR signaling and its roles in normal and abnormal brain development.

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Nobuyuki eTakei

2014-04-01

Full Text Available Target of rapamycin (TOR was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mTOR (mammalian TOR. mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system (CNS, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

Aberrant and alternative splicing in skeletal system disease.

Science.gov (United States)

Fan, Xin; Tang, Liling

2013-10-01

The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy. © 2013 Elsevier B.V. All rights reserved.

Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers

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Erick O. Hernández-Ochoa

2017-01-01

Full Text Available A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC—the sequential link between action potentials (AP, intracellular Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.. Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay; most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.

LINK BETWEEN SKELETAL RELATIONS AND ROOT RESORPTION IN ORTHODONTIC PATIENTS

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Cristina Teodora Preoteasa

2011-09-01

Full Text Available External root resorption is one of the possible complications of the orthodontic treatment, severe cases presenting a higher frequency. The aim of the present study was to test the existence of a relation between the severity of root resorption and the sagittal or vertical skeletal relations. A cross-sectional study was conducted on a group of 55 patients with fixed orthodontic devices, applied bimaxillarily for at least 6 months. The sample presented mostly mild or moderate apical root resorption, with an average value of 1.31 mm (standard deviation 0.60. Patients with abnormal sagittal skeletal relations presented a more severe root resorption compared to those with a normal pattern. The tendency towards more severe external root resorption was also noticed in cases with mandibular clockwise rotation and hiperdivergent facial pattern. A good knowledge on the variables associated to severe root resorption is essential for the identification of the high risk patients, as well as for the selection of the best suited treatment alternative in terms of low probability of root resorption occurrence.

Effects of hypodynamic simulations on the skeletal system of monkeys

Science.gov (United States)

Young, D. R.; Tremor, J. W.

1977-01-01

A research and development program was undertaken to evaluate the skeletal losses of subhuman primates in hypodynamic environments. The goals of the program are: (1) to uncover the mechanisms by which weightlessness affects the skeletal system; (2) to determine the consequences and reversibility of bone mineral losses; and (3) to acquire a body of data needed to formulate an appropriate countermeasure program for the prevention of skeletal deconditioning. Space flight experiment simulation facilities are under development and will be tested for their capability in supporting certain of the requirements for these investigations.

MR imaging of overuse injuries in the skeletally immature gymnast: spectrum of soft-tissue and osseous lesions in the hand and wrist

Energy Technology Data Exchange (ETDEWEB)

Dwek, Jerry R. [Department of Radiology, Rady Children' s Hospital and Health Center, San Diego, CA (United States); Cardoso, Fabiano; Chung, Christine B. [University of California at San Diego, Department of Radiology, San Diego, CA (United States)

2009-12-15

In the pediatric gymnast, stress-related physeal injuries have been well described with characteristic imaging findings. However, a spectrum of overuse injuries, some rarely reported in the literature, can be encountered in the gymnast's hand and wrist. To demonstrate the MR appearance of a spectrum of overuse injuries in the skeletally immature wrist and hand of pediatric gymnasts. A total of 125 MR exams of the hand and wrist in skeletally immature children were performed at our institution during a 2-year period. Clinical histories were reviewed for gymnastics participation. MR studies of that subpopulation were reviewed and abnormalities tabulated. Of the MR studies reviewed, ten gymnasts were identified, all girls age 12-16 years (mean age 14.2 years) who presented with wrist or hand pain. Three of these children had bilateral MR exams. Abnormalities included chronic physeal injuries in three children. Two girls exhibited focal lunate osteochondral defects. Triangular fibrocartilage tears were present in three girls, one of whom had a scapholunate ligament tear. Two girls manifested metacarpal head flattening and necrosis. A variety of soft-tissue and osseous lesions can be encountered in the skeletally immature gymnast. Familiarity with these stress-related injuries is important for accurate diagnosis. (orig.)

MR imaging of overuse injuries in the skeletally immature gymnast: spectrum of soft-tissue and osseous lesions in the hand and wrist

International Nuclear Information System (INIS)

Dwek, Jerry R.; Cardoso, Fabiano; Chung, Christine B.

2009-01-01

In the pediatric gymnast, stress-related physeal injuries have been well described with characteristic imaging findings. However, a spectrum of overuse injuries, some rarely reported in the literature, can be encountered in the gymnast's hand and wrist. To demonstrate the MR appearance of a spectrum of overuse injuries in the skeletally immature wrist and hand of pediatric gymnasts. A total of 125 MR exams of the hand and wrist in skeletally immature children were performed at our institution during a 2-year period. Clinical histories were reviewed for gymnastics participation. MR studies of that subpopulation were reviewed and abnormalities tabulated. Of the MR studies reviewed, ten gymnasts were identified, all girls age 12-16 years (mean age 14.2 years) who presented with wrist or hand pain. Three of these children had bilateral MR exams. Abnormalities included chronic physeal injuries in three children. Two girls exhibited focal lunate osteochondral defects. Triangular fibrocartilage tears were present in three girls, one of whom had a scapholunate ligament tear. Two girls manifested metacarpal head flattening and necrosis. A variety of soft-tissue and osseous lesions can be encountered in the skeletally immature gymnast. Familiarity with these stress-related injuries is important for accurate diagnosis. (orig.)

Upon the triple phase skeletal scintigraphy in traumatology

International Nuclear Information System (INIS)

Spitz, W.

1988-01-01

A broadly established indication catalogue for skeletal scintigraphy in traumatology is resulting from about 1500 skeletal scans. Aside from the exclusion of any osseous lesion, from the differentiation of uncertain X-ray findings, from the determination of the extent of osseous lesions in polytraumatic conditions and from the assessment of the relative fracture age, the follow-up after trauma and therapeutical intervention, the demonstration of battered child syndromes and of soft tissue lesions are of special importance with regard to these topics. For all that, the high sensitivity of the 3-phase skeletal scintigraphy for every enhancement of osseous turnover represents the elementary prerequisite for the employment of this non-invasive technique as an ideal screening method in traumatological diagnostics. The experiences from the past years have resulted in an increased frequency of skeletal scintigraphic studies to a similarly high level, as it is already established in the majority of institutions with respect to oncological problems, In the development of efficient and cost favourable diagnostic strategies with only little burden to the patient, skeletal scintigraphy will in future play an important role within the palette of modern skeletal diagnostics in traumatology. (orig.) [de

Protein-losing enteropathy with intestinal lymphangiectasia in skeletal dysplasia with Lys650Met mutation.

Science.gov (United States)

Yang, Chen; Dehner, Louis P

2016-11-01

Protein-losing enteropathy is a primary or secondary manifestation of a group of conditions, and etiologies which are broadly divisible into those with mucosal injury on the basis of inflammatory and ulcerative conditions, mucosal injury without erosions or ulcerations, and lymphatic abnormalities. We describe the first case of protein-losing enteropathy in a pediatric patient, with severe skeletal dysplasia consistent with thanatophoric dysplasia type I and DNA analysis that revealed a c.1949A>T (p.Lys650Met) in exon 15 of the FGFR3 gene. She presented with protein-losing enteropathy in her 6th month. Post-mortem examination revealed lymphangiectasia in the small intestine. To our knowledge, this is the first report of intestinal lymphangiectasia as a complication of skeletal dysplasia resulting in severe protein-losing enteropathy. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High sugar intake and development of skeletal muscle insulin resistance and inflammation in mice: a protective role for PPAR- δ agonism.

Science.gov (United States)

Benetti, Elisa; Mastrocola, Raffaella; Rogazzo, Mara; Chiazza, Fausto; Aragno, Manuela; Fantozzi, Roberto; Collino, Massimo; Minetto, Marco A

2013-01-01

Peroxisome Proliferator Activated Receptor (PPAR)- δ agonists may serve for treating metabolic diseases. However, the effects of PPAR- δ agonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR- δ agonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR- δ upregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR- δ activation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.

Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.

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Masaki Matsushita

Full Text Available Achondroplasia (ACH is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8 cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias.

Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

Science.gov (United States)

Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

2013-01-01

Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

STIM1 as a key regulator for Ca2+ homeostasis in skeletal-muscle development and function

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Kiviluoto Santeri

2011-04-01

Full Text Available Abstract Stromal interaction molecules (STIM were identified as the endoplasmic-reticulum (ER Ca2+ sensor controlling store-operated Ca2+ entry (SOCE and Ca2+-release-activated Ca2+ (CRAC channels in non-excitable cells. STIM proteins target Orai1-3, tetrameric Ca2+-permeable channels in the plasma membrane. Structure-function analysis revealed the molecular determinants and the key steps in the activation process of Orai by STIM. Recently, STIM1 was found to be expressed at high levels in skeletal muscle controlling muscle function and properties. Novel STIM targets besides Orai channels are emerging. Here, we will focus on the role of STIM1 in skeletal-muscle structure, development and function. The molecular mechanism underpinning skeletal-muscle physiology points toward an essential role for STIM1-controlled SOCE to drive Ca2+/calcineurin/nuclear factor of activated T cells (NFAT-dependent morphogenetic remodeling programs and to support adequate sarcoplasmic-reticulum (SR Ca2+-store filling. Also in our hands, STIM1 is transiently up-regulated during the initial phase of in vitro myogenesis of C2C12 cells. The molecular targets of STIM1 in these cells likely involve Orai channels and canonical transient receptor potential (TRPC channels TRPC1 and TRPC3. The fast kinetics of SOCE activation in skeletal muscle seem to depend on the triad-junction formation, favoring a pre-localization and/or pre-formation of STIM1-protein complexes with the plasma-membrane Ca2+-influx channels. Moreover, Orai1-mediated Ca2+ influx seems to be essential for controlling the resting Ca2+ concentration and for proper SR Ca2+ filling. Hence, Ca2+ influx through STIM1-dependent activation of SOCE from the T-tubule system may recycle extracellular Ca2+ losses during muscle stimulation, thereby maintaining proper filling of the SR Ca2+ stores and muscle function. Importantly, mouse models for dystrophic pathologies, like Duchenne muscular dystrophy, point towards an

Developmental expression of the alpha-skeletal actin gene

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Vonk Freek J

2008-06-01

Full Text Available Abstract Background Actin is a cytoskeletal protein which exerts a broad range of functions in almost all eukaryotic cells. In higher vertebrates, six primary actin isoforms can be distinguished: alpha-skeletal, alpha-cardiac, alpha-smooth muscle, gamma-smooth muscle, beta-cytoplasmic and gamma-cytoplasmic isoactin. Expression of these actin isoforms during vertebrate development is highly regulated in a temporal and tissue-specific manner, but the mechanisms and the specific differences are currently not well understood. All members of the actin multigene family are highly conserved, suggesting that there is a high selective pressure on these proteins. Results We present here a model for the evolution of the genomic organization of alpha-skeletal actin and by molecular modeling, illustrate the structural differences of actin proteins of different phyla. We further describe and compare alpha-skeletal actin expression in two developmental stages of five vertebrate species (mouse, chicken, snake, salamander and fish. Our findings confirm that alpha-skeletal actin is expressed in skeletal muscle and in the heart of all five species. In addition, we identify many novel non-muscular expression domains including several in the central nervous system. Conclusion Our results show that the high sequence homology of alpha-skeletal actins is reflected by similarities of their 3 dimensional protein structures, as well as by conserved gene expression patterns during vertebrate development. Nonetheless, we find here important differences in 3D structures, in gene architectures and identify novel expression domains for this structural and functional important gene.

Mechanisms of internal emitter skeletal toxicity

International Nuclear Information System (INIS)

Jee, W.S.S.

1985-01-01

The purpose of this program is to determine the mechanisms for the induction of skeletal cancers in dogs and man by α-emitting bone-seeking radionuclides from the nuclear fuel cycle. The role of microdistribution of radium-226 and plutonium-239, bone metabolism, bone cell turnover, and localized bone cell dosimetry in bone can induction will be determined. The osteogenic cell dose will be measured in dogs to develop better quantitative dose response information. Skeletal carcinogenesis models will be developed by correlating the local dosimetry, tumor site and incidence, age-dependent skeletal biology (bone morphometry, bone cell at risk, bone cell turnover, residence time and fate, remodeling rate, growth pattern and rate, hormonal influences, manipulation of bone cell populations of the bone modeling and remodeling systems, etc.). The authors will test the hypothesis that the frequency of osteosarcomas is proportional to the average dose delivered to cells at risk. They will also attempt to explain experimentally found toxicity ratios between volume- and bone surface-seeking radionuclides on the basis of radiation dose ratios

Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with positron emission tomography in correlation with CT

International Nuclear Information System (INIS)

Petren-Mallmin, M.; Andreasson, I.; Bergh, J.; Ljunggren, Oe.; Ahlstroem, H.; Antoni, G.; Laangstroem, B.; Bergstroem, M.

1998-01-01

Objective. To characterise the uptake of 18 F in skeletal metastases from breast cancer using positron emission tomography (PET) and to relate these findings to the appearance on CT. Patients and design. PET with 18 F and CT were performed in five patients with multiple skeletal metastases from breast cancer. The CT characteristics were analysed in areas with high uptake on the PET study. Dynamic PET imaging of the skeletal kinetics of the 18 F-fluoride ion were included. Results. The areas of abnormal high accumulation of 18 F correlated well with the pathological appearance on CT. Lytic as well as sclerotic lesions had markedly higher uptake than normal bone, with a 5-10 times higher transport rate constant for trapping of the tracer in the metastatic lesions than in normal bone. Conclusion. PET with 18 F-fluoride demonstrates very high uptake in lytic and sclerotic breast cancer metastases. (orig.)

Exercise Promotes Healthy Aging of Skeletal Muscle

DEFF Research Database (Denmark)

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M

2016-01-01

caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial...... respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle....

Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride: concise communication

International Nuclear Information System (INIS)

Schulz, E.E.; Libanati, C.R.; Farley, S.M.; Kirk, G.A.; Baylink, D.J.

1984-01-01

An appendicular skeletal response to sodium fluoride (NaF) was detected by total skeletal scintigrams. Twelve postmenopausal osteoporotic women were treated with NaF (88 mg/day) and calcium (1500 mg/day). Total skeletal scintigrams were obtained before and during treatment. Within 4 to 21 mo (mean: 8.3), all 12 patients showed new areas of increased uptake corresponding to metaphyseal regions and short bones of the appendicular skeleton. Nine patients showed an increase in serum alkaline phosphatase activity, which was attributed to an increase in the skeletal isoenzyme. Seven of 12 patients developed bone pain in one or more of the regions of increased uptake. This study establishes that the skeletal scintigram is a sensitive index of the peripheral skeletal response to NaF

A distinct subtype of ''metatropic dysplasia variant'' characterised by advanced carpal skeletal age and subluxation of the radial heads

International Nuclear Information System (INIS)

Nishimura, G.; Satoh, Masato; Aihara, Toshinori; Aida, Noriko; Yamamoto, Takehisa; Ozono, Keiichi

1998-01-01

Background. ''Metatropic dysplasia variants'' are a group of bone dysplasias whose skeletal abnormalities are similar to, but milder than, those of classical metatropic dysplasia. The genetic and phenotypic heterogeneity has not been thoroughly elucidated. Objective. The objective was to designate a distinct subtype of these metatropic dysplasia variants. Materials and methods. The subjects were four Japanese patients, two sporadic cases and two siblings, who all had identical skeletal changes. The radiological features in these patients were compared with those of previously reported metatropic dysplasia variants. Results. Moderate platyspondyly with pear-shaped and/or anterior-tongued vertebral bodies, halberd pelvis, and dumbbell deformity of the tubular bones were regarded as hallmarks of metatropic dysplasia variants. The peculiar skeletal change in our patients was advanced carpal skeletal age in childhood, unlike most patients reported as metatropic dysplasia variants who manifest delayed carpal ossification. Another hallmark was congenital dislocation of the radial heads. A description of a patient with similar skeletal changes was found in the literature. Conclusion. These patients are considered to represent a distinct subgroup of metatropic dysplasia variants. It remains unknown whether the present siblings represent an autosomal recessive trait or an autosomal dominant trait with germinal mosaicism related to increased paternal age. (orig.)

Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. I. An immunohistochemical analysis of creatine kinase isoenzyme expression patterns

NARCIS (Netherlands)

Wessels, A.; Vermeulen, J. L.; Virágh, S.; Kálmán, F.; Morris, G. E.; Man, N. T.; Lamers, W. H.; Moorman, A. F.

1990-01-01

Using monoclonal antibodies against the M and B subunit isoforms of creatine kinase (CK) we have investigated their distribution in developing human skeletal and cardiac muscle immunohistochemically. It is demonstrated that in skeletal muscle, a switch from CK-B to CK-M takes place around the week 8

Exercise Promotes Healthy Aging of Skeletal Muscle.

Science.gov (United States)

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

Skeletal deformities of acardius anceps: the gross and imaging features

Energy Technology Data Exchange (ETDEWEB)

Chen Chihping [Dept. of Medical Research, Mackay Memorial Hospital, Taipei (Taiwan, Province of China); Shih Shinlin [Dept. of Radiology, Mackay Memorial Hospital, Taipei (Taiwan, Province of China); Liu Fenfen [Dept. of Medical Research, Mackay Memorial Hospital, Taipei (Taiwan, Province of China); Jan Sheauwen [Dept. of Medical Research, Mackay Memorial Hospital, Taipei (Taiwan, Province of China); Lin Yunnan [Dept. of Pathology, Mackay Memorial Hospital, Taipei (Taiwan, Province of China); Lan Chungchi [Dept. of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei (Taiwan, Province of China)

1997-03-01

A morphology based imaging review is presented of the characteristic skeletal deformities associated with acardius anceps in three acardiac twins. These fetuses demonstrated poorly developed skulls, limb reduction defects, and phocomelia of the upper limbs, as well as narrow thoracic cages with or without the complete development of ribs, clavicles, scapulae, and cervical, thoracic, or lumbar vertebrae. However, their lower limbs and pelvic girdles were almost normal. The authors conclude that skeletal development is likely to be jeopardized in the area adjacent to the heart and in the cephalic portion of the body in fetuses with acardius anceps, and suggest vascular deficiency and hypoperfusion as pathogenetic mechanisms in this type of skeletal deformity. (orig.)

Skeletal deformities of acardius anceps: the gross and imaging features

International Nuclear Information System (INIS)

Chen Chihping; Shih Shinlin; Liu Fenfen; Jan Sheauwen; Lin Yunnan; Lan Chungchi

1997-01-01

A morphology based imaging review is presented of the characteristic skeletal deformities associated with acardius anceps in three acardiac twins. These fetuses demonstrated poorly developed skulls, limb reduction defects, and phocomelia of the upper limbs, as well as narrow thoracic cages with or without the complete development of ribs, clavicles, scapulae, and cervical, thoracic, or lumbar vertebrae. However, their lower limbs and pelvic girdles were almost normal. The authors conclude that skeletal development is likely to be jeopardized in the area adjacent to the heart and in the cephalic portion of the body in fetuses with acardius anceps, and suggest vascular deficiency and hypoperfusion as pathogenetic mechanisms in this type of skeletal deformity. (orig.)

Clinical significance of abnormal nonosseous soft tissue uptake of bone tracer

International Nuclear Information System (INIS)

Zhu Bao; Shang Yukun; Li Jiannan; Bai Jing; Cai Liang

2006-01-01

Objective: To evaluate the clinical significance of abnormal soft tissue uptake of bone tracer. Methods: Thirty patients with abnormal soft tissue uptake of bone tracer on 99 Tc m -methylene diphosphonic acid (MDP) skeletal imaging were analyzed. Radioactivity of soft tissue accumulated equal to or greater than the ribs were considered as abnormal. The result was compared with pathology, MRI, CT, X-ray, ultrasound, findings for evaluating its clinical significance. Results: In 7 patients with diffuse liver uptake of 99 Tc m -MDP, 6 were massive and 1 nodular liver cancer. In 2 patients with local liver uptake, one was metastatic and the other primary liver cancer. In 5 local lung uptake cases 4 were primary lung cancer and one metastatic. In 5 cases with colonic uptake 1 was schistosomiasis while the other 4 unexplainable. Subcutaneous tissue uptake was observed in 4 patients, symmetrical uptake in 2 patients with metastatic calcification microfoci in multiple myeloma, unsymmetrical uptake in 2 patients with hemangioma and abscess. Pleural uptake in 3 patients all was metastatic cancer. Abdominal uptake in 3 patients was omentum, paravertebral soft tissue metastasis and unknown cause. Breast uptake in one patient was due to breast cancer. Conclusions: There are many causes resulting in abnormal nonosseous soft tissue uptake of 99 Tc m -MDP. The final diagnosis should correlate with clinical data and other examinations. (authors)

Influence of nasoalveolar molding on skeletal development in patients with unilateral cleft lip and palate at 5 years of age.

Science.gov (United States)

Akarsu-Guven, Bengisu; Arisan, Arda; Ozgur, Figen; Aksu, Muge

2018-04-01

The aim of this retrospective study was to assess the influence of presurgical nasoalveolar molding (NAM) on skeletal development in patients with operated unilateral cleft lip and palate at 5 years of age. Lateral cephalometric radiographs of 26 unilateral cleft lip and palate patients who had undergone presurgical NAM (NAM group) and 20 unilateral cleft lip and palate patients who did not have any presurgical NAM (non-NAM group) were analyzed. The radiographs were digitally traced using Quick Ceph Studio software (version 3.5.1.r (1151); Quick Ceph Systems, San Diego, Calif). Independent samples t tests were performed for statistical analysis. No significant differences were observed in sagittal and vertical skeletal measurements between the NAM and non-NAM groups. NAM resulted in no significant difference in skeletal development in unilateral cleft lip and palate patients compared with those without NAM in early childhood. Copyright © 2018. Published by Elsevier Inc.

Proteomics of Skeletal Muscle

DEFF Research Database (Denmark)

Deshmukh, Atul

2016-01-01

, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle......Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance

DEFF Research Database (Denmark)

Kristensen, Jonas Møller; Skov, Vibe; Petersson, Stine Juhl

2014-01-01

Insulin resistance in obesity and type 2 diabetes is related to abnormalities in mitochondrial oxidative phosphorylation (OxPhos) in skeletal muscle. We tested the hypothesis that mitochondrial oxidative metabolism is impaired in muscle of patients with inherited insulin resistance and defective...

Development of Abnormal Operating Strategies for Station Blackout in Shutdown Operating Mode in Pressurized Water Reactor

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Yoon, Duk-Joo; Lee, Seung-Chan; Sung, Je-Joong; Ha, Sang-Jun [KHNP CRI, Daejeon (Korea, Republic of); Hwang, Su-Hyun [FNC Tech. Co., Yongin (Korea, Republic of)

2016-10-15

Loss of all AC power is classified as one of multiple failure accident by regulatory guide of Korean accident management program. Therefore we need develop strategies for the abnormal operating procedure both of power operating and shutdown mode. This paper developed abnormal operating guideline for loss of all AC power by analysis of accident scenario in pressurized water reactor. This paper analyzed the loss of ultimate heat sink (LOUHS) in shutdown operating mode and developed the operating strategy of the abnormal procedure. Also we performed the analysis of limiting scenarios that operator actions are not taken in shutdown LOUHS. Therefore, we verified the plant behavior and decided operator action to taken in time in order to protect the fuel of core with safety. From the analysis results of LOUHS, the fuel of core maintained without core uncovery for 73 minutes respectively for opened RCS states after the SBO occurred. Therefore, operator action for the emergency are required to take in 73 minutes for opened RCS state. Strategy is to cooldown by using spent fuel pool cooling system. This method required to change the plant design in some plant. In RCS boundary closed state, first abnormal operating strategy in shutdown LOUHS is first abnormal operating strategy in shutdown LOUHS is to remove the residual heat of core by steam dump flow and auxiliary feedwater of SG.

Prader-Willi Critical Region, a Non-Translated, Imprinted Central Regulator of Bone Mass: Possible Role in Skeletal Abnormalities in Prader-Willi Syndrome.

Directory of Open Access Journals (Sweden)

Ee-Cheng Khor

Full Text Available Prader-Willi Syndrome (PWS, a maternally imprinted disorder and leading cause of obesity, is characterised by insatiable appetite, poor muscle development, cognitive impairment, endocrine disturbance, short stature and osteoporosis. A number of causative loci have been located within the imprinted Prader-Willi Critical Region (PWCR, including a set of small non-translated nucleolar RNA's (snoRNA. Recently, micro-deletions in humans identified the snoRNA Snord116 as a critical contributor to the development of PWS exhibiting many of the classical symptoms of PWS. Here we show that loss of the PWCR which includes Snord116 in mice leads to a reduced bone mass phenotype, similar to that observed in humans. Consistent with reduced stature in PWS, PWCR KO mice showed delayed skeletal development, with shorter femurs and vertebrae, reduced bone size and mass in both sexes. The reduction in bone mass in PWCR KO mice was associated with deficiencies in cortical bone volume and cortical mineral apposition rate, with no change in cancellous bone. Importantly, while the length difference was corrected in aged mice, consistent with continued growth in rodents, reduced cortical bone formation was still evident, indicating continued osteoblastic suppression by loss of PWCR expression in skeletally mature mice. Interestingly, deletion of this region included deletion of the exclusively brain expressed Snord116 cluster and resulted in an upregulation in expression of both NPY and POMC mRNA in the arcuate nucleus. Importantly, the selective deletion of the PWCR only in NPY expressing neurons replicated the bone phenotype of PWCR KO mice. Taken together, PWCR deletion in mice, and specifically in NPY neurons, recapitulates the short stature and low BMD and aspects of the hormonal imbalance of PWS individuals. Moreover, it demonstrates for the first time, that a region encoding non-translated RNAs, expressed solely within the brain, can regulate bone mass in health

The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

Science.gov (United States)

Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

2005-09-01

The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group.

[Skeletal anchorage in the past, today and tomorrow].

Science.gov (United States)

Melsen, Birte; Dalstra, Michel

2017-03-01

Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect to the material and morphology, were developed. A bracket-like head allows for the use of the mini-implant as indirect anchorage, but should not be a tool for lost control resulting from badly planned biomechanics or failing compliance. Skeletal anchorage should serve as an adjunct to correct biomechanics, to enable treatments that could not be performed prior to the introduction of skeletal anchorage. The aim of this study was to test the hypothesis that temporary anchorage mini-screws help maintain bone density, height and width of alveolar processes in the extraction sites, and thus prevent the thinning of the alveolar ridge usually observed. In adult patients with degenerated dentitions the application of skeletal anchorage can allow for the displacement of teeth where no anchorage units are present, but also for the redevelopment and maintenance of atrophic alveolar bone. The basis for the optimal use of skeletal anchorage is that the correct line of action for the desired tooth displacement is defined and the necessary force system constructed either with the skeletal anchorage as direct or as indirect anchorage. After a period, during which osseointegrated implants were used as anchorage for tooth movement and bone maintenance, it was accepted that the mini-implants could serve also as anchorage for skeletal displacements avoiding loading of teeth. © EDP Sciences, SFODF, 2017.

Skeletal surveys in multiple myeloma

International Nuclear Information System (INIS)

Sebes, J.I.; Niell, H.B.; Palmieri, G.M.A.; Reidy, T.J.

1986-01-01

Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

Evaluation of thoracic abnormalities on 64-row multi-detector row CT: Comparison between axial images versus coronal reformations

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Nishino, Mizuki [Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (United States)]. E-mail: mnishino@bidmc.harvard.edu; Kubo, Takeshi [Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (United States); Kataoka, Milliam L. [Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (United States); Gautam, Shiva [Department of General Clinical Research Center and Biometrics, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (United States); Raptopoulos, Vassilios [Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (United States); Hatabu, Hiroto [Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215 (United States)

2006-07-15

Purpose: To evaluate the capability of coronal reformations of chest on 64-row MDCT in demonstrating thoracic abnormalities in comparison with axial images. Materials and methods: Thirty-eight consecutive patients who underwent pulmonary CTA on 64-row MDCT were retrospectively studied with institutional review board (IRB) approval. Contiguous 2 mm axial and coronal images were reviewed independently with a 1-week interval, by consensus reading of two board-certified radiologists. Overall image quality was graded using a five-point scale. Abnormalities in mediastinum, hilum, pulmonary vessels, aorta, heart, esophagus, pleura, chest wall, and lung parenchyma were scored: 1 = definitely absent, 2 = probably absent, 3 = equivocal, 4 probably present, 5 = definitely present. Scores on axial and coronal images were compared using weighted {kappa} analysis. Results: Overall image quality was not different with statistical relevance between axial and coronal images (mean/median scores; 3.7/4; 3.6/4, respectively, P = 0.286, Wilcoxon signed-rank test). Significant agreement was observed between axial and coronal scores (mean weighted {kappa}, 0.661; range, 0.362-1). Agreement was almost perfect for pneumothorax, lung and pleural mass, effusion and consolidation (weighted {kappa} = 0.833-1); substantial for pulmonary embolism, trachea, mediastinal lymphadenopathy and non-skeletal chest wall lesion, heart, esophagus, and emphysema (weighted {kappa}, 0.618-0.799); moderate for atelectasis, mediastinum, hilar nodes, aorta, other lung lesions, skeletal chest wall lesions, linear scarring, nodules >1 cm, pulmonary artery abnormalities and pleural thickening (weighted {kappa}, 0.405-0.592); and fair for nodules <1 cm (weighted {kappa} = 0.362). Conclusion: Coronal reformations on 64-row MDCT had substantial agreement with axial images for evaluation of the majority of thoracic abnormalities.

Evaluation of thoracic abnormalities on 64-row multi-detector row CT: Comparison between axial images versus coronal reformations

International Nuclear Information System (INIS)

Nishino, Mizuki; Kubo, Takeshi; Kataoka, Milliam L.; Gautam, Shiva; Raptopoulos, Vassilios; Hatabu, Hiroto

2006-01-01

Purpose: To evaluate the capability of coronal reformations of chest on 64-row MDCT in demonstrating thoracic abnormalities in comparison with axial images. Materials and methods: Thirty-eight consecutive patients who underwent pulmonary CTA on 64-row MDCT were retrospectively studied with institutional review board (IRB) approval. Contiguous 2 mm axial and coronal images were reviewed independently with a 1-week interval, by consensus reading of two board-certified radiologists. Overall image quality was graded using a five-point scale. Abnormalities in mediastinum, hilum, pulmonary vessels, aorta, heart, esophagus, pleura, chest wall, and lung parenchyma were scored: 1 = definitely absent, 2 = probably absent, 3 = equivocal, 4 probably present, 5 = definitely present. Scores on axial and coronal images were compared using weighted κ analysis. Results: Overall image quality was not different with statistical relevance between axial and coronal images (mean/median scores; 3.7/4; 3.6/4, respectively, P = 0.286, Wilcoxon signed-rank test). Significant agreement was observed between axial and coronal scores (mean weighted κ, 0.661; range, 0.362-1). Agreement was almost perfect for pneumothorax, lung and pleural mass, effusion and consolidation (weighted κ = 0.833-1); substantial for pulmonary embolism, trachea, mediastinal lymphadenopathy and non-skeletal chest wall lesion, heart, esophagus, and emphysema (weighted κ, 0.618-0.799); moderate for atelectasis, mediastinum, hilar nodes, aorta, other lung lesions, skeletal chest wall lesions, linear scarring, nodules >1 cm, pulmonary artery abnormalities and pleural thickening (weighted κ, 0.405-0.592); and fair for nodules <1 cm (weighted κ = 0.362). Conclusion: Coronal reformations on 64-row MDCT had substantial agreement with axial images for evaluation of the majority of thoracic abnormalities

Improvement of the abnormal diagnosis technology by the development of an abnormal parts assignment system for the engineered safety features actuating system of the HTTR

International Nuclear Information System (INIS)

Hirato, Yoji; Kozawa, Takayuki; Saito, Kenji

2015-01-01

The safety protection sequence panel of HTTR is a control panel to actuate an engineering safety system for protecting the reactor core, reactor coolant pressure boundary, and containment vessel boundary at the time of an accident of the nuclear reactor facilities. The safety code stipulates that the control panel should receive safety check at a frequency of once a month during reactor operation. When abnormality has been found, it is required to eliminate its causes and restore normal operation as soon as possible. However, since this control panel is composed of a complex control circuit, the cause check during abnormality requires the confirmation by a knowledgeable person spending quite a lot of time for chart checking, which leads to a delay of restoration. To achieve a rapid restoration, the abnormal part assignment system (APAS), which can specify abnormality instantaneously even by a common operator, was developed. It has been confirmed that with this system, rapid initial response and prompt restoration can be effectively made. (A.O.)

Evaluation of skeletal muscle metabolism in patients with congestive heart failure using phosphorus nuclear magnetic

International Nuclear Information System (INIS)

Wilson, J.R.

1988-01-01

Patients with congestive heart failure are frequently limited by muscular fatigue due skeletal muscle underperfusion and deconditioning. Muscle underperfusion and deconditioning both produce distinctive changes in metabolic parameters which are readily measured by phosphorus nuclear magnetic resonance (NMR). Therefore, phosphorus NMR should provide a useful noninvasive method of assessing muscle performance in heart failure. This chapter describes a protocol which allows detection of forearm muscle metabolic abnormalities in patients with heart failure, abnormalities that seem to be caused by muscle deconditioning. In the future, it is anticipated that this approach may prove to be an extremely useful method for objectively assessing muscle fatigue in patients with heart failure and for monitoring the effects on therapeutic interventions designed to treat this fatigue

Whole-body MRI in comparison to skeletal scintigraphy for detection of skeletal metastases in patients with solid tumors

International Nuclear Information System (INIS)

Ghanem, N.; Altehoefer, C.; Winterer, J.; Schaefer, O.; Bley, T.A.; Langer, M.; Kelly, T.; Moser, E.

2004-01-01

The aim of this study was to compare the diagnostic efficacy of whole-body magnetic resonance imaging (WB-MRI) as a new and rapid examination technique with skeletal scintigraphy for detection of skeletal metastases from solid tumors. In 129 patients with solid malignant tumors, WB-MRI was performed for individual comparison with skeletal scintigraphy. Examinations were performed with the innovative AngioSURF trademark rolling table with integrated phased array surface coil and coronary TIRM sequences for different body regions. The results for WB-MRI and skeletal scintigraphy were concordant in 81% of the cases, whereby both procedures excluded skeletal metastases in 43%. WB-MRI and skeletal scintigraphy demonstrated skeletal metastases in 38% of the cases, whereby WB-MRI provided more comprehensive findings in 45%. In 12% of the cases, skeletal scintigraphy was superior to WB-MRI and in 19% the findings were discordant, whereby WB-MRI detected skeletal metastases in 15 cases which had not been found on skeletal scintigraphy. In nine cases, skeletal scintigraphy was positive when the WB-MRI was negative. In 60% of the cases, WB-MRI evidenced tumor-associated findings. WB-MRI represents a promising new staging technique for detection of skeletal metastases, which is more sensitive in many cases than skeletal scintigraphy in detecting and assessing the extent of skeletal metastases - and tumor-associated findings that are relevant for treatment strategy. (orig.) [de

Abnormal pressures as hydrodynamic phenomena

Science.gov (United States)

Neuzil, C.E.

1995-01-01

So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

A skeletal mechanism for biodiesel blend surrogates combustion

International Nuclear Information System (INIS)

An, H.; Yang, W.M.; Maghbouli, A.; Li, J.; Chua, K.J.

2014-01-01

Highlights: • A skeletal biodiesel reaction mechanism with 112 species was constructed. • The developed mechanism contains the CO, NO x and soot formation kinetics. • It was well validated against detailed reaction mechanism and experimental results. • The mechanism is suitable to simulate biodiesel, diesel and their blend fuels. - Abstract: A tri-component skeletal reaction mechanism consisting of methyl decanoate, methyl-9-decenoate, and n-heptane was developed for biodiesel combustion in diesel engine. It comprises 112 species participating in 498 reactions with the CO, NO x and soot formation mechanisms embedded. In this study, a detailed tri-component biodiesel mechanism was used as the start of mechanism reduction and the reduced mechanism was combined with a previously developed skeletal reaction mechanism for n-heptane to integrate the soot formation kinetics. A combined mechanism reduction strategy including the directed relation graph with error propagation and sensitivity analysis (DRGEPSA), peak concentration analysis, isomer lumping, unimportant reactions elimination and reaction rate adjustment methods was employed. The reduction process for biodiesel was performed over a range of initial conditions covering the pressures from 1 to 100 atm, equivalence ratios from 0.5 to 2.0 and temperatures from 700 to 1800 K, whereas for n-heptane, ignition delay predictions were compared against 17 shock tube experimental conditions. Extensive validations were performed for the developed skeletal reaction mechanism with 0-D ignition delay testing and 3-D engine simulations. The results indicated that the developed mechanism was able to accurately predict the ignition delay timings of n-heptane and biodiesel, and it could be integrated into 3-D engine simulations to predict the combustion characteristics of biodiesel. As such, the developed 112-species skeletal mechanism can accurately mimic the significant reaction pathways of the detailed reaction

Skeletal development of the glenoid and glenoid-coracoid interface in the pediatric population: MRI features

Energy Technology Data Exchange (ETDEWEB)

Kothary, Shefali [Mount Sinai Beth Israel, Department of Radiology, New York, NY (United States); Radiology Department, NYU Langone Medical Center: Hospital for Joint Disease, New York, NY (United States); Rosenberg, Zehava Sadka; Poncinelli, Leonardo L. [NYU Hospital for Joint Disease, Radiology Department, New York, NY (United States); Radiology Department, NYU Langone Medical Center: Hospital for Joint Disease, New York, NY (United States); Kwong, Steven [School of Medicine, NYU Langone Medical Center, New York, NY (United States); Radiology Department, NYU Langone Medical Center: Hospital for Joint Disease, New York, NY (United States)

2014-09-15

To assess the MRI appearance of normal skeletal development of the glenoid and glenoid-coracoid interface in the pediatric population. To the best of our knowledge, this has not yet been studied in detail in the literature. An IRB-approved, HIPAA-compliant retrospective review of 105 consecutive shoulder MRI studies in children, ages 2 months to 18 years was performed. The morphology, MR signal, and development of the following were assessed: (1) scapular-coracoid bipolar growth plate, (2) glenoid and glenoid-coracoid interface secondary ossification centers, (3) glenoid advancing osseous surface. The glenoid and glenoid-coracoid interface were identified in infancy as a contiguous, cartilaginous mass. A subcoracoid secondary ossification center in the superior glenoid was identified and fused in all by age 12 and 16, respectively. In ten studies, additional secondary ossification centers were identified in the inferior two-thirds of the glenoid. The initial concavity of the glenoid osseous surface gradually transformed to convexity, matching the convex glenoid articular surface. The glenoid growth plate fused by 16 years of age. Our study, based on MRI, demonstrated a similar pattern of development of the glenoid and glenoid coracoid interface to previously reported anatomic and radiographic studies, except for an earlier development and fusion of the secondary ossification centers of the inferior glenoid. The pattern of skeletal development of the glenoid and glenoid-coracoid interface follows a chronological order, which can serve as a guideline when interpreting MRI studies in children. (orig.)

The role of the renin-angiotensin system in the development of insulin resistance in skeletal muscle.

Science.gov (United States)

Henriksen, Erik J; Prasannarong, Mujalin

2013-09-25

The canonical renin-angiotensin system (RAS) involves the initial action of renin to cleave angiotensinogen to angiotensin I (ANG I), which is then converted to ANG II by the angiotensin converting enzyme (ACE). ANG II plays a critical role in numerous physiological functions, and RAS overactivity underlies many conditions of cardiovascular dysregulation. In addition, ANG II, by acting on both endothelial and myocellular AT1 receptors, can induce insulin resistance by increasing cellular oxidative stress, leading to impaired insulin signaling and insulin-stimulated glucose transport activity. This insulin resistance associated with RAS overactivity, when coupled with progressive ß-cell dysfunction, eventually leads to the development of type 2 diabetes. Interventions that target RAS overactivity, including ACE inhibitors, ANG II receptor blockers, and, most recently, renin inhibitors, are effective both in reducing hypertension and in improving whole-body and skeletal muscle insulin action, due at least in part to enhanced Akt-dependent insulin signaling and insulin-dependent glucose transport activity. ANG-(1-7), which is produced from ANG II by the action of ACE2 and acts via Mas receptors, can counterbalance the deleterious actions of the ACE/ANG II/AT1 receptor axis on the insulin-dependent glucose transport system in skeletal muscle. This beneficial effect of the ACE2/ANG-(1-7)/Mas receptor axis appears to depend on the activation of Akt. Collectively, these findings underscore the importance of RAS overactivity in the multifactorial etiology of insulin resistance in skeletal muscle, and provide support for interventions that target the RAS to ameliorate both cardiovascular dysfunctions and insulin resistance in skeletal muscle tissue. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A Description of Skeletal Manifestation in Adult Case of Morquio Syndrome: Radiographic and MRI Appearance

Directory of Open Access Journals (Sweden)

Annalisa Di Cesare

2012-01-01

Full Text Available We report on a rare case of Morquio syndrome, an autosomal recessive mucopolysaccharidosis including type IVA, a deficiency of N-acetylgalctosamine-6-sulfatase and type IVB a deficiency of β-galactosidase. A 43-year-old female patient affected by IVB Morquio syndrome underwent instrumental investigation. Conventional plain films of the entire spine, pelvis, chest and knees together with magnetic resonance imaging of the entire column, hip, knees, and ankles demonstrated the characteristics of skeletal changes of this disease. The main abnormalities were platyspondily and hypoplasia of the odontoid process, genua valga deformity and severe multiple degenerative changes of the hips, knees, and ankle joints. Radiographs and above all magnetic resonance imaging are crucial to provide substantial information about the gravity, evolution of the skeletal and joints changes, and the rehabilitation strategies to be followed.

mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

Directory of Open Access Journals (Sweden)

Mee-Sup Yoon

2017-10-01

Full Text Available Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

Abnormal gastrointestinal accumulation of radiotracer by gastric bleeding during 99mTc-MDP bone scintigraphy

International Nuclear Information System (INIS)

Chun, Kyung A.; Lee, Sang Woo; Lee, Jae Tae; Lee, Kyu Bo

1998-01-01

We present a case in which a patient with acute hemorrhagic gastritis demonstrated abnormal gastrointestinal accumulation of radiotracer during 99m Tc-methylene diphosphonate (MDP) skeletal scintigraphy. A hemorrhagic gastritis was subsequently demonstrated by endoscopy. The mechanism for the intestinal localization of 99m Tc-MDP in this patients is not clear, but we guess that the extravasated blood containing the radiopharmaceutical cannot recirculate and stays at the bleeding site, so we can see the intestinal activity

Lyophilized skeletal imaging composition

International Nuclear Information System (INIS)

Vanduzee, B.F.

1983-01-01

This invention encompasses a process for producing a dry-powder skeletal imaging kit. An aqueous solution of a diphosphonate, a stannous reductant, and, optionally, a stabilizer is prepared. The solution is adjusted to a pH within the range 4.2 to 4.8 and the pH-adjusted solution is then lyophilized. The adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This improved performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent

Role of Active Contraction and Tropomodulins in Regulating Actin Filament Length and Sarcomere Structure in Developing Zebrafish Skeletal Muscle.

Science.gov (United States)

Mazelet, Lise; Parker, Matthew O; Li, Mei; Arner, Anders; Ashworth, Rachel

2016-01-01

Whilst it is recognized that contraction plays an important part in maintaining the structure and function of mature skeletal muscle, its role during development remains undefined. In this study the role of movement in skeletal muscle maturation was investigated in intact zebrafish embryos using a combination of genetic and pharmacological approaches. An immotile mutant line (cacnb1 (ts25) ) which lacks functional voltage-gated calcium channels (dihydropyridine receptors) in the muscle and pharmacological immobilization of embryos with a reversible anesthetic (Tricaine), allowed the study of paralysis (in mutants and anesthetized fish) and recovery of movement (reversal of anesthetic treatment). The effect of paralysis in early embryos (aged between 17 and 24 hours post-fertilization, hpf) on skeletal muscle structure at both myofibrillar and myofilament level was determined using both immunostaining with confocal microscopy and small angle X-ray diffraction. The consequences of paralysis and subsequent recovery on the localization of the actin capping proteins Tropomodulin 1 & 4 (Tmod) in fish aged from 17 hpf until 42 hpf was also assessed. The functional consequences of early paralysis were investigated by examining the mechanical properties of the larval muscle. The length-force relationship, active and passive tension, was measured in immotile, recovered and control skeletal muscle at 5 and 7 day post-fertilization (dpf). Recovery of muscle function was also assessed by examining swimming patterns in recovered and control fish. Inhibition of the initial embryonic movements (up to 24 hpf) resulted in an increase in myofibril length and a decrease in width followed by almost complete recovery in both moving and paralyzed fish by 42 hpf. In conclusion, myofibril organization is regulated by a dual mechanism involving movement-dependent and movement-independent processes. The initial contractile event itself drives the localization of Tmod1 to its sarcomeric

Growth hormone mediates pubertal skeletal development independent of hepatic IGF-1 production.

Science.gov (United States)

Courtland, Hayden-William; Sun, Hui; Beth-On, Mordechay; Wu, Yingjie; Elis, Sebastien; Rosen, Clifford J; Yakar, Shoshana

2011-04-01

Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine IGF-1. However, LID mice also have two- to threefold increases in GH, and this may contribute to the observed pubertal skeletal phenotype. To clarify the role of GH in skeletal development under conditions of significantly reduced serum IGF-1 levels (but normal tissue IGF-1 levels), we studied the skeletal response of male LID and control mice to GH inhibition by pegvisomant from 4 to 8 weeks of age. Treatment of LID mice with pegvisomant resulted in significant reductions in body weight, femur length (Le), and femur total area (Tt.Ar), as well as further reductions in serum IGF-1 levels by 8 weeks of age, compared with the mean values of vehicle-treated LID mice. Reductions in both Tt.Ar and Le were proportional after treatment with pegvisomant. On the other hand, the relative amount of cortical tissue formed (RCA) in LID mice treated with pegvisomant was significantly less than that in both vehicle-treated LID and control mice, indicating that antagonizing GH action, either directly (through GH receptor signaling inhibition) or indirectly (through further reductions in serum/tissue IGF-1 levels), results in disproportionate reductions in the amount of cortical bone formed. This resulted in bones with significantly reduced mechanical properties (femoral whole-bone stiffness and work to failure were markedly decreased), suggesting that compensatory increases of GH in states of IGF-1 deficiency (LID mice) act to protect against a severe inhibition of bone modeling during growth, which otherwise would result in bones that are too weak for normal and/or extreme loading conditions. Copyright © 2011 American Society for

Skeletal imaging composition

International Nuclear Information System (INIS)

Vanduzee, B.F.; Degenhardt, C.R.

1983-01-01

This invention is based on the discovery that the adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate-containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This increased performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent. The process for producing a dry-powder imaging kit comprises the steps of: preparing a solution of a diphosphonate carrier, stannous reductant, and a stabilizer in water; adjusting the pH to between 5.5 and 6.5; and lyophilizing the solution

DNA Methylation in Skeletal Muscle Stem Cell Specification, Proliferation, and Differentiation

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Rhianna C. Laker

2016-01-01

Full Text Available An unresolved and critically important question in skeletal muscle biology is how muscle stem cells initiate and regulate the genetic program during muscle development. Epigenetic dynamics are essential for cellular development and organogenesis in early life and it is becoming increasingly clear that epigenetic remodeling may also be responsible for the cellular adaptations that occur in later life. DNA methylation of cytosine bases within CpG dinucleotide pairs is an important epigenetic modification that reduces gene expression when located within a promoter or enhancer region. Recent advances in the field suggest that epigenetic regulation is essential for skeletal muscle stem cell identity and subsequent cell development. This review summarizes what is currently known about how skeletal muscle stem cells regulate the myogenic program through DNA methylation, discusses a novel role for metabolism in this process, and addresses DNA methylation dynamics in adult skeletal muscle in response to physical activity.

In vitro Differentiation of Functional Human Skeletal Myotubes in a Defined System.

Science.gov (United States)

Guo, Xiufang; Greene, Keshel; Akanda, Nesar; Smith, Alec; Stancescu, Maria; Lambert, Stephen; Vandenburgh, Herman; Hickman, James

2014-01-01

In vitro human skeletal muscle systems are valuable tools for the study of human muscular development, disease and treatment. However, published in vitro human muscle systems have so far only demonstrated limited differentiation capacities. Advanced differentiation features such as cross-striations and contractility have only been observed in co-cultures with motoneurons. Furthermore, it is commonly regarded that cultured human myotubes do not spontaneously contract, and any contraction has been considered to originate from innervation. This study developed a serum-free culture system in which human skeletal myotubes demonstrated advanced differentiation. Characterization by immunocytochemistry, electrophysiology and analysis of contractile function revealed these major features: A) well defined sarcomeric development, as demonstrated by the presence of cross-striations. B) finely developed excitation-contraction coupling apparatus characterized by the close apposition of dihydropyridine receptors on T-tubules and Ryanodine receptors on sarcoplasmic reticulum membranes. C) spontaneous and electrically controlled contractility. This report not only demonstrates an improved level of differentiation of cultured human skeletal myotubes, but also provides the first published evidence that such myotubes are capable of spontaneous contraction. Use of this functional in vitro human skeletal muscle system would advance studies concerning human skeletal muscle development and physiology, as well as muscle-related disease and therapy.

Skeletal metastases from hepatoma: frequency, distribution, and radiographic features

International Nuclear Information System (INIS)

Kuhlman, J.E.; Fishman, E.K.; Leichner, P.K.; Magid, D.; Order, S.E.; Siegelman, S.S.

1986-01-01

Over the past 6 years, the authors evaluated 300 patients with hepatoma as part of phase 1 and 2 treatment protocol trials. Analysis of the available clinical data and radiographic studies revealed 22 patients (7.3%) with skeletal metastases demonstrated by radiography, computed tomography (CT), and/or nuclear scintigraphy. The plain film appearance of skeletal metastases from hepatoma was osteolytic in all cases. CT scanning best demonstrated the expansile, destructive nature of these metastases, which were often associated with large, bulky soft-tissue masses. Skeletal metastases from hepatomas demonstrated increased radiotracer uptake on standard bone scans and were gallium avid, similar to the hepatoma itself. In addition, they could be targeted therapeutically with I-131 antiferritin immunoglobulin. The most frequent sites of skeletal metastases were the ribs, spine, femur, pelvis, and humerus. An initial symptom in ten patients was skeletal pain corresponding to the osseous metastases. In five patients, pathologic fractures of the proximal femur or humerus developed and required total hip replacement or open-reduction internal fixation. Patients with long-standing cirrhosis or known hepatocellular carcinoma who also have skeletal symptoms should be evaluated for possible osseous metastases

Glucose transporter expression in human skeletal muscle fibers

DEFF Research Database (Denmark)

Gaster, M; Handberg, A; Beck-Nielsen, H

2000-01-01

, but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...... amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation...

Samarium-153 EDTMP therapy of disseminated skeletal metastasis

International Nuclear Information System (INIS)

Turner, J.H.; Martindale, A.A.; Fleay, R.F.; Hoffman, R.F.; Claringbold, P.G.

1989-01-01

153 Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153 Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153 Sm-EDTMP in 15 of 19 patients (79%) who could vie evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153 Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow ≥270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153 Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153 Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 0.5% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153 Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153 Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients. (orig.)

Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

DEFF Research Database (Denmark)

Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke

2013-01-01

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin...... of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy...... expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance....

The role of mitochondrial DNA damage at skeletal muscle oxidative stress on the development of type 2 diabetes.

Science.gov (United States)

Dos Santos, Julia Matzenbacher; de Oliveira, Denise Silva; Moreli, Marcos Lazaro; Benite-Ribeiro, Sandra Aparecida

2018-04-20

Reduced cellular response to insulin in skeletal muscle is one of the major components of the development of type 2 diabetes (T2D). Mitochondrial dysfunction involves in the accumulation of toxic reactive oxygen species (ROS) that leads to insulin resistance. The aim of this study was to verify the involvement of mitochondrial DNA damage at ROS generation in skeletal muscle during development of T2D. Wistar rats were fed a diet containing 60% fat over 8 weeks and at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced). Control rats received standard food and an injection of citrate buffer. Blood and soleus muscle were collected. Abdominal fat was quantified as well as glucose, triglyceride, LDL, HDL, and total cholesterol in plasma and mtDNA copy number, cytochrome b (cytb) mRNA, 8-hydroxyguanosine, and 8-isoprostane (a marker of ROS) in soleus muscle. T2D-induced animal presented similar characteristics to humans that develop T2D such as changes in blood glucose, abdominal fat, LDL, HDL and cholesterol total. In soleus muscle 8-isoprostane, mtDNA copy number and 8-hydroxyguanosine were increased, while cytb mRNA was decreased in T2D. Our results suggest that in the development of T2D, when risks factors of T2D are present, intracellular oxidative stress increases in skeletal muscle and is associated with a decrease in cytb transcription. To overcome this process mtDNA increased but due to the proximity of ROS generation, mtDNA remains damaged by oxidation leading to an increase in ROS in a vicious cycle accounting to the development of insulin resistance and further T2D.

Growth Factors and Tension-Induced Skeletal Muscle Growth

Science.gov (United States)

Vandenburgh, Herman H.

1994-01-01

The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

High Sugar Intake and Development of Skeletal Muscle Insulin Resistance and Inflammation in Mice: A Protective Role for PPAR-δ Agonism

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Elisa Benetti

2013-01-01

Full Text Available Peroxisome Proliferator Activated Receptor (PPAR-δ agonists may serve for treating metabolic diseases. However, the effects of PPAR-δ agonism within the skeletal muscle, which plays a key role in whole-body glucose metabolism, remain unclear. This study aimed to investigate the signaling pathways activated in the gastrocnemius muscle by chronic administration of the selective PPAR-δ agonist, GW0742 (1 mg/kg/day for 16 weeks, in male C57Bl6/J mice treated for 30 weeks with high-fructose corn syrup (HFCS, the major sweetener in foods and soft-drinks (15% wt/vol in drinking water. Mice fed with the HFCS diet exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP-activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5 expression and membrane translocation. GW0742 administration induced PPAR-δ upregulation and improvement in glucose and lipid metabolism. Diet-induced activation of nuclear factor-κB and expression of inducible-nitric-oxide-synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment. These effects were accompanied by reduction in the serum concentration of interleukin-6 and increase in muscular expression of fibroblast growth factor-21. Overall, here we show that PPAR-δ activation protects the skeletal muscle against the metabolic abnormalities caused by chronic HFCS exposure by affecting multiple levels of the insulin and inflammatory cascades.

Abnormal megakaryocyte development and platelet function in Nbeal2−/− mice

Science.gov (United States)

Lo, Richard W.; Li, Ling; Pluthero, Fred G.; Christensen, Hilary; Ni, Ran; Vaezzadeh, Nima; Hawkins, Cynthia E.; Weyrich, Andrew S.; Di Paola, Jorge; Landolt-Marticorena, Carolina; Gross, Peter L.

2013-01-01

Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with macrothrombocytopenia and α-granule-deficient platelets. GPS has been linked to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe here a murine GPS model, the Nbeal2−/− mouse. As in GPS, Nbeal2−/− mice exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet α-granules and their cargo, including von Willebrand factor (VWF), thrombospondin-1, and platelet factor 4. The platelet α-granule membrane protein P-selectin is expressed at 48% of wild-type levels and externalized upon platelet activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in Nbeal2−/− platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at a later stage of α-granule biogenesis. Impaired Nbeal2−/− platelet function was shown by flow cytometry, platelet aggregometry, bleeding assays, and intravital imaging of laser-induced arterial thrombus formation. Microscopic analysis detected marked abnormalities in Nbeal2−/− bone marrow megakaryocytes, which when cultured showed delayed maturation, decreased survival, decreased ploidy, and developmental abnormalities, including abnormal extracellular distribution of VWF. Our results confirm that α-granule secretion plays a significant role in platelet function, and they also indicate that abnormal α-granule formation in Nbeal2−/− mice has deleterious effects on megakaryocyte survival, development, and platelet production. PMID:23861251

Effect of abnormal notochord delamination on hindgut development in the Adriamycin mouse model.

Science.gov (United States)

Sato, Hideaki; Hajduk, Piotr; Furuta, Shigeyuki; Wakisaka, Munechika; Murphy, Paula; Puri, Prem; Kitagawa, Hiroaki

2013-11-01

Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal malformations. We hypothesized hindgut anomalies observed in the AMM are the result of abnormal effect of the notochord. Time-mated CBA/Ca mice received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11, stained following whole mount in situ hybridization with labeled RNA probes to detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with endoderm marker Hnf3β was used to visualize morphology. Embryos were scanned by OPT to obtain 3D representations of expressions. In AMM, the notochord was abnormally displaced ventrally with attachment to the hindgut endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal hindgut ended blindly in a cystic structure, and both of types were remarked in 29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression were preserved around the hindgut cystic malformation. The delamination of the developing notochord in the AMM is disrupted, which may influence signaling mechanisms from the notochord to the hindgut resulting in abnormal patterning of the hindgut.

Inhibition of Endothelial p53 Improves Metabolic Abnormalities Related to Dietary Obesity

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Masataka Yokoyama

2014-06-01

Full Text Available Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy.

Science.gov (United States)

Bober, Michael B; Taylor, Megan; Heinle, Robert; Mackenzie, William

2012-09-01

Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

Genetic engineering for skeletal regenerative medicine.

Science.gov (United States)

Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

2007-01-01

The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

Comparative Study of Skeletal Stability between Postoperative Skeletal Intermaxillary Fixation and No Skeletal Fixation after Bilateral Sagittal Split Ramus Osteotomy

DEFF Research Database (Denmark)

Hartlev, Jens; Godtfredsen, Erik; Andersen, Niels Trolle

2014-01-01

OBJECTIVES: The purpose of the present study was to evaluate skeletal stability after mandibular advancement with bilateral sagittal split osteotomy. MATERIAL AND METHODS: Twenty-six patients underwent single-jaw bilateral sagittal split osteotomy (BSSO) to correct skeletal Class II malocclusion....

Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and chest deformity, and calvarial defects in mice

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Philip E. Lapinski

2013-11-01

In mice, induced global disruption of the Ptpn11 gene, which encodes the SHP-2 tyrosine phosphatase, results in severe skeletal abnormalities. To understand the extent to which skeletal abnormalities can be attributed to perturbation of SHP-2 function in bone-forming osteoblasts and chondrocytes, we generated mice in which disruption of Ptpn11 is restricted to mesenchymal stem cells (MSCs and their progeny, which include both cell types. MSC-lineage-specific SHP-2 knockout (MSC SHP-2 KO mice exhibited postnatal growth retardation, limb and chest deformity, and calvarial defects. These skeletal abnormalities were associated with an absence of mature osteoblasts and massive chondrodysplasia with a vast increase in the number of terminally differentiated hypertrophic chondrocytes in affected bones. Activation of mitogen activated protein kinases (MAPKs and protein kinase B (PKB; also known as AKT was impaired in bone-forming cells of MSC SHP-2 KO mice, which provides an explanation for the skeletal defects that developed. These findings reveal a cell-autonomous role for SHP-2 in bone-forming cells in mice in the regulation of skeletal development. The results add to our understanding of the pathophysiology of skeletal abnormalities observed in humans with germline mutations in the PTPN11 gene (e.g. Noonan syndrome and LEOPARD syndrome.

Abnormal gastrointestinal accumulation of radiotracer by gastric bleeding during {sup 99m}Tc-MDP bone scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Chun, Kyung A.; Lee, Sang Woo; Lee, Jae Tae; Lee, Kyu Bo [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of)

1998-06-01

We present a case in which a patient with acute hemorrhagic gastritis demonstrated abnormal gastrointestinal accumulation of radiotracer during {sup 99m}Tc-methylene diphosphonate (MDP) skeletal scintigraphy. A hemorrhagic gastritis was subsequently demonstrated by endoscopy. The mechanism for the intestinal localization of {sup 99m}Tc-MDP in this patients is not clear, but we guess that the extravasated blood containing the radiopharmaceutical cannot recirculate and stays at the bleeding site, so we can see the intestinal activity.

Infectivity in skeletal muscle of cattle with atypical bovine spongiform encephalopathy.

Science.gov (United States)

Suardi, Silvia; Vimercati, Chiara; Casalone, Cristina; Gelmetti, Daniela; Corona, Cristiano; Iulini, Barbara; Mazza, Maria; Lombardi, Guerino; Moda, Fabio; Ruggerone, Margherita; Campagnani, Ilaria; Piccoli, Elena; Catania, Marcella; Groschup, Martin H; Balkema-Buschmann, Anne; Caramelli, Maria; Monaco, Salvatore; Zanusso, Gianluigi; Tagliavini, Fabrizio

2012-01-01

The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (∼70% versus ∼10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and pre-symptomatic stage in natural BASE. The neuropathological phenotype and PrP(res) type were consistent in all affected mice and matched those of Tgbov XV mice infected with brain homogenate from natural BASE. The immunohistochemical analysis of skeletal muscles from cattle with natural and experimental BASE showed the presence of abnormal prion protein deposits within muscle fibers. Conversely, Tgbov XV mice challenged with lymphoid tissue and kidney from natural and experimental BASE did not develop disease. The novel information on the neuromuscular tropism of the BASE strain, efficiently overcoming species barriers, underlines the relevance of maintaining an active surveillance.

Positive identification by a skull with multiple epigenetic traits and abnormal structure of the neurocranium, viscerocranium, and the skeleton.

Science.gov (United States)

Kuharić, Josip; Kovacic, Natasa; Marusic, Petar; Marusic, Ana; Petrovecki, Vedrana

2011-05-01

Wormian bones are small ossicles appearing within the cranial sutures in more than 40% of skulls, most commonly at the lambdoid suture and pterion. During the skeletal analysis of an unidentified male war victim, we observed multiple wormian bones and a patent metopic suture. Additionally, the right elbow was deformed, probably as a consequence of an old trauma. The skull was analyzed by cranial measurements and computerized tomography, revealing the presence of cranial deformities including hyperbrachicrania, localized reduction in hemispheral widths, increased cranial capacity, and sclerosis of the viscerocranium. Besides unique anatomical features and their anthropological value, such skeletal abnormalities also have a forensic value as the evidence to support the final identification of the victim. © 2011 American Academy of Forensic Sciences.

THE EFFECTS OF AEROBIC EXERCISE ON SKELETAL MUSCLE METABOLISM, MORPHOLOGY AND IN SITU ENDURANCE IN DIABETIC RATS

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Nilay Ergen

2005-12-01

Full Text Available The effects of aerobic exercise training on skeletal muscle endurance capacity were examined in diabetic rats in situ. Moderate diabetes was induced by iv injection of streptozotocin and an exercise training program on a treadmill was carried out for 8 weeks. The animals randomly assigned to one of the four experimental groups: control-sedentary (CS, control-exercise (CE, diabetic-sedentary (DS or diabetic-exercise (DE. The changes in the muscle endurance capacity were evaluated through the square wave impulses (supramaximal of 0.2-ms duration at 1 Hz in the in situ gastrocnemius-soleus muscle complex. Muscle was stimulated continuously until tension development reduced to the half of this maximal value. Time interval between the beginning and the end of stimulation period is defined as contraction duration. Following the training period, blood glucose level reduced significantly in the DE group compared to DS group (p < 0.05. The soles muscle citrate synthase activity was increased significantly in both of the trained groups compared to sedentary animals (p < 0.05. Fatigued muscle lactate values were not significantly different from each other. Ultrastractural abnormality of the skeletal muscle in DS group disappeared with training. Presence of increased lipid droplets, mitochondria clusters and glycogen accumulation was observed in the skeletal muscle of DE group. The contraction duration was longer in the DE group than others (p < 0.001. Fatigue resistance of exercised diabetic animals may be explained by increased intramyocellular lipid droplets, high blood glucose level and muscle citrate synthase activity

A Brief History of the Development of Abnormal Psychology: A Training Guide. Final Report.

Science.gov (United States)

Phelps, William R.

Presented for practitioners is a history of the development of abnormal psychology. Areas covered include the following: Early medical concepts, ideas carried over from literature, early treatment of the mentally ill, development of the psychological viewpoint, Freud's psychoanalytic theory, Jung's analytic theory, the individual psychology of…

Abnormal secretion or extracellular matrix incorporation of fibrillin by dermal fibroblasts from patients with thoracic aortic aneurysms

Energy Technology Data Exchange (ETDEWEB)

Milewicz, D.; Cao, S.; Cosselli, J. [Univ. of Texas Medical School, Houston, TX (United States)

1994-09-01

Abnormal synthesis, secretion, and extracellular matrix incorporation of fibrillin is observed in the majority of fibroblast cell strains obtained from individuals with the Marfan syndrome (>85%). These fibrillin protein abnormalities are due to mutations in the FBN1 gene. We have screened fibroblast cell strains from patients with thoracic aortic aneurysms (TAA) without skeletal or ocular features of the Marfan syndrome for defects in fibrillin synthesis or processing. Dermal fibroblasts obtained from biopsies were pulse labeled with [{sup 35}S]cysteine for 30 minutes and then chased for 0, 4, and 20 hours. The media, cell lysate and extracellular matrix were harvested separately, then analyzed by SDS-PAGE. We selected fibroblasts from 17 TAA patients to study based on the development of a TAA at a young age or a family history of TAAs. Cells from 3 patients synthesized and secreted fibrillin normally, but did not incorporate the fibrillin in the extracellular matrix. None of the cell strains were found to have diminished synthesis of fibrillin when compared with control cells. We were unable to detect abnormalities in the synthesis, secretion, or matrix incorporation of fibrillin by cells from 9 of the 17 patients. These results indicate that fibrillin protein defects are found in a significant number of patients with TAAs who are young or have a family history of TAAs. Analysis of the FBN1 gene for mutations in these patients with fibrillin protein defects will determine if the observed protein abnormalities are the result of FBN1 gene mutations.

Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

Science.gov (United States)

Lee, Peter H U; Vandenburgh, Herman H

2013-10-01

Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

The exercised skeletal muscle: a review

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Marina Marini

2010-09-01

Full Text Available The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.

in Skeletal Muscle

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Espen E. Spangenburg

2011-01-01

Full Text Available Triglyceride storage is altered across various chronic health conditions necessitating various techniques to visualize and quantify lipid droplets (LDs. Here, we describe the utilization of the BODIPY (493/503 dye in skeletal muscle as a means to analyze LDs. We found that the dye was a convenient and simple approach to visualize LDs in both sectioned skeletal muscle and cultured adult single fibers. Furthermore, the dye was effective in both fixed and nonfixed cells, and the staining seemed unaffected by permeabilization. We believe that the use of the BODIPY (493/503 dye is an acceptable alternative and, under certain conditions, a simpler method for visualizing LDs stored within skeletal muscle.

Development of a porcine skeletal muscle cDNA microarray: analysis of differential transcript expression in phenotypically distinct muscles

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Stear Michael

2003-03-01

Full Text Available Abstract Background Microarray profiling has the potential to illuminate the molecular processes that govern the phenotypic characteristics of porcine skeletal muscles, such as hypertrophy or atrophy, and the expression of specific fibre types. This information is not only important for understanding basic muscle biology but also provides underpinning knowledge for enhancing the efficiency of livestock production. Results We report on the de novo development of a composite skeletal muscle cDNA microarray, comprising 5500 clones from two developmentally distinct cDNA libraries (longissimus dorsi of a 50-day porcine foetus and the gastrocnemius of a 3-day-old pig. Clones selected for the microarray assembly were of low to moderate abundance, as indicated by colony hybridisation. We profiled the differential expression of genes between the psoas (red muscle and the longissimus dorsi (white muscle, by co-hybridisation of Cy3 and Cy5 labelled cDNA derived from these two muscles. Results from seven microarray slides (replicates correctly identified genes that were expected to be differentially expressed, as well as a number of novel candidate regulatory genes. Quantitative real-time RT-PCR on selected genes was used to confirm the results from the microarray. Conclusion We have developed a porcine skeletal muscle cDNA microarray and have identified a number of candidate genes that could be involved in muscle phenotype determination, including several members of the casein kinase 2 signalling pathway.

Skeletal maturity assessment using mandibular canine calcification stages

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Vildana Džemidžić

2016-11-01

Full Text Available Objective. The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. Materials and methods. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years. The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI, as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Results. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. Conclusions. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase.

Automated analysis of whole skeletal muscle for muscular atrophy detection of ALS in whole-body CT images: preliminary study

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Kamiya, Naoki; Ieda, Kosuke; Zhou, Xiangrong; Yamada, Megumi; Kato, Hiroki; Muramatsu, Chisako; Hara, Takeshi; Miyoshi, Toshiharu; Inuzuka, Takashi; Matsuo, Masayuki; Fujita, Hiroshi

2017-03-01

Amyotrophic lateral sclerosis (ALS) causes functional disorders such as difficulty in breathing and swallowing through the atrophy of voluntary muscles. ALS in its early stages is difficult to diagnose because of the difficulty in differentiating it from other muscular diseases. In addition, image inspection methods for aggressive diagnosis for ALS have not yet been established. The purpose of this study is to develop an automatic analysis system of the whole skeletal muscle to support the early differential diagnosis of ALS using whole-body CT images. In this study, the muscular atrophy parts including ALS patients are automatically identified by recognizing and segmenting whole skeletal muscle in the preliminary steps. First, the skeleton is identified by its gray value information. Second, the initial area of the body cavity is recognized by the deformation of the thoracic cavity based on the anatomical segmented skeleton. Third, the abdominal cavity boundary is recognized using ABM for precisely recognizing the body cavity. The body cavity is precisely recognized by non-rigid registration method based on the reference points of the abdominal cavity boundary. Fourth, the whole skeletal muscle is recognized by excluding the skeleton, the body cavity, and the subcutaneous fat. Additionally, the areas of muscular atrophy including ALS patients are automatically identified by comparison of the muscle mass. The experiments were carried out for ten cases with abnormality in the skeletal muscle. Global recognition and segmentation of the whole skeletal muscle were well realized in eight cases. Moreover, the areas of muscular atrophy including ALS patients were well identified in the lower limbs. As a result, this study indicated the basic technology to detect the muscle atrophy including ALS. In the future, it will be necessary to consider methods to differentiate other kinds of muscular atrophy as well as the clinical application of this detection method for early ALS

Transcriptome Analysis for Abnormal Spike Development of the Wheat Mutant dms.

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Zhu, Xin-Xin; Li, Qiao-Yun; Shen, Chun-Cai; Duan, Zong-Biao; Yu, Dong-Yan; Niu, Ji-Shan; Ni, Yong-Jing; Jiang, Yu-Mei

2016-01-01

Wheat (Triticum aestivum L.) spike development is the foundation for grain yield. We obtained a novel wheat mutant, dms, characterized as dwarf, multi-pistil and sterility. Although the genetic changes are not clear, the heredity of traits suggests that a recessive gene locus controls the two traits of multi-pistil and sterility in self-pollinating populations of the medium plants (M), such that the dwarf genotype (D) and tall genotype (T) in the progeny of the mutant are ideal lines for studies regarding wheat spike development. The objective of this study was to explore the molecular basis for spike abnormalities of dwarf genotype. Four unigene libraries were assembled by sequencing the mRNAs of the super-bulked differentiating spikes and stem tips of the D and T plants. Using integrative analysis, we identified 419 genes highly expressed in spikes, including nine typical homeotic genes of the MADS-box family and the genes TaAP2, TaFL and TaDL. We also identified 143 genes that were significantly different between young spikes of T and D, and 26 genes that were putatively involved in spike differentiation. The result showed that the expression levels of TaAP1-2, TaAP2, and other genes involved in the majority of biological processes such as transcription, translation, cell division, photosynthesis, carbohydrate transport and metabolism, and energy production and conversion were significantly lower in D than in T. We identified a set of genes related to wheat floral organ differentiation, including typical homeotic genes. Our results showed that the major causal factors resulting in the spike abnormalities of dms were the lower expression homeotic genes, hormonal imbalance, repressed biological processes, and deficiency of construction materials and energy. We performed a series of studies on the homeotic genes, however the other three causal factors for spike abnormal phenotype of dms need further study.

Congenital skeletal malformations and cleft palate induced in goats by ingestion of Lupinus, Conium and Nicotiana species.

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Panter, K E; Keeler, R F; Bunch, T D; Callan, R J

1990-01-01

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

Role of active contraction and tropomodulins in regulating actin filament length and sarcomere structure in developing zebrafish skeletal muscle

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Lise eMazelet

2016-03-01

Full Text Available Whilst it is recognised that contraction plays an important part in maintaining the structure and function of mature skeletal muscle, its role during development remains undefined. In this study the role of movement in skeletal muscle maturation was investigated in intact zebrafish embryos using a combination of genetic and pharmacological approaches. An immotile mutant line (cacnb1ts25 which lacks functional voltage-gated calcium channels (dihydropyridine receptors in the muscle and pharmacological immobilisation of embryos with a reversible anaesthetic (Tricaine, allowed the study of paralysis (in mutants and anaesthetised fish and recovery of movement (reversal of anaesthetic treatment. The effect of paralysis in early embryos (aged between 17-24 hours post fertilisation, hpf on skeletal muscle structure at both myofibrillar and myofilament level was determined using both immunostaining with confocal microscopy and small angle X-ray diffraction. The consequences of paralysis and subsequent recovery on the localisation of the actin capping proteins Tropomodulin 1 &4 (Tmod in fish aged from 17hpf until 42hpf was also assessed. The functional consequences of early paralysis were investigated by examining the mechanical properties of the larval muscle. The length-force relationship, active and passive tension, was measured in immotile, recovered and control skeletal muscle at 5 and 7 day post fertilisation (dpf. Recovery of muscle function was also assessed by examining swimming patterns in recovered and control fish. Inhibition of the initial embryonic movements (up to 24 hpf resulted in an increase in myofibril length and a decrease in width followed by almost complete recovery in both moving and paralysed fish by 42hpf. In conclusion, myofibril organisation is regulated by a dual mechanism involving movement-dependent and movement-independent processes. The initial contractile event itself drives the localisation of Tmod1 to its sarcomeric

Diabetic Myopathy: Impact of Diabetes Mellitus on Skeletal Muscle Progenitor Cells

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Donna M D'Souza

2013-12-01

Full Text Available Diabetes mellitus is defined as a group of metabolic diseases that are associated with the presence of a hyperglycemic state due to impairments in insulin function. While the development of each form of diabetes (Type 1 or Type 2 drastically differs, resultant pathologies often overlap. In each diabetic condition a failure to maintain healthy muscle is often observed, and is termed diabetic myopathy. This significant, but often overlooked, complication is believed to contribute to the progression of additional diabetic pathologies due to the vital importance of skeletal muscle for our physical and metabolic well-being. While studies have investigated the link between changes to skeletal muscle metabolic health following diabetes mellitus onset (particularly Type 2 diabetes mellitus, few have examined the negative impact of diabetes mellitus on the growth and reparative capacities of skeletal muscle that often coincides with disease development. Importantly, evidence is accumulating that the muscle progenitor cell population (particularly the muscle satellite cell population is also negatively affected by the diabetic environment, and as such, likely contributes to the declining skeletal muscle health observed in diabetes mellitus. In this review, we summarize the current knowledge surrounding the influence of diabetes mellitus on skeletal muscle growth and repair, with a particular emphasis on the impact of diabetes mellitus on the progenitor cell population of skeletal muscle.

Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways.

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Rolfe, Rebecca A; Nowlan, Niamh C; Kenny, Elaine M; Cormican, Paul; Morris, Derek W; Prendergast, Patrick J; Kelly, Daniel; Murphy, Paula

2014-01-20

Mechanical stimulation is necessary for regulating correct formation of the skeleton. Here we test the hypothesis that mechanical stimulation of the embryonic skeletal system impacts expression levels of genes implicated in developmentally important signalling pathways in a genome wide approach. We use a mutant mouse model with altered mechanical stimulation due to the absence of limb skeletal muscle (Splotch-delayed) where muscle-less embryos show specific defects in skeletal elements including delayed ossification, changes in the size and shape of cartilage rudiments and joint fusion. We used Microarray and RNA sequencing analysis tools to identify differentially expressed genes between muscle-less and control embryonic (TS23) humerus tissue. We found that 680 independent genes were down-regulated and 452 genes up-regulated in humeri from muscle-less Spd embryos compared to littermate controls (at least 2-fold; corrected p-value ≤0.05). We analysed the resulting differentially expressed gene sets using Gene Ontology annotations to identify significant enrichment of genes associated with particular biological processes, showing that removal of mechanical stimuli from muscle contractions affected genes associated with development and differentiation, cytoskeletal architecture and cell signalling. Among cell signalling pathways, the most strongly disturbed was Wnt signalling, with 34 genes including 19 pathway target genes affected. Spatial gene expression analysis showed that both a Wnt ligand encoding gene (Wnt4) and a pathway antagonist (Sfrp2) are up-regulated specifically in the developing joint line, while the expression of a Wnt target gene, Cd44, is no longer detectable in muscle-less embryos. The identification of 84 genes associated with the cytoskeleton that are down-regulated in the absence of muscle indicates a number of candidate genes that are both mechanoresponsive and potentially involved in mechanotransduction, converting a mechanical stimulus

Congenital anomalies and normal skeletal variants

International Nuclear Information System (INIS)

Guebert, G.M.; Yochum, T.R.; Rowe, L.J.

1987-01-01

Congenital anomalies and normal skeletal variants are a common occurrence in clinical practice. In this chapter a large number of skeletal anomalies of the spine and pelvis are reviewed. Some of the more common skeletal anomalies of the extremities are also presented. The second section of this chapter deals with normal skeletal variants. Some of these variants may simulate certain disease processes. In some instances there are no clear-cut distinctions between skeletal variants and anomalies; therefore, there may be some overlap of material. The congenital anomalies are presented initially with accompanying text, photos, and references, beginning with the skull and proceeding caudally through the spine to then include the pelvis and extremities. The normal skeletal variants section is presented in an anatomical atlas format without text or references

Epigallocatechin-3-gallate (EGCG) consumption in the Ts65Dn model of Down syndrome fails to improve behavioral deficits and is detrimental to skeletal phenotypes.

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Stringer, Megan; Abeysekera, Irushi; Thomas, Jared; LaCombe, Jonathan; Stancombe, Kailey; Stewart, Robert J; Dria, Karl J; Wallace, Joseph M; Goodlett, Charles R; Roper, Randall J

2017-08-01

Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in phenotypes including intellectual disability and skeletal deficits. Ts65Dn mice have three copies of ~50% of the genes homologous to Hsa21 and display phenotypes associated with DS, including cognitive deficits and skeletal abnormalities. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including neurological development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have previously shown that EGCG treatment (~10mg/kg/day) improves skeletal abnormalities in Ts65Dn mice, yet the same dose, as well as ~20mg/kg/day did not rescue deficits in the Morris water maze spatial learning task (MWM), novel object recognition (NOR) or balance beam task (BB). In contrast, a recent study reported that an EGCG-containing supplement with a dose of 2-3mg per day (~40-60mg/kg/day) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated if an EGCG dosage similar to that study would yield similar improvements in either cognitive or skeletal deficits. Ts65Dn mice and euploid littermates were given EGCG [0.4mg/mL] or a water control, with treatments yielding average daily intakes of ~50mg/kg/day EGCG, and tested on the multivariate concentric square field (MCSF)-which assesses activity, exploratory behavior, risk assessment, risk taking, and shelter seeking-and NOR, BB, and MWM. EGCG treatment failed to improve cognitive deficits; EGCG also produced several detrimental effects on skeleton in both genotypes. In a refined HPLC-based assay, its first application in Ts65Dn mice, EGCG treatment significantly reduced kinase activity in femora but not in the cerebral cortex, cerebellum, or hippocampus. Counter to expectation, 9-week-old Ts65Dn mice exhibited a decrease in Dyrk1a protein levels in Western blot analysis

Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria During Linezolid-Induced Lactic Acidosis.

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Protti, Alessandro; Ronchi, Dario; Bassi, Gabriele; Fortunato, Francesco; Bordoni, Andreina; Rizzuti, Tommaso; Fumagalli, Roberto

2016-07-01

To better clarify the pathogenesis of linezolid-induced lactic acidosis. Case report. ICU. A 64-year-old man who died with linezolid-induced lactic acidosis. Skeletal muscle was sampled at autopsy to study mitochondrial function. Lactic acidosis developed during continuous infusion of linezolid while oxygen consumption and oxygen extraction were diminishing from 172 to 52 mL/min/m and from 0.27 to 0.10, respectively. Activities of skeletal muscle respiratory chain complexes I, III, and IV, encoded by nuclear and mitochondrial DNA, were abnormally low, whereas activity of complex II, entirely encoded by nuclear DNA, was not. Protein studies confirmed stoichiometric imbalance between mitochondrial (cytochrome c oxidase subunits 1 and 2) and nuclear (succinate dehydrogenase A) DNA-encoded respiratory chain subunits. These findings were not explained by defects in mitochondrial DNA or transcription. There were no compensatory mitochondrial biogenesis (no induction of nuclear respiratory factor 1 and mitochondrial transcript factor A) or adaptive unfolded protein response (reduced concentration of heat shock proteins 60 and 70). Linezolid-induced lactic acidosis is associated with diminished global oxygen consumption and extraction. These changes reflect selective inhibition of mitochondrial protein synthesis (probably translation) with secondary mitonuclear imbalance. One novel aspect of linezolid toxicity that needs to be confirmed is blunting of reactive mitochondrial biogenesis and unfolded protein response.

Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly

International Nuclear Information System (INIS)

Jacquemin, C.; Bosley, T.M.

2001-01-01

We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease. (orig.)

Abnormal development of the lesser wing of the sphenoid with microphthalmos and microcephaly

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Jacquemin, C. [King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia). Radiology Dept.; Mullaney, P. [Paediatric Ophthalmology Div., King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia); Bosley, T.M. [Neuro-Ophthalmology Div., King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

2001-02-01

We report two patients with abnormal development of the lesser wing of the sphenoid bone, globe, optic nerve and cerebral hemisphere without stigmata of neurofibromatosis type 1. The lesser wing of the sphenoid bone was abnormally formed and was not ossified ipsilateral to the dysmorphic eye and underdeveloped cerebral hemisphere. Maldevelopment of the sphenoid wing may interfere with the normal closure of the optic vesicle and normal growth of encephalic structures, possibly by disturbing developmental tissue interactions. These patients may exhibit a type of restricted primary sphenoid dysplasia, while the sphenoid dysplasia of neurofibromatosis type 1 may be secondary to orbital or ocular neurofibromas and other factors associated with that disease. (orig.)

Radium-223 in treatment of castration-resistant prostate cancer with skeletal metastases

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V. B. Matveev

2017-01-01

Full Text Available More than 90 % of patients with metastatic castration-resistant prostate cancer (CRPC have radiologically confirmed skeletal metastases. Traditional treatment methods such as administration of painkillers, external beam therapy, bisphosphonates or denosumab, as well as injections of strontium-89 or samarium-153 radionuclides, have only palliative effect and in some cases can postpone development of skeletal complications. Alpha-emitter radium-223 dichloride (Ra-223; alpharadin previously is currently one of the known drugs with proven effectiveness in relation to increasing overall survival of patients with CRPC. Ra-223 was developed specifically for patients with CRPC and symptomatic skeletal metastases. The drug targets the areas of skeletal tissue remodeling. Ra-223 is the therapy of choice in patients with CRPC and skeletal metastases and without confirmed visceral metastases before and after docetaxel chemotherapy. Chemotherapy after treatment with Ra-223 is a possible and satisfactory tolerable treatment option. Combination of Ra-223 with abiraterone, enzalutamide, or denosumab is, apparently, effective and safe, but further studies are necessary.

Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation

DEFF Research Database (Denmark)

Schwartz, Kristoffer; Rodrigo, Maria; Jensen, Thomas

2016-01-01

OBJECTIVES: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. MATERIAL AND METHODS......: A total of 33 consecutive patients underwent bimaxillary surgery to correct skeletal Class II malocclusion with a mandibular advancement (> 10 mm) measured at B-point and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal stability was evaluated using lateral cephalometric...... radiographs obtained preoperative (T1), 8 weeks postoperatively (T2), and 18 month postoperatively (T3). B-point and pogonion (Pog) was used to measure the skeletal relapse and the mandibular plane angle (MP-angle) was used to determine the vertical facial type. RESULTS: The mean advancement from T1 to T2...

Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: characterization of Tnnt3(tm2a(KOMP)Wtsi) mice.

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Ju, Yawen; Li, Jie; Xie, Chao; Ritchlin, Christopher T; Xing, Lianping; Hilton, Matthew J; Schwarz, Edward M

2013-09-01

The troponin complex, which consists of three regulatory proteins (troponin C, troponin I, and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is a fast skeletal muscle troponin believed to be expressed only in skeletal muscle cells. To determine the in vivo function and tissue-specific expression of Tnnt3, we obtained the heterozygous Tnnt3+/flox/lacZ mice from Knockout Mouse Project (KOMP) Repository. Tnnt3(lacZ/+) mice are smaller than their WT littermates throughout development but do not display any gross phenotypes. Tnnt3(lacZ/lacZ) embryos are smaller than heterozygotes and die shortly after birth. Histology revealed hemorrhagic tissue in Tnnt3(lacZ/lacZ) liver and kidney, which was not present in Tnnt3(lacZ/+) or WT, but no other gross tissue abnormalities. X-gal staining for Tnnt3 promoter-driven lacZ transgene expression revealed positive staining in skeletal muscle and diaphragm and smooth muscle cells located in the aorta, bladder, and bronchus. Collectively, these findings suggest that troponins are expressed in smooth muscle and are required for normal growth and breathing for postnatal survival. Moreover, future studies with this mouse model can explore TnnT3 function in adult muscle function using the conditional-inducible gene deletion approach Copyright © 2013 Wiley Periodicals, Inc.

The effect of regular strength training on telomere length in human skeletal muscle

DEFF Research Database (Denmark)

Kadi, F.; Ponsot, Elodie; Piehl-Aulin, Karin

2008-01-01

PURPOSE: The length of DNA telomeres is an important parameter of the proliferative potential of tissues. A recent study has reported abnormally short telomeres in skeletal muscle of athletes with exercise-associated fatigue. This important report raises the question of whether long-term practice...... of sports might have deleterious effects on muscle telomeres. Therefore, we aimed to compare telomere length of a group of power lifters (PL; N = 7) who trained for 8 +/- 3 yr against that of a group of healthy, active subjects (C; N = 7) with no history of strength training. METHODS: Muscle biopsies were...

Duchenne muscular dystrophy carriers. Proton spin-lattice relaxation times of skeletal muscles on magnetic resonance imaging

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Matsumura, K.; Nakano, I. (Shimoshizu National Hospital, Chiba (Japan). Dept. of Neurology); Fukuda, N.; Ikehira, H.; Tateno, Y. (National Inst. of Radiological Sciences, Chiba (Japan). Div. of Clinical Research); Aoki, Y. (National Inst. of Radiological Sciences, Chiba (Japan))

1989-11-01

By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated from the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly. (orig.).

Development of an in vitro potency assay for human skeletal muscle derived cells.

Science.gov (United States)

Thurner, Marco; Asim, Faheem; Garczarczyk-Asim, Dorota; Janke, Katrin; Deutsch, Martin; Margreiter, Eva; Troppmair, Jakob; Marksteiner, Rainer

2018-01-01

Potency is a quantitative measure of the desired biological function of an advanced therapy medicinal product (ATMP) and is a prerequisite for market approval application (MAA). To assess the potency of human skeletal muscle-derived cells (SMDCs), which are currently investigated in clinical trials for the regeneration of skeletal muscle defects, we evaluated acetylcholinesterase (AChE), which is expressed in skeletal muscle and nervous tissue of all mammals. CD56+ SMDCs were separated from CD56- SMDCs by magnetic activated cell sorting (MACS) and both differentiated in skeletal muscle differentiation medium. AChE activity of in vitro differentiated SMDCs was correlated with CD56 expression, fusion index, cell number, cell doubling numbers, differentiation markers and compared to the clinical efficacy in patients treated with SMDCs against fecal incontinence. CD56- SMDCs did not form multinucleated myotubes and remained low in AChE activity during differentiation. CD56+ SMDCs generated myotubes and increased in AChE activity during differentiation. AChE activity was found to accurately reflect the number of CD56+ SMDCs in culture, their fusion competence, and cell doubling number. In patients with fecal incontinence responding to SMDCs treatment, the improvement of clinical symptoms was positively linked with the AChE activity of the SMDCs injected. AChE activity was found to truly reflect the in vitro differentiation status of SMDCs and to be superior to the mere use of surface markers as it reflects not only the number of myogenic SMDCs in culture but also their fusion competence and population doubling number, thus combining cell quality and quantification of the expected mode of action (MoA) of SMDCs. Moreover, the successful in vitro validation of the assay proves its suitability for routine use. Most convincingly, our results demonstrate a link between clinical efficacy and the AChE activity of the SMDCs preparations used for the treatment of fecal

Comprehensive Validation of Skeletal Mechanism for Turbulent Premixed Methane–Air Flame Simulations

KAUST Repository

Luca, Stefano; Al-Khateeb, Ashraf N.; Attili, Antonio; Bisetti, Fabrizio

2017-01-01

A new skeletal mechanism, consisting of 16 species and 72 reactions, has been developed for lean methane–air premixed combustion from the GRI-Mech 3.0. The skeletal mechanism is validated for elevated unburnt temperatures (800 K) and pressures up

NPPB and ACAN, two novel SHOX2 transcription targets implicated in skeletal development.

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Miriam Aza-Carmona

Full Text Available SHOX and SHOX2 transcription factors are highly homologous, with even identical homeodomains. Genetic alterations in SHOX result in two skeletal dysplasias; Léri-Weill dyschondrosteosis (LWD and Langer mesomelic dysplasia (LMD, while no human genetic disease has been linked to date with SHOX2. SHOX2 is, though, involved in skeletal development, as shown by different knockout mice models. Due to the high homology between SHOX and SHOX2, and their functional redundancy during heart development, we postulated that SHOX2 might have the same transcriptional targets and cofactors as SHOX in limb development. We selected two SHOX transcription targets regulated by different mechanisms: 1 the natriuretic peptide precursor B gene (NPPB involved in the endochondral ossification signalling and directly activated by SHOX; and 2 Aggrecan (ACAN, a major component of cartilage extracellular matrix, regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9 via the protein interaction between SOX5/SOX6 and SHOX. Using the luciferase assay we have demonstrated that SHOX2, like SHOX, regulates NPPB directly whilst activates ACAN via its cooperation with the SOX trio. Subsequently, we have identified and characterized the protein domains implicated in the SHOX2 dimerization and also its protein interaction with SOX5/SOX6 and SHOX using the yeast-two hybrid and co-immunoprecipitation assays. Immunohistochemistry of human fetal growth plates from different time points demonstrated that SHOX2 is coexpressed with SHOX and the members of the SOX trio. Despite these findings, no mutation was identified in SHOX2 in a cohort of 83 LWD patients with no known molecular defect, suggesting that SHOX2 alterations do not cause LWD. In conclusion, our work has identified the first cofactors and two new transcription targets of SHOX2 in limb development, and we hypothesize a time- and tissue-specific functional redundancy between SHOX and SHOX2.

NPPB and ACAN, two novel SHOX2 transcription targets implicated in skeletal development.

Science.gov (United States)

Aza-Carmona, Miriam; Barca-Tierno, Veronica; Hisado-Oliva, Alfonso; Belinchón, Alberta; Gorbenko-del Blanco, Darya; Rodriguez, Jose Ignacio; Benito-Sanz, Sara; Campos-Barros, Angel; Heath, Karen E

2014-01-01

SHOX and SHOX2 transcription factors are highly homologous, with even identical homeodomains. Genetic alterations in SHOX result in two skeletal dysplasias; Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD), while no human genetic disease has been linked to date with SHOX2. SHOX2 is, though, involved in skeletal development, as shown by different knockout mice models. Due to the high homology between SHOX and SHOX2, and their functional redundancy during heart development, we postulated that SHOX2 might have the same transcriptional targets and cofactors as SHOX in limb development. We selected two SHOX transcription targets regulated by different mechanisms: 1) the natriuretic peptide precursor B gene (NPPB) involved in the endochondral ossification signalling and directly activated by SHOX; and 2) Aggrecan (ACAN), a major component of cartilage extracellular matrix, regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9) via the protein interaction between SOX5/SOX6 and SHOX. Using the luciferase assay we have demonstrated that SHOX2, like SHOX, regulates NPPB directly whilst activates ACAN via its cooperation with the SOX trio. Subsequently, we have identified and characterized the protein domains implicated in the SHOX2 dimerization and also its protein interaction with SOX5/SOX6 and SHOX using the yeast-two hybrid and co-immunoprecipitation assays. Immunohistochemistry of human fetal growth plates from different time points demonstrated that SHOX2 is coexpressed with SHOX and the members of the SOX trio. Despite these findings, no mutation was identified in SHOX2 in a cohort of 83 LWD patients with no known molecular defect, suggesting that SHOX2 alterations do not cause LWD. In conclusion, our work has identified the first cofactors and two new transcription targets of SHOX2 in limb development, and we hypothesize a time- and tissue-specific functional redundancy between SHOX and SHOX2.

Effect of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle.

Science.gov (United States)

Carter, W J; Van Der Weijden Benjamin, W S; Faas, F H

1980-10-01

Since experimental hyperthyroidism reduces skeletal muscle mass while simultaneously increasing cardiac muscle mass, the effect of hyperthyroidism on muscle protein degradation was compared in skeletal and cardiac muscle. Pulse-labeling studies using (3H) leucine and (14C) carboxyl labeled aspartate and glutamate were carried out. Hyperthyroidism caused a 25%-29% increase in protein breakdown in both sarcoplasmic and myofibrillar fractions of skeletal muscle. Increased muscle protein degradation may be a major factor in the development of skeletal muscle wasting and weakness in hyperthyroidism. In contrast, protein breakdown appeared to be reduced 22% in the sarcoplasmic fraction of hyperthyroid heart muscle and was unchanged in the myofibrillar fraction. Possible reasons for the contrasting effects of hyperthyroidism on skeletal and cardiac muscle include increased sensitivity of the hyperthyroid heart to catecholamines, increased cardiac work caused by the hemodynamic effects of hyperthyroidism, and a different direct effect of thyroid hormone at the nuclear level in cardiac as opposed to skeletal muscle.

Generation of skeletal muscle from transplanted embryonic stem cells in dystrophic mice

International Nuclear Information System (INIS)

Bhagavati, Satyakam; Xu Weimin

2005-01-01

Embryonic stem (ES) cells have great therapeutic potential because of their capacity to proliferate extensively and to form any fully differentiated cell of the body, including skeletal muscle cells. Successful generation of skeletal muscle in vivo, however, requires selective induction of the skeletal muscle lineage in cultures of ES cells and following transplantation, integration of appropriately differentiated skeletal muscle cells with recipient muscle. Duchenne muscular dystrophy (DMD), a severe progressive muscle wasting disease due to a mutation in the dystrophin gene and the mdx mouse, an animal model for DMD, are characterized by the absence of the muscle membrane associated protein, dystrophin. Here, we show that co-culturing mouse ES cells with a preparation from mouse muscle enriched for myogenic stem and precursor cells, followed by injection into mdx mice, results occasionally in the formation of normal, vascularized skeletal muscle derived from the transplanted ES cells. Study of this phenomenon should provide valuable insights into skeletal muscle development in vivo from transplanted ES cells

Engineered matrices for skeletal muscle satellite cell engraftment and function.

Science.gov (United States)

Han, Woojin M; Jang, Young C; García, Andrés J

2017-07-01

Regeneration of traumatically injured skeletal muscles is severely limited. Moreover, the regenerative capacity of skeletal muscle declines with aging, further exacerbating the problem. Recent evidence supports that delivery of muscle satellite cells to the injured muscles enhances muscle regeneration and reverses features of aging, including reduction in muscle mass and regenerative capacity. However, direct delivery of satellite cells presents a challenge at a translational level due to inflammation and donor cell death, motivating the need to develop engineered matrices for muscle satellite cell delivery. This review will highlight important aspects of satellite cell and their niche biology in the context of muscle regeneration, and examine recent progresses in the development of engineered cell delivery matrices designed for skeletal muscle regeneration. Understanding the interactions of muscle satellite cells and their niche in both native and engineered systems is crucial to developing muscle pathology-specific cell- and biomaterial-based therapies. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Dentoskeletal Overjet Measurements of Iraqi Adult Sample with Different Skeletal Jaw Relationship

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Shahbaa A Mohammed

2017-11-01

Full Text Available Background: Many attempts were done to develop a method that actually reflects the sagittal jaw discrepancies without depending on cranial landmarks or dental occlusion. This study aimed to use one of these methods (dentoskeletal overjet for assessing the sagittal jaw relationships of Iraqi adult sample with different skeletal jaw relationship. Materials and method: The sample consisted of 90 digital true lateral cephalometric radiographs of Iraqi individuals with no previous orthodontic treatment. Cephalometric analysis of skeletal sagittal jaw relationship -ANB angle, beta angle and Wits appraisal- will perform for everyone to divide the sample into three groups (skeletal class I, II, III for which the dentoskeletal overjet will be measured. All cephalometric measurements will be done using AutoCAD. Results: Descriptive statistics of all variables with different skeletal jaw relationship showed that mean values of dentoskeletal overjet were (1.15, 3.91 and –2.01 mm for skeletal class I, class II and class III jaw relationship respectively. Accurate reproducibility of dentoskeletal overjet in assessment of jaw skeletal relationship showed that the lowest value was for assessment of skeletal class III jaw relationship (73% and the value for assessment of both skeletal class I and class II was higher (93%. Conclusions: Dentoskeletal overjet could be utilized in accurate representation of skeletal jaw relationship.

Radiology of skeletal and soft tissue changes

International Nuclear Information System (INIS)

Walker, H.C. Jr.; Coleman, C.C.; Hunter, D.W.

1986-01-01

Skeletal complications are very common in renal transplant patients. Loss of bone mass in the posttransplant period places the skeletal system in jeopardy. Osteonecrosis, while not life threatening, often prevents rehabilitation. Spontaneous fractures are frequent but are usually not a major problem except in the diabetic transplant recipient. Septic arthritis and osteomyelitis are usually successfully managed by conservative measures, except when accompanied by severe occlusive vascular disease. Juvenile onset diabetic patients still may develop disabling neuropathic joint disease or occlusive vascular disease after renal transplantation. The authors hope that successful pancreas transplantation will avert these problems in the future

Secreted Protein Acidic and Rich in Cysteine (SPARC) in Human Skeletal Muscle

DEFF Research Database (Denmark)

Jørgensen, Louise H; Petersson, Stine J; Sellathurai, Jeeva

2009-01-01

indicated a function of SPARC in skeletal muscle. We therefore found it of interest to study SPARC expression in human skeletal muscle during development and in biopsies from Duchenne and Becker muscular dystrophy and congenital muscular dystrophy, congenital myopathy, inclusion body myositis...

Skeletal muscle wasting: new role of nonclassical renin-angiotensin system.

Science.gov (United States)

Cabello-Verrugio, Claudio; Rivera, Juan C; Garcia, Dominga

2017-05-01

Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance. Recent studies have shown that angiotensin (1-7) [Ang-(1-7)] - a vasoactive peptide of the nonclassical axis in the renin-angiotensin system (RAS) - and its Mas receptor are expressed in skeletal muscle. Ang-(1-7), through its Mas receptor, prevents or diminishes deleterious effects induced by skeletal muscle disease or injury. Specifically, the Ang-(1-7)-Mas receptor axis modulates molecular mechanisms involved in muscle mass regulation, such as the ubiquitin proteasome pathway, the insulin-like growth factor type 1/Akt (protein kinase B) pathway, or myonuclear apoptosis, and also inflammation and fibrosis pathways. Although further research into this topic and the possible side effects of Ang-(1-7) is necessary, these findings are promising, and suggest that the Ang-(1-7)-Mas axis can be considered a possible therapeutic target for treating patients with muscular disorders.

Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

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Atul S. Deshmukh

2016-02-01

Full Text Available Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs. Mass spectrometry (MS-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC, MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets.

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

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Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging.

Science.gov (United States)

Toledo, Frederico G S; Goodpaster, Bret H

2013-10-15

Mitochondria within skeletal muscle have been implicated in insulin resistance of obesity and type 2 diabetes mellitus as well as impaired muscle function with normal aging. Evaluating the potential of interventions to improve mitochondria is clearly relevant to the prevention or treatment of metabolic diseases and age-related dysfunction. This review provides an overview and critical evaluation of the effects of weight loss and exercise interventions on skeletal muscle mitochondria, along with implications for insulin resistance, obesity, type 2 diabetes and aging. The available literature strongly suggests that the lower mitochondrial capacity associated with obesity, type 2 diabetes and aging is not an irreversible lesion. However, weight loss does not appear to affect this response, even when the weight loss is extreme. In contrast, increasing physical activity improves mitochondrial content and perhaps the function of individual mitochondrion. Despite the consistent effect of exercise to improve mitochondrial capacity, studies mechanistically linking mitochondria to insulin resistance, reductions in intramyocellular lipid or improvement in muscle function remain inconclusive. In summary, studies of diet and exercise training have advanced our understanding of the link between mitochondrial oxidative capacity and insulin resistance in obesity, type 2 diabetes and aging. Nevertheless, additional inquiry is necessary to establish the significance and clinical relevance of those perturbations, which could lead to targeted therapies for a myriad of conditions and diseases involving mitochondria. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of myocardial and skeletal muscular involvement with thallium-201 myocardial emission computed tomography and whole body scintigraphy

International Nuclear Information System (INIS)

Yamamoto, Shuhei; Matsushima, Hideo; Sotobata, Iwao; Suzuki, Akio; Indo, Toshikatsu; Matsuoka, Yukihiko

1986-01-01

Thallium-201 (Tl-201) myocardial emission computed tomography and whole body scintigraphy were performed using a rotating gamma camera in 64 patients with neurologic disease and 14 normal subjects. Thallium-201 myocardial perfusion defects were seen in 40 % of the muscular involvement in 47 patients with muscular dystrophy (MD), in whom morphological abnormality of the heart was common. There was strong relationship between the degree of left ventricular perfusion defects and the degree of pulmonary uptake of Tl-201. Thallium-201 whole body scintigraphy showed homogeneous distribution of Tl-201 in the extremities in normal subjects, and perfusion defects in 73 % of the muscular lesions in MD patients. Muscular and skeletal lesions for MD appear to progress independently. Thallium-201 imaging seems to be of clinical value in assessing the muscular and skeletal lesions. (Namekawa, K.)

Satellite cells in human skeletal muscle plasticity

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Tim eSnijders

2015-10-01

Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodelling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

Satellite cells in human skeletal muscle plasticity.

Science.gov (United States)

Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

2015-01-01

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

MeCP2 Affects Skeletal Muscle Growth and Morphology through Non Cell-Autonomous Mechanisms.

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Valentina Conti

Full Text Available Rett syndrome (RTT is an autism spectrum disorder mainly caused by mutations in the X-linked MECP2 gene and affecting roughly 1 out of 10.000 born girls. Symptoms range in severity and include stereotypical movement, lack of spoken language, seizures, ataxia and severe intellectual disability. Notably, muscle tone is generally abnormal in RTT girls and women and the Mecp2-null mouse model constitutively reflects this disease feature. We hypothesized that MeCP2 in muscle might physiologically contribute to its development and/or homeostasis, and conversely its defects in RTT might alter the tissue integrity or function. We show here that a disorganized architecture, with hypotrophic fibres and tissue fibrosis, characterizes skeletal muscles retrieved from Mecp2-null mice. Alterations of the IGF-1/Akt/mTOR pathway accompany the muscle phenotype. A conditional mouse model selectively depleted of Mecp2 in skeletal muscles is characterized by healthy muscles that are morphologically and molecularly indistinguishable from those of wild-type mice raising the possibility that hypotonia in RTT is mainly, if not exclusively, mediated by non-cell autonomous effects. Our results suggest that defects in paracrine/endocrine signaling and, in particular, in the GH/IGF axis appear as the major cause of the observed muscular defects. Remarkably, this is the first study describing the selective deletion of Mecp2 outside the brain. Similar future studies will permit to unambiguously define the direct impact of MeCP2 on tissue dysfunctions.

Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.

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Kristen E Boyle

Full Text Available The rising prevalence of gestational diabetes mellitus (GDM affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM and obese pregnant women with normal glucose tolerance (ONGT. Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I subunits (NDUFS3, NDUFV2 and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4 in OGDM (n = 6 vs. ONGT (n = 6. Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (-60-75% in the OGDM (n = 8 compared with ONGT (n = 10 subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

Abnormal expression of ephrin-A5 affects brain development of congenital hypothyroidism rats.

Science.gov (United States)

Suo, Guihai; Shen, Feifei; Sun, Baolan; Song, Honghua; Xu, Meiyu; Wu, Youjia

2018-05-14

EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.

Phenotype abnormality: 32 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 32 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u538i abnormal for trait of behavioral quality... during process named organ development ... abnormal ... organ development ... behavioral quality

Development of Abnormal Operating Strategies for Loss of Ultimate Heat Sink (LOUHS) at Shutdown Mode in Westinghouse Type Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Yoon, Duk-Joo; Lee, Seung-Chan; Sung, Je-Joong; Ha, Sang Jun [KHNP CRI, Daejeon (Korea, Republic of); Hwang, Su-Hyun [FNC Tech. Co., Yongin (Korea, Republic of)

2016-10-15

Loss of all AC power is classified as one of multiple failure accident by regulatory guide of Korean accident management program. Therefore we need develop strategies for the abnormal operating procedure both of power operating and shutdown mode. This paper developed abnormal operating guideline for loss of all AC power by analysis of accident scenario in pressurized water reactor. This paper analyzed the extended SBO in shutdown operating mode and developed the operating strategy of the abnormal operation procedure. Operator action for the emergency are not required to take in 500 minutes and 60 minutes in intact and opened RCS state respectively.

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

Science.gov (United States)

Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-05-28

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

The skeletal consequences of thyrotoxicosis.

Science.gov (United States)

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

Gestational diabetes mellitus and subsequent development of overt diabetes mellitus

DEFF Research Database (Denmark)

Damm, P

1998-01-01

muscle biopsies from women with GDM and pregnant controls. No major abnormalities were found in GDM wherefore it is likely that the insulin resistance is caused by intracellular defects distal to the activation of the tyrosine kinase. Glucose tolerance returns to normal postpartum in the majority......GDM develops in 1-3% of all pregnancies. Women with GDM are characterized by a relatively diminished insulin secretion coupled with a pregnancy-induced insulin resistance primary located in skeletal muscle tissue. The cellular background for this insulin resistance is not known. The binding...... of insulin to its receptor and the subsequent activation of the insulin receptor tyrosine kinase have significant importance for the cellular effect of insulin. Thus, the pathogenesis to the insulin resistance was studied by investigating insulin receptor binding and tyrosine kinase activity in skeletal...

Meniscus transplantation in skeletally immature patients.

Science.gov (United States)

Kocher, Mininder S; Tepolt, Frances A; Vavken, Patrick

2016-07-01

Meniscal pathology in skeletally immature patients includes meniscal tears and discoid lateral meniscus. Total or subtotal meniscectomy may occur in patients with discoid lateral meniscus or severe meniscal tears. Meniscal transplantation may be an option in skeletally immature patients status after total or subtotal meniscectomy with knee symptoms or dysfunction. This study focuses on the surgical technique and short-term outcomes of meniscus transplantation in skeletally immature patients. We reviewed our clinical database for skeletally immature patients who had undergone meniscus transplantation with a minimum of 2 years of follow-up. Patients were contacted, invited for a physical exam, and asked to complete a Pedi-IKDC, Lysholm, and Tegner outcomes questionnaire. The study protocol was approved by the responsible institutional review board. Three patients (two females/one male) were eligible for the study, each of whom responded to our invitation indicating availability for physical exam and questionnaire. Two patients had undergone subtotal discoid meniscus resection, leading to early lateral compartment degeneration. One patient developed advanced degeneration after a delay in treatment for a medial bucket-handle tear associated with anterior cruciate ligament rupture. The mean age of the patients at the time of surgery was 12.6±2.3 years. At a mean follow-up of 31±20 months, the mean Pedi-IKDC score was 68.3±4, the mean Lysholm was 55.7±22.3, and the median Tegner was 7 points. There were no indications of growth deformity during the regular postoperative radiological assessments. One patient required subsequent lysis of adhesions along the lateral mini arthrotomy and mobilization under anesthesia. The other two patients were able to return to sports at the same level as before meniscus transplantation and were able to do so within 9 months postoperatively. Over-resection of discoid menisci as well as untreated meniscus injury, the latter typically in

Paraphyseal changes on bone-age studies predict risk of delayed radiation-associated skeletal complications following total body irradiation

International Nuclear Information System (INIS)

Kitazono Hammell, Mary T.; Edgar, J.C.; Jaramillo, Diego; Bunin, Nancy

2013-01-01

Children undergoing total body irradiation (TBI) often develop delayed skeletal complications. Bone-age studies in these children often reveal subtle paraphyseal changes including physeal widening, metaphyseal irregularity and paraphyseal exostoses. To investigate whether paraphyseal changes on a bone-age study following TBI indicate a predisposition toward developing other radiation-associated skeletal complications. We retrospectively reviewed medical records and bone-age studies of 77 children receiving TBI at our institution between 1995 and 2008 who had at least 2 years of clinical follow-up and one bone-age study after TBI. We graded bone-age studies according to the severity of paraphyseal changes. All documented skeletal complications following TBI were tabulated. Kendall's tau-b was used to examine associations between degree of paraphyseal change and development of a skeletal complication. Kendall's tau analyses showed that physeal widening and metaphyseal irregularity/sclerosis (tau = 0.87, P < 0.001) and paraphyseal exostoses (tau = 0.68, P < 0.001) seen on bone-age studies were significantly positively associated with the development of delayed skeletal complications following TBI. Thirty percent of children with no or mild paraphyseal changes developed a delayed skeletal complication, compared with 58% of children with moderate paraphyseal changes and 90% of children with severe paraphyseal changes. Paraphyseal changes identified on a bone-age study correlate positively with the development of delayed skeletal complications elsewhere in the skeleton following TBI. (orig.)

Development of an induction motor abnormality monitoring system(IMAMS) using power line signal analysis

International Nuclear Information System (INIS)

Jung, Jae Cheon

1997-02-01

An induction motor abnormality monitoring system using power line signal analysis is developed in this work. Various studies have focused their attention on the detection of particular harmonic frequencies produced from each defect mode of motors. However, these harmonic frequencies are valuable only when the motor has a continuous slip frequency and operate in constant torque/load condition. The basic concept of the system developed in this work is to detect the characteristic harmonic frequencies occurred when the motor is in abnormal state and to compare it with a predetermined setpoint. Based on these analyses, the place and degree of defect can be easily identified. The experimental results under test bench simulation are also introduced. To find out an alternative way to obtain a threshold level independent of slip/torque, with the rotating field theory, the ratio between harmonic current and total current was calculated with the simplified circuit that is equivalent to two abnormal cases, such as the spatial rotor resistance variation and the symmetrical components changes with field. Also, the threshold level calculation was done with performed the rotating field theory. The results show that they are in good agreement with a experimental results. Further studies are undertaken to extend this work to the on-line monitoring and diagnostic system with a likelihood ratio test method for field application

Development of Abnormality Detection System for Bathers using Ultrasonic Sensors

Science.gov (United States)

Ohnishi, Yosuke; Abe, Takehiko; Nambo, Hidetaka; Kimura, Haruhiko; Ogoshi, Yasuhiro

This paper proposes an abnormality detection system for bather sitting in bathtub. Increasing number of in-bathtub drowning accidents in Japan draws attention. Behind this large number of bathing accidents, Japan's unique social and cultural background come surface. For majority of people in Japan, bathing serves purpose in deep warming up of body, relax and enjoyable time. Therefore it is the custom for the Japanese to soak in bathtub. However overexposure to hot water may cause dizziness or fainting, which is possible to cause in-bathtub drowning. For drowning prevention, the system detects bather's abnormal state using an ultrasonic sensor array. The array, which has many ultrasonic sensors, is installed on the ceiling of bathroom above bathtub. The abnormality detection system uses the following two methods: posture detection and behavior detection. The function of posture detection is to estimate the risk of drowning by monitoring bather's posture. Meanwhile, the function of behavior detection is to estimate the risk of drowning by monitoring bather's behavior. By using these methods, the system detects bathers' different state from normal. As a result of experiment with a subject in the bathtub, the system was possible to detect abnormal state using subject's posture and behavior. Therefore the system is useful for monitoring bather to prevent drowning in bathtub.

Human skeletal muscle releases leptin in vivo

DEFF Research Database (Denmark)

Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

2012-01-01

Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

AMPK in skeletal muscle function and metabolism

DEFF Research Database (Denmark)

Kjøbsted, Rasmus; Hingst, Janne Rasmuss; Fentz, Joachim

2018-01-01

Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK's role as an energy sensor is particularly critical in tissues displaying...... highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation......, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives...

Accuracy of dental development for estimating the pubertal growth spurt in comparison to skeletal development: a systematic review and meta-analysis.

Science.gov (United States)

Bittencourt, MarcosAlan Vieira; Cericato, GrazielaOro; Franco, Ademir; Girão, RafaelaSilva; Lima, Anderson Paulo Barbosa; Paranhos, LuizRenato

2018-05-01

This study aimed to search for scientific evidence concerning the accuracy of dental development for estimating the pubertal growth spurt. It was conducted according to the statements of PRISMA. An electronic search was performed in six databases, including the grey literature. The PICOS strategy was used to define the eligibility criteria and only observational studies were selected. Out of 1,416 identified citations, 10 articles fulfilled the criteria and were included in this systematic review. The association between dental development and skeletal maturity was considered strong in seven studies, and moderate in two, although the association with the pubertal growth spurt had been verified in only four articles. According to half of the studies, the tooth that provided the greater association with the ossification centres was the lower canine. The meta-analysis performed also indicated a positive association, being stronger in females [0.725 (0.649-0.808)]. However, when the method used for dental evaluation was considered, it was possible to verify greater correlation coefficients for Nolla [0.736 (0.666-0.814)] than for Demirjian [0.631 (0.450-0.884)], at the boys sample. The heterogeneity test reached high values (Q = 51.00), suggesting a potential bias within the studies. Most of individual studies suggested a strong correlation between dental development and skeletal maturation, although the association with the peakof pubertal growth spurtwas clearly cited only in some of them. However, due to the high heterogeneity found among the studies included in this meta-analysis, a pragmatic recommendation about the use of dental stages is not possible.

In utero undernutrition programs skeletal and cardiac muscle metabolism

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Brittany eBeauchamp

2016-01-01

Full Text Available In utero undernutrition is associated with increased risk for insulin resistance, obesity, and cardiovascular disease during adult life. A common phenotype associated with low birth weight is reduced skeletal muscle mass. Given the central role of skeletal muscle in whole body metabolism, alterations in its mass as well as its metabolic characteristics may contribute to disease risk. This review highlights the metabolic alterations in cardiac and skeletal muscle associated with in utero undernutrition and low birth weight. These tissues have high metabolic demands and are known to be sites of major metabolic dysfunction in obesity, type 2 diabetes, and cardiovascular disease. Recent research demonstrates that mitochondrial energetics are decreased in skeletal and cardiac muscles of adult offspring from undernourished mothers. These effects apparently lead to the development of a thrifty phenotype, which may represent overall a compensatory mechanism programmed in utero to handle times of limited nutrient availability. However, in an environment characterized by food abundance, the effects are maladaptive and increase adulthood risks of metabolic disease.

Phenotype abnormality: 44 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 44 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u550i abnormal for trait of behavior...al quality in organ named root during process named organ development ... root ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 45 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 45 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u551i abnormal for trait of behavior...al quality in organ named stamen during process named organ development ... stamen ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 37 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 37 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u543i abnormal for trait of behavior...al quality in organ named cotyledon during process named organ development ... cotyledon ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 39 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 39 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u545i abnormal for trait of behavior...al quality in organ named flower during process named organ development ... flower ... abnormal ... organ development ... behavioral quality

Characteristics of Skeletal Musculature of Pheasants Hatched from Eggs of Different Eggshell Colour

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Dragan Zikic

2016-05-01

Full Text Available The aim of this paper was to examine morphodinamics of development of skeletal musculature of pheasants hatched from eggs of different eggshell colour. Four groups of pheasant eggs (dark brown, light brown, brown/green and blue/green were incubated. Samples of skeletal musculature of leg and breast were taken during the embryonic and neonatal period of development. From taken samples histological preparations were made. In pheasants hatched from blue/green eggs the smaller diameter of leg and breast muscle cells and the higher volume density of connective tissue in leg and breast muscles were recorded. It was concluded that pheasants hatched from blue/green eggs had the weakest development of skeletal musculature, which can be related to structural differences of eggshell of various colour.

Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses.

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Clara Mariquita Antoinette ten Broek

Full Text Available Fluctuating asymmetry (FA, as an indirect measure of developmental instability (DI, has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.

Structure–function relationship of skeletal muscle provides inspiration for design of new artificial muscle

International Nuclear Information System (INIS)

Gao, Yingxin; Zhang, Chi

2015-01-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure–function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure–function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure–function relationship of skeletal muscle into the design of artificial muscle. (topical review)

Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

Science.gov (United States)

Gao, Yingxin; Zhang, Chi

2015-03-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

Improvement of maternal vitamin D status with 25-hydroxycholecalciferol positively impacts porcine fetal skeletal muscle development and myoblast activity.

Science.gov (United States)

Hines, E A; Coffey, J D; Starkey, C W; Chung, T K; Starkey, J D

2013-09-01

There is little information available regarding the influence of maternal vitamin D status on fetal skeletal muscle development. Therefore, we investigated the effect of improved vitamin D status resulting from 25-hydroxycholecalciferol (25OHD3) supplementation of dams on fetal skeletal muscle developmental characteristics and myoblast activity using Camborough 22 gilts (n = 40) randomly assigned to 1 of 2 corn-soybean meal-based diets. The control diet (CTL) contained 2,500 IU cholecalciferol (D3)/kg diet, whereas the experimental diet contained 500 IU D3/kg diet plus 50 µg 25OHD3/kg diet. Gilts were fed 2.7 kg of their assigned diet once daily beginning 43 d before breeding through d 90 of gestation. On gestational d 90 (± 1), fetal LM and semitendinosus muscle samples were collected for analysis of developmental characteristics and myoblast activity, respectively. No treatment difference was observed in fetal LM cross-sectional area (P = 0.25). Fetuses from 25OHD3-supplemented gilts had more LM fibers (P = 0.04) that tended to be smaller in cross-sectional area compared with CTL fetuses (P = 0.11). A numerical increase in the total number of Pax7+ myoblasts was also observed in fetuses from 25OHD3-supplemented gilts (P = 0.12). Myoblasts derived from the muscles of fetuses from 25OHD3-fed dams displayed an extended proliferative phase in culture compared with those from fetuses of dams fed only D3 (P importance of maternal vitamin D status on the development of fetal skeletal muscle.

Phenotype abnormality: 48 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 48 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u554i abnormal for trait of behavior...al quality in organ named vascular leaf during process named organ development ... vascular leaf ... abnormal ... organ development ... behavioral quality

Poly-epiphyseal overgrowth: description of a previously unreported skeletal dysplasia

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Pazzaglia, Ugo E.; Bonaspetti, Giovanni [University of Brescia, Orthopaedic Clinic, Brescia (Italy); Beluffi, Giampiero [Fondazione IRCCS Policlinico San Matteo, Department of Paediatric Radiology, Pavia (Italy); Marchi, Antonietta; Bozzola, Mauro; Savasta, Salvatore [Fondazione IRCCS Policlinico San Matteo, Paediatric Clinic, University of Pavia, Pavia (Italy)

2007-10-15

A skeletal dysplasia with previously unreported features is presented. Its evolution was characterized by growth abnormalities of bones without involvement of other organs. Advanced bone age, increased stature and irregular epiphyseal ossification with stippling of the main long bones were documented. Physeal overgrowth was massive in the left proximal humerus and femur. Furthermore, the hip joint appeared fused with an abundant mass of pathological calcific tissue extending from the femur to the ilium. Pathological epiphyses were characterized by anarchic cartilaginous proliferation with multiple ossification centres, while lamellar bone apposition and remodelling were normal. The observed bone changes were different from those in any previously reported syndrome, metabolic defect or bone dysplasia. However, they clearly indicated a defect of endochondral ossification with some resemblance to phenotypes observed in dysplasia epiphysealis hemimelica. (orig.)

Poly-epiphyseal overgrowth: description of a previously unreported skeletal dysplasia

International Nuclear Information System (INIS)

Pazzaglia, Ugo E.; Bonaspetti, Giovanni; Beluffi, Giampiero; Marchi, Antonietta; Bozzola, Mauro; Savasta, Salvatore

2007-01-01

A skeletal dysplasia with previously unreported features is presented. Its evolution was characterized by growth abnormalities of bones without involvement of other organs. Advanced bone age, increased stature and irregular epiphyseal ossification with stippling of the main long bones were documented. Physeal overgrowth was massive in the left proximal humerus and femur. Furthermore, the hip joint appeared fused with an abundant mass of pathological calcific tissue extending from the femur to the ilium. Pathological epiphyses were characterized by anarchic cartilaginous proliferation with multiple ossification centres, while lamellar bone apposition and remodelling were normal. The observed bone changes were different from those in any previously reported syndrome, metabolic defect or bone dysplasia. However, they clearly indicated a defect of endochondral ossification with some resemblance to phenotypes observed in dysplasia epiphysealis hemimelica. (orig.)

Skeletal maturation, fundamental motor skills and motor coordination in children 7-10 years.

Science.gov (United States)

Freitas, Duarte L; Lausen, Berthold; Maia, José António; Lefevre, Johan; Gouveia, Élvio Rúbio; Thomis, Martine; Antunes, António Manuel; Claessens, Albrecht L; Beunen, Gaston; Malina, Robert M

2015-01-01

Relationships between skeletal maturation and fundamental motor skills and gross motor coordination were evaluated in 429 children (213 boys and 216 girls) 7-10 years. Skeletal age was assessed (Tanner-Whitehouse 2 method), and stature, body mass, motor coordination (Körperkoordinations Test für Kinder, KTK) and fundamental motor skills (Test of Gross Motor Development, TGMD-2) were measured. Relationships among chronological age, skeletal age (expressed as the standardised residual of skeletal age on chronological age) and body size and fundamental motor skills and motor coordination were analysed with hierarchical multiple regression. Standardised residual of skeletal age on chronological age interacting with stature and body mass explained a maximum of 7.0% of the variance in fundamental motor skills and motor coordination over that attributed to body size per se. Standardised residual of skeletal age on chronological age alone accounted for a maximum of 9.0% of variance in fundamental motor skills, and motor coordination over that attributed to body size per se and interactions between standardised residual of skeletal age on chronological age and body size. In conclusion, skeletal age alone or interacting with body size has a negligible influence on fundamental motor skills and motor coordination in children 7-10 years.

Identification of Histone Deacetylase 2 as a Functional Gene for Skeletal Muscle Development in Chickens

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Md. Shahjahan

2016-04-01

Full Text Available A previous genome-wide association study (GWAS exposed histone deacetylase 2 (HDAC2 as a possible candidate gene for breast muscle weight in chickens. The present research has examined the possible role of HDAC2 in skeletal muscle development in chickens. Gene expression was measured by quantitative polymerase chain reaction in breast and thigh muscles during both embryonic (four ages and post-hatch (five ages development and in cultures of primary myoblasts during both proliferation and differentiation. The expression of HDAC2 increased significantly across embryonic days (ED in breast (ED 14, 16, 18, and 21 and thigh (ED 14 and 18, and ED 14 and 21 muscles suggesting that it possibly plays a role in myoblast hyperplasia in both breast and thigh muscles. Transcript abundance of HDAC2 identified significantly higher in fast growing muscle than slow growing in chickens at d 90 of age. Expression of HDAC2 during myoblast proliferation in vitro declined between 24 h and 48 h when expression of the marker gene paired box 7 (PAX7 increased and cell numbers increased throughout 72 h of culture. During induced differentiation of myoblasts to myotubes, the abundance of HDAC2 and the marker gene myogenic differentiation 1 (MYOD1, both increased significantly. Taken together, it is suggested that HDAC2 is most likely involved in a suppressive fashion in myoblast proliferation and may play a positive role in myoblast differentiation. The present results confirm the suggestion that HDAC2 is a functional gene for pre-hatch and post-hatch (fast growing muscle development of chicken skeletal muscle.

Non-surgical alternative in the treatment of skeletal Class III problems.

Science.gov (United States)

Jefferson, Y

1995-01-01

The dental profession is not static, but dynamic. New research findings, along with medical and technological advances, necessitate constant re-examination of treatment philosophies and techniques. What were acceptable treatment techniques in the past may not necessarily be the most effective and best techniques for our patients today. Currently, many practitioners feel that the only treatment for the correction of a skeletal Class III abnormality is via orthognathic surgery in older patients. In some cases it may be the only treatment option. But in most cases today, there are more conservative, non-surgical treatment alternatives in correcting Class III problems in younger aged children. In treating facial-skeletal problems, it must be emphasized that the human face is a biological masterpiece of form and function. Its importance has been documented in arts and sciences since the beginning of modern civilization. It is important enough so that individuals who are blessed with attractive features are afforded greater opportunities in our society. Attractive faces are associated with intelligence, honesty and good work ethics. With the advent of orthognathic surgery, functional appliance, functional regulator, and myofunctional therapy, the dental profession has the capability of leveling out the playing field for many individuals in our society. It does so by being able to correct problems closely associated with the human psyche--the human face. The ability to change facial features brings tremendous prestige to our profession. Along with this prestige comes greater responsibility. Our ability to change facial features entails greater understanding of facial balance and harmony. Ricketts states that the face must conform to stringent proportions known as the "divine proportion" in order for it to be esthetically pleasing. Also, our ability to move facial-skeletal structures entails greater understanding of the biomechanics of the human face. Without this

Skeletal Muscle Na+ Channel Disorders

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Dina eSimkin

2011-10-01

Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

Effects of the belt electrode skeletal muscle electrical stimulation system on lower extremity skeletal muscle activity: Evaluation using positron emission tomography.

Science.gov (United States)

Numata, Hitoaki; Nakase, Junsuke; Inaki, Anri; Mochizuki, Takafumi; Oshima, Takeshi; Takata, Yasushi; Kinuya, Seigo; Tsuchiya, Hiroyuki

2016-01-01

Lower-extremity muscle weakness in athletes after lower limb trauma or surgery can hinder their return to sports, and the associated muscle atrophy may lead to deterioration in performance after returning to sports. Recently, belt electrode skeletal muscle electrical stimulation (B-SES) which can contract all the lower limb skeletal muscles simultaneously was developed. However, no study has evaluated skeletal muscle activity with B-SES. Since only superficial muscles as well as a limited number of muscles can be investigated using electromyography, we investigated whether positron emission tomography (PET) can evaluate the activity of all the skeletal muscles in the body simultaneously. The purpose of this study was to evaluate the effectiveness of the B-SES system using PET. Twelve healthy males (mean age, 24.3 years) were divided into two groups. The subjects in the control group remained in a sitting position for 10 min, and [(18)F] fluorodeoxyglucose (FDG) was intravenously injected. In the exercise group, subjects exercised using the B-SES system for 20 min daily for three consecutive days as a pre-test exercise. On the measurement day, they exercised for 10 min, received an injection of FDG, and exercised for another 10 min. PET-computed tomography images were obtained in each group 60 min after the FDG injection. Regions of interest were drawn in each lower-extremity muscle. We compared each skeletal muscle metabolism using the standardized uptake value. In the exercise group, FDG accumulation in the gluteus maximus, gluteus medius, gluteus minimus, quadriceps femoris, sartorius, and hamstrings was significantly higher than the muscles in the control (P skeletal muscle activity of the gluteal muscles as well as the most lower-extremity muscles simultaneously. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Selection, processing and clinical application of muscle-skeletal tissue

International Nuclear Information System (INIS)

Luna Z, D.; Reyes F, M.L.; Lavalley E, C.; Castaneda J, G.

2007-01-01

Due to the increase in the average of the world population's life, people die each time to more age, this makes that the tissues of support of the human body, as those muscle-skeletal tissues, when increasing the individual's age go weakening, this in turn leads to the increment of the illnesses like the osteoporosis and the arthritis, that undoubtedly gives as a result more injure of the muscle-skeletal tissues joined a greater number of traffic accidents where particularly these tissues are affected, for that the demand of tissues muscle-skeletal for transplant every day will be bigger. The production of these tissues in the Bank of Radio sterilized Tissues, besides helping people to improve its quality of life saved foreign currencies because most of the muscle-skeletal tissues transplanted in Mexico are of import. The use of the irradiation to sterilize tissues for transplant has shown to be one of the best techniques with that purpose for what the International Atomic Energy Agency believes a Technical cooperation program to establish banks of tissues using the nuclear energy, helping mainly to countries in development. In this work the stages that follows the bank of radio sterilized tissues of the National Institute of Nuclear Research for the cadaverous donor's of muscle-skeletal tissue selection are described, as well as the processing and the clinical application of these tissues. (Author)

Calcium model for mammalian skeletal muscle

NARCIS (Netherlands)

Wallinga, W.; Boom, H.B.K.; Heijink, R.J.; van der Vliet, G.H.

1981-01-01

A model is presented describing quantitatively the events between excitation and force development in skeletal muscle. It consists of a calcium mediated activation model (c.m.a.m.) in series with a force generator model (f.g.m.). The c.m.a.m. was based on intracellular processes such as cisternal

Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.

Science.gov (United States)

Tilignac, Thomas; Temparis, Sandrine; Combaret, Lydie; Taillandier, Daniel; Pouch, Marie-Noëlle; Cervek, Matjaz; Cardenas, Diana M; Le Bricon, Thierry; Debiton, Eric; Samuels, Susan E; Madelmont, Jean-Claude; Attaix, Didier

2002-05-15

Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting.

The role of SPECT in the evaluation of skeletal trauma

Energy Technology Data Exchange (ETDEWEB)

Murray, I P.C. [Prince of Wales Hospital, Randwick (Australia)

1993-02-01

Single photon emission computed tomography (SPECT) has, in the last decade, established a critical role in routine diagnosis. Skeletal scintigraphy exemplifies the impact in improving detection of lesions by delineation of their site and size. The advantage of minimizing the superimposed radioactivity from overlying and underlying structures is typified by the readiness with which avascular necrosis of the femoral head can be identified by removal of the surrounding hyperaemia which masks the classical photopaenia. However, the ability to achieve an accurate image at a plane at a prescribed depth is most characteristically shown by the study of a vertebra, a bone of irregular contour and subject to a variety of pathological disorders at different sites within it. The various focal abnormalities resulting from these can be localized exactly, readily distinguishing, for example, those in the body from those in the natural arch. In particular, the alterations resulting from trauma, such as pars interarticularis stress fracture, are readily seen. Consequently SPECT has an indispensable role in the investigation and management of low back pain. However, the ability of SPECT to delineate abnormal accumulation has provided a new approach to the evaluation of knee pain, especially when acute such as that resulting from athletic injury, since the identification of the presence or absence of focal abnormalities can be critical to patient management. The frequency of these various disorders in which SPECT is so useful explains why the procedure has become such a routine high-volume examination in so many departments. (author).

An Automated System for Skeletal Maturity Assessment by Extreme Learning Machines.

Science.gov (United States)

Mansourvar, Marjan; Shamshirband, Shahaboddin; Raj, Ram Gopal; Gunalan, Roshan; Mazinani, Iman

2015-01-01

Assessing skeletal age is a subjective and tedious examination process. Hence, automated assessment methods have been developed to replace manual evaluation in medical applications. In this study, a new fully automated method based on content-based image retrieval and using extreme learning machines (ELM) is designed and adapted to assess skeletal maturity. The main novelty of this approach is it overcomes the segmentation problem as suffered by existing systems. The estimation results of ELM models are compared with those of genetic programming (GP) and artificial neural networks (ANNs) models. The experimental results signify improvement in assessment accuracy over GP and ANN, while generalization capability is possible with the ELM approach. Moreover, the results are indicated that the ELM model developed can be used confidently in further work on formulating novel models of skeletal age assessment strategies. According to the experimental results, the new presented method has the capacity to learn many hundreds of times faster than traditional learning methods and it has sufficient overall performance in many aspects. It has conclusively been found that applying ELM is particularly promising as an alternative method for evaluating skeletal age.

An Automated System for Skeletal Maturity Assessment by Extreme Learning Machines

Science.gov (United States)

Mansourvar, Marjan; Shamshirband, Shahaboddin; Raj, Ram Gopal; Gunalan, Roshan; Mazinani, Iman

2015-01-01

Assessing skeletal age is a subjective and tedious examination process. Hence, automated assessment methods have been developed to replace manual evaluation in medical applications. In this study, a new fully automated method based on content-based image retrieval and using extreme learning machines (ELM) is designed and adapted to assess skeletal maturity. The main novelty of this approach is it overcomes the segmentation problem as suffered by existing systems. The estimation results of ELM models are compared with those of genetic programming (GP) and artificial neural networks (ANNs) models. The experimental results signify improvement in assessment accuracy over GP and ANN, while generalization capability is possible with the ELM approach. Moreover, the results are indicated that the ELM model developed can be used confidently in further work on formulating novel models of skeletal age assessment strategies. According to the experimental results, the new presented method has the capacity to learn many hundreds of times faster than traditional learning methods and it has sufficient overall performance in many aspects. It has conclusively been found that applying ELM is particularly promising as an alternative method for evaluating skeletal age. PMID:26402795

Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

Science.gov (United States)

Dantas, F P M; Medeiros, G X; Figueiredo, A P M; Thompson, K; Riet-Correa, F

2014-01-01

This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes. Copyright © 2013 Elsevier Ltd. All rights reserved.

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

Science.gov (United States)

Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

2018-01-09

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

Cerebellar medulloblastoma presenting with skeletal metastasis

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Barai Sukanta

2004-04-01

Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

Signalling and the control of skeletal muscle size

International Nuclear Information System (INIS)

Otto, Anthony; Patel, Ketan

2010-01-01

Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

Signalling and the control of skeletal muscle size

Energy Technology Data Exchange (ETDEWEB)

Otto, Anthony [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom); Patel, Ketan, E-mail: ketan.patel@reading.ac.uk [School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights Campus, Reading, Berkshire, RG6 6UB (United Kingdom)

2010-11-01

Skeletal muscle is highly adaptive to environmental stimuli and can alter its mass accordingly. This tissue is almost unique in that it can increase its size through two distinct mechanisms. It can grow through a cellular process mediated by cell fusion, or it can increase its size simply by increasing its protein content. Understanding how these processes are regulated is crucial for the development of potential therapies against debilitating skeletal muscle wasting diseases. Two key signalling molecules, Insulin like Growth Factor (IGF) and GDF-8/myostatin, have emerged in recent years to be potent regulators of skeletal muscle size. In this review we bring together recent data highlighting the important and novel aspects of both molecules and their signalling pathways, culminating in a discussion of the cellular and tissue phenotypic outcomes of their stimulation or antagonism. We emphasise the complex regulatory mechanisms and discuss the temporal and spatial differences that control their action, understanding of which is crucial to further their use as potential therapeutic targets.

Deep bite malocclusion: exploration of the skeletal and dental factors

International Nuclear Information System (INIS)

Bhateja, N.K.; Fida, M.; Shaikh, A.

2016-01-01

Correction of deep bite is crucial for maintenance of dental hard and soft tissue structures and for prevention of temporomandibular joint disorders. Exploration of underlying skeletal and dental factors is essential for efficient and individualized treatment planning. To date etiological factors of dental and skeletal deep bite have not been explored in Pakistani orthodontic patients. The objectives of this study were to explore frequencies of dental and skeletal etiological factors in deep bite patients and to determine correlations amongst dental and skeletal etiological factors of deep bite. Methods: The study included a total of 113 subjects (males=35; females=78) with no craniofacial syndromes or prior orthodontic treatment. Pre-treatment orthodontic records were used to evaluate various dental and skeletal parameters. Descriptive statistics of each parameter were calculated. The various study parameters were correlated using Pearson's Correlation. Results: Deep curve of Spee was most frequently seen factor of dental deep bite (72.6%), followed by increased coronal length of upper incisors (28.3%), retroclined upper incisors (17.7%), retroclined lower incisors (8%) and increased coronal length of lower incisors (5.3%). Decreased gonial angle was most commonly found factor of skeletal deep bite (43.4%), followed by decreased mandibular plane angle (27.4%) and maxillary plane's clockwise rotation (26.5%). Frankfort mandibular plane angle and gonial angle showed a strong positive correlation (r=0.66, p=0.000). Conclusions: Reduced gonial angle is most frequently seen skeletal factor, signifying the importance of angulation and growth of ramus in development of deep bite. Deep curve of Spee is most frequently seen dental etiological component in deep bite subjects, hence signifying the importance of intruding the lower anterior teeth. (author)

The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.

Science.gov (United States)

Kemp, C M; Oliver, W T; Wheeler, T L; Chishti, A H; Koohmaraie, M

2013-07-01

Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using μ-calpain knockout (KO) mice in comparison with control wild-type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up regulation of other proteolytic systems. The KO mice showed significantly greater m-calpain protein abundance (P proteolytic systems to ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain system's involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass.

Adipocyte-myocyte crosstalk in skeletal muscle insulin resistance; is there a role for thyroid hormone?

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Havekes, Bas; Sauerwein, Hans P

2010-11-01

To review original research studies and reviews that present data on adipocyte-myocyte crosstalk in the development of skeletal muscle insulin resistance with a specific focus on thyroid hormone. Adipose tissue communicates with skeletal muscle not only through free fatty acids but also through secretion of various products called adipokines. Adipokines came out as governors of insulin sensitivity and are deregulated in obesity. In addition to well known leptin, adiponectin, interleukin-6 and tumor necrosis factor-alpha, newer adipokines like retinol-binding protein 4 have been associated with insulin resistance. There is mounting evidence that not only adipose tissue but also skeletal muscle produces and secretes biologically active proteins or 'myokines' that facilitate metabolic crosstalk between organ systems. In recent years, increased expression of myostatin, a secreted anabolic inhibitor of muscle growth and development, has been associated with obesity and insulin resistance. Both hypothyroidism and hyperthyroidism affect insulin sensitivity in multiple ways that might overlap adipocyte-myocyte crosstalk. Recent studies have provided new insights in effects of processing of the parent hormone T4 to the active T3 at the level of the skeletal muscle. Adipocyte-myocyte crosstalk is an important modulator in the development of skeletal muscle insulin resistance. Thyroid disorders are very common and may have detrimental effects on skeletal muscle insulin resistance, potentially by interacting with adipocyte-myocyte crosstalk.

Spot light on skeletal muscles: optogenetic stimulation to understand and restore skeletal muscle function.

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van Bremen, Tobias; Send, Thorsten; Sasse, Philipp; Bruegmann, Tobias

2017-08-01

Damage of peripheral nerves results in paralysis of skeletal muscle. Currently, the only treatment option to restore proper function is electrical stimulation of the innervating nerve or of the skeletal muscles directly. However this approach has low spatial and temporal precision leading to co-activation of antagonistic muscles and lacks cell-type selectivity resulting in pain or discomfort by stimulation of sensible nerves. In contrast to electrical stimulation, optogenetic methods enable spatially confined and cell-type selective stimulation of cells expressing the light sensitive channel Channelrhodopsin-2 with precise temporal control over the membrane potential. Herein we summarize the current knowledge about the use of this technology to control skeletal muscle function with the focus on the direct, non-neuronal stimulation of muscle fibers. The high temporal flexibility of using light pulses allows new stimulation patterns to investigate skeletal muscle physiology. Furthermore, the high spatial precision of focused illumination was shown to be beneficial for selective stimulation of distinct nearby muscle groups. Finally, the cell-type specific expression of the light-sensitive effector proteins in muscle fibers will allow pain-free stimulation and open new options for clinical treatments. Therefore, we believe that direct optogenetic stimulation of skeletal muscles is a very potent method for basic scientists that also harbors several distinct advantages over electrical stimulation to be considered for clinical use in the future.

Traumatic skeletal changes

International Nuclear Information System (INIS)

Troeger, J.; Schofer, O.

1985-01-01

Skeleton scintiscanning is indicated in the following cases: (1) Suspected bone injury after clinical examination, the radiograph of the skeletal region in question contributing findings that either do not confirm suspision, or make not clear whether the changes observed are traumatic. (2) Polytrauma. (3) When the accident scenario reported by the persons taking care of the child does not sufficiently explain the skeletal changes observed, or when these persons expressly deny the possibility of a trauma being the cause of findings observed. (4) Suspected or proven battered-child syndrome. (orig./MG) [de

Skeletal sequelae of radiation therapy for malignant childhood tumors

International Nuclear Information System (INIS)

Butler, M.S.; Robertson, W.W. Jr.; Rate, W.; D'Angio, G.J.; Drummond, D.S.

1990-01-01

One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) had scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy

The diagnostic performance of chronologic age in the assessment of skeletal maturity.

Science.gov (United States)

Baccetti, Tiziano; Franchi, Lorenzo; De Toffol, Laura; Ghiozzi, Bruno; Cozza, Paola

2006-01-01

The aim of this study was to analyze the relationship between chronologic age the and individual skeletal maturity as assessed by means of the cervical vertebral maturation (CVM) method during the circumpubertal period. The evaluated sample of 600 subjects consisted of 100 subjects (50 males and 50 females) for each of 6 age groups, from 9 years through 14 years of age. Individual skeletal maturity for all subjects was determined by using the CVM method. The relationship between chronologic age and the most prevalent CVM stage at each age group was evaluated statistically by means of indicators of diagnostic test performance that specify the ability of a diagnostic test to identify a condition. The diagnostic performance of chronologic age for the detection of the onset of the adolescent peak in skeletal maturation was very low both in males and in females. In male subjects, the chronologic age of 9 years +/- 6 months presented with strong diagnostic power for the identification of a pre-pubertal stage in skeletal maturation. In female subjects, the chronologic age of 14 years +/- 6 months corresponded with a strong probability of a postpubertal stage in skeletal maturation. In males, chronologic age can identify a pre-pubertal stage of skeletal development, and in females a post-pubertal stage. In both males and females, chronologic age cannot recognize the onset of the adolescent peak in skeletal maturation.

Comprehensive Validation of Skeletal Mechanism for Turbulent Premixed Methane–Air Flame Simulations

KAUST Repository

Luca, Stefano

2017-08-01

A new skeletal mechanism, consisting of 16 species and 72 reactions, has been developed for lean methane–air premixed combustion from the GRI-Mech 3.0. The skeletal mechanism is validated for elevated unburnt temperatures (800 K) and pressures up to 4 atm, thereby addressing realistic gas turbine conditions. The skeletal mechanism is obtained by applying the directed relation graph method and performing sensitivity analysis on the detailed mechanism. The mechanism has been validated for flame speed and flame structure in a wide range of conditions and configurations. A good agreement between the skeletal mechanism and GRI-3.0 was obtained. The configurations considered include one-dimension laminar premixed flames, laminar non-premixed counterflow burners, and two- and three-dimensional unsteady configurations with variations of temperature, pressure, and composition. The skeletal mechanism allows for the inclusion of accurate finite rate chemistry in large-scale direct numerical simulations of lean turbulent premixed flames. In a large-scale direct numerical simulation, the use of the skeletal mechanism reduces the memory requirements by more than a factor of 3 and accelerates the simulation by a factor of 7 compared with the detailed mechanism. The skeletal mechanism is suitable for unsteady three-dimensional simulations of methane turbulent premixed, non-premixed, and globally lean partially premixed flames and is available as supplementary material.

Identification and profiling of microRNAs and their target genes from developing caprine skeletal Muscle.

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Yanhong Wang

Full Text Available Goat is an important agricultural animal for meat production. Functional studies have demonstrated that microRNAs (miRNAs regulate gene expression at the post-transcriptional level and play an important role in various biological processes. Although studies on miRNAs expression profiles have been performed in various animals, relatively limited information about goat muscle miRNAs has been reported. To investigate the miRNAs involved in regulating different periods of skeletal muscle development, we herein performed a comprehensive research for expression profiles of caprine miRNAs during two developmental stages of skeletal muscles: fetal stage and six month-old stage. As a result, 15,627,457 and 15,593,721 clean reads were obtained from the fetal goat library (FC and the six month old goat library (SMC, respectively. 464 known miRNAs and 83 novel miRNA candidates were identified. Furthermore, by comparing the miRNA profile, 336 differentially expressed miRNAs were identified and then the potential targets of the differentially expressed miRNAs were predicted. To understand the regulatory network of miRNAs during muscle development, the mRNA expression profiles for the two development stages were characterized and 7322 differentially expressed genes (DEGs were identified. Then the potential targets of miRNAs were compared to the DEGs, the intersection of the two gene sets were screened out and called differentially expressed targets (DE-targets, which were involved in 231 pathways. Ten of the 231 pathways that have smallest P-value were shown as network figures. Based on the analysis of pathways and networks, we found that miR-424-5p and miR-29a might have important regulatory effect on muscle development, which needed to be further studied. This study provided the first global view of the miRNAs in caprine muscle tissues. Our results help elucidation of complex regulatory networks between miRNAs and mRNAs and for the study of muscle

Skeletal sarcoidosis; Skelettsarkoidose

Energy Technology Data Exchange (ETDEWEB)

Freyschmidt, J. [Klinikum Bremen-Mitte, Beratungsstelle und Referenzzentrum fuer Osteoradiologie, Bremen (Germany); Freyschmidt, P. [Dermatologische Gemeinschaftspraxis, Schwalmstadt (Germany)

2016-10-15

Presentation of the etiology, pathology, clinical course, radiology and differential diagnostics of skeletal sarcoidosis. Noncaseating epithelioid cell granulomas can trigger solitary, multiple or disseminated osteolysis, reactive osteosclerosis and/or granulomatous synovitis. The incidence of sarcoidosis is 10-12 per 100,000 inhabitants per year. Skeletal involvement is approximately 14 %. Skeletal involvement occurs almost exclusively in the stage of lymph node and pulmonary manifestation. Most cases of skeletal involvement are clinically asymptomatic. In the case of synovial involvement, unspecific joint complaints (arthralgia) or less commonly arthritis can occur. Typical skin alterations can be diagnostically significant. Punch out lesions osteolysis, coarse destruction and osteosclerosis can occur, which are best visualized with projection radiography and/or computed tomography. Pure bone marrow foci without interaction with the bone can only be detected with magnetic resonance imaging (MRI) and more recently with positron emission tomography (PET), mostly as incidental findings. There is a predeliction for the hand and trunk skeleton. Skeletal tuberculosis, metastases, multiple myeloma, Langerhans cell histiocytosis and sarcoid-like reactions in solid tumors must be differentiated. The key factors for correct diagnosis are thorax radiography, thorax CT and dermatological manifestations. (orig.) [German] Darstellung von Aetiologie, Pathologie, Klinik, Radiologie und Differenzialdiagnose der Skelettsarkoidose. Nichtverkaesende Epitheloidzellgranulome koennen solitaere, multiple oder disseminierte Osteolysen, reaktive Osteosklerosen und/oder eine granulomatoese Synovialitis ausloesen. Inzidenz der Sarkoidose: 10-12/100.000 Einwohner/Jahr. Skelettbeteiligung ca. 14 %. Skelettbeteiligungen kommen fast ausschliesslich im Stadium einer Lymphknoten- und pulmonalen Manifestation vor. Die meisten Skelettbeteiligungen verlaufen klinisch stumm. Bei synovialer

Chiral Orientation of Skeletal Muscle Cells Requires Rigid Substrate

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Ninghao Zhu

2017-06-01

Full Text Available Reconstitution of tissue morphology with inherent left–right (LR asymmetry is essential for tissue/organ functions. For skeletal muscle, the largest tissue in mammalian organisms, successful myogenesis requires the regulation of the LR asymmetry to form the appropriate muscle alignment. However, the key factor for reproducing the LR asymmetry of skeletal tissues in a controllable, engineering context remains largely unknown. Recent reports indicate that cell chirality may underlie the LR development in tissue morphogenesis. Here, we report that a rigid substrate is required for the chirality of skeletal muscle cells. By using alternating micropatterned cell-adherent and cell-repellent stripes on a rigid substrate, we found that C2C12 skeletal muscle myoblasts exhibited a unidirectional tilted orientation with respect to the stripe boundary. Importantly, such chiral orientation was reduced when soft substrates were used instead. In addition, we demonstrated the key role of actin stress fibers in the formation of the chiral orientation. This study reveals that a rigid substrate is required for the chiral pattern of myoblasts, paving the way for reconstructing damaged muscle tissue with inherent LR asymmetry in the future.

Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

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Marino DiFranco

Full Text Available Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

Effect of young maternal age and skeletal growth on placental growth and development.

Science.gov (United States)

Hayward, C E; Greenwood, S L; Sibley, C P; Baker, P N; Jones, R L

2011-12-01

Teenagers are susceptible to delivering small-for-gestational-age infants. Previous studies implicate continued skeletal growth as a contributory factor, and impaired placental development was the primary cause of fetal growth restriction in growing adolescent sheep. The aims of this study were to examine the impact of young maternal age and growth on placental development. Placentas were collected from 31 teenagers, of which 12 were growing and 17 non-growing based on knee height measurements. An adult control group (n = 12) was included. Placental weight and morphometric measurements of villous, syncytiotrophoblast, fibrin and vessel areas, as well as indices of proliferation and apoptosis, were analysed in relation to maternal growth and age. Growing teenagers had a higher birthweight:placental weight ratio than non-growing teenagers (p adult and teenage pregnancies. Maternal smoking, a potential confounding factor, did not exert a major influence on the placental parameters examined, except for a stimulatory effect on placental proliferation (p development, and is consistent with our recent observations that maternal growth was not detrimental to fetal growth. Copyright © 2011 Elsevier Ltd. All rights reserved.

Quantitative sonoelastography for the in vivo assessment of skeletal muscle viscoelasticity

International Nuclear Information System (INIS)

Hoyt, Kenneth; Kneezel, Timothy; Castaneda, Benjamin; Parker, Kevin J

2008-01-01

A novel quantitative sonoelastography technique for assessing the viscoelastic properties of skeletal muscle tissue was developed. Slowly propagating shear wave interference patterns (termed crawling waves) were generated using a two-source configuration vibrating normal to the surface. Theoretical models predict crawling wave displacement fields, which were validated through phantom studies. In experiments, a viscoelastic model was fit to dispersive shear wave speed sonoelastographic data using nonlinear least-squares techniques to determine frequency-independent shear modulus and viscosity estimates. Shear modulus estimates derived using the viscoelastic model were in agreement with that obtained by mechanical testing on phantom samples. Preliminary sonoelastographic data acquired in healthy human skeletal muscles confirm that high-quality quantitative elasticity data can be acquired in vivo. Studies on relaxed muscle indicate discernible differences in both shear modulus and viscosity estimates between different skeletal muscle groups. Investigations into the dynamic viscoelastic properties of (healthy) human skeletal muscles revealed that voluntarily contracted muscles exhibit considerable increases in both shear modulus and viscosity estimates as compared to the relaxed state. Overall, preliminary results are encouraging and quantitative sonoelastography may prove clinically feasible for in vivo characterization of the dynamic viscoelastic properties of human skeletal muscle

Cytogenetic studies of 1232 patients with different sexual development abnormalities from the Sultanate of Oman.

Science.gov (United States)

Al-Alawi, Intisar; Goud, Tadakal Mallana; Al-Harasi, Salma; Rajab, Anna

2016-02-01

The aim of this study was to evaluate cytogenetic findings in Omani patients who had been referred for suspicion of sex chromosome abnormalities that resulted in different clinical disorders. Furthermore, it sought to examine the frequency of chromosomal anomalies in these patients and to compare the obtained results with those reported elsewhere. Cytogenetic analysis was performed on 1232 cases with variant characteristics of sexual development disorders who had been referred to the cytogenetic department, National Genetic Centre, Ministry of Health, from different hospitals in the Sultanate of Oman between 1999 and 2014. The karyotype results demonstrated chromosomal anomalies in 24.2% of the cases, where 67.5% of abnormalities were identified in referral females, whereas only 32.6% were in referral males. Of all sex chromosome anomalies detected, Turner syndrome was the most frequent (38.2%) followed by Klinefelter syndrome (24.9%) and XY phenotypic females (16%). XXX syndrome and XX phenotypic males represented 6.8% and 3.8% of all sex chromosome anomalies, respectively. Cytogenetic analysis of patients referred with various clinical suspicions of chromosomal abnormalities revealed a high rate of chromosomal anomalies. This is the first broad cytogenetic study reporting combined frequencies of sex chromosome anomalies in sex development disorders in Oman. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Retrospective review to determine the utility of follow-up skeletal surveys in child abuse evaluations when the initial skeletal survey is normal

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Kachelmeyer Andrea

2011-09-01

Full Text Available Abstract Objective The AAP recommends that a follow-up skeletal survey be obtained for all children Methods A retrospective review of radiology records from September 1, 1998 - January 31, 2007 was conducted. Suspected victims of child abuse who were Results Forty-seven children had a negative initial skeletal survey and were included for analysis. The mean age was 6.9 months (SD 5.7; the mean number of days between skeletal surveys was 18.7 (SD 10.1 Four children (8.5% had signs of healing bone trauma on a follow-up skeletal survey. Three of these children (75% had healing rib fractures and one child had a healing proximal humerus fracture. The findings on the follow-up skeletal survey yielded forensically important information in all 4 cases and strengthened the diagnosis of non-accidental trauma. Conclusion 8.5 percent of children with negative initial skeletal surveys had forensically important findings on follow-up skeletal survey that increased the certainty of the diagnosis of non-accidental trauma. A follow-up skeletal survey can be useful even when the initial skeletal survey is negative.

Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.

Science.gov (United States)

Sgariglia, Federica; Candela, Maria Elena; Huegel, Julianne; Jacenko, Olena; Koyama, Eiki; Yamaguchi, Yu; Pacifici, Maurizio; Enomoto-Iwamoto, Motomi

2013-11-01

Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss

Developing software to "track and catch" missed follow-up of abnormal test results in a complex sociotechnical environment.

Science.gov (United States)

Smith, M; Murphy, D; Laxmisan, A; Sittig, D; Reis, B; Esquivel, A; Singh, H

2013-01-01

Abnormal test results do not always receive timely follow-up, even when providers are notified through electronic health record (EHR)-based alerts. High workload, alert fatigue, and other demands on attention disrupt a provider's prospective memory for tasks required to initiate follow-up. Thus, EHR-based tracking and reminding functionalities are needed to improve follow-up. The purpose of this study was to develop a decision-support software prototype enabling individual and system-wide tracking of abnormal test result alerts lacking follow-up, and to conduct formative evaluations, including usability testing. We developed a working prototype software system, the Alert Watch And Response Engine (AWARE), to detect abnormal test result alerts lacking documented follow-up, and to present context-specific reminders to providers. Development and testing took place within the VA's EHR and focused on four cancer-related abnormal test results. Design concepts emphasized mitigating the effects of high workload and alert fatigue while being minimally intrusive. We conducted a multifaceted formative evaluation of the software, addressing fit within the larger socio-technical system. Evaluations included usability testing with the prototype and interview questions about organizational and workflow factors. Participants included 23 physicians, 9 clinical information technology specialists, and 8 quality/safety managers. Evaluation results indicated that our software prototype fit within the technical environment and clinical workflow, and physicians were able to use it successfully. Quality/safety managers reported that the tool would be useful in future quality assurance activities to detect patients who lack documented follow-up. Additionally, we successfully installed the software on the local facility's "test" EHR system, thus demonstrating technical compatibility. To address the factors involved in missed test results, we developed a software prototype to account for

Bio-impedance analysis for appendicular skeletal muscle mass assessment in (pre-) frail elderly people

NARCIS (Netherlands)

Baar, van H.; Hulshof, P.J.M.; Tieland, C.A.B.; Groot, de C.P.G.M.

2015-01-01

Background & aims Screening populations for skeletal muscle mass (SMM) is important for early detection of sarcopenia. Our aim was to develop an age specific bio-impedance (BI) prediction equation for the assessment of appendicular skeletal muscle mass (ASMM) in (pre-) frail elderly people aged

A modern documented Italian identified skeletal collection of 2127 skeletons: the CAL Milano Cemetery Skeletal Collection.

Science.gov (United States)

Cattaneo, Cristina; Mazzarelli, Debora; Cappella, Annalisa; Castoldi, Elisa; Mattia, Mirko; Poppa, Pasquale; De Angelis, Danilo; Vitello, Antonio; Biehler-Gomez, Lucie

2018-06-01

The CAL Milano Cemetery Skeletal Collection is a modern and continuously growing identified osteological collection of 2127 skeletons under study in the Laboratorio di Antropologia e Odontologia Forense (LABANOF) in the Department of Biomedical Sciences for Health of the University of Milan (Italy), and part of the Collezione Antropologica LABANOF (CAL). The collection presents individuals of both sexes and of all age groups with a high representation of the elderly and an interesting sample of infants. Each individual is associated with a documentation that includes sex, age-at-death, dates of birth and death, and a death certificate that specifies the exact cause of death and the chain of events that led to it (related pathological conditions or traumatic events). It was also possible to recover for several individuals the autopsy reports and antemortem photographs. This documented osteological collection is of crucial interest in physical and forensic anthropology: it provides unique teaching opportunities and more importantly considerable research possibilities to test and develop sex and age estimation methods, investigate key subjects of forensic relevance and discuss pathological markers, among others. The aim of this paper is to introduce the CAL Milano Cemetery Skeletal Collection as a new identified skeletal collection and present its research and teaching potential. Copyright © 2018 Elsevier B.V. All rights reserved.

Skeletal Dysplasias Associated with Mild Myopathy—A Clinical and Molecular Review

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Katarzyna A. Piróg

2010-01-01

Full Text Available Musculoskeletal system is a complex assembly of tissues which acts as scaffold for the body and enables locomotion. It is often overlooked that different components of this system may biomechanically interact and affect each other. Skeletal dysplasias are diseases predominantly affecting the development of the osseous skeleton. However, in some cases skeletal dysplasia patients are referred to neuromuscular clinics prior to the correct skeletal diagnosis. The muscular complications seen in these cases are usually mild and may stem directly from the muscle defect and/or from the altered interactions between the individual components of the musculoskeletal system. A correct early diagnosis may enable better management of the patients and a better quality of life. This paper attempts to summarise the different components of the musculoskeletal system which are affected in skeletal dysplasias and lists several interesting examples of such diseases in order to enable better understanding of the complexity of human musculoskeletal system.

Evaluation of solitary rib lesions in CA. breast patients for development of skeletal metastasis

International Nuclear Information System (INIS)

Fatima, A.; Fatima, S.; Khursheed, K.; Jafri, S.; Asghar, S.

2004-01-01

Determination of nature of single or double rib lesion on a bone scan is important but very difficult. In case of breast carcinoma rib lesion have particular importance, as they are one of the most common sites of metastasis. On the contrary surgical trauma and radiotherapy can induce metabolic changes, which can lead to rib lesions of benign etiology. As it is known that breast carcinoma patients having skeletal metastasis have worse prognosis so it is particularly important to differentiate between malignant and benign rib lesions. In this study etiology of rib lesions detected on bone scan was analyzed retrospectively patients. Study population consisted of breast cancer patients having solitary rib lesions on baseline or follow-up bone scan were included in the study. The etiology of solitary rib involvement was established using all the clinical, radiological and biochemical data available. The clinical and serial scintigraphic data were collected and analyzed for correlation in forty-two patients. Patients were followed up for at least two subsequent bone scans. Out of total study population nine patients (21.42%) developed skeletal metastasis on follow-up. Rest of the study population is disease free till last follow-up. All these patients developed metastasis within two years of appearance of the rib lesions. Correlation between sites of initial rib lesion, uptake pattern, size of tumor, mode of primary therapy, age of involvement, interval from initial therapy, biochemical and radiological findings was done. Correlation was seen between sites of uptake, uptake pattern, mode of primary therapy and biochemical findings with subsequent outcome of the patient. It is concluded from our study that solitary rib lesion have low incidence of malignancy if other risk factors are absent. (authors)

Ocular abnormalities in congenital Zika syndrome: are the ophthalmoscopic findings "the top of the iceberg"?

Science.gov (United States)

de Oliveira Dias, João Rafael; Ventura, Camila V; de Paula Freitas, Bruno; Prazeres, Juliana; Ventura, Liana O; Bravo-Filho, Vasco; Aleman, Tomas; Ko, Albert Icksang; Zin, Andréa; Belfort, Rubens; Maia, Mauricio

2018-04-23

Zika virus (ZIKV) is an arbovirus mainly transmitted to humans by mosquitoes from Aedes genus. Other ways of transmission include the perinatal and sexual routes, blood transfusion, and laboratory exposure. Although the first human cases were registered in 1952 in African countries, outbreaks were only reported since 2007, when entire Pacific islands were affected. In March 2015, the first cases of ZIKV acute infection were notified in Brazil and, to date, 48 countries and territories in the Americas have confirmed local mosquito-borne transmission of ZIKV. Until 2015, ZIKV infection was thought to only cause asymptomatic or mild exanthematous febrile infections. However, after explosive ZIKV outbreaks in Polynesia and Latin American countries, it was confirmed that ZIKV could also lead to Guillain-Barré syndrome and congenital birth abnormalities. These abnormalities, which can include neurologic, ophthalmologic, audiologic, and skeletal findings, are now considered congenital Zika syndrome (CZS). Brain abnormalities in CZS include cerebral calcifications, malformations of cortical development, ventriculomegaly, lissencephaly, hypoplasia of the cerebellum and brainstem. The ocular findings, which are present in up to 70% of infants with CZS, include iris coloboma, lens subluxation, cataract, congenital glaucoma, and especially posterior segment findings. Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were seen in histologic analyses of eyes from deceased fetuses. To date, there is no ZIKV licensed vaccines or antiviral therapies are available for treatment. Preventive measures include individual protection from mosquito bites, control of mosquito populations and the use of barriers measures such as condoms during sexual intercourse or sexual abstinence for couples either at risk or after confirmed infection. A literature review based on studies that

Improvement of livestock breeding strategies using physiologic and functional genomic information of the muscle regulatory factors gene family for skeletal muscle development

NARCIS (Netherlands)

Pas, te M.F.W.; Soumillon, A.

2001-01-01

A defined number of skeletal muscle fibers are formed in two separate waves during prenatal development, while postnatal growth is restricted to hypertrophic muscle fiber growth. The genes of the MRF (muscle regulatory factors) gene family, consisting of 4 structurally related transcription factors

Intracellular compartmentalization of skeletal muscle glycogen metabolism and insulin signalling

DEFF Research Database (Denmark)

Prats Gavalda, Clara; Gomez-Cabello, Alba; Vigelsø Hansen, Andreas

2011-01-01

The interest in skeletal muscle metabolism and insulin signalling has increased exponentially in recent years as a consequence of their role in the development of type 2 diabetes mellitus. Despite this, the exact mechanisms involved in the regulation of skeletal muscle glycogen metabolism...... and insulin signalling transduction remain elusive. We believe that one of the reasons is that the role of intracellular compartmentalization as a regulator of metabolic pathways and signalling transduction has been rather ignored. This paper briefly reviews the literature to discuss the role of intracellular...... compartmentalization in the regulation of skeletal muscle glycogen metabolism and insulin signalling. As a result, a hypothetical regulatory mechanism is proposed by which cells could direct glycogen resynthesis towards different pools of glycogen particles depending on the metabolic needs. Furthermore, we discuss...

Skeletal muscle lymphoma: observations at MR imaging

International Nuclear Information System (INIS)

Eustace, S.; Winalski, C.S.; McGowen, A.; Lan, H.; Dorfman, D.

1996-01-01

We present the MR appearances of three patients with biopsy-proven primary lymphoma of skeletal muscle. In each case lymphoma resulted in bulky expansion of the involved muscle, homogeneously isointense to skeletal muscle on T1-weighted images, homogeneously hyperintense to skeletal muscle on T2-weighted images and diffusely enhancing following intravenous administration of gadopentate dimeglumine. (orig.)

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

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Grant, R W; Vester Boler, B M; Ridge, T K; Graves, T K; Swanson, K S

2013-08-01

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation

Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges.

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Duffy, Rebecca M; Feinberg, Adam W

2014-01-01

Skeletal muscle is a scalable actuator system used throughout nature from the millimeter to meter length scales and over a wide range of frequencies and force regimes. This adaptability has spurred interest in using engineered skeletal muscle to power soft robotics devices and in biotechnology and medical applications. However, the challenges to doing this are similar to those facing the tissue engineering and regenerative medicine fields; specifically, how do we translate our understanding of myogenesis in vivo to the engineering of muscle constructs in vitro to achieve functional integration with devices. To do this researchers are developing a number of ways to engineer the cellular microenvironment to guide skeletal muscle tissue formation. This includes understanding the role of substrate stiffness and the mechanical environment, engineering the spatial organization of biochemical and physical cues to guide muscle alignment, and developing bioreactors for mechanical and electrical conditioning. Examples of engineered skeletal muscle that can potentially be used in soft robotics include 2D cantilever-based skeletal muscle actuators and 3D skeletal muscle tissues engineered using scaffolds or directed self-organization. Integration into devices has led to basic muscle-powered devices such as grippers and pumps as well as more sophisticated muscle-powered soft robots that walk and swim. Looking forward, current, and future challenges include identifying the best source of muscle precursor cells to expand and differentiate into myotubes, replacing cardiomyocytes with skeletal muscle tissue as the bio-actuator of choice for soft robots, and vascularization and innervation to enable control and nourishment of larger muscle tissue constructs. © 2013 Wiley Periodicals, Inc.

Direct and indirect assessment of skeletal muscle blood flow in chronic congestive heart failure

International Nuclear Information System (INIS)

LeJemtel, T.H.; Scortichini, D.; Katz, S.

1988-01-01

In patients with chronic congestive heart failure (CHF), skeletal muscle blood flow can be measured directly by the continuous thermodilution technique and by the xenon-133 clearance method. The continuous thermodilution technique requires retrograde catheterization of the femoral vein and, thus, cannot be repeated conveniently in patients during evaluation of pharmacologic interventions. The xenon-133 clearance, which requires only an intramuscular injection, allows repeated determination of skeletal muscle blood flow. In patients with severe CHF, a fixed capacity of the skeletal muscle vasculature to dilate appears to limit maximal exercise performance. Moreover, the changes in peak skeletal muscle blood flow noted during long-term administration of captopril, an angiotensin-converting enzyme inhibitor, appears to correlate with the changes in aerobic capacity. In patients with CHF, resting supine deep femoral vein oxygen content can be used as an indirect measurement of resting skeletal muscle blood flow. The absence of a steady state complicates the determination of peak skeletal muscle blood flow reached during graded bicycle or treadmill exercise in patients with chronic CHF. Indirect assessments of skeletal muscle blood flow and metabolism during exercise performed at submaximal work loads are currently developed in patients with chronic CHF

Comparison of second molar eruption patterns in patients with skeletal Class II and skeletal Class I malocclusions.

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Brin, Ilana; Camasuvi, Semin; Dali, Nasser; Aizenbud, Dror

2006-12-01

The eruptive positions of the second molars in Class I and Class II malocclusions were studied. Pretreatment records of 221 patients with a mean age of 11.3 years were evaluated. About 19% of them had skeletal Class I, 31% had skeletal maxillary Class II, and 50% had skeletal mandibular Class II malocclusions. The mean values of the dental and chronologic ages of the subjects were similar. The eruptive positions in relation to a reference line, the developmental stages of the patients' second molars and dental ages were recorded from the panoramic roentgenograms. The distribution of the various developmental stages in each malocclusion group was similar, and no association between skeletal malocclusion and dental developmental stage of the second molars was encountered. The eruptive position of the maxillary second molars was more occlusal only in the oldest maxillary Class II group, above 12 years of age (P = .02). These results support, in part, previous reports suggesting that the maxillary second molars may erupt earlier in patients with skeletal maxillary Class II malocclusions.

Skeletal muscle contraction-induced vasodilation in the microcirculation.

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Hong, Kwang-Seok; Kim, Kijeong

2017-10-01

Maximal whole body exercise leads skeletal muscle blood flow to markedly increase to match metabolic demands, a phenomenon termed exercise hyperaemia that is accomplished by increasing vasodilation. However, local vasodilatory mechanisms in response to skeletal muscle contraction remain uncertain. This review highlights metabolic vasodilators released from contracting skeletal muscle, endothelium, or blood cells. As a considerable skeletal muscle vasodilation potentially results in hypotension, sympathetic nerve activity needs to be augmented to elevate cardiac output and blood pressure during dynamic exercise. However, since the enhanced sympathetic vasoconstriction restrains skeletal muscle blood flow, intramuscular arteries have an indispensable ability to blunt sympathetic activity for exercise hyperaemia. In addition, we discuss that mechanical compression of the intramuscular vasculature contributes to causing the initial phase of increasing vasodilation following a single muscle contraction. We have also chosen to focus on conducted (or ascending) electrical signals that evoke vasodilation of proximal feed arteries to elevate blood flow in the microcirculation of skeletal muscle. Endothelial hyperpolarization originating within distal arterioles ascends into the proximal feed arteries, thereby increasing total blood flow in contracting skeletal muscle. This brief review summarizes molecular mechanisms underlying the regulation of skeletal muscle blood flow to a single or sustained muscle contraction.

Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

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Gerhard Sengle

2015-06-01

Full Text Available Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that

The skeletal endocannabinoid system: clinical and experimental insights.

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Raphael, Bitya; Gabet, Yankel

2016-05-01

Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

Selenium regulates gene expression of selenoprotein W in chicken skeletal muscle system.

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Ruan, Hongfeng; Zhang, Ziwei; Wu, Qiong; Yao, Haidong; Li, Jinlong; Li, Shu; Xu, Shiwen

2012-01-01

Selenoprotein W (SelW) is abundantly expressed in skeletal muscles of mammals and necessary for the metabolism of skeletal muscles. However, its expression pattern in skeletal muscle system of birds is still uncovered. Herein, to investigate the distribution of SelW mRNA in chicken skeletal muscle system and its response to different selenium (Se) status, 1-day-old chickens were exposed to various concentrations of Se as sodium selenite in the feed for 35 days. In addition, myoblasts were treated with different concentrations of Se in the medium for 72 h. Then the levels of SelW mRNA in skeletal muscles (wing muscle, pectoral muscle, thigh muscle) and myoblasts were determined on days 1, 15, 25, and 35 and at 0, 24, 48, and 72 h, respectively. The results showed that SelW was detected in all these muscle components and it increased both along with the growth of organism and the differentiation process of myoblasts. The thigh muscle is more responsive to Se intake than the other two skeletal muscle tissues while the optimal Se supplementation for SelW mRNA expression in chicken myoblasts was 10(-7) M. In summary, Se plays important roles in the development of chicken skeletal muscles. To effect optimal SelW gene expression, Se must be provided in the diet and the media in adequate amounts and neither at excessive nor deficient levels.

External skeletal robusticity of children and adolescents - European references from birth to adulthood and international comparisons.

Science.gov (United States)

Mumm, Rebekka; Godina, Elena; Koziel, Slawomir; Musalek, Martin; Sedlak, Petr; Wittwer-Backofen, Ursula; Hesse, Volker; Dasgupta, Parasmani; Henneberg, Maciej; Scheffler, Christiane

2018-02-20

Background: In our modern world, the way of life in nutritional and activity behaviour has changed. As a consequence, parallel trends of an epidemic of overweight and a decline in external skeletal robusticity are observed in children and adolescents. Aim: We aim to develop reference centiles for external skeletal robusticity of European girls and boys aged 0 to 18 years using the Frame Index as an indicator and identify population specific age-related patterns. Methods: We analysed cross-sectional & longitudinal data on body height and elbow breadth of boys and girls from Europe (0-18 years, n = 41.679), India (7-18 years, n = 3.297) and South Africa (3-18 years, n = 4.346). As an indicator of external skeletal robusticity Frame Index after Frisancho (1990) was used. We developed centiles for boys and girls using the LMS-method and its extension. Results: Boys have greater external skeletal robusticity than girls. Whereas in girls Frame Index decreases continuously during growth, an increase of Frame Index from 12 to 16 years in European boys can be observed. Indian and South African boys are almost similar in Frame Index to European boys. In girls, the pattern is slightly different. Whereas South African girls are similar to European girls, Indian girls show a lesser external skeletal robusticity. Conclusion: Accurate references for external skeletal robusticity are needed to evaluate if skeletal development is adequate per age. They should be used to monitor effects of changes in way of life and physical activity levels in children and adolescents to avoid negative health outcomes like osteoporosis and arthrosis.

Presentation : Development of an age-specific genome-scale model of skeletal muscle metabolism

NARCIS (Netherlands)

Cabbia, A.; van Riel, N.A.W.

2017-01-01

Skeletal myocytes are among the most metabolically active cell types, implicated in nutrient balance, contributing to the insulin-stimulated clearance of glucose from the blood, and secreting myokines that contribute in regulating inflammation and the ageing process. The loss of muscle mass and

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

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Ruixue Song

2017-01-01

Full Text Available Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC. Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

Osseous abnormalities and CT findings in stueve-wiedemann-syndrome (SWS); Ossaere Manifestationen und CT-Befunde bei der seltenen Skelettdysplasie Stueve-Wiedemann (SWS)

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Langer, R. [UAE University, Dept. of Radiology, Al Ain (United Arab Emirates); Al-Gazali, L. [UAE University, Dept. of Paediatrics (United Arab Emirates); Haas, D. [FMHS - UAE Univ. and Tawam Hospital - Dept. of Radiology (United Arab Emirates); Raupp, P.; Varady, E. [Dept. of Paediatrics Al Ain (United Arab Emirates)

2004-02-01

Purpose: analysis of typical conventional radiological and CT findings in our group of patients with the rare skeletal dysplasia Stueve-Wiedemann-Syndrome (SWS) and comparison with published data. Materials and methods: in 16 newborns with clinically dysmorphic features, dwarfism, and bowed limbs, radiographs of the chest and skeleton were obtained for classification of the underlying skeletal dysplasia. For the first time, computed tomography was performed for further investigation of midface hypoplasia. The early diagnosis of SWS could be made by correlation of the radiological and clinical findings. For evaluation of progression, follow-up radiological examinations of the skeleton were performed in four children surviving infancy. Results: clinically, the newborns with SWS showed dwarfisms, midface hypoplasia, bowed extremities with contractures and had severe problems with respiration, feeding, and swallowing as well as episodes of hyperthermia. Skeletal radiographs revealed bowing of the long tubular bones, most pronounced at the lower extremities. Additional findings were internal triangular cortical diaphyseal thickening at the concave side of the bowing, wide metaphyses with abnormal trabecular pattern and radiolucencies. Four patients survived infancy. Clinically, they suffered from recurrent aspiration pneumonia and recurrent episodes of hyperthermia as well as form cutaneous and mucosal infections. The follow-up radiographs showed progressive bowing of the long tubular bones as well as progressive metaphyseal decalcification. Conclusions: skeletal abnormalities in SWS are so characteristic that an early post partum diagnosis can be made. However, a close cooperation between radiologists, clinicians, and geneticists is required for correlation of clinical and radiological findings. The few cases that survive infancy have progressing orthopaedic problems. (orig.) [German] Ziel: Die typischen radiologischen und CT-Befunde beim kongenitalen Stueve

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

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Keisuke Nagao

Full Text Available BACKGROUND: EpCAM (CD326 is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts, eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

Science.gov (United States)

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Radiographic correlation of dental and skeletal age: Third molar, an age indicator.

Science.gov (United States)

Suma, Gn; Rao, Balaji B; Annigeri, Rajeshwari G; Rao, Dayashankara Jk; Goel, Sumit

2011-01-01

Age estimation plays a great role in forensic investigations, orthodontic and surgical treatment planning, and tooth transplantation. Teeth offer an excellent material for age determination by stages of development below the age of 25 years and by secondary changes after the age of 25 years. Third molar is often not included for this purpose due to its notorious developmental patterns. The aim of this study was to evaluate the development of third molar anlage in relation to skeletal maturities and the chronological age. One hundred and fifty-six young individuals, 78 males and 78 females, were selected. The stages of development of all the third molars in every individual were determined from panoramic radiographs. The skeletal development was assessed using hand wrist radiographs. Data were analyzed statistically for mean value, standard deviation and the relationship between the recorded characteristics. A STRONG CORRELATION WAS FOUND BETWEEN THIRD MOLAR DEVELOPMENT AND SKELETAL MATURITY (IN MALES: r=0.88, Pthird molar and 0.89 for mandibular third molar, Page, developmental stages of third molars and maturation of epiphyses of hand. Any of the three parameters could be used for the assessment of other maturities.

Skeletal shape correspondence via entropy minimization

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Tu, Liyun; Styner, Martin; Vicory, Jared; Paniagua, Beatriz; Prieto, Juan Carlos; Yang, Dan; Pizer, Stephen M.

2015-03-01

Purpose: Improving the shape statistics of medical image objects by generating correspondence of interior skeletal points. Data: Synthetic objects and real world lateral ventricles segmented from MR images. Method(s): Each object's interior is modeled by a skeletal representation called the s-rep, which is a quadrilaterally sampled, folded 2-sided skeletal sheet with spoke vectors proceeding from the sheet to the boundary. The skeleton is divided into three parts: up-side, down-side and fold-curve. The spokes on each part are treated separately and, using spoke interpolation, are shifted along their skeletal parts in each training sample so as to tighten the probability distribution on those spokes' geometric properties while sampling the object interior regularly. As with the surface-based correspondence method of Cates et al., entropy is used to measure both the probability distribution tightness and sampling regularity. The spokes' geometric properties are skeletal position, spoke length and spoke direction. The properties used to measure the regularity are the volumetric subregions bounded by the spokes, their quadrilateral sub-area and edge lengths on the skeletal surface and on the boundary. Results: Evaluation on synthetic and real world lateral ventricles demonstrated improvement in the performance of statistics using the resulting probability distributions, as compared to methods based on boundary models. The evaluation measures used were generalization, specificity, and compactness. Conclusions: S-rep models with the proposed improved correspondence provide significantly enhanced statistics as compared to standard boundary models.

Management of severe skeletal Class III malocclusion with bimaxillary orthognathic surgery

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Jitesh Haryani

2016-01-01

Full Text Available Orthognathic surgery in conjunction with fixed orthodontics is a common indication for interdisciplinary management of severe skeletal Class III malocclusion. A thorough analysis of pretreatment investigations and development of a surgical visual treatment objective is essential to plan the type of surgical technique required. Bimaxillary orthognathic surgery is the most common type of surgical procedure for severe skeletal discrepancies. The present case report is a combined ortho-surgical team management of a skeletally Class III patient. The severity of the case required bilateral upper first premolar extraction for dentoalveolar decompensation and simultaneous “Two-jaw surgery” with maxillary advancement of 4 mm and mandibular setback of 7 mm. Postsurgery, a pleasing good facial profile was achieved with Class II molar relation and positive overjet.

[Molecular mechanisms of skeletal muscle hypertrophy].

Science.gov (United States)

Astratenkova, I V; Rogozkin, V A

2014-06-01

Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

Archform comparisons between skeletal class II and III malocclusions.

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Wei Zou

Full Text Available The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2 and Skeletal Class III (SC3 malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crownand WALA points (the most prominent point on the soft-tissue ridgewere employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2. In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

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Marquette, Michele L.; Sognier, Marguerite A.

2013-01-01

An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

Generalized skeletal pathology: Results of radionuclide studies

International Nuclear Information System (INIS)

Fueger, G.F.; Aigner, R.

1987-01-01

Generalized pathological changes may involve the skeleton systematically (bone tissue, bone marrow) or at multiple sites involving destruction or infiltration. Appropriate radionuclide studies include total-body bone or bone marrow scintigraphy, absorptiometry (osteodensitometry) and the 24 h whole-body retention measurement. Established radioindicators are 99m-Tc-(hydroxy)methylendiphosphonate (HMDP or MDP) and 99m-Tc-human serumalbumin-nanocolloid. Absorptiometry of the forearm, extended by computer-assisted transaxial tomography, may be expected to prove as the most efficient method of bone density measurement. The 24 h whole-body retention measurement is useful for the diagnosis and follow-up of metabolic and endocrine osteopathies, if the very same osteotropic 99m-Tc-chelate is used. Whole-body bone scintigraphy today is one of the most important radionuclide studies for diagnosis and follow-up of skeletal metastases. Scintigraphy provides evidence of skeletal metastases several months earlier than radiological examinations. In about 40 percent of patients with cancer of the prostate, scintigraphy provided positive findings of skeletal metastases in the absence of both pain and increased levels of phosphatase. In patients with a history of malignancy, 60 percent of solitary findings on skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy ranges from 2 to 4%. Compared to skeletal scintigraphy, bone marrow scintigraphy frequently yields significant additional findings in cases of plasmocytoma, histiocytoma, lymphoma and haemoblastoses. (orig.) [de

Factors regulating fat oxidation in human skeletal muscle

DEFF Research Database (Denmark)

Kiens, Bente; Alsted, Thomas Junker; Jeppesen, Jacob

2011-01-01

In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin...

The importance of conventional radiography in the mutational analysis of skeletal dysplasias (the TRPV4 mutational family)

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Nemec, Stefan F.; Cohn, Daniel H.; Krakow, Deborah; Funari, Vincent A.; Rimoin, David L.; Lachman, Ralph S. [Medical Genetics Institute, Cedars Sinai Medical Center, International Skeletal Dysplasia Registry, Los Angeles, CA (United States)

2012-01-15

The spondylo and spondylometaphyseal dysplasias (SMDs) are characterized by vertebral changes and metaphyseal abnormalities of the tubular bones, which produce a phenotypic spectrum of disorders from the mild autosomal-dominant brachyolmia to SMD Kozlowski to autosomal-dominant metatropic dysplasia. Investigations have recently drawn on the similar radiographic features of those conditions to define a new family of skeletal dysplasias caused by mutations in the transient receptor potential cation channel vanilloid 4 (TRPV4). This review demonstrates the significance of radiography in the discovery of a new bone dysplasia family due to mutations in a single gene. (orig.)

Constitutive activation of IKK2/NF-κB impairs osteogenesis and skeletal development.

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Gaurav Swarnkar

Indian hedgehog and alkaline phosphatase, and the early markers Aggrecan and type-II collagen were reduced in Cre+IKK2ca_w/f and Cre+IKK2ca_f/f mice. Altogether, the in-vitro, in vivo and ex-vivo evidence suggest that IKK2ca perturbs osteoblast and chondrocyte maturation and impairs skeletal development.

Cardiac troponin T and fast skeletal muscle denervation in ageing.

Science.gov (United States)

Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

2017-10-01

Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii

MicroRNA in Skeletal Muscle: Its Crucial Roles in Signal Proteins, Mus cle Fiber Type, and Muscle Protein Synthesis.

Science.gov (United States)

Zhang, Jing; Liu, Yu Lan

2017-01-01

Pork is one of the most economical sources of animal protein for human consumption. Meat quality is an important economic trait for the swine industry, which is primarily determined by prenatal muscle development and postnatal growth. Identification of the molecular mechanisms underlying skeletal muscle development is a key priority. MicroRNAs (miRNAs) are a class of small noncoding RNAs that have emerged as key regulators of skeletal muscle development. A number of muscle-related miRNAs have been identified by functional gain and loss experiments in mouse model. However, determining miRNA-mRNA interactions involved in pig skeletal muscle still remains a significant challenge. For a comprehensive understanding of miRNA-mediated mechanisms underlying muscle development, miRNAome analyses of pig skeletal muscle have been performed by deep sequencing. Additionally, porcine miRNA single nucleotide polymorphisms have been implicated in muscle fiber types and meat quality. The present review provides an overview of current knowledge on recently identified miRNAs involved in myogenesis, muscle fiber type and muscle protein metabolism. Undoubtedly, further systematic understanding of the functions of miRNAs in pig skeletal muscle development will be helpful to expand the knowledge of basic skeletal muscle biology and be beneficial for the genetic improvement of meat quality traits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development

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Bringas Pablo

2008-03-01

Full Text Available Abstract Background Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM. Since early embryos are barely susceptible to CMV infection, and the extant evidence suggests that the differentiation program needs to be well underway for embryonic tissues to be susceptible to viral infection and viral-induced pathology, the aim of this study was to determine if first branchial arch NCM cells are susceptible to mCMV infection prior to differentiation of NCM derivatives. Results E11 mouse mandibular processes (MANs were infected with mouse CMV (mCMV for up to 16 days in vitro. mCMV infection of undifferentiated embryonic mouse MANs induced micrognathia consequent to decreased Meckel's cartilage chondrogenesis and mandibular osteogenesis. Specifically, mCMV infection resulted in aberrant stromal cellularity, a smaller, misshapen Meckel's cartilage, and mandibular bone and condylar dysmorphogenesis. Analysis of viral distribution indicates that mCMV primarily infects NCM cells and derivatives. Initial localization studies indicate that mCMV infection changed the cell-specific expression of FN, NF-κB2, RelA, RelB, and Shh and Smad7 proteins. Conclusion Our results indicate that mCMV dysregulation of key signaling pathways in primarily NCM cells and their derivatives severely disrupts mandibular morphogenesis and skeletogenesis. The pathogenesis appears to be centered around the canonical and noncanonical NF-κB pathways, and there is unusual juxtaposition of abnormal stromal

Developing Software to “Track and Catch” Missed Follow-up of Abnormal Test Results in a Complex Sociotechnical Environment

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Smith, M.; Murphy, D.; Laxmisan, A.; Sittig, D.; Reis, B.; Esquivel, A.; Singh, H.

2013-01-01

Summary Background Abnormal test results do not always receive timely follow-up, even when providers are notified through electronic health record (EHR)-based alerts. High workload, alert fatigue, and other demands on attention disrupt a provider’s prospective memory for tasks required to initiate follow-up. Thus, EHR-based tracking and reminding functionalities are needed to improve follow-up. Objectives The purpose of this study was to develop a decision-support software prototype enabling individual and system-wide tracking of abnormal test result alerts lacking follow-up, and to conduct formative evaluations, including usability testing. Methods We developed a working prototype software system, the Alert Watch And Response Engine (AWARE), to detect abnormal test result alerts lacking documented follow-up, and to present context-specific reminders to providers. Development and testing took place within the VA’s EHR and focused on four cancer-related abnormal test results. Design concepts emphasized mitigating the effects of high workload and alert fatigue while being minimally intrusive. We conducted a multifaceted formative evaluation of the software, addressing fit within the larger socio-technical system. Evaluations included usability testing with the prototype and interview questions about organizational and workflow factors. Participants included 23 physicians, 9 clinical information technology specialists, and 8 quality/safety managers. Results Evaluation results indicated that our software prototype fit within the technical environment and clinical workflow, and physicians were able to use it successfully. Quality/safety managers reported that the tool would be useful in future quality assurance activities to detect patients who lack documented follow-up. Additionally, we successfully installed the software on the local facility’s “test” EHR system, thus demonstrating technical compatibility. Conclusion To address the factors involved in missed

Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity.

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Jinze Qian

2010-05-01

Full Text Available Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II deposits as amyloid fibrils (AApoAII and can be transmitted from one animal to another both by the feces and milk excreted by mice with amyloidosis. Thus, mouse AApoAII amyloidosis has been demonstrated to be a "transmissible disease". In this study, to further characterize the transmissibility of amyloidosis, AApoAII amyloid fibrils were injected into transgenic Apoa2(cTg(+/- and normal R1.P1-Apoa2(c mice to induce AApoAII systemic amyloidosis. Two months later, AApoAII amyloid deposits were found in the skeletal muscles of amyloid-affected mice, primarily in the blood vessels and in the interstitial tissues surrounding muscle fibers. When amyloid fibrils extracted from the skeletal muscles were subjected to Western blot analysis, apoA-II was detected. Amyloid fibril fractions isolated from the muscles not only demonstrated the structure of amyloid fibrils but could also induce amyloidosis in young mice depending on its fibril conformation. These findings present a possible pathogenesis of amyloidosis: transmission of amyloid fibril conformation through muscle, and shed new light on the etiology involved in amyloid disorders.

Methods for the determination of skeletal muscle blood flow: development, strengths and limitations

DEFF Research Database (Denmark)

Gliemann, Lasse; Mortensen, Stefan P.; Hellsten, Ylva

2018-01-01

Since the first measurements of limb blood flow at rest and during nerve stimulation were conducted in the late 1800s, a number of methods have been developed for the determination of limb and skeletal muscle blood flow in humans. The methods, which have been applied in the study of aspects...... such as blood flow regulation, oxygen uptake and metabolism, differ in terms of strengths and degree of limitations but most have advantages for specific settings. The purpose of this review is to describe the origin and the basic principles of the methods, important aspects and requirements of the procedures....... One of the earliest methods, venous occlusion plethysmography, is a noninvasive method which still is extensively used and which provides similar values as other more direct blood flow methods such as ultrasound Doppler. The constant infusion thermodilution method remains the most appropriate...

Inactivation of Stac3 causes skeletal muscle defects and perinatal death in mice

OpenAIRE

Reinholt, Brad Michael

2012-01-01

The Src homology 3 domain (SH3) and cysteine rich domain (C1) 3 (Stac3) gene is a novel gene copiously expressed in skeletal muscle. The objective of this research was to determine the role of Stac3 in development, specifically in skeletal muscle. We achieved this objective by evaluating the phenotypic effects of Stac3 gene inactivation on development in mice. At birth homozygous Stac3 null (Stac3-/-) mice died perinatally and remained in fetal position with limp limbs, but possessed otherwis...

Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

Science.gov (United States)

Fernald, Charles D.

1980-01-01

Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

Essential role of RSK2 in c-Fos-dependent osteosarcoma development.

Science.gov (United States)

David, Jean-Pierre; Mehic, Denis; Bakiri, Latifa; Schilling, Arndt F; Mandic, Vice; Priemel, Matthias; Idarraga, Maria Helena; Reschke, Markus O; Hoffmann, Oskar; Amling, Michael; Wagner, Erwin F

2005-03-01

Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.

Latrunculin A treatment prevents abnormal chromosome segregation for successful development of cloned embryos.

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Yukari Terashita

Full Text Available Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA, an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2 could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene-essential for normal development but never before expressed in cloned embryos-was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning.

Latrunculin A Treatment Prevents Abnormal Chromosome Segregation for Successful Development of Cloned Embryos

Science.gov (United States)

Terashita, Yukari; Yamagata, Kazuo; Tokoro, Mikiko; Itoi, Fumiaki; Wakayama, Sayaka; Li, Chong; Sato, Eimei; Tanemura, Kentaro; Wakayama, Teruhiko

2013-01-01

Somatic cell nuclear transfer to an enucleated oocyte is used for reprogramming somatic cells with the aim of achieving totipotency, but most cloned embryos die in the uterus after transfer. While modifying epigenetic states of cloned embryos can improve their development, the production rate of cloned embryos can also be enhanced by changing other factors. It has already been shown that abnormal chromosome segregation (ACS) is a major cause of the developmental failure of cloned embryos and that Latrunculin A (LatA), an actin polymerization inhibitor, improves F-actin formation and birth rate of cloned embryos. Since F-actin is important for chromosome congression in embryos, here we examined the relation between ACS and F-actin in cloned embryos. Using LatA treatment, the occurrence of ACS decreased significantly whereas cloned embryo-specific epigenetic abnormalities such as dimethylation of histone H3 at lysine 9 (H3K9me2) could not be corrected. In contrast, when H3K9me2 was normalized using the G9a histone methyltransferase inhibitor BIX-01294, the Magea2 gene—essential for normal development but never before expressed in cloned embryos—was expressed. However, this did not increase the cloning success rate. Thus, non-epigenetic factors also play an important role in determining the efficiency of mouse cloning. PMID:24205216

Skeletal mass in patients receiving chronic anticonvulsant therapy

Energy Technology Data Exchange (ETDEWEB)

Zanzi, I.; Roginsky, M.S.; Rosen, A.; Cohn, S.H.

1981-01-01

The technique of in vivo total body neutron activation analysis was used to measure total body calcium (TBCa), a sensitive and precise index of skeletal mass, expressed as the Ca ratio (TBCa observed/TBCa predicted). 23 unselected, ambulatory, noninstitutionalized, adult epileptic patients under long-term anticonvulsant therapy were studied. Ca ratio was normal in 20 of the patients, low in only 2 and borderline in 1 patient. Plasma alkaline phosphatase values were elevated in half the subjects. Plasma Ca (uncorrected) was in the normal range in all. Serum 25-hydroxvitamin D (25-OHD) was low in 67% of the subjects, but only 1 patient had a value below 5 ng/ml. There was no correlation between the Ca ratio and the alkaline phosphatase or 25-OHD values. No radiographic or other evidences of osteomalacia were observed. This study does not support the notion of a prevalence of osteopenia in ambulatory, noninstitutionalized, adult epileptic patients receiving chronic anticonvulsant therapy in this geographical area despite the frequent findings of biochemical abnormalities.

Prediction of heart abnormality using MLP network

Science.gov (United States)

Hashim, Fakroul Ridzuan; Januar, Yulni; Mat, Muhammad Hadzren; Rizman, Zairi Ismael; Awang, Mat Kamil

2018-02-01

Heart abnormality does not choose gender, age and races when it strikes. With no warning signs or symptoms, it can result to a sudden death of the patient. Generally, heart's irregular electrical activity is defined as heart abnormality. Via implementation of Multilayer Perceptron (MLP) network, this paper tries to develop a program that allows the detection of heart abnormality activity. Utilizing several training algorithms with Purelin activation function, an amount of heartbeat signals received through the electrocardiogram (ECG) will be employed to condition the MLP network.

Knee radiography in the diagnosis of skeletal dysplasias

International Nuclear Information System (INIS)

Kwee, Thomas C.; Beek, Frederik J.A.; Nievelstein, Rutger A.J.; Beemer, Frits A.

2006-01-01

Flattening of the epiphyses of long bones is seen in several skeletal dysplasias and standardized measurements on a radiograph of the knee to detect skeletal dysplasias using this feature have been described. Since then only two other studies in which this method was used have been published, and both included only a small number of children and neither had a control group. In addition, the Dutch National Working Group on Skeletal Dysplasias began to have doubts about the reliability of the method. We therefore decided to re-evaluate its accuracy in a population of children with and without a skeletal dysplasia. To determine the diagnostic value of standardized measurements on conventional AP radiographs of the knee in children with a skeletal dysplasia. Subjects and methods: We measured the distal femoral metaphysis and epiphysis according to the published method on conventional AP radiographs of the knee in 45 healthy children and 52 children with a skeletal dysplasia. We compared graphically the height of the distal femoral epiphysis with its width and with the width of the femoral metaphysis. Receiver operating characteristic (ROC) curves were calculated for each group of children. All graphs showed a considerable overlap between children with a skeletal dysplasia and healthy children. The size of the area under the ROC curves for the different groups was small, varying between 0.567 and 0.653. This method does not discriminate between children with a skeletal dysplasia and healthy children. We therefore consider it to be of little diagnostic value. (orig.)

Mechanical modeling of skeletal muscle functioning

NARCIS (Netherlands)

van der Linden, B.J.J.J.

1998-01-01

For movement of body or body segments is combined effort needed of the central nervous system and the muscular-skeletal system. This thesis deals with the mechanical functioning of skeletal muscle. That muscles come in a large variety of geometries, suggest the existence of a relation between muscle

Regulation of gene expression in vertebrate skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Carvajal, Jaime J., E-mail: jaime.carvajal@icr.ac.uk; Rigby, Peter W.J., E-mail: peter.rigby@icr.ac.uk

2010-11-01

During embryonic development the integration of numerous synergistic signalling pathways turns a single cell into a multicellular organism with specialized cell types and highly structured, organized tissues. To achieve this, cells must grow, proliferate, differentiate and die according to their spatiotemporal position. Unravelling the mechanisms by which a cell adopts the correct fate in response to its local environment remains one of the fundamental goals of biological research. In vertebrates skeletal myogenesis is coordinated by the activation of the myogenic regulatory factors (MRFs) in response to signals that are interpreted by their associated regulatory elements in different precursor cells during development. The MRFs trigger a cascade of transcription factors and downstream structural genes, ultimately resulting in the generation of one of the fundamental histotypes. In this review we discuss the regulation of the different MRFs in relation to their position in the myogenic cascade, the changes in the general transcriptional machinery during muscle differentiation and the emerging importance of miRNA regulation in skeletal myogenesis.

Immunohistochemical abnormalities of fibrillin in cardiovascular tissues in Marfan's syndrome.

Science.gov (United States)

Fleischer, K J; Nousari, H C; Anhalt, G J; Stone, C D; Laschinger, J C

1997-04-01

Molecular defects in the glycoprotein fibrillin are believed to be responsible for impaired structural integrity of cardiovascular, skeletal, and ocular tissues in Marfan's syndrome (MFS). Traditionally, excellent results have been achieved with the Bentall composite graft repair of aneurysms of the ascending aorta in MFS. However, because of the potential complications associated with prosthetic valves, there is growing interest in techniques that preserve the native aortic valve. Between May 1994 and February 1995, 15 patients with a history of concomitant or remote aortic root aneurysms or dissection underwent operation for valvular heart disease. Specimens of aortic valve, ascending aortic wall, and mitral valve were obtained specifically to observe differences in fibrillin content and architecture between patients with (n = 9) and without (n = 6) MFS. In addition, control specimens of aortic valve, aortic wall, and mitral valve were obtained from 4 patients with isolated valvular or coronary artery disease but no evidence of connective tissue disorders or other aortic pathologic conditions. Fibrillin immunostaining using indirect immunofluorescence was used. Specimens were coded and graded by a blinded observer to determine quantity, homogeneity, and fragmentation of fibrillin. Observed fibrillin abnormalities in MFS and control patients were limited to the midportion (elastin-associated microfibrils) of the aortic valve, aortic wall, and mitral valve tissues. Fibrillin abnormalities of aortic valve, aortic wall, and mitral valve tissues were seen in all patients with MFS and were most severe in those older than 20 years. Similar fibrillin abnormalities of aortic valve and aortic wall specimens were observed in control patients more than 60 years old. Even in the setting of a normal-appearing aortic valve, the current rationale for widespread use of valve-sparing repairs of aortic root aneurysms in patients with MFS and patients older than 60 years should be

Skeletal muscle cutpoints associated with elevated physical disability risk in older men and women.

Science.gov (United States)

Janssen, Ian; Baumgartner, Richard N; Ross, Robert; Rosenberg, Irwin H; Roubenoff, Ronenn

2004-02-15

The purpose of this study was to determine skeletal muscle cutpoints for identifying elevated physical disability risk in older adults. Subjects included 4,449 older (> or = 60 years) participants from the Third National Health and Nutrition Examination Survey during 1988-1994. Physical disability was assessed by questionnaire, and bioimpedance was used to estimate skeletal muscle, which was normalized for height. Receiver operating characteristics were used to develop the skeletal muscle cutpoints associated with a high likelihood of physical disability. Odds for physical disability were compared in subjects whose measures fell above and below these cutpoints. Skeletal muscle cutpoints of 5.76-6.75 and values in men were 8.51-10.75 and skeletal muscle values, women with moderate- and high-risk skeletal muscle values had odds for physical disability of 1.41 (95% confidence interval (CI): 0.97, 2.04) and 3.31 (95% CI: 1.91, 5.73), respectively. The corresponding odds in men were 3.65 (95% CI: 1.92, 6.94) and 4.71 (95% CI: 2.28, 9.74). This study presents skeletal muscle cutpoints for physical disability risk in older adults. Future applications of these cutpoints include the comparison of morbidity risk in older persons with normal muscle mass and those with sarcopenia, the determination and comparison of sarcopenia prevalences, and the estimation of health-care costs attributable to sarcopenia.

The skeletal phenotype of achondrogenesis type 1A is caused exclusively by cartilage defects.

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Bird, Ian M; Kim, Susie H; Schweppe, Devin K; Caetano-Lopes, Joana; Robling, Alexander G; Charles, Julia F; Gygi, Steven P; Warman, Matthew L; Smits, Patrick J

2018-01-08

Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by Trip11 ) cause achondrogenesis type 1A (ACG1A). ACG1A is surprisingly tissue specific, mainly affecting cartilage development. Bone development is also abnormal, but as chondrogenesis and osteogenesis are closely coupled, this could be a secondary consequence of the cartilage defect. A possible explanation for the tissue specificity of ACG1A is that cartilage and bone are highly secretory tissues with a high use of the membrane trafficking machinery. The perinatal lethality of ACG1A prevents investigating this hypothesis. We therefore generated mice with conditional Trip11 knockout alleles and inactivated Trip11 in chondrocytes, osteoblasts, osteoclasts and pancreas acinar cells, all highly secretory cell types. We discovered that the ACG1A skeletal phenotype is solely due to absence of GMAP-210 in chondrocytes. Mice lacking GMAP-210 in osteoblasts, osteoclasts and acinar cells were normal. When we inactivated Trip11 in primary chondrocyte cultures, GMAP-210 deficiency affected trafficking of a subset of chondrocyte-expressed proteins rather than globally impairing membrane trafficking. Thus, GMAP-210 is essential for trafficking specific cargoes in chondrocytes but is dispensable in other highly secretory cells. © 2018. Published by The Company of Biologists Ltd.

Omega-3 Fatty Acids and Skeletal Muscle Health

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Stewart Jeromson

2015-11-01

Full Text Available Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

Robust generation and expansion of skeletal muscle progenitors and myocytes from human pluripotent stem cells.

Science.gov (United States)

Shelton, Michael; Kocharyan, Avetik; Liu, Jun; Skerjanc, Ilona S; Stanford, William L

2016-05-15

Human pluripotent stem cells provide a developmental model to study early embryonic and tissue development, tease apart human disease processes, perform drug screens to identify potential molecular effectors of in situ regeneration, and provide a source for cell and tissue based transplantation. Highly efficient differentiation protocols have been established for many cell types and tissues; however, until very recently robust differentiation into skeletal muscle cells had not been possible unless driven by transgenic expression of master regulators of myogenesis. Nevertheless, several breakthrough protocols have been published in the past two years that efficiently generate cells of the skeletal muscle lineage from pluripotent stem cells. Here, we present an updated version of our recently described 50-day protocol in detail, whereby chemically defined media are used to drive and support muscle lineage development from initial CHIR99021-induced mesoderm through to PAX7-expressing skeletal muscle progenitors and mature skeletal myocytes. Furthermore, we report an optional method to passage and expand differentiating skeletal muscle progenitors approximately 3-fold every 2weeks using Collagenase IV and continued FGF2 supplementation. Both protocols have been optimized using a variety of human pluripotent stem cell lines including patient-derived induced pluripotent stem cells. Taken together, our differentiation and expansion protocols provide sufficient quantities of skeletal muscle progenitors and myocytes that could be used for a variety of studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Introduction to skeletal radiology and bone growth

International Nuclear Information System (INIS)

Rogers, L.F.

1987-01-01

Radiographic examination is the key to the diagnosis of many skeletal abnormalities. It is essential that each bone be examined in its entirety, including the cortex, medullary canal (cancellous bone or spongiosa), and articular ends. The position and alignment of joints are determined. In children, the epiphysis and epiphyseal line or physis must be observed. The adjacent soft tissues are examined. Obliteration of normal soft-tissue lines and the presence of a joint effusion are of particular importance. When disease is present, it is important to determine whether the process is limited to a single bone or joint or whether multiple bones or joints are involved. The distribution of disease is also a consideration. The presence and type of bone destruction and bone production, the appearance of the edges or borders of the lesion, and the presence or absence of cortical expansion and periosteal reaction are also noted. The radiographic findings are then correlated with the clinical history and the age and sex of the patient to arrive at a logical diagnosis. The diagnosis may be firm in some instances; in other cases, a differential diagnosis is offered since the exact diagnosis cannot be determined

Impact of placental insufficiency on fetal skeletal muscle growth

Science.gov (United States)

Hay, William W.

2016-01-01

Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

The skeletal vascular system - Breathing life into bone tissue.

Science.gov (United States)

Stegen, Steve; Carmeliet, Geert

2017-08-26

During bone development, homeostasis and repair, a dense vascular system provides oxygen and nutrients to highly anabolic skeletal cells. Characteristic for the vascular system in bone is the serial organization of two capillary systems, each typified by specific morphological and physiological features. Especially the arterial capillaries mediate the growth of the bone vascular system, serve as a niche for skeletal and hematopoietic progenitors and couple angiogenesis to osteogenesis. Endothelial cells and osteoprogenitor cells interact not only physically, but also communicate to each other by secretion of growth factors. A vital angiogenic growth factor is vascular endothelial growth factor and its expression in skeletal cells is controlled by osteogenic transcription factors and hypoxia signaling, whereas the secretion of angiocrine factors by endothelial cells is regulated by Notch signaling, blood flow and possibly hypoxia. Bone loss and impaired fracture repair are often associated with reduced and disorganized blood vessel network and therapeutic targeting of the angiogenic response may contribute to enhanced bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

DEFF Research Database (Denmark)

Richter, Erik; Hansen, B F; Hansen, S A

1988-01-01

in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

Skeletal and muscular status in juveniles with GFD treated clinical and newly diagnosed atypical celiac disease--preliminary data.

Science.gov (United States)

Płudowski, Paweł; Karczmarewicz, Elzbieta; Socha, Jerzy; Matusik, Halina; Syczewska, Małgorzata; Lorenc, Roman S

2007-01-01

Undiagnosed and untreated celiac disease (CD) constitutes an increasing skeletal health problem due to its association with low bone density and fractures. Examinations of skeletal status in children using dual-energy X-ray absorptiometry (DXA) are prone to size-related misinterpretation. In contrary, the analysis of muscle-bone relationship seems to limit a possibility of misdiagnosis because skeletal status is evaluated from the functional perspective. The study was aimed to assess skeletal status of children suffering from CD with the use of muscle-bone functional algorithm. The study group comprised 29 celiac patients (13.7yr+/-2.9) on gluten-free diet (GFD), and 24 newly diagnosed atypical celiac patients, including subgroup with normal height (n=14; 12.6yr+/-3.9) and subgroup with short stature (n=10; 12.2yr+/-2.9). Muscular and skeletal status was evaluated by DXA (DPX-L, GE). Anthropometry, total body bone mineral density (TBBMD, g/cm(2)). and total body bone mineral content (TBBMC, g) as well as lean body mass (LBM, g) were evaluated. Muscle-bone interactions were estimated using TBBMC/LBM ratio. Previously established references for healthy controls were used for the calculation of Z-scores (age-matched) and SD-scores (height-matched). GFD treated celiacs and atypical celiacs with normal body height had TBBMD, TBBMC, LBM, and TBBMC/LBM ratio Z-scores and SD-scores within normal range for healthy controls. In contrary, atypical celiacs with short stature had significantly lower Z-scores for TBBMD (-2.3+/-0.4), TBBMC (-2.1+/-0.3), LBM (-1.4+/-0.3). and TBBMC/LBM ratio (-2.3+/-0.6) when compared to respective values observed in GFD treated celiacs (pnormal height (pvalues observed in GFD treated celiacs (+0.04+/-0.2; pnormal height (-0.4+/-0.2; pvalues of DXA assessed indicators of bone and muscle status as well as normal muscle-bone interactions. Untreated atypical celiacs may present a broad spectrum of heterogeneous abnormalities from normal to markedly

A compact skeletal mechanism for n -dodecane with optimized semi-global low-temperature chemistry for diesel engine simulations

Energy Technology Data Exchange (ETDEWEB)

Yao, Tong; Pei, Yuanjiang; Zhong, Bei-Jing; Som, Sibendu; Lu, Tianfeng; Luo, Kai Hong

2017-03-01

A skeletal mechanism with 54 species and 269 reactions was developed to predict pyrolysis and oxidation of n-dodecane as a diesel fuel surrogate involving both high-temperature (high-T) and low-temperature (low-T) conditions. The skeletal mechanism was developed from a semi-detailed mechanism developed at the University of Southern California (USC). Species and reactions for high-T pyrolysis and oxidation of C5-C12 were reduced by using reaction flow analysis (RFA), isomer lumping, and then merged into a skeletal C0-C4 core to form a high-T sub-mechanism. Species and lumped semi-global reactions for low-T chemistry were then added to the high-T sub-mechanism and a 54-species skeletal mechanism is obtained. The rate parameters of the low-T reactions were tuned against a detailed mechanism by the Lawrence Livermore National Laboratory (LLNL), as well as the Spray A flame experimental data, to improve the prediction of ignition delay at low-T conditions, while the high-T chemistry remained unchanged. The skeletal mechanism was validated for auto-ignition, perfectly stirred reactors (PSR), flow reactors and laminar premixed flames over a wide range of flame conditions. The skeletal mechanism was then employed to simulate three-dimensional turbulent spray flames at compression ignition engine conditions and validated against experimental data from the Engine Combustion Network (ECN).

Linear scleroderma en coup de sabre including abnormal dental development

DEFF Research Database (Denmark)

Hørberg, M; Lauesen, S R; Daugaard-Jensen, J

2015-01-01

BACKGROUND: Linear scleroderma en coup de sabre (SCS) is a rare skin condition, where dense collagen is deposited in a localised groove of the head and neck area resembling the stroke of a sabre. The SCS may involve the oral cavity, but the severity and relation to this skin abnormality is unknow...... with a left-sided skin defect (SCS) and a left-sided local malformation in her dentition. It is possible that there is a developmental connection between these two left-sided defects, both with an ectodermal origin.......-UP: The patient has been regularly controlled and treated since she was first diagnosed. A surgical and orthodontic treatment was performed to ensure optimal occlusion, space and alveolar bone development. The present age of the patient is 14 years and 10 months. CONCLUSION: This case demonstrated a patient...

Activation of the skeletal alpha-actin promoter during muscle regeneration.

Science.gov (United States)

Marsh, D R; Carson, J A; Stewart, L N; Booth, F W

1998-11-01

Little is known concerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5-10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal alpha-actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal alpha-actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal alpha-actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal alpha-actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by -424 skeletal alpha-actin and -99 skeletal alpha-actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal alpha-actin promoter activities were similar to control values. Thus, initial activation of the skeletal alpha-actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal alpha-actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal alpha-actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box.

Bex1 knock out mice show altered skeletal muscle regeneration

International Nuclear Information System (INIS)

Koo, Jae Hyung; Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

2007-01-01

Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca 2+ /CaM may be involved in skeletal muscle regeneration

Skeletal Muscle Cell Induction from Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Yusaku Kodaka

2017-01-01

Full Text Available Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD. Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

Evaluating two-dimensional skeletal structure parameters using radiological bone morphometric analysis

International Nuclear Information System (INIS)

Asa, Kensuke; Sakurai, Takashi; Kashima, Isamu; Kumasaka, Satsuki

2005-01-01

The objectives of this study was to investigate the reliability of two-dimensional (2D) skeletal structure parameters obtained using radiological bone morphometric analysis. The 2D skeletal parameters in the regions of interest (ROIs) were measured on computed radiography (CR) images of first phalanges from racehorses, using radiological bone morphometric analysis. Cancellous bone blocks were made from the phalanges in the same position as the ROI determined on CR images. Three-dimensional (3D) trabecular parameters were measured using micro-computed tomography (μCT). The correlations between the 2D skeletal parameters and 3D trabecular parameters were evaluated in relation to the measured bone strength. The following 2D skeletal structure parameters were correlated with bone strength (r=0.61-0.69): skeletal perimeter (Sk.Pm), skeletal number (Sk.N), skeletal separation (Sk.Sp), skeletal spacing (Sk.Spac), fractal dimension (FD), and skeletal pattern factor (SkPf). The 3D trabecular structure parameters were closely correlated with bone strength (r=0.74-0.86). The 2D skeletal parameters Sk.N, Sk.Pm, FD, SkPf, and Sk.Spac were correlated with the 3D trabecular parameters (r=0.61-0.70). The 2D skeletal parameters obtained using radiological bone morphometric analysis may be useful indicators of trabecular strength. (author)

Skeletal remodelling suggests the turtle's shell is not an evolutionary straitjacket.

Science.gov (United States)

Cordero, Gerardo Antonio; Quinteros, Kevin

2015-04-01

Recent efforts to decipher the enigma of the turtle's shell revealed that distantly related turtle species deploy diverse processes during shell development. Even so, extant species share in common a shoulder blade (scapula) that is encapsulated within the shell. Thus, evolutionary change in the correlated development of the shell and scapula probably underpins the evolution of highly derived shell morphologies. To address this expectation, we conducted one of the most phylogenetically comprehensive surveys of turtle development, focusing on scapula growth and differentiation in embryos, hatchlings and adults of 13 species. We report, to our knowledge, the first description of secondary differentiation owing to skeletal remodelling of the tetrapod scapula in turtles with the most structurally derived shell phenotypes. Remodelling and secondary differentiation late in embryogenesis of box turtles (Emys and Terrapene) yielded a novel skeletal segment (i.e. the suprascapula) of high functional value to their complex shell-closing system. Remarkably, our analyses suggest that, in soft-shelled turtles (Trionychidae) with extremely flattened shells, a similar transformation is linked to truncated scapula growth. Skeletal remodelling, as a form of developmental plasticity, might enable the seemingly constrained turtle body plan to diversify, suggesting the shell is not an evolutionary straitjacket. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

COLEC10 is mutated in 3MC patients and regulates early craniofacial development

DEFF Research Database (Denmark)

Munye, Mustafa M.; Diaz-Font, Anna; Ocaka, Louise

2017-01-01

3MC syndrome is an autosomal recessive heterogeneous disorder with features linked to developmental abnormalities. The main features include facial dysmorphism, craniosynostosis and cleft lip/palate; skeletal structures derived from cranial neural crest cells (cNCC). We previously reported...

SoxB2 in sea urchin development: implications in neurogenesis, ciliogenesis and skeletal patterning.

Science.gov (United States)

Anishchenko, Evgeniya; Arnone, Maria Ina; D'Aniello, Salvatore

2018-01-01

Current studies in evolutionary developmental biology are focused on the reconstruction of gene regulatory networks in target animal species. From decades, the scientific interest on genetic mechanisms orchestrating embryos development has been increasing in consequence to the fact that common features shared by evolutionarily distant phyla are being clarified. In 2011, a study across eumetazoan species showed for the first time the existence of a highly conserved non-coding element controlling the SoxB2 gene, which is involved in the early specification of the nervous system. This discovery raised several questions about SoxB2 function and regulation in deuterostomes from an evolutionary point of view. Due to the relevant phylogenetic position within deuterostomes, the sea urchin Strongylocentrotus purpuratus represents an advantageous animal model in the field of evolutionary developmental biology. Herein, we show a comprehensive study of SoxB2 functions in sea urchins, in particular its expression pattern in a wide range of developmental stages, and its co-localization with other neurogenic markers, as SoxB1 , SoxC and Elav . Moreover, this work provides a detailed description of the phenotype of sea urchin SoxB2 knocked-down embryos, confirming its key function in neurogenesis and revealing, for the first time, its additional roles in oral and aboral ectoderm cilia and skeletal rod morphology. We concluded that SoxB2 in sea urchins has a neurogenic function; however, this gene could have multiple roles in sea urchin embryogenesis, expanding its expression in non-neurogenic cells. We showed that SoxB2 is functionally conserved among deuterostomes and suggested that in S. purpuratus this gene acquired additional functions, being involved in ciliogenesis and skeletal patterning.

Cardiac abnormality prediction using HMLP network

Science.gov (United States)

Adnan, Ja'afar; Ahmad, K. A.; Mat, Muhamad Hadzren; Rizman, Zairi Ismael; Ahmad, Shahril

2018-02-01

Cardiac abnormality often occurs regardless of gender, age and races but depends on the lifestyle. This problem sometimes does not show any symptoms and usually detected once it already critical which lead to a sudden death to the patient. Basically, cardiac abnormality is the irregular electrical signal that generate by the pacemaker of the heart. This paper attempts to develop a program that can detect cardiac abnormality activity through implementation of Hybrid Multilayer Perceptron (HMLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP and HMLP network by using Modified Recursive Prediction Error (MRPE) algorithm and to test the network performance.

Measurement of skeletal muscle collagen breakdown by microdialysis

DEFF Research Database (Denmark)

Miller, B F; Ellis, D; Robinson, M M

2011-01-01

Exercise increases the synthesis of collagen in the extracellular matrix of skeletal muscle. Breakdown of skeletal muscle collagen has not yet been determined because of technical limitations. The purpose of the present study was to use local sampling to determine skeletal muscle collagen breakdown...... collagen breakdown 17–21 h post-exercise, and our measurement of OHP using GC–MS was in agreement with traditional assays....

Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems.

Science.gov (United States)

Walmsley, Gemma L; Blot, Stéphane; Venner, Kerrie; Sewry, Caroline; Laporte, Jocelyn; Blondelle, Jordan; Barthélémy, Inès; Maurer, Marie; Blanchard-Gutton, Nicolas; Pilot-Storck, Fanny; Tiret, Laurent; Piercy, Richard J

2017-02-01

Mutations in HACD1/PTPLA cause recessive congenital myopathies in humans and dogs. Hydroxyacyl-coA dehydratases are required for elongation of very long chain fatty acids, and HACD1 has a role in early myogenesis, but the functions of this striated muscle-specific enzyme in more differentiated skeletal muscle remain unknown. Canine HACD1 deficiency is histopathologically classified as a centronuclear myopathy (CNM). We investigated the hypothesis that muscle from HACD1-deficient dogs has membrane abnormalities in common with CNMs with different genetic causes. We found progressive changes in tubuloreticular and sarcolemmal membranes and mislocalized triads and mitochondria in skeletal muscle from animals deficient in HACD1. Furthermore, comparable membranous abnormalities in cultured HACD1-deficient myotubes provide additional evidence that these defects are a primary consequence of altered HACD1 expression. Our novel findings, including T-tubule dilatation and disorganization, associated with defects in this additional CNM-associated gene provide a definitive pathophysiologic link with these disorders, confirm that dogs deficient in HACD1 are relevant models, and strengthen the evidence for a unifying pathogenesis in CNMs via defective membrane trafficking and excitation-contraction coupling in muscle. These results build on previous work by determining further functional roles of HACD1 in muscle and provide new insight into the pathology and pathogenetic mechanisms of HACD1 CNM. Consequently, alterations in membrane properties associated with HACD1 mutations should be investigated in humans with related phenotypes. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A metabolic link to skeletal muscle wasting and regeneration

Directory of Open Access Journals (Sweden)

René eKoopman

2014-02-01

Full Text Available Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed ‘metabolic reprogramming’.

Bone-seeking radiopharmaceuticals in skeletal malignancy: evolution, not revolution

International Nuclear Information System (INIS)

MacFarlane, D.

2003-01-01

Many advanced malignancies are complicated by skeletal metastases, with attendant pain and disability. External beam radiotherapy is still the most effective treatment for isolated lesions. Bone-seeking radiopharmaceuticals were perceived as a means of delivering radiation to multiple lesions simultaneously. A wide variety of radioisotopes have been used in this endeavor, with myelosuppression being the most significant potential adverse effect. Benefits of treatment are modest, including a transient improvement in pain control and perhaps prolongation of the treatment-free period. This is best demonstrated in prostate cancer with lower responses by skeletal metastases from breast and lung cancers. However, the treatment is yet to produce any improvement in patient survival. Experimental approaches to improve treatment efficacy include combination with cytotoxic therapy, and administration earlier in the course of the disease. Bone seeking radiopharmaceuticals have been used in treatment of advanced osteosarcoma in humans and canines and achieved effective palliation. The myelosuppressive effects of these agents have been exploited in patients with multiple myeloma to assist in attaining myeloablation prior to stem cell transplantation. Development of more potent non-radiolabelled bisphosphonates and recognition of their antitumour effect against several tumours has sparked a recrudescence of interest in their use for bone metastases. Set against these developments, the role of bone-seeking radiopharmaceuticals in skeletal metastases may need to be redefined

Disease-Induced Skeletal Muscle Atrophy and Fatigue

NARCIS (Netherlands)

Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

2016-01-01

Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal

Expanding the phenome and variome of skeletal dysplasia.

Science.gov (United States)

Maddirevula, Sateesh; Alsahli, Saud; Alhabeeb, Lamees; Patel, Nisha; Alzahrani, Fatema; Shamseldin, Hanan E; Anazi, Shams; Ewida, Nour; Alsaif, Hessa S; Mohamed, Jawahir Y; Alazami, Anas M; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Abouelhoda, Mohamed; Monies, Dorota; Al Tassan, Nada; Alshammari, Muneera; Alsagheir, Afaf; Seidahmed, Mohammed Zain; Sogati, Samira; Aglan, Mona S; Hamad, Muddathir H; Salih, Mustafa A; Hamed, Ahlam A; Alhashmi, Nadia; Nabil, Amira; Alfadli, Fatima; Abdel-Salam, Ghada M H; Alkuraya, Hisham; Peitee, Winnie Ong; Keng, W T; Qasem, Abdullah; Mushiba, Aziza M; Zaki, Maha S; Fassad, Mahmoud R; Alfadhel, Majid; Alexander, Saji; Sabr, Yasser; Temtamy, Samia; Ekbote, Alka V; Ismail, Samira; Hosny, Gamal Ahmed; Otaify, Ghada A; Amr, Khalda; Al Tala, Saeed; Khan, Arif O; Rizk, Tamer; Alaqeel, Aida; Alsiddiky, Abdulmonem; Singh, Ankur; Kapoor, Seema; Alhashem, Amal; Faqeih, Eissa; Shaheen, Ranad; Alkuraya, Fowzan S

2018-04-05

PurposeTo describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized.MethodsDetailed phenotyping and next-generation sequencing (panel and exome).ResultsOur analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.ConclusionBy expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.GENETICS in MEDICINE advance online publication, 5 April 2018; doi:10.1038/gim.2018.50.

SKIBO diseases: a concept to avoid bloody diagnostic procedures in ambiguous skeletal lesions

International Nuclear Information System (INIS)

Freyschmidt, J.; Freyschmidt-Paul, P.

2001-01-01

In cases with an ''atypical'' radiologic pattern-osteolytic as well as osteosclerotic or mixed - the radiologist should pay attention to the patient's skin. There he will often find specific changes that are the key to a correct interpretation of the radiologic abnormalities. In such cases the synopsis is of more value in differential diagnosis than more or less unspecific histologic findings. Entities with a non-arbitrary conjunction of changes of the skin and bones we call SKIBO diseases. Some of them have a high potential for mimicking malignant bone lesions, often with the consequence of unnecessary biopsies. In this article we present the typical dermatologic and radiologic signs and symptoms of neurofibromatosis, sarcoidosis and pustulotic arteroosteitis (PAO) with special focus on such skeletal lesions that may mimic malignancy. (orig.)

Immunology Guides Skeletal Muscle Regeneration

Directory of Open Access Journals (Sweden)

F. Andrea Sass

2018-03-01

Full Text Available Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

Using the Optical Fractionator to Estimate Total Cell Numbers in the Normal and Abnormal Developing Human Forebrain

DEFF Research Database (Denmark)

Larsen, Karen B

2017-01-01

abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples...

The Correlation of Skeletal and Cardiac Muscle Dysfunction in Duchenne Muscular Dystrophy.

Science.gov (United States)

Posner, Andrew D; Soslow, Jonathan H; Burnette, W Bryan; Bian, Aihua; Shintani, Ayumi; Sawyer, Douglas B; Markham, Larry W

2016-01-01

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle and cardiac dysfunction. While skeletal muscle dysfunction precedes cardiomyopathy, the relationship between the progressive decline in skeletal and cardiac muscle function is unclear. This relationship is especially important given that the myocardial effects of many developing DMD therapies are largely unknown. Our objective was to assess the relationship between progression of skeletal muscle weakness and onset of cardiac dysfunction in DMD. A total of 77 DMD subjects treated at a single referral center were included. Demographic information, quantitative muscle testing (QMT), subjective muscle strength, cardiac function, and current and retrospective medications were collected. A Spearman rank correlation was used to evaluate for an association between subjective strength and fractional shortening. The effects of total QMT and arm QMT on fractional shortening were examined in generalized least square with and without adjustments for age, ambulatory status, and duration of corticosteroids and cardiac specific medications. We found a significant correlation between maintained subjective skeletal muscle arm and leg strength and maintained cardiac function as defined by fractional shortening (rho=0.47, p=0.004 and rho=0.48, p=0.003, respectively). We also found a significant association between QMT and fractional shortening among non-ambulatory DMD subjects (p=0.03), while this association was not significant in ambulatory subjects. Our findings allow us to conclude that in this population, there exists a significant relationship between skeletal muscle and cardiac function in non-ambulatory DMD patients. While this does not imply a causal relationship, a possible association between skeletal and cardiac muscle function suggests that researchers should carefully monitor cardiac function, even when the primary outcome measures are not cardiac in nature.

Oxidative stress (glutathionylation and Na,K-ATPase activity in rat skeletal muscle.