WorldWideScience

Sample records for canine cone-rod dystrophy

  1. Cone rod dystrophies.

    Science.gov (United States)

    Hamel, Christian P

    2007-01-01

    Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

  2. Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone-Rod Dystrophy

    NARCIS (Netherlands)

    Thiadens, Alberta A. H. J.; Phan, T. My Lan; Zekveld-Vroon, Renate C.; Leroy, Bart P.; van den Born, L. Ingeborgh; Hoyng, Carel B.; Klaver, Caroline C. W.; Roosing, Susanne; Pott, Jan-Willem R.; van Schooneveld, Mary J.; van Moll-Ramirez, Norka; van Genderen, Maria M.; Boon, Camiel J. F.; den Hollander, Anneke I.; Bergen, Arthur A. B.; De Baere, Elfride; Cremers, Frans P. M.; Lotery, Andrew J.

    2012-01-01

    Objective: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). Design: Clinic-based, longitudinal, multicenter study. Participants: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N =

  3. Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy

    NARCIS (Netherlands)

    Thiadens, A.A.; Phan, T.M.; Zekveld-Vroon, R.C.; Leroy, B.P.; Born, L.I. van den; Hoyng, C.B.; Klaver, C.C.; Writing Committee for the Cone Disorders Study Group, C.; Roosing, S.; Pott, J.W.; Schooneveld, M.J. van; Moll-Ramirez, N. van; Genderen, M.M. van; Boon, C.J.F.; Hollander, A.I. den; Bergen, A.A.; Baere, E. de; Cremers, F.P.; Lotery, A.J.

    2012-01-01

    OBJECTIVE: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). DESIGN: Clinic-based, longitudinal, multicenter study. PARTICIPANTS: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N =

  4. Mutations in PCYT1A Cause Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy

    Science.gov (United States)

    Yamamoto, Guilherme L.; Baratela, Wagner A.R.; Almeida, Tatiana F.; Lazar, Monize; Afonso, Clara L.; Oyamada, Maria K.; Suzuki, Lisa; Oliveira, Luiz A.N.; Ramos, Ester S.; Kim, Chong A.; Passos-Bueno, Maria Rita; Bertola, Débora R.

    2014-01-01

    Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare autosomal-recessive disorder characterized by severe short stature, progressive lower-limb bowing, flattened vertebral bodies, metaphyseal involvement, and visual impairment caused by cone-rod dystrophy. Whole-exome sequencing of four individuals affected by this disorder from two Brazilian families identified two previously unreported homozygous mutations in PCYT1A. This gene encodes the alpha isoform of the phosphate cytidylyltransferase 1 choline enzyme, which is responsible for converting phosphocholine into cytidine diphosphate-choline, a key intermediate step in the phosphatidylcholine biosynthesis pathway. A different enzymatic defect in this pathway has been previously associated with a muscular dystrophy with mitochondrial structural abnormalities that does not have cartilage and/or bone or retinal involvement. Thus, the deregulation of the phosphatidylcholine pathway may play a role in multiple genetic diseases in humans, and further studies are necessary to uncover its precise pathogenic mechanisms and the entirety of its phenotypic spectrum. PMID:24387991

  5. Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy.

    Science.gov (United States)

    Shaikh, Rehan S; Reuter, Peggy; Sisk, Robert A; Kausar, Tasleem; Shahzad, Mohsin; Maqsood, Muhammad I; Yousif, Ateeq; Ali, Muhammad; Riazuddin, Saima; Wissinger, Bernd; Ahmed, Zubair M

    2015-04-01

    We assessed a large consanguineous Pakistani family (PKAB157) segregating early onset low vision problems. Funduscopic and electroretinographic evaluation of affected individuals revealed juvenile cone-rod dystrophy (CRD) with maculopathy. Other clinical symptoms included loss of color discrimination, photophobia and nystagmus. Whole-exome sequencing, segregation and haplotype analyses demonstrated that a transition variant (c.955T>C; p.(Cys319Arg)) in CNGA3 co-segregated with the CRD phenotype in family PKAB157. The ability of CNGA3 channel to influx calcium in response to agonist, when expressed either alone or together with the wild-type CNGB3 subunit in HEK293 cells, was completely abolished due to p.Cys319Arg variant. Western blotting and immunolocalization studies suggest that a decreased channel density in the HEK293 cell membrane due to impaired folding and/or trafficking of the CNGA3 protein is the main pathogenic effect of the p.Cys319Arg variant. Mutant alleles of the human cone photoreceptor cyclic nucleotide-gated channel (CNGA3) are frequently associated with achromatopsia. In rare cases, variants in CNGA3 are also associated with cone dystrophy, Leber's congenital amaurosis and oligo cone trichromacy. The identification of predicted p.(Cys319Arg) missense variant in CNGA3 expands the repertoire of the known genetic causes of CRD and phenotypic spectrum of CNGA3 alleles. PMID:25052312

  6. An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy

    Science.gov (United States)

    Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido

    2015-01-01

    Purpose To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. Methods Patients underwent a detailed ophthalmic evaluation, including eye examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potential (VEP). Genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing. Results The affected family members are three siblings who have various degrees of progressive visual deterioration, glare, color vision abnormalities, and night vision difficulties. Visual field tests revealed central scotomas of different extension. Cone and rod ERG responses were reduced, with cones more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice sites. However, in intron 21, proximate to the intron–exon junction, we observed a homozygous 10 bp deletion between positions −26 and −17 (c.2281–26_-17del). The deletion was linked to a known SNP, c.2281–6C>G. The deletion cosegregated with the disease in the family, and was not detected in public databases or in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence. The in vitro splicing assay demonstrated that c.2281–26_-17del leads to

  7. A new family of Greek origin maps to the CRD locus for autosomal dominant cone-rod dystrophy on 19q.

    OpenAIRE

    Papaioannou, M.; BESSANT, D.; Payne, A.; Bellingham, J.; Rougas, C; Loutradis-Anagnostou, A; Gregory-Evans, C; Balassopoulou, A; Bhattacharya, S.

    1998-01-01

    Retinal photoreceptor dystrophies (RD) are a highly heterogeneous group of genetic disorders of the retina, representing the most frequently inherited form of visual handicap, affecting approximately 1.5 million people world wide. To date, more than 40 genetic loci have been implicated in RD. One of them, the CORD2 locus, for an autosomal dominant form of cone-rod dystrophy (CRD), maps to chromosome 19q and has previously been reported in a single large family of British origin. We now report...

  8. Mutations in CEP78 Cause Cone-Rod Dystrophy and Hearing Loss Associated with Primary-Cilia Defects.

    Science.gov (United States)

    Nikopoulos, Konstantinos; Farinelli, Pietro; Giangreco, Basilio; Tsika, Chrysanthi; Royer-Bertrand, Beryl; Mbefo, Martial K; Bedoni, Nicola; Kjellström, Ulrika; El Zaoui, Ikram; Di Gioia, Silvio Alessandro; Balzano, Sara; Cisarova, Katarina; Messina, Andrea; Decembrini, Sarah; Plainis, Sotiris; Blazaki, Styliani V; Khan, Muhammad Imran; Micheal, Shazia; Boldt, Karsten; Ueffing, Marius; Moulin, Alexandre P; Cremers, Frans P M; Roepman, Ronald; Arsenijevic, Yvan; Tsilimbaris, Miltiadis K; Andréasson, Sten; Rivolta, Carlo

    2016-09-01

    Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs(∗)18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa. PMID:27588451

  9. Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation

    OpenAIRE

    Sisodiya, S.M.; Thompson, P J; Need, A.; Harris, S.E.; M.E. Weale; Wilkie, S. E.; Michaelides, M.; Free, S.L.; Walley, N; Gumbs, C.; Gerrelli, D.; Ruddle, P.; Whalley, L.J.; Starr, J M; Hunt, D M

    2007-01-01

    Background: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active- zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function.Objective: An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy d...

  10. 一个视锥-视杆营养不良大家系致病基因的初步鉴定%Identification of mutated gene in a large pedigree with cone-rod dystrophy

    Institute of Scientific and Technical Information of China (English)

    陈蕾; 顾蕾; 顾鸣敏; 吴星伟

    2016-01-01

    目的:明确一个常染色体显性遗传眼底病大家系中患者的临床特征,找出该家系的致病基因,并进行基因诊断。方法:受累患者接受问诊及各项眼科检查;对先证者进行覆盖372个眼科遗传病基因的外显子测序芯片突变筛查,并对其中的10个可疑突变位点进行Sanger测序及验证。结果:该家系患者均表现出类似进展型视锥-视杆细胞营养不良(cone-rod dystrophy,CORD)的特征,且起病较早,症状较重。外显子测序分析发现,在患者视锥-视杆同源盒(cone-rod homeobox,CRX)基因的第3个外显子上存在一个错义突变(c.238G>A),导致该基因编码蛋白第80位的谷氨酸变成赖氨酸。结论:本研究首次在黄种人中发现一个CRX[c.238G>A(p.E80K)]基因突变的CORD大家系,同时提示由该基因突变所致CORD患者的临床表现比p.E80A及p.E80Q所致患者更为严重。%Objective To investigate the clinical manifestations of a large Chinese family presenting with autosomal dominant hereditary retinopathy, and to identify the pathogenic gene. Methods Interrogation and ophthalmological examinations were performed in all the affected members. Three hundred and seventy-two exons in ophthalmic disease-associated genes were sequenced with Illumina HiSeq 2000 platform. Ten highly suspected mutation sites were sequenced and verified with Sanger sequencing. Results All affected members presented manifestations of progressive cone-rod dystrophy, with early-onset and serious symptoms. A missense mutation in exon 3 (c.238G>A) of CRX gene was identified, resulting in an amino acid change from glutamic acid to lysine (E80K). Conclusions This is the first report of CRX mutation (p.E80K) pedigree in yellow race, and it revealed that manifestations of patients with mutation in p.E80K were more serious than those with mutation in p.E80A and p.E80Q.

  11. Duchenne muscular dystrophy gene therapy in the canine model.

    Science.gov (United States)

    Duan, Dongsheng

    2015-03-01

    Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same way as human patients do. Further, the size of a mouse is hundredfolds smaller than a boy, making it impossible to scale-up gene therapy in a mouse model. None of these limitations exist in the canine DMD (cDMD) model. For this reason, cDMD dogs have been considered a highly valuable platform to test experimental DMD gene therapy. Over the last three decades, a variety of gene therapy approaches have been evaluated in cDMD dogs using a number of nonviral and viral vectors. These studies have provided critical insight for the development of an effective gene therapy protocol in human patients. This review discusses the history, current status, and future directions of the DMD gene therapy in the canine model. PMID:25710459

  12. Duchenne Muscular Dystrophy Gene Therapy in the Canine Model

    OpenAIRE

    Duan, Dongsheng

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disease caused by dystrophin deficiency. Gene therapy has significantly improved the outcome of dystrophin-deficient mice. Yet, clinical translation has not resulted in the expected benefits in human patients. This translational gap is largely because of the insufficient modeling of DMD in mice. Specifically, mice lacking dystrophin show minimum dystrophic symptoms, and they do not respond to the gene therapy vector in the same wa...

  13. Microdystrophin Ameliorates Muscular Dystrophy in the Canine Model of Duchenne Muscular Dystrophy

    OpenAIRE

    Shin, Jin-Hong; Pan, Xiufang; Hakim, Chady H.; Yang, Hsiao T.; Yue, Yongping; Zhang, Keqing; Ronald L Terjung; Duan, Dongsheng

    2013-01-01

    Dystrophin deficiency results in lethal Duchenne muscular dystrophy (DMD). Substituting missing dystrophin with abbreviated microdystrophin has dramatically alleviated disease in mouse DMD models. Unfortunately, translation of microdystrophin therapy has been unsuccessful in dystrophic dogs, the only large mammalian model. Approximately 70% of the dystrophin-coding sequence is removed in microdystrophin. Intriguingly, loss of ≥50% dystrophin frequently results in severe disease in patients. T...

  14. Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy.

    Science.gov (United States)

    Miskew Nichols, Bailey; Aoki, Yoshitsugu; Kuraoka, Mutsuki; Lee, Joshua J A; Takeda, Shin'ichi; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is one of the most common lethal genetic diseases worldwide, caused by mutations in the dystrophin (DMD) gene. Exon skipping employs short DNA/RNA-like molecules called antisense oligonucleotides (AONs) that restore the reading frame and produce shorter but functional proteins. However, exon skipping therapy faces two major hurdles: limited applicability (up to only 13% of patients can be treated with a single AON drug), and uncertain function of truncated proteins. These issues were addressed with a cocktail AON approach. While approximately 70% of DMD patients can be treated by single exon skipping (all exons combined), one could potentially treat more than 90% of DMD patients if multiple exon skipping using cocktail antisense drugs can be realized. The canine X-linked muscular dystrophy (CXMD) dog model, whose phenotype is more similar to human DMD patients, was used to test the systemic efficacy and safety of multi-exon skipping of exons 6 and 8. The CXMD dog model harbors a splice site mutation in intron 6, leading to a lack of exon 7 in dystrophin mRNA. To restore the reading frame in CXMD requires multi-exon skipping of exons 6 and 8; therefore, CXMD is a good middle-sized animal model for testing the efficacy and safety of multi-exon skipping. In the current study, a cocktail of antisense morpholinos targeting exon 6 and exon 8 was designed and it restored dystrophin expression in body-wide skeletal muscles. Methods for transfection/injection of cocktail oligos and evaluation of the efficacy and safety of multi-exon skipping in the CXMD dog model are presented. PMID:27285612

  15. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    OpenAIRE

    MartinKChilders; DanielJBogan; MelanieHolder; HanselGreiner; RobertGrange

    2012-01-01

    Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD). Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystroph...

  16. Profiles of Steroid Hormones in Canine X-Linked Muscular Dystrophy via Stable Isotope Dilution LC-MS/MS.

    Directory of Open Access Journals (Sweden)

    Helio A Martins-Júnior

    Full Text Available Golden retriever muscular dystrophy (GRMD provides the best animal model for characterizing the disease progress of the human disorder, Duchenne muscular dystrophy (DMD. The purpose of this study was to determine steroid hormone concentration profiles in healthy golden retriever dogs (control group - CtGR versus GRMD-gene carrier (CaGR and affected female dogs (AfCR. Therefore, a sensitive and specific analytical method was developed and validated to determine the estradiol, progesterone, cortisol, and testosterone levels in the canine serum by isotope dilution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. To more accurately understand the dynamic nature of the serum steroid profile, the fluctuating levels of these four steroid hormones over the estrous cycle were compared across the three experimental groups using a multivariate statistical analysis. The concentration profiles of estradiol, cortisol, progesterone, and testosterone revealed a characteristic pattern for each studied group at each specific estrous phase. Additionally, several important changes in the serum concentrations of cortisol and estradiol in the CaGR and AfCR groups seem to be correlated with the status and progression of the muscular dystrophy. A comprehensive and quantitative monitoring of steroid profiles throughout the estrous cycle of normal and GRMD dogs were achieved. Significant differences in these profiles were observed between GRMD and healthy animals, most notably for estradiol. These findings contribute to a better understanding of both dog reproduction and the muscular dystrophy pathology. Our data open new venues for hormonal behavior studies in dystrophinopathies and that may affect the quality of life of DMD patients.

  17. Successful Regional Delivery and Long-term Expression of a Dystrophin Gene in Canine Muscular Dystrophy: A Preclinical Model for Human Therapies

    OpenAIRE

    Wang, Zejing; Storb, Rainer; Halbert, Christine L.; Banks, Glen B.; Butts, Tiffany M.; Finn, Eric E.; Allen, James M.; Miller, A. Dusty; Jeffrey S. Chamberlain; Tapscott, Stephen J.

    2012-01-01

    Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle disease caused by mutations in the dystrophin gene. Adeno-associated viral (AAV) vector-mediated gene replacement strategies hold promise as a treatment. Studies in animal models and human trials suggested that immune responses to AAV capsid proteins and transgene products prevented efficient gene therapy. In this study, we used widespread intramuscular (i.m.) injection to deliver AAV6-canine micro-dystrophin (c-µdys) throughout a ...

  18. Number and topography of cones, rods and optic nerve axons in New and Old World primates.

    Science.gov (United States)

    Finlay, Barbara L; Franco, Edna Cristina S; Yamada, Elizabeth S; Crowley, Justin C; Parsons, Michael; Muniz, José Augusto P C; Silveira, Luiz Carlos L

    2008-01-01

    To better understand the evolution of spatial and color vision, the number and spatial distributions of cones, rods, and optic nerve axon numbers were assessed in seven New World primates (Cebus apella, Saimiri ustius, Saguinus midas niger, Alouatta caraya, Aotus azarae, Calllithrix jacchus, and Callicebus moloch). The spatial distribution and number of rods and cones was determined from counts of retinal whole mounts. Optic axon number was determined from optic nerve sections by electron microscopy. These data were amassed with existing data on retinal cell number and distribution in Old World primates, and the scaling of relative densities and numbers with respect to retinal area, eye and brain sizes, and foveal specializations were evaluated. Regular scaling of all cell types was observed, with the exceptionally large, rod-enriched retina of the nocturnal owl monkey Aotus azarae, and the unusually high cone density of the fovea of the trichromatic howler monkey Alouatta caraya presenting interesting variations on this basic plan. Over all species, the lawful scaling of rods, cones, and retinal ganglion cell number is hypothesized to result from a conserved sequence of cell generation that defends retinal acuity and sensitivity over a large range of eye sizes. PMID:18598400

  19. Clinical characteristics of rod and cone photoreceptor dystrophies in patients with mutations in the C8orf37 gene

    NARCIS (Netherlands)

    Huet, R.A.C. van; Estrada-Cuzcano, A.; Banin, E.; Rotenstreich, Y.; Hipp, S.; Kohl, S.; Hoyng, C.B.; Hollander, A.I. den; Collin, R.W.J.; Klevering, B.J.

    2013-01-01

    PURPOSE: To provide the clinical features in patients with retinal disease caused by C8orf37 gene mutations. METHODS: Eight patients--four diagnosed with retinitis pigmentosa (RP) and four with cone-rod dystrophy (CRD), carrying causal C8orf37 mutations--were clinically evaluated, including extensiv

  20. Molecular genetics of X-linked cone-rod dystrophy and Åland Island eye disease

    OpenAIRE

    Jalkanen, Reetta

    2008-01-01

    Inherited retinal diseases are the most common cause of vision loss among the working population in Western countries. It is estimated that ~1 of the people worldwide suffer from vision loss due to inherited retinal diseases. The severity of these diseases varies from partial vision loss to total blindness, and at the moment no effective cure exists. To date, nearly 200 mapped loci, including 140 cloned genes for inherited retinal diseases have been identified. By a rough estimation 50% of t...

  1. Chronic administration of a leupeptin-derived calpain inhibitor fails to ameliorate severe muscle pathology in a canine model of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Martin K Childers

    2012-01-01

    Full Text Available Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD. Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD. Young (6 week-old GRMD dogs were treated daily with either C101 (17mg/kg twice daily oral dose, n=9 or placebo (vehicle only, n=7 for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every two weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors. C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.

  2. Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry

    Science.gov (United States)

    2016-08-26

    Myotonic Dystrophy; Facioscapulohumeral Muscular Dystrophy; Muscular Dystrophy; Myotonic Dystrophy Type 1; Myotonic Dystrophy Type 2; Congenital Myotonic Dystrophy; PROMM (Proximal Myotonic Myopathy); Steinert's Disease; Myotonic Muscular Dystrophy

  3. Homeobox Genes and Melatonin Synthesis: Regulatory Roles of the Cone-Rod Homeobox Transcription Factor in the Rodent Pineal Gland

    Directory of Open Access Journals (Sweden)

    Kristian Rohde

    2014-01-01

    Full Text Available Nocturnal synthesis of melatonin in the pineal gland is controlled by a circadian rhythm in arylalkylamine N-acetyltransferase (AANAT enzyme activity. In the rodent, Aanat gene expression displays a marked circadian rhythm; release of norepinephrine in the gland at night causes a cAMP-based induction of Aanat transcription. However, additional transcriptional control mechanisms exist. Homeobox genes, which are generally known to encode transcription factors controlling developmental processes, are also expressed in the mature rodent pineal gland. Among these, the cone-rod homeobox (CRX transcription factor is believed to control pineal-specific Aanat expression. Based on recent advances in our understanding of Crx in the rodent pineal gland, we here suggest that homeobox genes play a role in adult pineal physiology both by ensuring pineal-specific Aanat expression and by facilitating cAMP response element-based circadian melatonin production.

  4. Duchenne muscular dystrophy

    Science.gov (United States)

    Pseudohypertrophic muscular dystrophy; Muscular dystrophy - Duchenne type ... Duchenne muscular dystrophy is a form of muscular dystrophy . It worsens quickly. Other muscular dystrophies (including Becker's muscular dystrophy ) ...

  5. Learning about Myotonic Dystrophy

    Science.gov (United States)

    ... How is myotonic dystrophy diagnosed? What is the treatment for myotonic dystrophy? Is myotonic dystrophy inherited? NHGRI Clinical Research on Myotonic Dystrophy Additional Resources on Myotonic Muscular Dystrophy What is myotonic dystrophy? Myotonic dystrophy is ...

  6. Hypothalamic neurosecretory and circadian vasopressinergic neuronal systems in the blind cone-rod homeobox knock out mouse (Crx(-/-) ) and the 129sv wild type mouse

    DEFF Research Database (Denmark)

    Rovsing, Louise; Rath, Martin Fredensborg; Møller, Morten

    2013-01-01

    circadian AVP-rhythm. We have in this study of the brown 129sv mouse and the visual blind cone-rod homeobox gene knock out mouse (Crx(-/-) ) with degeneration of the retinal rods and cones, but a preserved non-image forming optic system, studied the temporal Avp-expression in both the neurosecretory...... at late day time and nadir during the dark in both the Crx(-/-) and the wild type mouse. None of the magnocellular neurosecretory neurons exhibited a diurnal vasopressin expression. Light stimulation of both genotypes during the dark period did not change the Avp-expression in the SCN. This shows that Avp......-expression in the mouse SCN is independent of Crx-regulated photoreceptor systems. J. Comp. Neurol., 2013. © 2013 Wiley Periodicals, Inc....

  7. Muscular dystrophy

    Science.gov (United States)

    ... CPK level Genetic testing for some forms of muscular dystrophy Treatment There are no known cures for the various muscular dystrophies. The goal of treatment is to control symptoms. Physical therapy may help ...

  8. Muscular Dystrophy

    Science.gov (United States)

    ... 1 (DM1) . The International Myotonic Dystrophy Consortium (IDMC). Neurology. Mar 28 2000;54(6):1218-1221. 5. ... Udd B. Distal muscular dystrophies. Handbook of clinical neurology. 2011;101:239-262. 4. Nonaka I. Distal ...

  9. Becker muscular dystrophy

    Science.gov (United States)

    ... other family members have been diagnosed with Becker muscular dystrophy Prevention Genetic counseling may be advised if there is a family history of Becker muscular dystrophy. Alternative Names Benign pseudohypertrophic muscular dystrophy; Becker's dystrophy ...

  10. Facioscapulohumeral Dystrophy.

    Science.gov (United States)

    Wang, Leo H; Tawil, Rabi

    2016-07-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a clinically recognizable and relatively common muscular dystrophy. It is inherited mostly as an autosomal dominant disease or in a minority of cases, in a digenic pattern. The disease manifestation is variable and most likely dependent on genetic and epigenetic factors. We review the history, epidemiology, clinical presentation, and genetics of the disease, present the recently elucidated molecular pathogenesis, discuss the pathology and the possible consequence of the inflammation seen in the muscle biopsies, and consider future treatments. PMID:27215221

  11. Muscular Dystrophy

    Science.gov (United States)

    Muscular dystrophy (MD) is a group of more than 30 inherited diseases. They all cause muscle weakness and muscle loss. Some forms of MD appear in infancy ... types can vary in whom they affect, which muscles they affect, and what the symptoms are. All ...

  12. Muscular dystrophy - resources

    Science.gov (United States)

    Resources - muscular dystrophy ... The following organizations are good resources for information on muscular dystrophy : Muscular Dystrophy Association -- www.mdausa.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih. ...

  13. Myotonic Muscular Dystrophy

    Science.gov (United States)

    ... a Difference How to Get Involved Donate Myotonic Muscular Dystrophy (MMD) Share print email share facebook twitter google plus linkedin Myotonic Muscular Dystrophy (MMD) What is myotonic muscular dystrophy (MMD)? Myotonic ...

  14. Canine Distemper

    Science.gov (United States)

    Although this brochure provides basic information about canine distemper, your veterinarian is always your best source of ... Consult your veterinarian for more information about canine distemper and its prevention. And Now A Note On ...

  15. Muscular Dystrophy (MD)

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Muscular Dystrophy Information Page Clinical Trials Finding the Optimum Regimen ... en Español Additional resources from MedlinePlus What is Muscular Dystrophy? The muscular dystrophies (MD) are a group of ...

  16. FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY

    OpenAIRE

    van der Maarel, Silvère M.; Frants, Rune R; Padberg, George W.

    2008-01-01

    Facioscapulohumeral muscular dystrophy (FSHD), a dominantly inherited disorder, is the third most common dystrophy after Duchenne and myotonic muscular dystrophy. No known effective treatments exist for FSHD. The lack of an understanding of the underlying pathophysiology remains an obstacle in the development of targeted therapeutic interventions. The genetic defect is a loss of a critical number of a repetitive element (D4Z4) in the 4q subtelomeric region. The loss of the repeats results in ...

  17. Evaluation of Limb-Girdle Muscular Dystrophy

    Science.gov (United States)

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  18. Ullrich Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Goknur Haliloglu

    2011-09-01

    Full Text Available ObjectiveUllrich congenital muscular dystrophy is a rather severe type of congenitalmuscular dystrophy with early onset features related to motor development.In general it is inherited in autosomal recessive principles, however in theWestern world mostly seen with de novo dominant mutations in the collagenVI genes. Milder form of the condition is the Bethlem myopathy. There may beoverlap forms in the clinic resembling the Ehler-Danlos syndrome. There hasbeen some radical efforts for cure especially through the apoptosis cascades.Key words: Ullrich congenital muscular dystrophy, collgen VI genes, Bethlemmyopathy, autophagy.

  19. X-linked cone dystrophy caused by mutation of the red and green cone opsins.

    Science.gov (United States)

    Gardner, Jessica C; Webb, Tom R; Kanuga, Naheed; Robson, Anthony G; Holder, Graham E; Stockman, Andrew; Ripamonti, Caterina; Ebenezer, Neil D; Ogun, Olufunmilola; Devery, Sophie; Wright, Genevieve A; Maher, Eamonn R; Cheetham, Michael E; Moore, Anthony T; Michaelides, Michel; Hardcastle, Alison J

    2010-07-01

    X-linked cone and cone-rod dystrophies (XLCOD and XLCORD) are a heterogeneous group of progressive disorders that solely or primarily affect cone photoreceptors. Mutations in exon ORF15 of the RPGR gene are the most common underlying cause. In a previous study, we excluded RPGR exon ORF15 in some families with XLCOD. Here, we report genetic mapping of XLCOD to Xq26.1-qter. A significant LOD score was detected with marker DXS8045 (Z(max) = 2.41 [theta = 0.0]). The disease locus encompasses the cone opsin gene array on Xq28. Analysis of the array revealed a missense mutation (c. 529T>C [p. W177R]) in exon 3 of both the long-wavelength-sensitive (LW, red) and medium-wavelength-sensitive (MW, green) cone opsin genes that segregated with disease. Both exon 3 sequences were identical and were derived from the MW gene as a result of gene conversion. The amino acid W177 is highly conserved in visual and nonvisual opsins across species. We show that W177R in MW opsin and the equivalent W161R mutation in rod opsin result in protein misfolding and retention in the endoplasmic reticulum. We also demonstrate that W177R misfolding, unlike the P23H mutation in rod opsin that causes retinitis pigmentosa, is not rescued by treatment with the pharmacological chaperone 9-cis-retinal. Mutations in the LW/MW cone opsin gene array can, therefore, lead to a spectrum of disease, ranging from color blindness to progressive cone dystrophy (XLCOD5). PMID:20579627

  20. Facioscapulohumeral muscular dystrophy

    Science.gov (United States)

    ... of cases, the parents do not carry the gene. Facioscapulohumeral muscular dystrophy affects about 5 out of 100,000 people. ... Treatment There is no ... worse. Physical therapy may help maintain muscle strength. Other possible treatments ...

  1. Muscular Dystrophy Association

    Science.gov (United States)

    ... Families Live Unlimited Read More Deflazacort demonstrates significant muscle strength improvement in DMD Read More NDA Filing ... the Boot to Support Kids and Adults with Muscular Dystrophy, ALS and Related Diseases Read More Visit ...

  2. Facioscapulohumeral Muscular Dystrophy

    OpenAIRE

    Statland, Jeffrey M; Tawil, Rabi

    2014-01-01

    Facioscapulohumeral muscular dystrophy (FSHSD) is one of the most common adult muscular dystrophies and is divided into types 1 and 2 based on genetic mutation. Clinically both FSHD types 1 and 2 demonstrate often asymmetric and progressive muscle weakness affecting initially the face, shoulder, and arms, followed by the distal and then proximal lower extremities later in the disease course. Approximately 95% of patients, termed FSHD1, have a deletion of a key number of repetitive elements on...

  3. Duchenne muscular dystrophy

    OpenAIRE

    Yiu Eppie; Kornberg Andrew

    2008-01-01

    Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most common muscular dystrophy in children, presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys. Patients usually become wheelchair-bound by the age of 12 years, and die of cardiorespiratory complications in their late teens to early twenties. Advances in the management of DMD, including treatment with corticosteroids and the use of intermittent positive pressure venti...

  4. How Is Muscular Dystrophy Diagnosed?

    Science.gov (United States)

    ... Information Clinical Trials Resources and Publications How is muscular dystrophy diagnosed? Skip sharing on social media links Share this: Page Content The first step in diagnosing muscular dystrophy (MD) is a visit with a health care ...

  5. Ullrich Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Goknur Haliloglu

    2011-06-01

    Full Text Available ObjectiveUllrich congenital muscular dystrophy is a rather severe type of congenital muscular dystrophy with early onset features related to motor development.In general it is inherited in autosomal recessive principles, however in the Western world mostly seen with de novo dominant mutations in the collagen VI genes. Milder form of the condition is the Bethlem myopathy. There may be overlap forms in the clinic resembling the Ehler-Danlos syndrome. There has been some radical efforts for cure especially through the apoptosis cascades.

  6. Generation of muscular dystrophy model rats with a CRISPR/Cas system

    OpenAIRE

    Katsuyuki Nakamura; Wataru Fujii; Masaya Tsuboi; Jun Tanihata; Naomi Teramoto; Shiho Takeuchi; Kunihiko Naito; Keitaro Yamanouchi; Masugi Nishihara

    2014-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin1 2. DMD model animals, such as mdx mice and canine X-linked muscular dystrophy dogs, have been widely utilized in the development of a treatment for DMD3. Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats. We simul...

  7. Central areolar choroidal dystrophy.

    NARCIS (Netherlands)

    Boon, C.J.F.; Klevering, B.J.; Cremers, F.P.M.; Zonneveld-Vrieling, M.N.; Theelen, T.; Hollander, A.I. den; Hoyng, C.B.

    2009-01-01

    OBJECTIVE: To describe the clinical characteristics, follow-up data and molecular genetic background in a large group of patients with central areolar choroidal dystrophy (CACD). DESIGN: Retrospective case series study. PARTICIPANTS: One hundred three patients with CACD from the Netherlands. METHODS

  8. Successful Gene Therapy in the RPGRIP1-deficient Dog: a Large Model of Cone–Rod Dystrophy

    Science.gov (United States)

    Lhériteau, Elsa; Petit, Lolita; Weber, Michel; Le Meur, Guylène; Deschamps, Jack-Yves; Libeau, Lyse; Mendes-Madeira, Alexandra; Guihal, Caroline; François, Achille; Guyon, Richard; Provost, Nathalie; Lemoine, Françoise; Papal, Samantha; El-Amraoui, Aziz; Colle, Marie-Anne; Moullier, Philippe; Rolling, Fabienne

    2014-01-01

    For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. For inherited retinal dystrophies primarily involving photoreceptor cells, the efficacy of gene therapy has been demonstrated in canine models of stationary cone dystrophies and progressive rod–cone dystrophies but not in large models of progressive cone–rod dystrophies, another important cause of blindness. To address the last issue, we evaluated gene therapy in the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model exhibiting a severe cone–rod dystrophy similar to that seen in humans. Subretinal injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved photoreceptor survival in transduced areas of treated retinas. Cone function was significantly and stably rescued in all treated eyes (18–72% of those recorded in normal eyes) up to 24 months postinjection. Rod function was also preserved (22–29% of baseline function) in four of the five treated dogs up to 24 months postinjection. No detectable rod function remained in untreated contralateral eyes. More importantly, treatment preserved bright- and dim-light vision. Efficacy of gene therapy in this large animal model of cone–rod dystrophy provides great promise for human treatment. PMID:24091916

  9. Genetics Home Reference: Fukuyama congenital muscular dystrophy

    Science.gov (United States)

    ... Health Conditions Fukuyama congenital muscular dystrophy Fukuyama congenital muscular dystrophy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Fukuyama congenital muscular dystrophy is an inherited condition that predominantly affects the ...

  10. Genetics Home Reference: tibial muscular dystrophy

    Science.gov (United States)

    ... Names for This Condition tardive tibial muscular dystrophy TMD Udd distal myopathy Udd-Markesbery muscular dystrophy Udd ... titin may cause more severe tibial muscular dystrophy (TMD). Neuromuscul Disord. 2008 Dec;18(12):922-8. ...

  11. Therapeutic approaches to muscular dystrophy

    OpenAIRE

    Goyenvalle, Aurélie; Seto, Jane T.; Davies, Kay E.; Chamberlain, Jeffrey

    2011-01-01

    Muscular dystrophies are a heterogeneous group of genetic disorders characterized by muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, and although the molecular mechanisms of the disease have been extensively investigated since the discovery of the gene in 1986, there is currently no effective treatment. However, new gene-based therapies have recently emerged with particular noted advances in using conventional gene repla...

  12. Therapeutic advances in muscular dystrophy

    OpenAIRE

    Leung, Doris G.; Wagner, Kathryn R.

    2013-01-01

    The muscular dystrophies comprise a heterogeneous group of genetic disorders that produce progressive skeletal muscle weakness and wasting. There has been rapid growth and change in our understanding of these disorders in recent years, and advances in basic science are being translated into increasing numbers of clinical trials. This review will discuss therapeutic developments in 3 of the most common forms of muscular dystrophy: Duchenne muscular dystrophy, facioscapulohumeral muscular dystr...

  13. Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Yiu Eppie

    2008-01-01

    Full Text Available Duchenne muscular dystrophy (DMD, an X-linked disorder, is the most common muscular dystrophy in children, presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys. Patients usually become wheelchair-bound by the age of 12 years, and die of cardiorespiratory complications in their late teens to early twenties. Advances in the management of DMD, including treatment with corticosteroids and the use of intermittent positive pressure ventilation have provided improvements in function, ambulation, quality of life and life expectancy, although novel therapies still aim to provide a cure for this devastating disorder. The clinical features, investigations, and management of DMD are reviewed, as well as the latest in some of the novel therapies.

  14. A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy

    OpenAIRE

    Steffen, Frank; Bilzer, Thomas; Brands, Jan; Golini, Lorenzo; Jagannathan, Vidhya; Wiedmer, Michaela; Drögemüller, Michaela; Drögemüller, Cord; Leeb, Tosso

    2015-01-01

    A novel canine muscular dystrophy in Landseer dogs was observed. We had access to five affected dogs from two litters. The clinical signs started at a few weeks of age, and the severe progressive muscle weakness led to euthanasia between 5 and 15 months of age. The pedigrees of the affected dogs suggested a monogenic autosomal-recessive inheritance of the trait. Linkage and homozygosity mapping indicated two potential genome segments for the causative variant on chromosomes 10 and 31 harborin...

  15. A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy.

    OpenAIRE

    Steffen, Frank; Bilzer, Thomas; Brands, Jan; Golini, Lorenzo; Jagannathan, Vidhya; Wiedmer, Michaela; Drögemüller, Michaela; Drögemüller, Cord; Leeb, Tosso

    2015-01-01

    A novel canine muscular dystrophy in Landseer dogs was observed. We had access to five affected dogs from two litters. The clinical signs started at a few weeks of age and the severe progressive muscle weakness led to euthanasia between 5 and 15 months of age. The pedigrees of the affected dogs suggested a monogenic autosomal recessive inheritance of the trait. Linkage and homozygosity mapping indicated two potential genome segments for the causative variant on chromosomes 10 and 31 harboring...

  16. Halofuginone and muscular dystrophy

    OpenAIRE

    Pines, Mark; Halevy, Orna

    2011-01-01

    Muscular dystrophies (MDs) include different inherited diseases that all result in progressive muscle degeneration, impaired locomotion and often premature death. The major focus of MD research has been on alleviating the primary genetic deficit - using gene therapy and myoblast-transfer approaches to promote expression of the deficient or mutated genes in the muscle fibers. Although promising, these approaches have not yet entered into clinical practice and unfortu...

  17. Disease: H01015 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available mental disorder CNNM4 [HSA:26504] [KO:K16302] Cone-rod dystrophy and amelogenesis...consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet 84:266-73 (...2009) PMID:20706282 (descritpion) Jalili IK Cone-rod dystrophy and amelogenesis i...ogenesis imperfecta. It is caused mutations in the CNNM4 gene that encodes a putati...H01015 Jalili syndrome Jalili syndrome is a combination of recessively inherited cone-rod dystrophy and amel

  18. Limb-girdle muscular dystrophies

    Science.gov (United States)

    ... it may involve other muscles. Causes Limb-girdle muscular dystrophies are a large group of genetic diseases in which there is muscle weakness and ... or a family member has been diagnosed with muscular dystrophy and you are planning a pregnancy. ... Genetic counseling may help some couples and families learn ...

  19. Orocaecal transit time in Duchenne muscular dystrophy.

    OpenAIRE

    Korman, S H; Bar-Oz, B.; E. Granot; Meyer, S

    1991-01-01

    Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.

  20. Muscle diseases: the muscular dystrophies.

    Science.gov (United States)

    McNally, Elizabeth M; Pytel, Peter

    2007-01-01

    Dystrophic muscle disease can occur at any age. Early- or childhood-onset muscular dystrophies may be associated with profound loss of muscle function, affecting ambulation, posture, and cardiac and respiratory function. Late-onset muscular dystrophies or myopathies may be mild and associated with slight weakness and an inability to increase muscle mass. The phenotype of muscular dystrophy is an endpoint that arises from a diverse set of genetic pathways. Genes associated with muscular dystrophies encode proteins of the plasma membrane and extracellular matrix, and the sarcomere and Z band, as well as nuclear membrane components. Because muscle has such distinctive structural and regenerative properties, many of the genes implicated in these disorders target pathways unique to muscle or more highly expressed in muscle. This chapter reviews the basic structural properties of muscle and genetic mechanisms that lead to myopathy and muscular dystrophies that affect all age groups.

  1. Duchenne muscular dystrophy gene therapy: Lost in translation?

    Directory of Open Access Journals (Sweden)

    Dongsheng Duan

    2011-03-01

    Full Text Available Dongsheng DuanDepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USAAbstract: A milestone of molecular medicine is the identification of dystrophin gene mutation as the cause of Duchenne muscular dystrophy (DMD. Over the last 2 decades, major advances in dystrophin biology and gene delivery technology have created an opportunity to treat DMD with gene therapy. Remarkable success has been achieved in treating dystrophic mice. Several gene therapy strategies, including plasmid transfer, exon skipping, and adeno-associated virus-mediated microdystrophin therapy, have entered clinical trials. However, therapeutic benefit has not been realized in DMD patients. Bridging the gap between mice and humans is no doubt the most pressing issue facing DMD gene therapy now. In contrast to mice, dystrophin-deficient dogs are genetically and phenotypically similar to human patients. Preliminary gene therapy studies in the canine model may offer critical insights that cannot be obtained from murine studies. It is clear that the canine DMD model may represent an important link between mice and humans. Unfortunately, our current knowledge of dystrophic dogs is limited, and the full picture of disease progression remains to be clearly defined. We also lack rigorous outcome measures (such as in situ force measurement to monitor therapeutic efficacy in dystrophic dogs. Undoubtedly, maintaining a dystrophic dog colony is technically demanding, and the cost of dog studies cannot be underestimated. A carefully coordinated effort from the entire DMD community is needed to make the best use of the precious dog resource. Successful DMD gene therapy may depend on valid translational studies in dystrophin-deficient dogs.Keywords: Duchenne muscular dystrophy, gene therapy, dystrophin, adeno-associated virus, exon-skipping, canine model

  2. Reflex Sympathetic Dystrophy in Children

    OpenAIRE

    Adnan Ayvaz

    2013-01-01

       Reflex sympathetic dystrophy (chronic regional pain syndrome) isn’t frequently encountered in practical pediatrics and childhood. Reflex sympathetic dystrophy syndrome (RSD) is a disorder characterized by widespread localized pain, often along with swelling, discoloration, trophic changes and autonomic abnormalities such as vasomotor disorders. Its etio-pathogenesis hasn’t been completely determined.The disease can form in an area innerved by a partially damaged nerve...

  3. Modifying muscular dystrophy through TGFβ

    OpenAIRE

    Ceco, Ermelinda; McNally, Elizabeth M.

    2013-01-01

    Muscular dystrophy arises from ongoing muscle degeneration and insufficient regeneration. This imbalance leads to loss of muscle with replacement by scar or fibrosis resulting in muscle weakness and, eventually, loss of muscle function. Human muscular dystrophy is characterized by a wide range of disease severity, even when the same genetic mutation is present. This variability implies that other factors, both genetic and environmental, modify the disease outcome. There has been an ongoing ef...

  4. Adult foveomacular vitelliform dystrophy

    Directory of Open Access Journals (Sweden)

    Valdir Balarin

    2013-06-01

    Full Text Available Adult foveomacular vitelliform dystrophy is a rare pathology. Less than 1% of the reported cases display perifoveal capillary permeability. The three-year follow-up period of the case revealed a rare form, which had not yet been documented. The patient was a 40-year-old female with normal visual acuity, and a minor complaint of metamorphopsia on the left eye. Retinography showed a perifoveal yellowish subretinal area OS.Angiography showed perifoveal leakage OS. Follow up showed that, over 3 years, capillary incompetence disappeared and the yellow area underwent alterations, becoming atrophic OS. Angiography also showed hyperfluorescence (windows defect. Towards the end, it resembled the appearance of late stage of Best's Disease.

  5. Duchenne muscular dystrophy carriers

    International Nuclear Information System (INIS)

    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.)

  6. What Are the Types of Muscular Dystrophy?

    Science.gov (United States)

    ... Resources and Publications What are the types of muscular dystrophy? Skip sharing on social media links Share this: ... Content There are more than 30 forms of muscular dystrophy (MD), with information on the primary types included ...

  7. How Do People Cope with Muscular Dystrophy?

    Science.gov (United States)

    ... NICHD Research Information Clinical Trials Resources and Publications Muscular Dystrophy: Other FAQs Skip sharing on social media links ... in this section. How do people cope with muscular dystrophy (MD)? Although MD presents many challenges in many ...

  8. Treatment of facioscapulohumeral muscular dystrophy with Denosumab

    OpenAIRE

    Lefkowitz, Stanley S; Doris L. Lefkowitz; Kethley, Jeremy

    2012-01-01

    Summary Background: Facioscapulohumeral muscular dystrophy (FSHD) is the 3rd most common form of muscular dystrophy. Effective treatments for any of the muscular dystrophies have yet to be realized. This report describes such a treatment. Case Report: A 66 year old female was diagnosed with osteoporosis. She had been diagnosed with FSHD muscular dystrophy a number of years previously by both genetic and clinical studies. Following a 2 year course with Forteo for osteoporosis, she was given an...

  9. [Reflex sympathetic dystrophy].

    Science.gov (United States)

    Oliveira, Marta; Manuela, Manuela; Cantinho, Guilhermina

    2011-01-01

    Reflex Sympathetic Dystrophy is rare in pediatrics. It is a complex regional pain syndrome, of unknown etiology, usually post-traumatic, characterized by dysfunctions of the musculoskeletal, vascular and skin systems: severe persistent pain of a limb, sensory and vascular alterations, associated disability and psychosocial dysfunction. The diagnosis is based in high clinical suspection. In children and adolescents there are aspects that are different from the adult ones. Excessive tests may result in worsening of the clinical symptoms. Bone scintigraphy can help. Pain treatment is difficult, not specific. Physical therapies and relaxation technics give some relief. Depression must be treated. This syndrome includes fibromyalgia and complex regional pain syndrome type I. We present a clinical report of an adolescent girl, referred for pain, cold temperature, pallor and functional disability of an inferior limb, all signals disclosed by a minor trauma. She had been diagnosed depression the year before. The bone scintigraphy was a decisive test. The treatment with gabapentin, C vitamin, physiotherapy and pshycotherapy has been effective. PMID:22713207

  10. Genetics of corneal endothelial dystrophies

    Indian Academy of Sciences (India)

    Chitra Kannabiran

    2009-12-01

    The corneal endothelium maintains the level of hydration in the cornea. Dysfunction of the endothelium results in excess accumulation of water in the corneal stroma, leading to swelling of the stroma and loss of transparency. There are four different corneal endothelial dystrophies that are hereditary, progressive, non-inflammatory disorders involving dysfunction of the corneal endothelium. Each of the endothelial dystrophies is genetically heterogeneous with different modes of transmission and/or different genes involved in each subtype. Genes responsible for disease have been identified for only a subset of corneal endothelial dystrophies. Knowledge of genes involved and their function in the corneal endothelium can aid understanding the pathogenesis of the disorder as well as reveal pathways that are important for normal functioning of the endothelium.

  11. CT findings of muscular dystrophy

    International Nuclear Information System (INIS)

    CT scans of muscles in patients with limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD) dystrophies were obtained at five different body levels: the neck, L3 vertebral body, pelvic girdle, thigh and lower leg. CT numbers, cross sectional areas (CSA) and %CSA of muscle or fat were evaluated in each muscle. The characteristic CT patterns for each type of muscular dystrophy were obtained. Compared with DMD, the gracilis and soleus were more severely damaged in LG and the biceps femoris remained relatively preserved among the hamstrings. In addition, the multifidus of the neck and sternocleidomastoid also were more severely damaged in MYD. This study suggests that CT scan will be useful in the differential diagnosis of these types of muscular dystrophy as well as in planning appropriate rehabilitation and detecting damaged muscles. (author)

  12. Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

    2016-05-01

    Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. PMID:26963343

  13. Identification of muscle-specific microRNAs in serum of muscular dystrophy animal models: promising novel blood-based markers for muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Hideya Mizuno

    Full Text Available Duchenne muscular dystrophy (DMD is a lethal X-linked disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin. Creatine kinase (CK is generally used as a blood-based biomarker for muscular disease including DMD, but it is not always reliable since it is easily affected by stress to the body, such as exercise. Therefore, more reliable biomarkers of muscular dystrophy have long been desired. MicroRNAs (miRNAs are small, ∼22 nucleotide, noncoding RNAs which play important roles in the regulation of gene expression at the post-transcriptional level. Recently, it has been reported that miRNAs exist in blood. In this study, we hypothesized that the expression levels of specific serum circulating miRNAs may be useful to monitor the pathological progression of muscular diseases, and therefore explored the possibility of these miRNAs as new biomarkers for muscular diseases. To confirm this hypothesis, we quantified the expression levels of miRNAs in serum of the dystrophin-deficient muscular dystrophy mouse model, mdx, and the canine X-linked muscular dystrophy in Japan dog model (CXMD(J, by real-time PCR. We found that the serum levels of several muscle-specific miRNAs (miR-1, miR-133a and miR-206 are increased in both mdx and CXMD(J. Interestingly, unlike CK levels, expression levels of these miRNAs in mdx serum are little influenced by exercise using treadmill. These results suggest that serum miRNAs are useful and reliable biomarkers for muscular dystrophy.

  14. Dystrophin Gene Replacement and Gene Repair Therapy for Duchenne Muscular Dystrophy in 2016: An Interview.

    Science.gov (United States)

    Duan, Dongsheng

    2016-03-01

    After years of relentless efforts, gene therapy has now begun to deliver its therapeutic promise in several diseases. A number of gene therapy products have received regulatory approval in Europe and Asia. Duchenne muscular dystrophy (DMD) is an X-linked inherited lethal muscle disease. It is caused by mutations in the dystrophin gene. Replacing and/or repairing the mutated dystrophin gene holds great promises to treated DMD at the genetic level. Last several years have evidenced significant developments in preclinical experimentations in murine and canine models of DMD. There has been a strong interest in moving these promising findings to clinical trials. In light of rapid progress in this field, the Parent Project Muscular Dystrophy (PPMD) recently interviewed me on the current status of DMD gene therapy and readiness for clinical trials. Here I summarized the interview with PPMD. PMID:27003751

  15. Benign concentric annular macular dystrophy

    Directory of Open Access Journals (Sweden)

    Luísa Salles de Moura Mendonça

    2015-06-01

    Full Text Available The purpose of the authors is to show clinical findings of a patient with benign concentric annular macular dystrophy, which is an unusual condition, and part of the "bull’s eye" maculopathy differential diagnosis. An ophthalmologic examination with color perception, fluorescein angiography, and ocular electrophysiology was performed.

  16. Prednisone Therapy for Duchenne Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available The effects of prednisone on muscle function and the extent of steroid-related adverse effects were studied in 17 ambulant children with Duchenne muscular dystrophy (DMD at University Hospital, Groningen; Rehabilitation Centre, Utrecht; and Leiden University Medical Centre, the Netherlands.

  17. Glucocorticoids for Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-07-01

    Full Text Available Investigators at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, and other centers in the UK, conducted a prospective longitudinal study across 17 neuromuscular centers in the UK of 360 boys aged 3-15 years with Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off prednisolone for a mean duration of 4 years.

  18. Wasting Mechanisms in Muscular Dystrophy

    OpenAIRE

    Shin, Jonghyun; Tajrishi, Marjan M; Ogura, Yuji; Kumar, Ashok

    2013-01-01

    Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ...

  19. Porcine models of muscular dystrophy

    Science.gov (United States)

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

  20. Muscular Dystrophy: Data and Statistics

    Science.gov (United States)

    ... duration and time to loss of ambulation. J Child Neurol. 2015 Sept;30(10):1275-80. Fox DJ, Kumar A, West N, DiRienzo AG, James KA, Oleszek J; Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STAR net ). Trends with corticosteroid use in males with ...

  1. Mammalian Models of Duchenne Muscular Dystrophy: Pathological Characteristics and Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    Akinori Nakamura

    2011-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is a devastating X-linked muscle disorder characterized by muscle wasting which is caused by mutations in the DMD gene. The DMD gene encodes the sarcolemmal protein dystrophin, and loss of dystrophin causes muscle degeneration and necrosis. Thus far, therapies for this disorder are unavailable. However, various therapeutic trials based on gene therapy, exon skipping, cell therapy, read through therapy, or pharmaceutical agents have been conducted extensively. In the development of therapy as well as elucidation of pathogenesis in DMD, appropriate animal models are needed. Various animal models of DMD have been identified, and mammalian (murine, canine, and feline models are indispensable for the examination of the mechanisms of pathogenesis and the development of therapies. Here, we review the pathological features of DMD and therapeutic applications, especially of exon skipping using antisense oligonucleotides and gene therapies using viral vectors in murine and canine models of DMD.

  2. Genetics Home Reference: Emery-Dreifuss muscular dystrophy

    Science.gov (United States)

    ... Health Conditions Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Emery-Dreifuss muscular dystrophy is a condition that chiefly affects muscles used ...

  3. Genetics Home Reference: limb-girdle muscular dystrophy

    Science.gov (United States)

    ... Health Conditions limb-girdle muscular dystrophy limb-girdle muscular dystrophy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description Limb-girdle muscular dystrophy is a term for a group of diseases ...

  4. Genetics Home Reference: LAMA2-related muscular dystrophy

    Science.gov (United States)

    ... Health Conditions LAMA2-related muscular dystrophy LAMA2-related muscular dystrophy Enable Javascript to view the expand/collapse boxes. ... All Open All Close All Description LAMA2 -related muscular dystrophy is a disorder that causes weakness and wasting ( ...

  5. Genetics Home Reference: Duchenne and Becker muscular dystrophy

    Science.gov (United States)

    ... Duchenne and Becker muscular dystrophy Duchenne and Becker muscular dystrophy Enable Javascript to view the expand/collapse boxes. Print All Open All Close All Description Muscular dystrophies are a group of genetic conditions characterized by ...

  6. Congenital muscular dystrophy with characteristic radiological findings similar to those with Fukuyama congenital muscular dystrophy

    OpenAIRE

    Garg Ajay; Gulati Sheffali; Gupta Vipul; Kalra Veena

    2004-01-01

    Fukuyama congenital muscular dystrophy (FCMD) is the most common congenital muscular dystrophy in Japan and there are isolated reports of non-Japanese patients with FCMD. We report an Indian patient with congenital muscular dystrophy and characteristic radiological findings similar to those with FCMD.

  7. Zebrafish orthologs of human muscular dystrophy genes

    OpenAIRE

    Zon Leonard I; Zhou Yi; Pusack Timothy J; Beltre Rosanna; Vogel Emily D; Guyon Jeffrey R; Steffen Leta S; Kunkel Louis M

    2007-01-01

    Abstract Background Human muscular dystrophies are a heterogeneous group of genetic disorders which cause decreased muscle strength and often result in premature death. There is no known cure for muscular dystrophy, nor have all causative genes been identified. Recent work in the small vertebrate zebrafish Danio rerio suggests that mutation or misregulation of zebrafish dystrophy orthologs can also cause muscular degeneration phenotypes in fish. To aid in the identification of new causative g...

  8. Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS.

    OpenAIRE

    Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc

    2012-01-01

    Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscula...

  9. Arrhythmias in the Muscular Dystrophies

    OpenAIRE

    Rajdev, Archana; William J Groh

    2015-01-01

    In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occur with variable prevalence mirroring the phenotypic variability seen among and within the various hereditary myopathies. These patients are at risk for development for bradyarrhythmias and tachyarrhythmias including sudden cardiac death. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate man...

  10. Dysautonomia, fibromyalgia and reflex dystrophy

    OpenAIRE

    Eisinger, Jean

    2007-01-01

    Autonomic nervous system dysfunction observed in fibromyalgia, characterized without exception by a sympathetic hyperactivity and hyporeactivity, has been reported. However, several studies demonstrated reduced levels of norepinephrine and neuropeptide Y at rest and after tilt table in some patients, which was improved by beta-stimulating agents. These findings support heterogeneity in fibromyalgia-associated dysautonomia. Fibromyalgia could be a generalized sympathetic dystrophy since both c...

  11. Vaccines for Canine Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Faeze Foroughi-Parvar

    2014-01-01

    Full Text Available Leishmania infantum is the obligatory intracellular parasite of mammalian macrophages and causes zoonotic visceral leishmaniasis (ZVL. The presence of infected dogs as the main reservoir host of ZVL is regarded as the most important potential risk for human infection. Thus the prevention of canine visceral leishmaniasis (CVL is essential to stop the current increase of the Mediterranean visceral leishmaniasis. Recently considerable advances in achieving protective immunization of dogs and several important attempts for achieving an effective vaccine against CVL lead to attracting the scientists trust in its important role for eradication of ZVL. This paper highlights the recent advances in vaccination against canine visceral leishmaniasis from 2007 until now.

  12. Becker muscular dystrophy: an unusual presentation.

    OpenAIRE

    Bush, A; Dubowitz, V

    1993-01-01

    A 15 year old boy who presented with passing painless dark urine was found to have myoglobinuria. His creatine phosphokinase was raised, and a muscle biopsy specimen showed non-specific dystrophic changes. Subsequent DNA analysis led to the diagnosis of Becker muscular dystrophy. Myoglobinuria may be a presenting symptom of Becker muscular dystrophy.

  13. Occurrence of Duchenne dystrophy in Klinefelter's syndrome.

    OpenAIRE

    Ramesh, V.; Mountford, R; Kingston, H. M.; Kelsey, A; Noronha, M. J.; Clarke, M A

    1993-01-01

    A boy with Duchenne muscular dystrophy and facial dysmorphism in conjunction with Klinefelter's genotype 47XXY is presented; this is an unusual situation with two genetic errors evolving over two generations. Karyotyping should be considered in boys with Duchenne muscular dystrophy who have unusual features.

  14. Prevalence of generalized retinal dystrophy in Denmark

    DEFF Research Database (Denmark)

    Bertelsen, Mette; Jensen, Hanne; Bregnhøj, Jesper F;

    2014-01-01

    PURPOSE: Generalized retinal dystrophy is a frequent cause of visual impairment and blindness in younger individuals and a subject of new clinical intervention trials. Nonetheless, there are few nation-wide population-based epidemiological data of generalized retinal dystrophy. The purpose of thi...

  15. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Eder Zucconi

    2011-01-01

    Full Text Available Umbilical cord mesenchymal stromal cells (MSC have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs, independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1 human umbilical cord tissue (hUCT MSCs into the caudal vein of SJL mice; (2 hUCT and canine umbilical cord vein (cUCV MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies.

  16. Preclinical Studies with Umbilical Cord Mesenchymal Stromal Cells in Different Animal Models for Muscular Dystrophy

    Science.gov (United States)

    Zucconi, Eder; Vieira, Natassia Moreira; Bueno, Carlos Roberto; Secco, Mariane; Jazedje, Tatiana; Costa Valadares, Marcos; Fussae Suzuki, Miriam; Bartolini, Paolo; Vainzof, Mariz; Zatz, Mayana

    2011-01-01

    Umbilical cord mesenchymal stromal cells (MSC) have been widely investigated for cell-based therapy studies as an alternative source to bone marrow transplantation. Umbilical cord tissue is a rich source of MSCs with potential to derivate at least muscle, cartilage, fat, and bone cells in vitro. The possibility to replace the defective muscle cells using cell therapy is a promising approach for the treatment of progressive muscular dystrophies (PMDs), independently of the specific gene mutation. Therefore, preclinical studies in different models of muscular dystrophies are of utmost importance. The main objective of the present study is to evaluate if umbilical cord MSCs have the potential to reach and differentiate into muscle cells in vivo in two animal models of PMDs. In order to address this question we injected (1) human umbilical cord tissue (hUCT) MSCs into the caudal vein of SJL mice; (2) hUCT and canine umbilical cord vein (cUCV) MSCs intra-arterially in GRMD dogs. Our results here reported support the safety of the procedure and indicate that the injected cells could engraft in the host muscle in both animal models but could not differentiate into muscle cells. These observations may provide important information aiming future therapy for muscular dystrophies. PMID:21785565

  17. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  18. Arrhythmias in the muscular dystrophies.

    Science.gov (United States)

    Rajdev, Archana; Groh, William J

    2015-06-01

    In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occurs with variable prevalence, mirroring the phenotypic variability seen among and within the various hereditary myopathies. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate management of these patients, thereby improving survival. The noncardiac manifestations can lead to delayed recognition of symptoms, affect the decision to implant a prophylactic device, and once a decision is made to proceed with device implant, increase peri-procedural respiratory and anesthesia-related complications. PMID:26002394

  19. Valley sign in Becker muscular dystrophy and outliers of Duchenne and Becker muscular dystrophy

    OpenAIRE

    Pradhan Sunil

    2004-01-01

    Valley sign has been described in patients with Duchenne muscular dystrophy (DMD). As there are genetic and clinical similarities between DMD and Becker muscular dystrophy (BMD), this clinical sign is evaluated in this study in BMD and DMD/BMD outliers. To evaluate the sign, 28 patients with Becker muscular dystrophy (BMD), 8 DMD/BMD outliers and 44 age-matched male controls with other neuromuscular diseases were studied. The sign was examined after asking patients to abduct their arms to abo...

  20. The canine vomeronasal organ.

    OpenAIRE

    Adams, D. R.; Wiekamp, M D

    1984-01-01

    The vomeronasal organ was studied in mature dogs with the optical, transmission electron, and scanning electron microscopes. The canine vomeronasal complex is structurally well developed. Large blood vessels are present deep to both the lateral, 'non-receptor' and medial, 'receptor' epithelia. In addition to the unmyelinated vomeronasal nerves in the lamina propria deep to the 'receptor' epithelium, numerous nerves containing both myelinated and unmyelinated fibres are present deep to the 'no...

  1. The molecular genetics of the corneal dystrophies--current status.

    Science.gov (United States)

    Klintworth, Gordon K

    2003-05-01

    The pertinent literature on inherited corneal diseases is reviewed in terms of the chromosomal localization and identification of the responsible genes. Disorders affecting the cornea have been mapped to human chromosome 1 (central crystalline corneal dystrophy, familial subepithelial corneal amyloidosis, early onset Fuchs dystrophy, posterior polymorphous corneal dystrophy), chromosome 4 (Bietti marginal crystalline dystrophy), chromosome 5 (lattice dystrophy types 1 and IIIA, granular corneal dystrophy types 1, 2 and 3, Thiel-Behnke corneal dystrophy), chromosome 9 (lattice dystrophy type II), chromosome 10 (Thiel-Behnke corneal dystrophy), chromosome 12 (Meesmann dystrophy), chromosome 16 (macular corneal dystrophy, fish eye disease, LCAT disease, tyrosinemia type II), chromosome 17 (Meesmann dystrophy, Stocker-Holt dystrophy), chromosome 20 (congenital hereditary endothelial corneal dystrophy types I and II, posterior polymorphous corneal dystrophy), chromosome 21 (autosomal dominant keratoconus) and the X chromosome (cornea verticillata, cornea farinata, deep filiform corneal dystrophy, keratosis follicularis spinulosa decalvans, Lisch corneal dystrophy). Mutations in nine genes (ARSC1, CHST6, COL8A2, GLA, GSN, KRT3, KRT12, M1S1and TGFBI [BIGH3]) account for some of the corneal diseases and three of them are associated with amyloid deposition in the cornea (GSN, M1S1, TGFBI) including most of the lattice corneal dystrophies (LCDs) [LCD types I, IA, II, IIIA, IIIB, IV, V, VI and VII] recognized by their lattice pattern of linear opacities. Genetic studies on inherited diseases affecting the cornea have provided insight into some of these disorders at a basic molecular level and it has become recognized that distinct clinicopathologic phenotypes can result from specific mutations in a particular gene, as well as some different mutations in the same gene. A molecular genetic understanding of inherited corneal diseases is leading to a better appreciation of the

  2. [Exon-skipping therapy for Duchenne muscular dystrophy].

    Science.gov (United States)

    Takeda, Shin'ichi

    2011-11-01

    Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin at the sarcolemma. Exon skipping by antisense oligonucleotides is a novel method to restore the reading frame of the mutated DMD gene, and rescue dystrophin expression. We recently reported that systemic delivery of Morpholino antisense oligonucleotides targeting exon 6 and 8 of the canine DMD gene, efficiently recovered functional dystrophin at the sarcolamma of dystrophic dogs, and improved phenotypes of affected dogs without serious side effects (Ann Neurol. 65: 667-676, 2009). To optimize therapeutic antisense Morpholinos for more frequent mutations of the DMD gene, we designed antisense Morpholinos targeting exon 51 of the mouse DMD gene, and injected them separately or in combination into the muscles of mdx52 mice, in which exon 52 has been deleted by a gene targeting technique. We also tried systemic delivery of antisense Morpholino to skip exon 51 in mdx 52 mice and found the amelioration of the phenotypes (Mol Ther, 2010). Clinical trials of exon 51 skipping for DMD patients is now going in our country and application of antisense strategy to other hereditary neuromuscular diseases is largely expected. PMID:22277414

  3. [Muscular Dystrophies Involving the Retinal Function].

    Science.gov (United States)

    Jägle, H

    2016-03-01

    Muscular dystrophies are rare disorders, with an incidence of approx. 20 in 100 000. Some dystrophies also affect retinal or optic nerve function. In such cases, the ophthalmological findings may be critical for differential diagnosis or patient counseling. For example in Duchenne muscular dystrophy, where the alteration in retinal function seems to reflect cerebral involvement. Other important forms are mitochondrial and metabolic disorders, such as the Kearns-Sayre syndrome and the Refsum syndrome. Molecular genetic analysis has become a major tool for differential diagnosis, but may be complex and demanding. This article gives an overview of major muscular dystrophies involving retinal function and their genetic origin, in order to guide differential diagnosis.

  4. Limb-Girdle Muscular Dystrophy (LGMD)

    Science.gov (United States)

    ... supported scientists are pursuing several exciting strategies in muscular dystrophy research that have implications for LGMD. These strategies include gene therapy, exon skipping, stop codon-read through and myostatin ...

  5. Non-Coding RNAs in Muscle Dystrophies

    Directory of Open Access Journals (Sweden)

    Alessandra Ferlini

    2013-09-01

    Full Text Available ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies.

  6. Brain MRI Findings in Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-03-01

    Full Text Available Brain magnetic resonance imaging (MRI findings in 13 patients with congenital muscular dystrophy (MDCIC and Fukutin-related protein (FKRP gene mutations were retrospectively reviewed in a study at Hammersmith Hospital, London, UK, and European centers.

  7. The Muscular Dystrophies: From Genes to Therapies

    OpenAIRE

    Richard M. Lovering; Porter, Neil C; Bloch, Robert J.

    2005-01-01

    The genetic basis of many muscular disorders, including many of the more common muscular dystrophies, is now known. Clinically, the recent genetic advances have improved diagnostic capabilities, but they have not yet provided clues about treatment or management. Thanks to better management strategies and therapeutic interventions, however, many patients with a muscular dystrophy are more active and are living longer. Physical therapists, therefore, are more likely to see a patient with a musc...

  8. New therapies for muscular dystrophy: cautious optimism

    OpenAIRE

    Cossu, G.; Sampaolesi, Maurilio

    2004-01-01

    The quest for a therapy for muscular dystrophy has been the driving force behind the past 40 years of advances in this field. Numerous results, such as the identification of satellite cells and gene mutations that are responsible for most forms of dystrophies, advances in gene transfer and modification technology and, more recently, stem cells, have fueled hopes. However, administering cortical-steroids still remains the only effective treatment available. Several recent advances have uncover...

  9. Duchenne muscular dystrophy: the management of scoliosis

    Science.gov (United States)

    Gardner, Adrian C.; Roper, Helen P.; Chikermane, Ashish A.; Tatman, Andrew J.

    2016-01-01

    This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group.

  10. Cellular and molecular mechanisms underlying muscular dystrophy

    OpenAIRE

    Rahimov, Fedik; Kunkel, Louis M

    2013-01-01

    The muscular dystrophies are a group of heterogeneous genetic diseases characterized by progressive degeneration and weakness of skeletal muscle. Since the discovery of the first muscular dystrophy gene encoding dystrophin, a large number of genes have been identified that are involved in various muscle-wasting and neuromuscular disorders. Human genetic studies complemented by animal model systems have substantially contributed to our understanding of the molecular pathomechanisms underlying ...

  11. Obstructive apnoeas in Duchenne muscular dystrophy.

    OpenAIRE

    Khan, Y.; Heckmatt, J Z

    1994-01-01

    BACKGROUND--In order to clarify the treatment of sleep hypoxaemias in Duchenne muscular dystrophy polysomnographic studies were performed on patients at home with the purpose of recruiting them into two clinical therapeutic trials. Observations concerning the nature of sleep hypoxaemia in these patients are presented. METHODS--Twenty one non-ambulant patients with Duchenne muscular dystrophy aged 13-23 years with no symptoms of sleep hypoventilation or apnoea were studied for two consecutive ...

  12. Genetics Home Reference: lattice corneal dystrophy type I

    Science.gov (United States)

    ... Diagnosis & Management These resources address the diagnosis or management of lattice corneal dystrophy type I: American Foundation for the Blind: Living with Vision Loss Genetic Testing Registry: Lattice corneal dystrophy Type ...

  13. FDA OKs 1st Drug to Treat Duchenne Muscular Dystrophy

    Science.gov (United States)

    ... html FDA OKs 1st Drug to Treat Duchenne Muscular Dystrophy Exondys 51 seems to fill unmet need ... the first drug for a rare form of muscular dystrophy. Exondys 51 (eteplirsen) was granted accelerated approval ...

  14. Myogenic potential of canine craniofacial satellite cells

    Directory of Open Access Journals (Sweden)

    Rita Maria Laura La Rovere

    2014-05-01

    Full Text Available The skeletal fibres have different embryological origin; the extraocular and jaw-closer muscles develop from prechordal mesoderm while the limb and trunk muscles from somites. These different origins characterise also the adult muscle stem cells, known as satellite cells (SCs and responsible for the fibre growth and regeneration. The physiological properties of presomitic SCs and their epigenetics are poorly studied despite their peculiar characteristics to preserve muscle integrity during chronic muscle degeneration. Here we isolated SCs from canine somitic (SDM: vastus lateralis, rectus abdominus, gluteus superficialis, biceps femoris, psoas and presomitic (PSDM: lateral rectus, temporalis and retractor bulbi muscles as myogenic progenitor cells from young and old animals. In addition, SDM and PSDM satellite cells were obtained also from Golden retrievers affected by muscular dystrophy (GRMD. We characterised the lifespan, the myogenic potential and functions and oxidative stress of both somitic and presomitic SCs with the aim to reveal differences with ageing and between healthy and dystrophic animals. The different proliferation rate was consistent with higher telomerase activity in PSDM-SCs compared to SDM-SCs, although restricted at early passages. SDM-SCs express early (Pax7, MyoD and late (MyHC, Myogenin myogenic markers differently from PSDM-SCs resulting in a more efficient and faster cell differentiation. Taken together our results showed that PSDM-SCs elicit a stronger stem cell phenotype compared to SDM ones. Finally, myomiR expression profile reveals a unique epigenetic signature in GRMD satellite cells and miR-206, highly expressed in dystrophic SCs, seems to play a critical role in muscle degeneration. Thus, miR-206 could represent a potential target for novel therapeutic approaches.

  15. Dystrophin analysis in the diagnosis of muscular dystrophy.

    OpenAIRE

    Norman, A M; Hughes, H E; Gardner-Medwin, D; Nicholson, L V

    1989-01-01

    We present a family in which the differential diagnosis between X linked Duchenne muscular dystrophy and autosomal recessive Duchenne-like muscular dystrophy was resolved in favour of the latter by analysis of dystrophin, which is the protein product of the Duchenne muscular dystrophy locus.

  16. Disease: H00481 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available autosomal dominant cone, cone-rod, and macular dystrophies. Mol Vis 17:1103-9 (2011) PMID:21882291 Wissing...er B, Schaich S, Baumann B, Bonin M, Jagle H, Friedburg C, Varsanyi B, Hoyng CB, Do

  17. [The heartache of muscular dystrophy].

    Science.gov (United States)

    Hoogerwaard, E M; Ginjaar, H B; Wilde, A A; Leschot, N J; de Voogt, W G; de Visser, M

    2000-11-11

    Duchenne and Becker muscular dystrophy are caused by a mutation in the dystrophin gene, located on the short arm of the X chromosome. Three so called dystrophinopathy patients, a women aged 54 and two men aged 23 and 21 years, suffered from a severe dilated cardiomyopathy. Such a cardiomyopathy can develop in both carriers and patients. In addition, it is often more important for prognosis than muscle weakness. For these two reasons it is important to screen both groups for (early) cardiological abnormalities. If these are present, regular follow-up is necessary to start timely therapy. When cardiological investigations yield normal results, it is advised to screen carriers with a five-year interval. Dystrophinopathy patients should be checked every year, because the cardiomyopathy sometimes develops and deteriorates over a short period of time. Patients with dilated cardiomyopathy and with a positive family history for dilated cardiomyopathy, muscle weakness or high serum creatine kinase activity should be screened for a mutation in the dystrophin gene. PMID:11103252

  18. Advances in gene therapy for muscular dystrophies.

    Science.gov (United States)

    Abdul-Razak, Hayder; Malerba, Alberto; Dickson, George

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments. PMID:27594988

  19. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Science.gov (United States)

    2010-01-01

    ... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing cell... hepatitis, the test is inconclusive and may be repeated. (B) If at least 19 of the 20 vaccinates do...

  20. FHL1 Reduces Dystrophy in Transgenic Mice Overexpressing FSHD Muscular Dystrophy Region Gene 1 (FRG1)

    OpenAIRE

    Feeney, Sandra J.; McGrath, Meagan J.; Absorn Sriratana; Stefan M Gehrig; Gordon S Lynch; Colleen E D'Arcy; John T Price; McLean, Catriona A.; Rossella Tupler; Mitchell, Christina A.

    2015-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease with no effective treatment. The genetic cause of FSHD is complex and the primary pathogenic insult underlying the muscle disease is unknown. Several disease candidate genes have been proposed including DUX4 and FRG1. Expression analysis studies of FSHD report the deregulation of genes which mediate myoblast differentiation and fusion. Transgenic mice overexpressing FRG1 recapitulate the FSHD muscular dystrophy phe...

  1. Cardiomyopathy in becker muscular dystrophy: Overview

    Science.gov (United States)

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-01-01

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID:27354892

  2. Brain Function in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available The role of dystrophin disorders in the CNS function of boys with Duchenne muscular dystrophy (DMD and the dystrophin-deficient mdx mouse, an animal model of DMD, is reviewed at the University of New South Wales, University of Sydney, Australia.

  3. INTESTINAL PSEUDOOBSTRUCTION IN MYOTONIC-DYSTROPHY

    NARCIS (Netherlands)

    BRUNNER, HG; HAMEL, BCJ; RIEU, P; HOWELER, CJ; PETERS, FTM

    1992-01-01

    We describe four myotonic dystrophy (DM) patients who developed recurrent intestinal pseudo-obstruction. Some episodes were associated with gastroenteritis, while abdominal crowding may have occurred in one case during the third trimester of pregnancy. In most instances, however, no apparent cause c

  4. Genetics Home Reference: Bietti crystalline dystrophy

    Science.gov (United States)

    ... Hayakawa M, Kanai A, Shy Chen M, Alan Lewis R, Heckenlively J, Weleber RG, Traboulsi EI, Zhang Q, Xiao X, Kaiser-Kupfer M, Sergeev YV, Hejtmancik JF. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet. 2004 May;74( ...

  5. Cardiomyopathy in becker muscular dystrophy: Overview.

    Science.gov (United States)

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID:27354892

  6. Swivel walkers in Duchenne muscular dystrophy.

    OpenAIRE

    Sibert, J R; Williams, V; Burkinshaw, R; Sibert, S

    1987-01-01

    Swivel walkers were used to provide low energy ambulation in 11 boys with Duchenne muscular dystrophy in schools for the physically handicapped in South Glamorgan. Our preliminary experience suggests that these walkers improve the quality of life and provide a useful part of the physical treatment of the condition.

  7. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy

    OpenAIRE

    Sonal, Choudhary; Michael, McLeod; Daniele, Torchia; Paolo, Romanelli

    2012-01-01

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is a rare autoimmune disorder. The clinical spectrum of symptoms is diverse; the diagnosis relying on the presence of at least two out of the three main conditions defining the syndrome: chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease.

  8. Genetics Home Reference: facioscapulohumeral muscular dystrophy

    Science.gov (United States)

    ... Padberg GW, Lunt PW, van der Maarel SM. Best practice guidelines on genetic diagnostics of Facioscapulohumeral muscular dystrophy: ... Reviewed : August 2014 Published : August 30, 2016 The resources on this site should not be used as a ... of Health & Human Services National Institutes of Health National Library of ...

  9. Hereditary muscular dystrophies and the heart

    NARCIS (Netherlands)

    M.C.E. Hermans; Y.M. Pinto; I.S.J. Merkies; C.E.M. de Die-Smulders; H.J.G.M. Crijns; C.G. Faber

    2010-01-01

    Cardiac disease is a common clinical manifestation of neuromuscular disorders, particularly of muscular dystrophies. Heart muscle cells as well as specialized conducting myocardial fibres may be affected by the dystrophic process. The incidence and nature of cardiac involvement vary with different t

  10. Merosin/laminin-2 and muscular dystrophy

    DEFF Research Database (Denmark)

    Wewer, U M; Engvall, E

    1996-01-01

    and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations...

  11. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    Science.gov (United States)

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  12. In vivo confocal microscopy in different types of posterior polymorphous dystrophy

    Directory of Open Access Journals (Sweden)

    Babu Kalpana

    2007-01-01

    Full Text Available Posterior polymorphous dystrophy is a rare corneal dystrophy, usually detected by chance. This case series describes the morphologic features in the three different types of posterior polymorphous dystrophy using confocal microscopy.

  13. Emerging strategies for cell and gene therapy of the muscular dystrophies

    OpenAIRE

    Muir, Lindsey A.; Jeffrey S. Chamberlain

    2009-01-01

    The muscular dystrophies are a heterogeneous group of over 40 disorders that are characterised by muscle weakness and wasting. The most common are Duchenne muscular dystrophy and Becker muscular dystrophy, which result from mutations within the gene encoding dystrophin; myotonic dystrophy type 1, which results from an expanded trinucleotide repeat in the myotonic dystrophy protein kinase gene; and facioscapulohumeral dystrophy, which is associated with contractions in the subtelomeric region ...

  14. Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

    Science.gov (United States)

    2014-10-15

    Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  15. An unusual central retinal dystrophy associated with ichthyosis vulgaris.

    Science.gov (United States)

    Saatci, O A; Ozbek, Z; Köse, S; Durak, I; Kavukçu, S

    2000-06-01

    A number of ichthyosis syndromes may have retinal abnormalities such as the retinitis pigmentosa-like diffuse rod-cone dystrophy in Refsum's syndrome and the maculopathy in Sjögren-Larsson syndrome. We present two sisters who have an unusual, almost identical, bilaterally symmetric central retinal dystrophy associated with ichthyosis vulgaris in the absence of other systemic disorders. We believe that this dystrophy has not been previously described in patients with any of the known varieties of ichthyosis.

  16. Stem cell transplantation for treating Duchenne muscular dystrophy

    OpenAIRE

    Yang, Xiaofeng

    2012-01-01

    OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy in...

  17. Gene Therapy for Muscular Dystrophy: Moving the Field Forward

    OpenAIRE

    Al-Zaidy, Samiah; Rodino-Klapac, Louise; Mendell, Jerry R.

    2014-01-01

    Gene therapy for the muscular dystrophies has evolved as a promising treatment for this progressive group of disorders. While corticosteroids and/or supportive treatments remain standard of care for Duchenne muscular dystrophy (DMD), loss of ambulation, respiratory failure and compromised cardiac function is the inevitable outcome. Recent developments in genetically mediated therapies have allowed for personalized treatments that strategically target individual muscular dystrophy subtypes bas...

  18. Distinct genetic regions modify specific muscle groups in muscular dystrophy

    OpenAIRE

    Swaggart, Kayleigh A.; Heydemann, Ahlke; Palmer, Abraham A.; McNally, Elizabeth M.

    2010-01-01

    Phenotypic expression in the muscular dystrophies is variable, even with the identical mutation, providing strong evidence that genetic modifiers influence outcome. To identify genetic modifier loci, we used quantitative trait locus mapping in two differentially affected mouse strains with muscular dystrophy. Using the Sgcg model of limb girdle muscular dystrophy that lacks the dystrophin-associated protein γ-sarcoglycan, we evaluated chromosomal regions that segregated with two distinct quan...

  19. Molecular mechanisms in muscular dystrophy: a gene expression profiling study.

    OpenAIRE

    Turk, Rolf

    2006-01-01

    The muscular dystrophies are a group of neuromuscular disorders characterized by progres¬sive muscle weakness and wasting. Although the underlying genetic defects of a large number of muscular dystrophies are now know, the molecular mechanisms resulting in the devastating effects of the disease are not yet clear. Furthermore, the muscular dystrophies differ in clinical presentation and severity. The processes responsible for this di¬vergence are largely unknown as well. In this thesis, gene e...

  20. Therapeutic Targeting of Signaling Pathways in Muscular Dystrophy

    OpenAIRE

    Bhatnagar, Shephali; Kumar, Ashok

    2009-01-01

    Muscular dystrophy refers to a group of genetic diseases that cause severe muscle weakness and loss of skeletal muscle mass. Although research has helped understanding the molecular basis of muscular dystrophy, there is still no cure for this devastating disorder. Numerous lines of investigation suggest that the primary deficiency of specific proteins causes aberrant activation of several cell signaling pathways in skeletal and cardiac muscle leading to the pathogenesis of muscular dystrophy....

  1. Approaching a new age in Duchenne muscular dystrophy treatment

    OpenAIRE

    Wagner, Kathryn R.

    2008-01-01

    Duchenne muscular dystrophy is the most common and severe form of muscular dystrophy. The cornerstones of current treatment include corticosteroids for skeletal muscle weakness, afterload reduction for cardiomyopathy, and noninvasive ventilation for respiratory failure. With these interventions, patients are walking and living longer. However, the current status is still far from adequate. Increased private and federal funding of studies in Duchenne muscular dystrophy has led to a large numbe...

  2. Cardiac involvement in Emery Dreifuss muscular dystrophy: a case series

    OpenAIRE

    Buckley, A.; Dean, J.; Mahy, I

    1999-01-01

    Three patients with Emery Dreifuss muscular dystrophy are reported. Emery Dreifuss muscular dystrophy is an X linked muscular dystrophy, in which locomotor involvement is characteristically mild and slowly progressive. The effect on the heart becomes apparent in the teenage years and is characterised by cardiac conduction defects and infiltration of the myocardium by fibrous and adipose tissue. It first affects the atria, which results in atrial paralysis; treatment with ventricular pacing is...

  3. CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

    International Nuclear Information System (INIS)

    We analyzed the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin and a decrease in the γ-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, γ-globulin fraction is shown in the myotonic dystrophy. In addition to the abnormality of IQ, EEG, and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy. (author)

  4. Current developments in canine genetics.

    Science.gov (United States)

    Marschall, Yvonne; Distl, Ottmar

    2010-01-01

    In recent years, canine genetics had made huge progress. In 1999 the first complete karyotype and ideogram of the dog was published. Several linkage and RH maps followed. Using these maps, sets of microsatellite markers for whole genome scans were compiled. In 2003 the sequencing of the DNA of a female Boxer began. Now the second version of the dog genome assembly has been put online, and recently, a microchip SNP array became available. Parallel to these developments, some causal mutations for different traits have been identified. Most of the identified mutations were responsible for monogenic canine hereditary diseases. With the tools available now, it is possible to use the advantages of the population structure of the various dog breeds to unravel complex genetic traits. Furthermore, the dog is a suitable model for the research of a large number of human hereditary diseases and particularly for cancer genetics, heart and neurodegenerative diseases. There are some examples where it was possible to benefit from the knowledge of canine genetics for human research. The search for quantitative trait loci (QTL), the testing of candidate genes and genome-wide association studies can now be performed in dogs. QTL for skeletal size variations and for canine hip dysplasia have been already identified and for these complex traits the responsible genes and their possible interactions can now be identified. PMID:20690545

  5. Prognostic markers of canine pyometra

    OpenAIRE

    M.C. Sant'Anna; L.G.P. Giordano; K.K.M.C. Flaiban; Muller, E.E.; M.I.M. Martins

    2014-01-01

    The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra tre...

  6. Surgical innovations in canine gonadectomy

    NARCIS (Netherlands)

    Van Goethem, Bart

    2016-01-01

    In this thesis some recent technological developments in human surgery are evaluated for their potential use in veterinary medicine by introducing them as surgical innovations for canine gonadectomy. Barbed sutures achieve wound apposition without surgical knot tying and thus avoid knot-associated n

  7. Anoctamin 5 muscular dystrophy in Denmark

    DEFF Research Database (Denmark)

    Witting, Nanna; Duno, Morten; Petri, Helle;

    2013-01-01

    Since the initial description in 2010 of anoctamin 5 deficiency as a cause of muscular dystrophy, a handful of papers have described this disease in cases of mixed populations. We report the first large regional study and present data on new aspects of prevalence, muscular and cardiac phenotypic...... characteristics, and muscle protein expression. All patients in our neuromuscular unit with genetically unclassified, recessive limb girdle muscular dystrophy (LGMD2), Miyoshi-type distal myopathy (MMD) or persistent asymptomatic hyperCK-emia (PACK) were assessed for mutations in the ANO5 gene. Genetically...... confirmed patients were evaluated with muscular and cardiopulmonary examination. Among 40 unclassified patients (28 LGMD2, 5 MMD, 7 PACK), 20 were homozygous or compound heterozygous for ANO5 mutations, (13 LGMD2, 5 MMD, 2 PACK). Prevalence of ANO5 deficiency in Denmark was estimated at 1:100.000 and ANO5...

  8. Myotonic dystrophy protein kinase (DMPK) and its role in the pathogenesis of myotonic dystrophy 1.

    Science.gov (United States)

    Kaliman, Perla; Llagostera, Esther

    2008-11-01

    Myotonic dystrophy 1 (DM1) is an autosomal, dominant inherited, neuromuscular disorder. The DM1 mutation consists in the expansion of an unstable CTG-repeat in the 3'-untranslated region of a gene encoding DMPK (myotonic dystrophy protein kinase). Clinical expression of DM1 is variable, presenting a progressive muscular dystrophy that affects distal muscles more than proximal and is associated with the inability to relax muscles appropriately (myotonia), cataracts, cardiac arrhythmia, testicular atrophy and insulin resistance. DMPK is a Ser/Thr protein kinase homologous to the p21-activated kinases MRCK and ROCK/rho-kinase/ROK. The most abundant isoform of DMPK is an 80 kDa protein mainly expressed in smooth, skeletal and cardiac muscles. Decreased DMPK protein levels may contribute to the pathology of DM1, as revealed by gene target studies. Here we review current understanding of the structural, functional and pathophysiological characteristics of DMPK. PMID:18583094

  9. Severe dystrophy in DiGeorge syndrome

    Institute of Scientific and Technical Information of China (English)

    Barnabás Rózsai; (A)kos Kiss; Gy(o)rgyi Csábi; Márta Czakó; Tamás Decsi

    2009-01-01

    We present the case history of a 3-year-old girl who was examined because of severe dystrophy. In the background, cow's milk allergy was found, but her body weight was unchanged after eliminating milk from her diet. Other types of malabsorption were excluded. Based on nasal regurgitation and facial dysmorphisms, the possibility of DiGeorge syndrome was suspected and was confirmed by fluorescence in situ hybridization. The authors suggest a new feature associated with DiGeorge syndrome.

  10. Targeting Fibrosis in Duchenne Muscular Dystrophy

    OpenAIRE

    Zhou, Lan; Lu, Haiyan

    2010-01-01

    Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease affecting 1 in 3,500 live male births. It is an X-linked recessive disease caused by a defective dystrophin gene. The disease is characterized by progressive limb weakness, respiratory and cardiac failure and premature death. Fibrosis is a prominent pathological feature of muscle biopsies from patients with DMD. It directly causes muscle dysfunction and contributes to the lethal DMD phenotype. Although gene therapy an...

  11. Recent advances in Duchenne muscular dystrophy

    OpenAIRE

    Perkins KJ; Davies KE

    2012-01-01

    Kelly J Perkins,1,2 Kay E Davies21Sir William Dunn School of Pathology, 2MRC Functional Genomics Unit, University of Oxford, Oxford, UKAbstract: Duchenne muscular dystrophy (DMD), an allelic X-linked progressive muscle-wasting disease, is one of the most common single-gene disorders in the developed world. Despite knowledge of the underlying genetic causation and resultant pathophysiology from lack of dystrophin protein at the muscle sarcolemma, clinical intervention is currently restricted t...

  12. Pathophysiology of duchenne muscular dystrophy: current hypotheses.

    OpenAIRE

    Deconinck, Nicolas; Dan, Bernard

    2007-01-01

    Duchenne muscular dystrophy is a devastating inherited neuromuscular disorder that affects one in 3300 live male births. Although the responsible gene and its product, dystrophin, have been characterized for more than 15 years, and a mouse model (mdx) has been developed, comprehensive understanding of the mechanism leading from the absence of dystrophin to the muscular degeneration is still debated. First, dystrophin is considered a key structural element in the muscle fiber, and the primary ...

  13. Molecular Therapeutic Strategies Targeting Duchenne Muscular Dystrophy

    OpenAIRE

    Mendell, Jerry R.; Rodino-Klapac, Louise R.; Malik, Vinod

    2010-01-01

    Since discovery of the gene for Duchenne muscular dystrophy more than 20 years ago, scientists have worked to apply molecular principles for restoration of the dystrophin protein and correction of the underlying physiologic defect that predisposes muscle fibers to injury. Recent studies provide realistic hope that molecular therapies may help patients who have this disorder. At present only corticosteroids can improve walking ability and increase quality of life for boys with this disease. Th...

  14. Epigenetic Mechanisms of Facioscapulohumeral Muscular Dystrophy

    OpenAIRE

    de Greef, Jessica C; Frants, Rune R; van der Maarel, Silvère M.

    2008-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) seems to be caused by a complex epigenetic disease mechanism as a result of contraction of the polymorphic macrosatellite repeat D4Z4 on chromosome 4qter. Currently, the exact mechanism causing the FSHD phenotype is still not elucidated. In this review, we discuss the genetic and epigenetic changes observed in patients with FSHD and the possible disease mechanisms that may be associated with FSHD pathogenesis.

  15. Targeting Latent TGFβ release in muscular dystrophy

    OpenAIRE

    Ceco, Ermelinda; Bogdanovich, Sasha; Gardner, Brandon; Miller, Tamari; DeJesus, Adam; Earley, Judy U.; Hadhazy, Michele; Smith, Lucas R.; Barton, Elisabeth R; Molkentin, Jeffery D.; McNally, Elizabeth M.

    2014-01-01

    Latent TGFβ binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolyzed, and that proteolysis could be blocked by an antibody to the hinge region. Transgenic mice were generated to carry a bacterial artificial chromos...

  16. Genetic counselling in facioscapulohumeral muscular dystrophy.

    OpenAIRE

    Lunt, P W; Harper, P S

    1991-01-01

    Clinical data are presented from a survey of 41 families with dominantly inherited facioscapulohumeral muscular dystrophy (FSHD) in which over 500 family members were examined, including 168 affected subjects. New mutation could account for six isolated cases. Results suggest that 33% of heterozygotes over 40 years are mildly affected and a majority develop significant lower limb weakness; 19% over 40 years require wheelchairs. Presymptomatic testing of serum creatine kinase level (CK) is lim...

  17. Natural history of Duchenne muscular dystrophy

    OpenAIRE

    KE, QING; ZHANG Li

    2015-01-01

    Duchenne muscular dystrophy (DMD) is X-linked recessive hereditary disease. DMD gene mutations result in dystrophin deficiency, which causes not only muscle movement disorders but also scoliosis, cognitive dysfunction, urinary tract diseases, respiratory diseases and heart diseases. Most patients die in early adult for respiratory and circulatory failure. Early multidisciplinary therapies will significantly delay disease progression and improve patients' quality of life. However, DMD diagnosi...

  18. Optimizing Bone Health in Duchenne Muscular Dystrophy

    OpenAIRE

    Buckner, Jason L.; Bowden, Sasigarn A.; Mahan, John D

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serio...

  19. Duchenne Muscular Dystrophy: From Diagnosis to Therapy

    OpenAIRE

    Maria Sofia Falzarano; Chiara Scotton; Chiara Passarelli; Alessandra Ferlini

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay ...

  20. Management of myocardial damage in muscular dystrophy

    International Nuclear Information System (INIS)

    Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future. (author)

  1. Upper limb function in adults with Duchenne muscular dystrophy

    NARCIS (Netherlands)

    B. Bartels (Bart); R.F. Pangalila; M.P. Bergen (Michael); N.A.M. Cobben (Nicolle); H.J. Stam (Henk); M.E. Roebroeck (Marij)

    2011-01-01

    textabstractTo determine upper limb function and associated factors in adults with Duchenne muscular dystrophy. Design: Cross-sectional study. Subjects: A sample of 70 men with Duchenne muscular dystrophy (age range 20-43 years). Methods: General motor function and, in particular, upper limb distal

  2. Emery dreifuss muscular dystrophy: A clinico-pathological study

    OpenAIRE

    Gayathri N; Taly A; Sinha S; Suresh T; Gorai D

    2006-01-01

    Emery-Dreifuss muscular dystrophy (EDMD) is a rare and genetically heterogeneous disorder. We report two patients with emerin deficient X-linked EDMD and two probable patients with EDMD with typical early contractures, progressive muscle weakness and cardiac involvement. Family history was noted in one case. Muscle biopsy revealed features of dystrophy in all.

  3. Purloined Mechanisms of Bacterial Immunity Can Cure Muscular Dystrophy

    OpenAIRE

    Tidball, James G.; Bertoni, Carmen

    2014-01-01

    Myriad strategies have been explored to compensate for the lack of dystrophin or to skip mutations that cause the lethal disease Duchenne muscular dystrophy (DMD). A new study shows that gene editing strategies used by bacteria can be applied in zygotes of a mouse model of DMD to correct the genetic defect that causes muscular dystrophy (Long et al., 2014).

  4. Dysphagia is present but mild in myotonic dystrophy type 2

    NARCIS (Netherlands)

    Swart, Bert de; Tieleman, A.; Knuijt, S.; Vliet, J. van; Ensink, R.; Engelen, Baziel van

    2009-01-01

    The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of

  5. Dysphagia is present but mild in myotonic dystrophy type 2.

    NARCIS (Netherlands)

    Tieleman, A.A.; Knuijt, S.; Vliet, J. van; Swart, B.J.M. de; Ensink, R.J.H.; Engelen, B.G.M. van

    2009-01-01

    The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of

  6. Resistance training in patients with limb-girdle and becker muscular dystrophies

    DEFF Research Database (Denmark)

    Sveen, Marie-Louise; Andersen, Søren P; Ingelsrud, Lina H;

    2013-01-01

    In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD).......In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD)....

  7. First Identification of a Triple Corneal Dystrophy Association: Keratoconus, Epithelial Basement Membrane Corneal Dystrophy and Fuchs' Endothelial Corneal Dystrophy

    Directory of Open Access Journals (Sweden)

    Cosimo Mazzotta

    2014-09-01

    Full Text Available Purpose: To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC, epithelial basement membrane corneal dystrophy (EBMCD and Fuchs' endothelial corneal dystrophy (FECD. Methods: A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing. Results: Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman's layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1. Conclusion: This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.

  8. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands : a cohort study

    NARCIS (Netherlands)

    Hoogerwaard, EM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; Leschot, NJ; Van Essen, AJ; Brunner, HG; van der Wouw, PA; Wilde, AAM; de Visser, M

    1999-01-01

    Background Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of definit

  9. Surgical innovations in canine gonadectomy

    OpenAIRE

    Van Goethem, Bart

    2016-01-01

    In this thesis some recent technological developments in human surgery are evaluated for their potential use in veterinary medicine by introducing them as surgical innovations for canine gonadectomy. Barbed sutures achieve wound apposition without surgical knot tying and thus avoid knot-associated negative consequences (lengthy placement, impaired wound healing around bulky knots, and the effect of unsightly knots on cosmetics). A study in 9 dogs found that celiotomy closure was easily achiev...

  10. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  11. Genome Sequence of Canine Herpesvirus.

    Directory of Open Access Journals (Sweden)

    Konstantinos V Papageorgiou

    Full Text Available Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the genome sequences of three viral strains (0194, V777 and V1154 isolated in the United Kingdom between 1985 and 2000. The sequences are very closely related to each other. The canine herpesvirus genome is estimated to be 125 kbp in size and consists of a unique long sequence (97.5 kbp and a unique short sequence (7.7 kbp that are each flanked by terminal and internal inverted repeats (38 bp and 10.0 kbp, respectively. The overall nucleotide composition is 31.6% G+C, which is the lowest among the completely sequenced alphaherpesviruses. The genome contains 76 open reading frames predicted to encode functional proteins, all of which have counterparts in other alphaherpesviruses. The availability of the sequences will facilitate future research on the diagnosis and treatment of canine herpesvirus-associated disease.

  12. [Treatment progress of Duchenne Muscular Dystrophy (DMD)].

    Science.gov (United States)

    Smogorzewska, Elzbieta Monika; Weinberg, Kenneth I

    2004-01-01

    Duchenne muscular dystrophy (DMD) is a common lethal disease for which no effective treatment is currently available. There exists a mouse model of the disease in which the usefulness of gene therapy was established. However, no progress towards human application was made due to the lack of a proper method for gene delivery. During the past several years, researchers acquired data which led them to believe that bone marrow stem cells are capable of generating not only blood cells, but also liver, heart, skin, muscle, and other tissue. Although the term "stem cell plasticity" became very popular, other studies have suggested that bone marrow might contain different types of stem cells that can produce non-hematopoietic cells. For example, mesenchymal stem cell (MSC) in bone marrow give rise to osteocytes, chondrocytes, adipocytes, and skeletal muscle. Recently, researchers have been able to show that transplanted bone marrow cells can contribute to muscle cells in a human patient who was diagnosed with two genetic diseases: severe combined immunodeficiency (SCID) and Duchenne muscular dystrophy. The odds of this happening is estimated at one in seven million. The results of studying this patient's medical history were reported by collaborating researchers at Children's Hospital, Los Angeles and Children's Hospital, Boston in an article titled "Long-term persistence of donor nuclei in a Duchenne muscular dystrophy (DMD) patient receiving bone marrow transplantation" published in the September 2002 issue of the Journal of Clinical Investigation. This patient was transplanted 15 years ago at Children's Hospital Los Angeles with paternal HLA-haploidentical T cell-depleted bone marrow. He engrafted and became a hematopoietic chimera having T and NK lymphocytes of donor origin. Studies performed on the muscle biopsy from the patient 13 years after transplantation demonstrated that the muscle showed evidence of donor derived nuclei. In addition, analysis of his bone marrow

  13. 9 CFR 113.306 - Canine Distemper Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine. 113.306... Virus Vaccines § 113.306 Canine Distemper Vaccine. Canine Distemper Vaccine shall be prepared from virus... distemper virus, each of five canine distemper susceptible ferrets shall be injected with a sample of...

  14. Canine and feline parasitic zoonoses in China

    Directory of Open Access Journals (Sweden)

    Chen Jia

    2012-07-01

    Full Text Available Abstract Canine and feline parasitic zoonoses have not been given high priority in China, although the role of companion animals as reservoirs for zoonotic parasitic diseases has been recognized worldwide. With an increasing number of dogs and cats under unregulated conditions in China, the canine and feline parasitic zoonoses are showing a trend towards being gradually uncontrolled. Currently, canine and feline parasitic zoonoses threaten human health, and cause death and serious diseases in China. This article comprehensively reviews the current status of major canine and feline parasitic zoonoses in mainland China, discusses the risks dogs and cats pose with regard to zoonotic transmission of canine and feline parasites, and proposes control strategies and measures.

  15. Muscle MRI findings in facioscapulohumeral muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gerevini, Simonetta; Caliendo, Giandomenico; Falini, Andrea [IRCCS San Raffaele Scientific Institute, Neuroradiology Unit, Head and Neck Department, Milan (Italy); Scarlato, Marina; Previtali, Stefano Carlo [IRCCS San Raffaele Scientific Institute, Department of Neurology, INSPE and Division of Neuroscience, Milan (Italy); Maggi, Lorenzo; Pasanisi, Barbara; Morandi, Lucia [Fondazione IRCCS Istituto Neurologico ' ' Carlo Besta' ' , Neuromuscular Diseases and Neuroimmunology Unit, Milan (Italy); Cava, Mariangela [IRCCS San Raffaele Scientific Institute, Department of Radiology and Center for Experimental Imaging, Milan (Italy)

    2016-03-15

    Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. (orig.)

  16. The superhealing MRL background improves muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Heydemann Ahlke

    2012-12-01

    Full Text Available Abstract Background Mice from the MRL or “superhealing” strain have enhanced repair after acute injury to the skin, cornea, and heart. We now tested an admixture of the MRL genome and found that it altered the course of muscle pathology and cardiac function in a chronic disease model of skeletal and cardiac muscle. Mice lacking γ-sarcoglycan (Sgcg, a dystrophin-associated protein, develop muscular dystrophy and cardiomyopathy similar to their human counterparts with limb girdle muscular dystrophy. With disruption of the dystrophin complex, the muscle plasma membrane becomes leaky and muscles develop increased fibrosis. Methods MRL/MpJ mice were bred with Sgcg mice, and cardiac function was measured. Muscles were assessed for fibrosis and membrane leak using measurements of hydroxyproline and Evans blue dye. Quantitative trait locus mapping was conducted using single nucleotide polymorphisms distinct between the two parental strains. Results Introduction of the MRL genome reduced fibrosis but did not alter membrane leak in skeletal muscle of the Sgcg model. The MRL genome was also associated with improved cardiac function with reversal of depressed fractional shortening and the left ventricular ejection fraction. We conducted a genome-wide analysis of genetic modifiers and found that a region on chromosome 2 was associated with cardiac, diaphragm muscle and abdominal muscle fibrosis. Conclusions These data are consistent with a model where the MRL genome acts in a dominant manner to suppress fibrosis in this chronic disease setting of heart and muscle disease.

  17. Antisense Oligonucleotide Therapy for Inherited Retinal Dystrophies.

    Science.gov (United States)

    Gerard, Xavier; Garanto, Alejandro; Rozet, Jean-Michel; Collin, Rob W J

    2016-01-01

    Inherited retinal dystrophies (IRDs) are an extremely heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Over the last decade, significant progress has been made utilizing gene augmentation therapy for a few genetic subtypes of IRD, although several technical challenges so far prevent a broad clinical application of this approach for other forms of IRD. Many of the mutations leading to these retinal diseases affect pre-mRNA splicing of the mutated genes . Antisense oligonucleotide (AON)-mediated splice modulation appears to be a powerful approach to correct the consequences of such mutations at the pre-mRNA level , as demonstrated by promising results in clinical trials for several inherited disorders like Duchenne muscular dystrophy, hypercholesterolemia and various types of cancer. In this mini-review, we summarize ongoing pre-clinical research on AON-based therapy for a few genetic subtypes of IRD , speculate on other potential therapeutic targets, and discuss the opportunities and challenges that lie ahead to translate splice modulation therapy for retinal disorders to the clinic. PMID:26427454

  18. Limb girdle muscular dystrophies: The clinicopathological viewpoint

    Directory of Open Access Journals (Sweden)

    Urtizberea J

    2007-01-01

    Full Text Available Limb girdle muscular dystrophies (LGMD are characterized by involvement of the pelvic and shoulder girdles, classically with an onset in the second or third decade and a slow progression as opposed to Duchenne muscular dystrophy. In fact, there are many clinical variants that are related to this broad definition. For the past 13 years and since the discovery of calpain-3 as the underlying defect in LGMD 2A in 1995, a number of different genes have been found to cause LGMD; some of whose encoding proteins are located either in the sarcolemma, nucleus, cytosol or in the extra-cellular matrix. Very little is known regarding a possible common pathogenesis between all these entities. The current nomenclature of LGMDs, although a bit confusing, is still necessary to continue the establishment of homogeneous cohorts of patients and to look for unknown genes. The diagnosis of LGMD is nowadays based on a complementary clinical, immunocytochemical and genetic approach that is best achieved in specialized myology centers. In this context, India can make a significant contribution to improve the routine diagnosis in LGMD patients and to find new LGMD genes in genetic isolates. Therapeutic prospects in LGMD, although quite exciting, remain at a preliminary stage, especially those with gene-therapy orientation.

  19. Muscle MRI findings in facioscapulohumeral muscular dystrophy

    International Nuclear Information System (INIS)

    Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. (orig.)

  20. Developments in gene therapy for muscular dystrophy.

    Science.gov (United States)

    Hartigan-O'Connor, D; Chamberlain, J S

    Gene therapy for muscular dystrophy (MD) presents significant challenges, including the large amount of muscle tissue in the body, the large size of many genes defective in different muscular dystrophies, and the possibility of a host immune response against the therapeutic gene. Overcoming these challenges requires the development and delivery of suitable gene transfer vectors. Encouraging progress has been made in modifying adenovirus (Ad) vectors to reduce immune response and increase capacity. Recently developed gutted Ad vectors can deliver full-length dystrophin cDNA expression vectors to muscle tissue. Using muscle-specific promoters to drive dystrophin expression, a strong immune response has not been observed in mdx mice. Adeno-associated virus (AAV) vectors can deliver small genes to muscle without provocation of a significant immune response, which should allow long-term expression of several MD genes. AAV vectors have also been used to deliver sarcoglycan genes to entire muscle groups. These advances and others reviewed here suggest that barriers to gene therapy for MD are surmountable. PMID:10679969

  1. Congenital muscular dystrophy with inflammation: Diagnostic considerations

    Directory of Open Access Journals (Sweden)

    Kaumudi Konkay

    2016-01-01

    Full Text Available Background and Purpose: Muscle biopsy features of congenital muscular dystrophies (CMD vary from usual dystrophic picture to normal or nonspecific myopathic picture or prominent fibrosis or striking inflammatory infiltrate, which may lead to diagnostic errors. A series of patients of CMD with significant inflammatory infiltrates on muscle biopsy were correlated with laminin α 2 deficiency on immunohistochemistry (IHC. Material and Methods: Cryostat sections of muscle biopsies from the patients diagnosed as CMD on clinical and muscle biopsy features from 1996 to 2014 were reviewed with hematoxylin and eosin(H&E, enzyme and immunohistochemistry (IHC with laminin α 2. Muscle biopsies with inflammatory infiltrate were correlated with laminin α 2 deficiency. Results: There were 65 patients of CMD, with inflammation on muscle biopsy in 16. IHC with laminin α 2 was available in nine patients, of which six showed complete absence along sarcolemma (five presented with floppy infant syndrome and one with delayed motor milestones and three showed discontinuous, and less intense staining. Conclusions: CMD show variable degrees of inflammation on muscle biopsy. A diagnosis of laminin α 2 deficient CMD should be considered in patients of muscular dystrophy with inflammation, in children with hypotonia/delayed motor milestones.

  2. MR imaging of fukuyama congenital muscular dystrophy; a case report

    International Nuclear Information System (INIS)

    Fukuyama congenital muscular dystrophy is a genetic disease and common in Japan. The typical clinical features are hypotonia with an early infantile onset and severe developmental delay. The diagnosis is based on pathologic evidence of muscular dystrophy revealed by biopsy or an increased serum creatine kinase levels. Involvement of the brain is characterized by abnormal cerebral cortical dysplasia, cerebellar dysplasia, and white matter changes. We encountered a case of Fukuyama congenital muscular dystrophy in which brain MRI findings were typical, and present this case together with a review of the literature

  3. MR imaging of fukuyama congenital muscular dystrophy; a case report

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Jeong Hyun; Kim, Yoo Kyung; Koo, Hae Soo; Park, Ki Deuk [Ewha Womans Univ. College of Medicine, Seoul (Korea, Republic of)

    2000-11-01

    Fukuyama congenital muscular dystrophy is a genetic disease and common in Japan. The typical clinical features are hypotonia with an early infantile onset and severe developmental delay. The diagnosis is based on pathologic evidence of muscular dystrophy revealed by biopsy or an increased serum creatine kinase levels. Involvement of the brain is characterized by abnormal cerebral cortical dysplasia, cerebellar dysplasia, and white matter changes. We encountered a case of Fukuyama congenital muscular dystrophy in which brain MRI findings were typical, and present this case together with a review of the literature.

  4. Alpha-1-antitrypsin studies: canine serum and canine surfactant protein

    International Nuclear Information System (INIS)

    Canine serum alpha-1-antitrypsin was isolated by gel filtration and affinity chromatography and characterized by polyacrylamide gel electrophoresis and immunoelectrophoresis. Measurement of the trypsin inhibitory capacity of the separated protein indicated a ninefold concentration of functional trypsin inhibitor during the isolation procedure. Electrophoresis demonstrated the presence of a single protein with alpha-globulin mobility and a molecular weight near that of human alpha-1-antitrypsin. The trypsin inhibitory capacity of pulmonary surfactant protein from five Beagle dogs was measured, related to total surfactant protein concentration, and compared with similar measurements on whole serum from the same animals. Results indicated a variable concentration of trypsin inhibitor in the canine pulmonary surfactant protein. However, the concentration in the surfactant protein was always significantly higher than that in the corresponding serum sample. Preliminary experiments designed to separate the trypsin inhibitory fraction(s) from the other surfactant proteins by gel filtration chromatography indicated that the trypsin inhibitor was probably a single protein with a molecular weight near that of alpha-1-antitrypsin. (U.S.)

  5. Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy

    DEFF Research Database (Denmark)

    Sveen, Marie-Louise; Thune, Jens Jakob; Køber, Lars;

    2008-01-01

    OBJECTIVE: To investigate the extent of cardiac involvement in patients with 1 of the 12 groups of recessively inherited limb-girdle muscular dystrophy type 2 (LGMD2A-L) and Becker muscular dystrophy (BMD). DESIGN: Prospective screening. SETTING: Neuromuscular Clinic and Department of Cardiology......-I and in 14 of 30 patients (47%) with BMD. Only a few patients with LGMD2A and unclassified LGMD2 had mild cardiac involvement, whereas 29% and 67% of patients with LGMD2I and LGMD2E, respectively, had cardiac involvement. Cardiac involvement was not correlated with age, muscle strength, or the level...... of dystrophic changes on muscle biopsy. CONCLUSIONS: This study demonstrates a high prevalence of cardiac involvement in patients with LGMD2I, LGMD2E, and BMD. Patients with LGMD2A, LGMD2D, and unclassified LGMD2 have a much lower and milder prevalence of cardiac involvement....

  6. Bilateral cloudy cornea: is the usual suspect congenital hereditary endothelial dystrophy or stromal dystrophy?

    Science.gov (United States)

    Acar, Banu Torun; Bozkurt, Kansu Tahir; Duman, Erkan; Acar, Suphi

    2016-01-01

    We provide the diagnosis, treatment and follow-up period of a patient with cloudy cornea in both eyes from birth. A 4-year-old girl presented with blurring in both eyes. Penetrating keratoplasty (PK) was performed with the preliminary diagnosis of congenital hereditary endothelial dystrophy in June 2012. According to the pathology report for extracted host tissue, the Descemet's membrane (DM) and endothelium were healthy and diagnosis was reported to be congenital hereditary stromal dystrophy. Deep anterior lamellar keratoplasty was performed on the left eye. The DM was transparent at follow-up. Cornea transplantation is the only choice to provide visual rehabilitation in children with congenital cloudy cornea. However, it is known that the prognosis of traditional PK in the paediatric age group is not good. Therefore, when using alternative keratoplasty (deep anterior lamellar keratoplasty, Descemet's stripping automated endothelial keratoplasty) options, pathological examination of the host tissue should be made. PMID:27107055

  7. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy.

    Science.gov (United States)

    McGreevy, Joe W; Hakim, Chady H; McIntosh, Mark A; Duan, Dongsheng

    2015-03-01

    Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. PMID:25740330

  8. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

    Directory of Open Access Journals (Sweden)

    Joe W. McGreevy

    2015-03-01

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs.

  9. [Exon skipping therapy for Duchenne muscular dystrophy by using antisense Morpholino].

    Science.gov (United States)

    Takeda, Shin'ichi

    2009-11-01

    Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin protein at the sarcolemma. Exon skipping by antisense oligonucleotides is a novel method to restore the reading frame of the mutated DMD gene, and rescue dystrophin production. We recently reported that systemic delivery of Morpholino antisense oligonucleotides targeting exon 6 and 8 of the canine DMD gene, efficiently recovered functional dystrophin proteins at the sarcolamma of dystrophic dogs, and improved performance of affected dogs without serious side effects (Yokota et al., Ann Neurol. 65 (6): 667-676, 2009). To optimize therapeutic antisense Morpholinos for more frequent mutations of the DMD gene, we designed antisense Morpholinos targeting exon 51 of the mouse DMD gene, and injected them separately or in combination into the muscles of mdx52 mice, in which exon 52 has been deleted by a gene targeting technique (Araki et al., 1997). We also tried systemic delivery of antisense Morpholino to skip exon 51 in mdx52 mice. It is important to verify the effectiveness and side effects of antisense Morpholino in experimental animal models such as dystrophic dogs or mdx52 mice, before clinical trials in DMD patients. PMID:20030230

  10. Valley sign in Becker muscular dystrophy and outliers of Duchenne and Becker muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Pradhan Sunil

    2004-04-01

    Full Text Available Valley sign has been described in patients with Duchenne muscular dystrophy (DMD. As there are genetic and clinical similarities between DMD and Becker muscular dystrophy (BMD, this clinical sign is evaluated in this study in BMD and DMD/BMD outliers. To evaluate the sign, 28 patients with Becker muscular dystrophy (BMD, 8 DMD/BMD outliers and 44 age-matched male controls with other neuromuscular diseases were studied. The sign was examined after asking patients to abduct their arms to about 90ºwith hands directed upwards; the muscle bulk over the back of the shoulders was observed. The sign was considered positive if the infraspinatus and deltoid muscles were enlarged and between these two muscles, the muscles forming the posterior axillary fold were wasted as if there were a valley between the two mounts. Twenty-five BMD patients and 7 DMD/BMD outliers had positive valley sign. However, it was less remarkable in comparison to DMD. It was absent in all the 44 controls. It was concluded that the presence of valley sign may help in differentiating BMD from other progressive neuromuscular disorders of that age group.

  11. Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies

    OpenAIRE

    J. Van Heerden; J. Bingham; M. Van Vuuren; R.E.J. Burroughs; E. Stylianides

    2002-01-01

    Wild dogs Lycaon pictus (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use ...

  12. Genetics Home Reference: lattice corneal dystrophy type II

    Science.gov (United States)

    ... Diagnosis & Management These resources address the diagnosis or management of lattice corneal dystrophy type II: American Foundation for the Blind: Living with Vision Loss Genetic Testing Registry: Meretoja syndrome Merck Manual ...

  13. Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy

    NARCIS (Netherlands)

    Lassche, S.; Stienen, G.J.; Irving, T.C.; Maarel, S.M. van der; Voermans, N.C.; Padberg, G.W.A.M.; Granzier, H.; Engelen, B.G. van; Ottenheijm, C.A.C.

    2013-01-01

    OBJECTIVE: To investigate whether sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). METHODS: Sarcomeric function was evaluated by contractile studies on demembranated single muscle fibers obtained from quadriceps muscle biopsies of 4 patients wit

  14. Cardiac assessment of patients with late stage Duchenne muscular dystrophy

    NARCIS (Netherlands)

    van Bockel, E. A. P.; Lind, J. S.; Zijlstra, J. G.; Wijkstra, P. J.; Meijer, P. M.; van den Berg, M. P.; Slart, R. H. J. A.; Aarts, L. P. H. J.; Tulleken, J. E.

    2009-01-01

    Background. Duchenne muscular dystrophy (DMD) patients used to die mainly from pulmonary problems. However, as advances in respiratory care increase life expectancy, mortality due to cardiomyopathy rises. Echocardiography remains the standard diagnostic modality for cardiomyopathy in DMD patients, b

  15. Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.

    Science.gov (United States)

    Kamal-Salah, Radua; Baquero-Aranda, Isabel; Grana-Pérez, María Del Mar; García-Campos, Jose Manuel

    2015-03-12

    We report an unusual association of a pattern dystrophy of the retinal pigment epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome.

  16. Aerobic training and postexercise protein in facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Grete; Prahm, Kira P; Dahlqvist, Julia R;

    2015-01-01

    OBJECTIVE: To investigate the effect of regular aerobic training and postexercise protein-carbohydrate supplementation in patients with facioscapulohumeral muscular dystrophy (FSHD). METHODS: In this randomized, double-blind, placebo-controlled parallel study, we randomized untrained men (n = 21...

  17. TRIM Proteins in Therapeutic Membrane Repair of Muscular Dystrophy

    OpenAIRE

    Alloush, Jenna; Weisleder, Noah

    2013-01-01

    Muscular dystrophy represents a major unmet medical need as only palliative treatments exist for these debilitating diseases. Since multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity a therapeutic approach that can target this loss of membrane barrier function could be applicable to a number of these distinct genetic diseases. One pathway that presents an excellent opportunity to affect compromised membrane integrity is the process that the cell uses to...

  18. Gene Therapy in Large Animal Models of Muscular Dystrophy

    OpenAIRE

    Wang, Zejing; Jeffrey S. Chamberlain; Tapscott, Stephen J.; Storb, Rainer

    2009-01-01

    The muscular dystrophies are a group of genetically and phenotypically heterogeneously inherited diseases characterized by progressive muscle wasting, which can lead to premature death in severe forms such as Duchenne muscular dystrophy (DMD). In many cases they are caused by the absence of proteins that are critical components of the dystrophin-glycoprotein complex, which links the cytoskeleton and the basal lamina. There is no effective treatment for these disorders at present, but several ...

  19. Gene Therapy for Muscular Dystrophy: Lessons Learned and Path Forward

    OpenAIRE

    Mendell, Jerry R.; Rodino-Klapac, Louise; Sahenk, Zarife; Malik, Vinod; Kaspar, Brian K.; Walker, Christopher M.; Clark, K. Reed

    2012-01-01

    Our Translational Gene Therapy Center has used small molecules for exon skipping and mutation suppression and gene transfer to replace or provide surrogate genes as tools for molecular-based approaches for the treatment of muscular dystrophies. Exon skipping is targeted at the pre-mRNA level allowing one or more exons to be omitted to restore the reading frame. In Duchenne Muscular Dystrophy (DMD), clinical trials have been performed with two different oligomers, a 2′O-methyl-ribo-oligonucleo...

  20. Sarcopenia and Sarcopenic Obesity in Patients with Muscular Dystrophy

    OpenAIRE

    Luciano eMerlini; Alessandro eVagheggini; Daniela eCocchi

    2014-01-01

    Aging sarcopenia and muscular dystrophy are two conditions characterized by lower skeletal muscle quantity, lower muscle strength, and lower physical performance. Aging is associated with a peculiar alteration in body composition called sarcopenic obesity characterized by a decrease in lean body mass and increase in fat mass. To evaluate the presence of sarcopenia and obesity in a cohort of adult patients with muscular dystrophy we have used the measurement techniques considered golden standa...

  1. The importance of genetic diagnosis for Duchenne muscular dystrophy

    OpenAIRE

    Aartsma-Rus, Annemieke; Ginjaar, Ieke B; Bushby, Kate

    2016-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligibl...

  2. Annexin A6 modifies muscular dystrophy by mediating sarcolemmal repair

    OpenAIRE

    Swaggart, KA; Demonbreun, AR; Vo, AH; Swanson, KE; Kim, EY; Fahrenbach, JP; Holley-Cuthrell, J; Eskin, A; Z. Chen; Squire, K; Heydemann, A; Palmer, AA; Nelson, SF; McNally, EM

    2014-01-01

    Many monogenic disorders, including the muscular dystrophies, display phenotypic variability despite the same disease-causing mutation. To identify genetic modifiers of muscular dystrophy and its associated cardiomyopathy, we used quantitative trait locus mapping and whole genome sequencing in a mouse model. This approach uncovered a modifier locus on chromosome 11 associated with sarcolemmal membrane damage and heart mass. Whole genome and RNA sequencing identified Anxa6, encoding annexin A6...

  3. Dasatinib as a treatment for Duchenne muscular dystrophy

    OpenAIRE

    Lipscomb, Leanne; Piggott, Robert W.; Emmerson, Tracy; Winder, Steve J.

    2015-01-01

    Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using...

  4. Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy

    OpenAIRE

    Francesca Sciandra; Maria Giulia Bigotti; Bruno Giardina; Manuela Bozzi; Andrea Brancaccio

    2015-01-01

    In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1) have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review ...

  5. The fibrinolitys system in muscle regeneration and dystrophy

    OpenAIRE

    Vidal Iglesias, Berta

    2008-01-01

    Duchenne muscular dystrophy (DMD) is a fatal degenerative disorder of locomotor and respiratory muscles, in which myofibers are progressively replaced by non-muscular fibrotic tissue. Here, we show that fibrin/ogen accumulates in dystrophic muscles of DMD patients and of the mdx mouse model of DMD. Genetic loss or pharmacological depletion of fibrin/ogen in mdx mice attenuated muscular dystrophy progression and improved locomotor capacity. More importantly, fibrin/ogen depletion reduced fibro...

  6. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy

    OpenAIRE

    Parvaneh KARIMZADEH; Ahad GHAZAVI

    2012-01-01

    How to Cite this Article: Karimzadeh P, Ghazavi A. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy. IranianJournal of Child Neurology 2012;6(1):5-12.ObjectiveDuchenne muscular dystrophy (DMD) is a degenerative disease that usually becomes clinically detectable in childhood as progressive proximal weakness. No cure is yet available for DMD, but the use of steroids improves muscle strength and function. This study has been carried out to select the best steroid for the m...

  7. Autophagy as a new therapeutic target in Duchenne muscular dystrophy

    OpenAIRE

    Palma, C.; F. Morisi; Cheli, S; S. Pambianco; Cappello, V; Vezzoli, M; Rovere-Querini, P; Moggio, M; Ripolone, M.; Francolini, M; Sandri, M.; Clementi, E

    2012-01-01

    A resolutive therapy for Duchene muscular dystrophy, a severe degenerative disease of the skeletal muscle, is still lacking. Because autophagy has been shown to be crucial in clearing dysfunctional organelles and in preventing tissue damage, we investigated its pathogenic role and its suitability as a target for new therapeutic interventions in Duchenne muscular dystrophy (DMD). Here we demonstrate that autophagy is severely impaired in muscles from patients affected by DMD and mdx mice, a mo...

  8. RESPIRATORY DYSFUNCTION IN UNSEDATED DOGS WITH GOLDEN RETRIEVER MUSCULAR DYSTROPHY

    OpenAIRE

    DeVanna, Justin C.; Kornegay, Joe N; Bogan, Daniel J.; Bogan, Janet R; Dow, Jennifer L.; Hawkins, Eleanor C.

    2013-01-01

    Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a ...

  9. Cardiac involvement in Duchenne and Becker muscular dystrophy

    OpenAIRE

    Mavrogeni, Sophie; Markousis-Mavrogenis, George; Papavasiliou, Antigoni; Kolovou, Genovefa

    2015-01-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation, not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction, heart block or malignant arrhythmias. Not only DMD/BMD patients, but also female carriers may present cardiac invol...

  10. The new frontier in muscular dystrophy research: booster genes

    DEFF Research Database (Denmark)

    Engvall, Eva; Wewer, Ulla M

    2003-01-01

    More than 30 different forms of muscular dystrophy (MD) have been molecularly characterized and can be diagnosed, but progress toward treatment has been slow. Gene replacement therapy has met with great difficulty because of the large size of the defective genes and because of difficulties...... of the boosters are better understood, drugs may be developed to provide the boost to muscle. Some of the experiences in models of muscular dystrophy may inspire new approaches in other genetic degenerative diseases as well....

  11. Current and emerging treatment strategies for Duchenne muscular dystrophy

    OpenAIRE

    Mah JK

    2016-01-01

    Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the...

  12. Bilateral coexistence of keratoconus and macular corneal dystrophy

    Directory of Open Access Journals (Sweden)

    Ghazi Al-Hamdan

    2009-01-01

    The authors hereby report a 21-year-old female who presented with the typical signs and topographic evidence of keratoconus in association with macular corneal dystrophy. Histopathologic evaluation from the excised corneal button after corneal transplant confirmed the diagnosis. To our knowledge, there is only one previous report in the literature linking the association of keratoconus and macular corneal dystrophy in the same eye bilaterally.

  13. Prognostic markers of canine pyometra

    Directory of Open Access Journals (Sweden)

    M.C. Sant'Anna

    2014-12-01

    Full Text Available The pyometra is a disease that affects middle age and elderly female dogs during diestrus. Hormonal, microbiological, biochemical and hematological aspects are well described. However, few studies have evaluated the role of each in the prognosis of canine pyometra. The aim of this study was to identify markers associated with clinical worsening of dogs with pyometra. We prospectively evaluated 80 dogs with pyometra treated surgically. Group 1 consisted of dogs that were discharged within 48 hours after surgery and Group 2 consisted of those who required prolonged hospitalization or died. The findings of hematological, biochemical and blood lactate levels were compared between groups and variables such as bacterial multidrug resistance, systemic inflammatory response syndrome (SIRS, hyperlactatemia and increased creatinine were analyzed through the dispersion of frequencies between groups. Among the variables studied, the presence of SIRS and elevated serum creatinine >2.5mg/mL were effective in predicting the worsening of the disease and can be used as prognostic markers of canine pyometra.

  14. Oculopharyngeal muscular dystrophy: a polyalanine myopathy.

    Science.gov (United States)

    Brais, Bernard

    2009-01-01

    It has been 10 years since the identification of the first PABPN1 gene (GCN)(n)/polyalanine mutations responsible for oculopharyngeal muscular dystrophy (OPMD). These mutations have been found in most cases of OPMD diagnosed in more than 35 countries. Sequence analyses have shown that such mutations have occurred numerous times in human history. Although PABPN1 was found early on to be a component of the classic filamentous intranuclear inclusions (INIs), mRNA and other proteins also have been found to coaggregate in the INIs. It is still unclear if the INIs play a pathologic or a protective role. The generation of numerous cell and animal models of OPMD has led to greater insight into its complex molecular pathophysiology and identified the first candidate therapeutic molecules. This paper reviews basic and clinical research on OPMD, with special emphasis on recent developments in the understanding of its pathophysiology. PMID:19080757

  15. Fibroblast cultures in duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-(3H)-proline for 24 hours. Intracellular collagen incoption was significantly decreased (2.2 X) and extracellular collagen incorporation significantly increased (1.8 X) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts. (author)

  16. Intramuscular degeneration process in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T1-weighted longitudinal images (TR=215∼505 ms, TE=19∼20 ms). The following results were obtained. Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. These findings were more prominent toward myotendon junction than muscle bellies. Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. (author)

  17. Natural history of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Qing KE

    2015-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is X-linked recessive hereditary disease. DMD gene mutations result in dystrophin deficiency, which causes not only muscle movement disorders but also scoliosis, cognitive dysfunction, urinary tract diseases, respiratory diseases and heart diseases. Most patients die in early adult for respiratory and circulatory failure. Early multidisciplinary therapies will significantly delay disease progression and improve patients' quality of life. However, DMD diagnosis and treatment exist significantly time delay now. In this study, we review the natural history of DMD, including motor, cognitive, respiratory and heart function, for improving DMD early recognition, diagnosis and treatment, so as to benefit DMD patients. DOI: 10.3969/j.issn.1672-6731.2015.05.004

  18. Oculopharyngeal muscular dystrophy: a polyalanine myopathy.

    Science.gov (United States)

    Brais, Bernard

    2009-01-01

    It has been 10 years since the identification of the first PABPN1 gene (GCN)(n)/polyalanine mutations responsible for oculopharyngeal muscular dystrophy (OPMD). These mutations have been found in most cases of OPMD diagnosed in more than 35 countries. Sequence analyses have shown that such mutations have occurred numerous times in human history. Although PABPN1 was found early on to be a component of the classic filamentous intranuclear inclusions (INIs), mRNA and other proteins also have been found to coaggregate in the INIs. It is still unclear if the INIs play a pathologic or a protective role. The generation of numerous cell and animal models of OPMD has led to greater insight into its complex molecular pathophysiology and identified the first candidate therapeutic molecules. This paper reviews basic and clinical research on OPMD, with special emphasis on recent developments in the understanding of its pathophysiology.

  19. Recent advances in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Perkins KJ

    2012-10-01

    Full Text Available Kelly J Perkins,1,2 Kay E Davies21Sir William Dunn School of Pathology, 2MRC Functional Genomics Unit, University of Oxford, Oxford, UKAbstract: Duchenne muscular dystrophy (DMD, an allelic X-linked progressive muscle-wasting disease, is one of the most common single-gene disorders in the developed world. Despite knowledge of the underlying genetic causation and resultant pathophysiology from lack of dystrophin protein at the muscle sarcolemma, clinical intervention is currently restricted to symptom management. In recent years, however, unprecedented advances in strategies devised to correct the primary defect through gene- and cell-based therapeutics hold particular promise for treating dystrophic muscle. Conventional gene replacement and endogenous modification strategies have greatly benefited from continued improvements in encapsidation capacity, transduction efficiency, and systemic delivery. In particular, RNA-based modifying approaches such as exon skipping enable expression of a shorter but functional dystrophin protein and rapid progress toward clinical application. Emerging combined gene- and cell-therapy strategies also illustrate particular promise in enabling ex vivo genetic correction and autologous transplantation to circumvent a number of immune challenges. These approaches are complemented by a vast array of pharmacological approaches, in particular the successful identification of molecules that enable functional replacement or ameliorate secondary DMD pathology. Animal models have been instrumental in providing proof of principle for many of these strategies, leading to several recent trials that have investigated their efficacy in DMD patients. Although none has reached the point of clinical use, rapid improvements in experimental technology and design draw this goal ever closer. Here, we review therapeutic approaches to DMD, with particular emphasis on recent progress in strategic development, preclinical evaluation and

  20. Extrusion processing : effects on dry canine diets

    NARCIS (Netherlands)

    Tran, Q.D.

    2008-01-01

    Keywords: Extrusion, Canine diet, Protein, Lysine, Starch gelatinization, Palatability, Drying. Extrusion cooking is a useful and economical tool for processing animal feed. This high temperature, short time processing technology causes chemical and physical changes that alter the nutritional and

  1. Triple bone labeling of canine mandibles

    DEFF Research Database (Denmark)

    Pinholt, E M; Kwon, P H

    1990-01-01

    Fluorescence microscopy was used for evaluation of new bone formation in 16 canine mandibles augmented with hydroxylapatite (HA) granules. Three fluorochromes were injected at different time intervals during therapeutic radiation treatment. Oxytetracycline, DCAF, and alizarin-complexone were give...

  2. Cardiac Dysrhythmias, Cardiomyopathy and Muscular Dystrophy in Patients with Emery-Dreifuss Muscular Dystrophy and Limb-Girdle Muscular Dystrophy Type 1B

    OpenAIRE

    Hong, Jong-Seo; Ki, Chang-Seok; Kim, Jong-Won; Suh, Yeon-Lim; Kim, June Soo; Baek, Kyung Kee; Kim, Byoung Joon; Ahn, Kyoung Ju; Kim, Duk-Kyung

    2005-01-01

    Emery-Dreifuss muscular dystrophy (EDMD) and limb-girdle muscular dystrophy type 1B (LGMD1B) are characterized by cardiac dysrhythmias, late-onset cardiomyopathy, slowly progressive skeletal myopathy and contractures of the neck, elbows and ankles. The causative mutation is either in the emerin gene (X-linked recessive EDMD) or lamin A/C gene (autosomal dominant EDMD2 or LGMD1B). We report three cases of EDMD, EDMD2 and LGMD1B. A 14-yr-old boy showed limitation of cervical flexion and contrac...

  3. Canine babesiosis: from molecular taxonomy to control

    Directory of Open Access Journals (Sweden)

    Irwin Peter J

    2009-03-01

    Full Text Available Abstract Canine babesiosis is a clinically significant emerging vector-borne disease caused by protozoan haemoparasites. This review article considers recent literature pertaining to the taxonomic classification of Babesia and Theileria species affecting dogs and the geographical distribution of these parasites. The diagnosis of canine babesiosis by traditional, molecular and serological methods is reviewed, together with recent advances in our understanding of the pathophysiology of piroplasmosis, and of the treatment and prevention of this disease.

  4. [Nonsurgical endodontic treatment of an invaginated canine].

    Science.gov (United States)

    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment. PMID:2638021

  5. Systemic inflammarory response in canine pyometra

    OpenAIRE

    Fransson, Boel

    2003-01-01

    Research efforts have focused mainly on the hormonal aspects of canine pyometra for more than 6 decades. However, this disease is often manifested as systemic illness in response to the bacterial uterine infection. Studies I-II were undertaken to clarify bacteriological aspects of canine pyometra; i.e. the origin of the infecting bacteria, the infecting bacteria’s impact on severity of the systemic illness and the presence of bacterial endotoxin in the systemic circulation. Study I, a bacteri...

  6. [Nonsurgical endodontic treatment of an invaginated canine].

    Science.gov (United States)

    Fernández Guerrero, F; Miñana Laliga, R; Bullon Fernandez, P

    1989-01-01

    We present a case of a maxillary canine with a dens invaginatus treated successfully. The patient had pain, swelling and a sinus tract coming from the inmature apex of the canine. The canals were enlarged and cleaned and the main canal was filled with Calcium Hydroxide to allow the root development. Seven months later, the patient was asymptomatic and the tooth was obturated with guttapercha. One year later it was confirm the success in the treatment.

  7. Treatment modalities of palatal impacted canines

    OpenAIRE

    Dimova, Cena; Papakoca, Kiro; Ristoska, Sonja; Kovacevska, Ivona

    2012-01-01

    Introduction: The orthodontic treatment of impacted maxillary canine remains a challenge to today’s clinicians. The treatment of this clinical entity usually involves surgical exposure of the impacted tooth, followed by orthodontic traction to guide and align it into the dental arch. The impacted palatal canine requires a combination of both treatment modalities: orthodontic management and oral surgical treatment. Two types of approach are commonly used: simple exposure, or exposure with brac...

  8. Proliferative histiocytic disorders of canine skin.

    Science.gov (United States)

    Middleton, D J

    1997-06-01

    Proliferative histiocytic disorders of canine skin present a clinical spectrum from the innocuous self-limiting solitary dermal lesion of cutaneous histiocytoma, through the recurrent deep dermal nodules of cutaneous histiocytosis to the generally fatal condition of Bernese Mountain Dogs termed systemic histiocytosis, in which visceral involvement is commonly encountered. Immunocytochemical characterization of the constituent histiocytic cells and accompanying lymphoid infiltrate using canine species specific reagents has elucidated considerably the mechanism by which these conditions exhibit their various biologic behaviours.

  9. Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Søren P; Sveen, Marie-Louise; Hansen, Regitze S;

    2013-01-01

    We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.......We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies....

  10. Muscular Dystrophy Campaign: Putting Some Financial Muscle Behind Finding a Cure

    OpenAIRE

    Pohlschmidt, Marita

    2012-01-01

    The Muscular Dystrophy Campaign, a London-based charitable organization, funds research on muscle function and muscle disease, including the study of muscle stem cells. Dr. Marita Pohlschmidt, the Muscular Dystrophy Campaign's director of research, describes its vision and goals.

  11. Outcome of Long-Term Corticosteroid Treatment in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-06-01

    Full Text Available The clinical orthopedic effects of chronic daily corticosteroid treatment were evaluated by chart review in boys with genetically confirmed Duchenne muscular dystrophy (DMD followed at the Ohio State University Muscular Dystrophy Clinic between 2000 and 2003.

  12. Outcome of Long-Term Corticosteroid Treatment in Duchenne Muscular Dystrophy

    OpenAIRE

    J Gordon Millichap

    2007-01-01

    The clinical orthopedic effects of chronic daily corticosteroid treatment were evaluated by chart review in boys with genetically confirmed Duchenne muscular dystrophy (DMD) followed at the Ohio State University Muscular Dystrophy Clinic between 2000 and 2003.

  13. NIH study shows increased risk for two types of myotonic muscular dystrophy

    Science.gov (United States)

    Adults with a form of muscular dystrophy called myotonic muscular dystrophy (MMD) may be at increased risk of developing cancer, according to a study by investigators at the National Cancer Institute (NCI), part of the National Institutes of Health.

  14. Despre babesioza canină

    Directory of Open Access Journals (Sweden)

    Andrei Nanu

    2016-06-01

    Full Text Available The objective of this bibliographic essay, addressed both to veterinary clinicians and researchers, is to bring to mind the disease in terms of etiology, clinical manifestations and therapeutic and prophylactic management, as well as to remind the issues arising from recent researches. Depending on the virulence of the parasite species, body's immune response and therapeutic management approached, the plateau of disease evolution can be quite wide - from a favorable prognosis to a lethal outcome of the animal. The complexity of the pathogenic mechanism in babesiosis is due to soluble parasite antigens (SPA which, according to recent studies, have been obtained in vitro and then used as immunological product in disease prevention. Producing a vaccine against canine babesiosis with parasite antigens of local strains could play an important role to prevent the clinical expression of this disease in Romania.

  15. Environmental contamination by canine geohelminths.

    Science.gov (United States)

    Traversa, Donato; Frangipane di Regalbono, Antonio; Di Cesare, Angela; La Torre, Francesco; Drake, Jason; Pietrobelli, Mario

    2014-01-01

    Intestinal nematodes affecting dogs, i.e. roundworms, hookworms and whipworms, have a relevant health-risk impact for animals and, for most of them, for human beings. Both dogs and humans are typically infected by ingesting infective stages, (i.e. larvated eggs or larvae) present in the environment. The existence of a high rate of soil and grass contamination with infective parasitic elements has been demonstrated worldwide in leisure, recreational, public and urban areas, i.e. parks, green areas, bicycle paths, city squares, playgrounds, sandpits, beaches. This review discusses the epidemiological and sanitary importance of faecal pollution with canine intestinal parasites in urban environments and the integrated approaches useful to minimize the risk of infection in different settings. PMID:24524656

  16. Biomarkers in canine parvovirus enteritis.

    Science.gov (United States)

    Schoeman, J P; Goddard, A; Leisewitz, A L

    2013-07-01

    Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

  17. CANINE: a robotic mine dog

    Science.gov (United States)

    Stancil, Brian A.; Hyams, Jeffrey; Shelley, Jordan; Babu, Kartik; Badino, Hernán.; Bansal, Aayush; Huber, Daniel; Batavia, Parag

    2013-01-01

    Neya Systems, LLC competed in the CANINE program sponsored by the U.S. Army Tank Automotive Research Development and Engineering Center (TARDEC) which culminated in a competition held at Fort Benning as part of the 2012 Robotics Rodeo. As part of this program, we developed a robot with the capability to learn and recognize the appearance of target objects, conduct an area search amid distractor objects and obstacles, and relocate the target object in the same way that Mine dogs and Sentry dogs are used within military contexts for exploration and threat detection. Neya teamed with the Robotics Institute at Carnegie Mellon University to develop vision-based solutions for probabilistic target learning and recognition. In addition, we used a Mission Planning and Management System (MPMS) to orchestrate complex search and retrieval tasks using a general set of modular autonomous services relating to robot mobility, perception and grasping.

  18. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  19. Interpretation of "Diagnosis and management of Duchenne muscular dystrophy: a guide for families (2011 version)"

    OpenAIRE

    Xi-hua LI

    2015-01-01

    The guideline "Diagnosis and management of Duchenne muscular dystrophy" was supported by a 3-year-long project guided by US Centers for Disease Control and Prevention (CDC), in collaboration with patient advocacy groups [Muscular Dystrophy Association (MDA), Parent Project Muscular Dystrophy (PPMD) and United Parent Projects Muscular Dystrophy (UPPMD)] and Translational Research in Europe: Assessment and Treatment of Neuromuscular Disease (TREAT-NMD) network. The main document was published i...

  20. Continuous Infusion Propofol General Anesthesia for Dental Treatment in Patients With Progressive Muscular Dystrophy

    OpenAIRE

    Kawaai, Hiroyoshi; Tanaka, Kazuho; Yamazaki, Shinya

    2005-01-01

    Progressive muscular dystrophy may produce abnormal reactions to several drugs. There is no consensus of opinion regarding the continuous infusion of propofol in patients with progressive muscular dystrophy. We successfully treated 2 patients with progressive muscular dystrophy who were anesthetized with a continuous infusion of propofol. In case 1, a 19-year-old, 59-kg man with Becker muscular dystrophy and mental retardation was scheduled for dental treatment under general anesthesia. Gener...

  1. FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1.

    Directory of Open Access Journals (Sweden)

    Sandra J Feeney

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an autosomal-dominant disease with no effective treatment. The genetic cause of FSHD is complex and the primary pathogenic insult underlying the muscle disease is unknown. Several disease candidate genes have been proposed including DUX4 and FRG1. Expression analysis studies of FSHD report the deregulation of genes which mediate myoblast differentiation and fusion. Transgenic mice overexpressing FRG1 recapitulate the FSHD muscular dystrophy phenotype. Our current study selectively examines how increased expression of FRG1 may contribute to myoblast differentiation defects. We generated stable C2C12 cell lines overexpressing FRG1, which exhibited a myoblast fusion defect upon differentiation. To determine if myoblast fusion defects contribute to the FRG1 mouse dystrophic phenotype, this strain was crossed with skeletal muscle specific FHL1-transgenic mice. We previously reported that FHL1 promotes myoblast fusion in vitro and FHL1-transgenic mice develop skeletal muscle hypertrophy. In the current study, FRG1 mice overexpressing FHL1 showed an improvement in the dystrophic phenotype, including a reduced spinal kyphosis, increased muscle mass and myofiber size, and decreased muscle fibrosis. FHL1 expression in FRG1 mice, did not alter satellite cell number or activation, but enhanced myoblast fusion. Primary myoblasts isolated from FRG1 mice showed a myoblast fusion defect that was rescued by FHL1 expression. Therefore, increased FRG1 expression may contribute to a muscular dystrophy phenotype resembling FSHD by impairing myoblast fusion, a defect that can be rescued by enhanced myoblast fusion via expression of FHL1.

  2. Successful treatment of murine muscular dystrophy with the proteinase inhibitor leupeptin.

    OpenAIRE

    Sher, J H; Stracher, A.; Shafiq, S A; Hardy-Stashin, J

    1981-01-01

    Mice with genetic muscular dystrophy were treated with intraperitoneal injections of the proteinase inhibitor leupeptin, beginning before the onset of weakness. A significant number of the treated animals failed to develop histological evidence of dystrophy, compared with controls. Leupeptin treatment prevented (or delayed) the onset of muscular dystrophy in this experiment.

  3. The Link Between Stress Disorders and Autonomic Dysfunction in Muscular Dystrophy

    OpenAIRE

    Rasna eSabharwal

    2014-01-01

    Muscular dystrophy is a progressive disease of muscle weakness, muscle atrophy and cardiac dysfunction. Patients afflicted with muscular dystrophy exhibit autonomic dysfunction along with cognitive impairment, severe depression, sadness, and anxiety. Although the psychological aspects of cardiovascular disorders and stress disorders are well known, the physiological mechanism underlying this relationship is not well understood, particularly in muscular dystrophy. Therefore, the goal of this p...

  4. Three-dimensional canine loop for management of buccally erupted canines

    Directory of Open Access Journals (Sweden)

    Praveen Mehrotra

    2015-01-01

    Full Text Available Maxillary canines are known as the cornerstones of mouth. They are considered to be important for esthetics and for functional occlusion. Any disturbance in the eruption process leading to an aberrant position will hamper esthetics as well as function. Orthodontic tooth movement of total buccally blocked-out canine is usually difficult as it is related with the problems of severe crowding, midline deviation, involvement of long root movement and risk of gingival recession. Such conditions can be treated orthodontically in various ways, but this clinical innovation helps to correct the buccally placed canines into the arch with a precise control of the canine in all the Three-dimensions (3D of space as well as providing maximum comfort to the patient by placing the canine loop on the palatal surface of the tooth, reducing soreness on the labial mucosa. It can be easily fabricated and activated at chairside for either simultaneous or sequential control in 3D.

  5. Skin features in myotonic dystrophy type 1: an observational study.

    Science.gov (United States)

    Campanati, A; Giannoni, M; Buratti, L; Cagnetti, C; Giuliodori, K; Ganzetti, G; Silvestrini, M; Provinciali, L; Offidani, A

    2015-05-01

    Poor data regarding skin involvement in Myotonic Dystrophy, also named Dystrophia Myotonica type 1, have been reported. This study aimed to investigate the prevalence and types of skin disorders in adult patients with Myotonic Dystrophy type 1. Fifty-five patients and one hundred age- and sex-matched healthy subjects were referred to a trained dermatologist for a complete skin examination to check for potential cutaneous hallmarks of disease. No difference in prevalence of preneoplastic, neoplastic, and cutaneous lesions was detected between the two groups. Among morphofunctional, proliferative and inflammatory lesions, focal hyperhidrosis (p androgenic alopecia (p = 0.01), nail pitting (p = 0.003), pedunculus fibromas (p = 0. 01), twisted hair (p = 0.01), seborrheic dermatitis (p = 0.02), macules of hyperpigmentation (p = 0.03) were significantly more frequent in patients compared with controls. In patients with Myotonic Dystrophy type 1 significant differences according to sex were found for: early androgenic alopecia, twisted hair and seborrheic dermatitis, whose prevalence was higher in males (p < 0.0001). Our preliminary results seem to rule out an increased prevalence of pre-neoplastic, and neoplastic skin lesions in Myotonic Dystrophy type 1. On the other hand, an increased prevalence of morphofunctional, inflammatory, and proliferative diseases involving adnexal structures seems to characterize adult patients with Myotonic Dystrophy type 1. PMID:25813338

  6. Prevalence of cardiomyopathy in duchenne and becker's muscular dystrophy

    International Nuclear Information System (INIS)

    Cardiac assessment was not done routinely in Duchenne (DMD) and Becker muscular dystrophy (BMD) patients in Northern region of England while evidence was gathering on progressive cardiomyopathy in these patients. We wanted to find out the prevalence, progression and clinical features of cardiac involvement in Duchenne and Becker muscular dystrophy. Methods: It is a retrospective review of clinical, electrocardiographic and echocardiographic assessments. The notes of 52 Duchenne and Becker muscular dystrophy patients were reviewed out of which 32 had DMD, 6 had Intermediate muscular dystrophy (IMD) and 14 had BMD. Prevalence of preclinical and clinically evident cardiac involvement was 88.4% in DMD and BMD patients. Sixty nine% of patients had clinically evident cardiac involvement but only four patients had cardiac symptoms in the form of palpitations, out of which two were due to respiratory dysfunction and others was due to cardiac failure. Clinical examination of the rest of all of the patients was unremarkable. Electrocardiogram was abnormal in 88.4% of patients. Conduction defects were found in 19.4% of patients. Echocardiogram was abnormal in 80.7% of patients but all were poor echo subjects including those who had normal echocardiogram. Though most patients were asymptomatic, a high percentage had evidence of preclinical and clinically evident cardiac involvement. So in all patients with Xp21 linked muscular dystrophy a routine baseline cardiac assessment should be done at the age of 10 years and reviewed after intervals of one to two years. (author)

  7. Morphologic imaging in muscular dystrophies and inflammatory myopathies

    Energy Technology Data Exchange (ETDEWEB)

    Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick [CHU de Lille, Clinique neurologique, Lille (France); Morillon, David; Cotten, Anne [CHRU de Lille, Service de Radiologie Osteoarticulaire, Hopital Roger Salengro, Lille (France); Stojkovic, Tanya [G-H Pitie-Salpetriere, Institut de Myologie, Paris (France)

    2010-12-15

    To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic inflammatory myopathies for describing the topography of muscle involvement. MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n = 4) or 2 (n = 4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy associated with fukutin-related protein mutation; 3 with Becker muscular dystrophy; and 9 with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, and sporadic inclusion body myositis. Analysis of T1 images enabled us to describe the most affected muscles and the muscles usually spared for each muscular disease. In particular, examination of pelvis, thigh, and leg muscles demonstrated significant differences between the muscular diseases. On STIR images, hyperintensities were present in 62% of our patients with muscular dystrophies. A specific pattern of muscular involvement was established for each muscular disease. Hyperintensities observed on STIR images precede fatty degeneration and are not specific for inflammatory myopathies. (orig.)

  8. Canine distemper virus detection in asymptomatic and non vaccinated dogs

    OpenAIRE

    Del Puerto, Helen L; Vasconcelos, Anilton C.; Luciana Moro; Fabiana Alves; Braz, Gissandra F; Almir S. Martins

    2010-01-01

    A quantitative real time polymerase chain reaction (PCR) revealed canine distemper virus presence in peripheral blood samples from asymptomatic and non vaccinated dogs. Samples from eleven domestic dogs with no signs of canine distemper and not vaccinated at the month of collection were used. Canine distemper virus vaccine samples in VERO cells were used as positive controls. RNA was isolated with Trizol®, and treated with a TURBO DNA-free kit. Primers were designed for canine distemper virus...

  9. Serum Creatinine Level: A Supplemental Index to Distinguish Duchenne Muscular Dystrophy from Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Huili Zhang

    2015-01-01

    Full Text Available Background. To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn level reflects disease severity. Methods. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Results. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r=-0.793 and partial correlation analysis after adjustment for age, height, and weight (r=-0.791; both P<0.01. Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations (Z=-4.716, P<0.01 and in Becker muscular dystrophy (BMD patients than Duchenne muscular dystrophy (DMD patients at ages 4, 5, 7, and 9 yr (all P<0.0125. After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β=7.140, t=6.277, P<0.01. Conclusions. Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

  10. The effects of myotonic dystrophy and Duchenne muscular dystrophy on the orofacial muscles and dentofacial morphology.

    Science.gov (United States)

    Kiliaridis, S; Katsaros, C

    1998-12-01

    This article takes a closer view of two of the less rare myopathies, myotonic dystrophy (MyD) and Duchenne muscular dystrophy (DMD). A high prevalence of malocclusions was found among the patients affected by these diseases. The development of the malocclusions in MyD patients seems to be strongly related to the vertical aberration of their craniofacial growth due to the involvement of the masticator, muscles in association with the possibly less affected suprahyoid musculature. Thus, a new situation is established around the teeth transversely. The lowered tongue is not in a position to counterbalance the forces developed during the lowering of the mandible by the stretched facial musculature. This may affect the teeth transversely, decreasing the width of the palate and causing posterior crossbite. The lowered position of the mandible, in combination with the decreased biting forces, may permit an overeruption of the posterior teeth, with increased palatal vault height and development of anterior open bite. The development of the malocclusions in DMD patients also seems to be strongly related to the involvement of the orofacial muscles by the disease. However, the posterior crossbite is not developed owing to the narrow maxillary arch, as is the case in MyD patients. On the contrary, the posterior crossbite in DMD is due to the transversal expansion of the mandibular arch, possibly because of the decreased tonus of the masseter muscle near the molars, in combination with the enlarged hypotonic tongue and the predominance of the less affected orbicularis oris muscle.

  11. Autophagy in granular corneal dystrophy type 2.

    Science.gov (United States)

    Choi, Seung-Il; Kim, Eung Kweon

    2016-03-01

    Autophagy is a lysosomal degradative process that is essential for cellular homeostasis and metabolic stress adaptation. Defective autophagy is involved in the pathogenesis of many diseases including granular corneal dystrophy type 2 (GCD2). GCD2 is an autosomal dominant disorder caused by substitution of histidine for arginine at codon 124 (R124H) in the transforming growth factor β-induced gene (TGFBI) on chromosome 5q31. Transforming growth factor β-induced protein (TGFBIp) is degraded by autophagy, but mutant-TGFBIp accumulates in autophagosomes and/or lysosomes, despite significant activation of basal autophagy, in GCD2 corneal fibroblasts. Furthermore, inhibition of autophagy induces cell death of GCD2 corneal fibroblasts through active caspase-3. As there is currently no pharmacological treatment for GCD2, development of novel therapies is required. A potential strategy for preventing cytoplasmic accumulation of mutant-TGFBIp in GCD2 corneal fibroblasts is to enhance mutant-TGFBIp degradation. This could be achieved by activation of the autophagic pathway. Here, we will consider the role and the potential therapeutic benefits of autophagy in GCD2, with focus on TGFBIp degradation, in light of the recently established role of autophagy in protein degradation.

  12. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  13. 9 CFR 113.201 - Canine Distemper Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Distemper Vaccine, Killed Virus..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper...

  14. Canine hypothyroidism. A diagnostic challenge?

    International Nuclear Information System (INIS)

    Hypothyroidism is one of the most common endocrinopathies in dogs. Clinical symptoms and hematological and biochemical parameters lead to a first suspicion. To confirm diagnosis can be challenging, however. Determination of total serum T4 concentration is accepted as the primary screening test for the disease, and low serum T4 concentrations are intuitively suggestive of hypothyroidism. However it is well known that low T4 concentrations are frequently encountered in euthyroid dogs with various nonthyroidal diseases and in dogs receiving certain pharmacologic agents. Since assessment of endogenous TSH (canine TSH) using current canine TSH assays shows normal values in a high percentage of hypothyroid dogs (up to 40%), its diagnostic value is only limited. The TSH-stimulation test can still be recognized as the gold standard for the diagnosis of hypothyroidism in dogs. Determination of circulating T4 concentration before and 6 hours after the administration of exogenous TSH (recombinant human TSH, Thyrogen registered) provides an assessment of the functional reserve capacity of the thyroid gland with minimal change in post-TSH T4 concentration, compared with the basal concentration, expected in dogs with hypothyroidism. Also this test can be influenced by nonthyroidal illness and by medications known to affect thyroid function. This suppressing influence seems to be less pronounced using a higher dose of TSH. Therefore, to improve the discriminatory power of the TSH stimulation test to differentiate between euthyroid-sick and primary hypothyroidism, the higher dose should be used in cases in which testing cannot be delayed. More recently, ultrasonography and scintigraphy have been used for the diagnosis of primary hypothyroidism. Using ultrasonography, a sensitivity of 98% was reported if size and echogenicity of the gland were combined. However, specificity was as low as 77%. and care must be taken when measuring the gland because of a relatively high interobserver

  15. Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype.

    Science.gov (United States)

    Vieira, Natassia M; Elvers, Ingegerd; Alexander, Matthew S; Moreira, Yuri B; Eran, Alal; Gomes, Juliana P; Marshall, Jamie L; Karlsson, Elinor K; Verjovski-Almeida, Sergio; Lindblad-Toh, Kerstin; Kunkel, Louis M; Zatz, Mayana

    2015-11-19

    Duchenne muscular dystrophy (DMD), caused by mutations at the dystrophin gene, is the most common form of muscular dystrophy. There is no cure for DMD and current therapeutic approaches to restore dystrophin expression are only partially effective. The absence of dystrophin in muscle results in dysregulation of signaling pathways, which could be targets for disease therapy and drug discovery. Previously, we identified two exceptional Golden Retriever muscular dystrophy (GRMD) dogs that are mildly affected, have functional muscle, and normal lifespan despite the complete absence of dystrophin. Now, our data on linkage, whole-genome sequencing, and transcriptome analyses of these dogs compared to severely affected GRMD and control animals reveals that increased expression of Jagged1 gene, a known regulator of the Notch signaling pathway, is a hallmark of the mild phenotype. Functional analyses demonstrate that Jagged1 overexpression ameliorates the dystrophic phenotype, suggesting that Jagged1 may represent a target for DMD therapy in a dystrophin-independent manner. PAPERCLIP. PMID:26582133

  16. The quality of life in boys with Duchenne muscular dystrophy.

    Science.gov (United States)

    Zamani, Gholamreza; Heidari, Morteza; Azizi Malamiri, Reza; Ashrafi, Mahmoud Reza; Mohammadi, Mahmoud; Shervin Badv, Reza; Hosseini, Seyed Ahmad; Salehi, Soodeh; Shahrokhi, Amin; Qorbani, Mostafa; Fathi, Mohammad Reza

    2016-07-01

    We conducted a study to evaluate the quality of life in boys with Duchenne muscular dystrophy aged 8-18 years, compared with that in matched healthy controls. A total of 85 boys with Duchenne muscular dystrophy aged 8-18 years and 136 age, sex and living place matched healthy controls were included in this study. Patients and one of their parents separately completed the 27-item Persian version of KIDSCREEN questionnaire (child and adolescent version and parent version). From the children's perspective, the quality of life in patients was found to be lower in two subclasses: "physical activities and health" (p muscular dystrophy have quite a satisfactory quality of life. A happier and more hopeful life can be promoted through increasing social support and improving the parental knowledge regarding their child's more positive life perspective. PMID:27234309

  17. Transmigration of mandibular canine – case report

    International Nuclear Information System (INIS)

    Transmigration is a phenomenon of movement of an unerupted tooth in the bone across the midline. This anomaly is not often found. Transmigration is more prevalent in females than in males, and more often encountered in the mandible than maxilla, it affects mostly canines. The aim of this study was to present a case report of a mandibular canine transmigration in a patient aged 12. Intraoral examination determined hypodontia of right second premolar and delayed eruption of left second premolar in maxilla, as well as persistent deciduous teeth: right second molar, left canine and second molar. The patient was referred for a Cone-Beam CT examination, which allowed precise visualization of the transmigrating canine as well as ruled out resorption of roots of mandibular incisors. The treatment with a maxillary fixed orthodontic appliance was finished after obtaining a satisfactory result. Proper alignment of the incisors in the anterior-posterior plane and correct midline position were accepted by the patient. Transmigrating canine after consultation with the surgeon was designed to further radiological observation

  18. Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): Case Definition in Surveillance for Childhood-Onset Duchenne/Becker Muscular Dystrophy

    OpenAIRE

    Mathews, Katherine D.; Cunniff, Chris; Kantamneni, Jiji R.; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F. John; Sladky, John; Romitti, Paul A.

    2010-01-01

    The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in one of the participating sites. Critical diagnostic elements of each abstracted record...

  19. Analysis of human transforming growth factor β-induced gene mutation in corneal dystrophy

    Institute of Scientific and Technical Information of China (English)

    李杨; 孙旭光; 任慧媛; 董冰; 王智群; 孙秀英

    2004-01-01

    Background Corneal dystrophy is a group of inherited blinding diseases of the cornea. This study was to identify the mutations of the keratoepithelin (KE) gene for proper diagnosis of corneal dystrophy. Methods Three families with corneal dystrophy were analysed. Thirteen individuals at risk for corneal dystrophy in family A, the proband and her son in family B, and the proband in family C were examined after their blood samples were obtained. Mutation screening of human transforming growth factor β-induced gene (BIGH3 gene) was performed. Results Five individuals in family A were found by clinical evaluation to be affected with granular corneal dystrophy and carried the BIGH3 mutation W555R. However, both probands in families B and C, also diagnosed with granular corneal dystrophy, harboured the BIGH3 mutation R124H. Conclusion Molecular genetic analysis can improve accurate diagnosis of corneal dystrophy.

  20. Cystic dystrophy of heterotopic pancreas in duodenal wall

    Directory of Open Access Journals (Sweden)

    Gandhi Minesh B

    2014-05-01

    Full Text Available Cystic dystrophy in heterotopic pancreas is a rare, poorly understood benign disease of gastric and duodenal wall, which was described for the first time by the French authors in 1970, who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of duodenum & the head of pancreas. We report a case of 33 years old male patient with complaint of recurrent abdominal pain with the probable diagnosis of groove pancreatitis on the clinoradiological findings. Whipple surgery was done. Diagnosis of cystic dystrophy in heterotopic pancreas in duodenal wall with chronic pancreatitis was given histopathologically

  1. uPA deficiency exacerbates muscular dystrophy in MDX mice

    OpenAIRE

    Suelves, Mònica; Vidal, Berta; Serrano, Antonio L.; Tjwa, Marc; Roma, Josep; López-Alemany, Roser; Luttun, Aernout; de Lagrán, María Martínez; Díaz, Maria Àngels; Jardí, Mercè; Roig, Manuel; Dierssen, Mara; Dewerchin, Mieke; Carmeliet, Peter; Muñoz-Cánoves, Pura

    2007-01-01

    Duchenne muscular dystrophy (DMD) is a fatal and incurable muscle degenerative disorder. We identify a function of the protease urokinase plasminogen activator (uPA) in mdx mice, a mouse model of DMD. The expression of uPA is induced in mdx dystrophic muscle, and the genetic loss of uPA in mdx mice exacerbated muscle dystrophy and reduced muscular function. Bone marrow (BM) transplantation experiments revealed a critical function for BM-derived uPA in mdx muscle repair via three mechanisms: (...

  2. Muscle regeneration and inflammation in patients with facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Hauerslev, S; Ørngreen, M C; Hertz, J M;

    2013-01-01

    The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A.......The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A....

  3. Composite mandibular allografts in canines

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To evaluate the feasibility of transplanting composite mandibular allografts to repair large mandibular defects. Methods: Three composite mandibular transplantation models were established. The first model consisted of hemimandible with the attached teeth, muscle and skin, and oral mucosa. The second model was transplanted in the same way with the first one excluding oral mucosa and some teeth, and third one excluding the oral mucosa and all dental crowns. Fourteen transplanting operations were performed in canines. Cyclosporine A and methylprednisone were given for immunosuppression. Results: The composite mandibular organs had an effective and closed return circuit. Transplantation of vascularized allograft of mandibular compound organs was feasible. Two longest time survivors of 67 d and 76 d were in the third model group. Cyclosporine A was successful in suppressing rejection of transplanted composite allograft and prolonging survival time of transplantation models. Conclusions: The composite mandibular allografts were available with large block of living composite tissue,and helpful in restoration of appearance and function for severe mandibular defects.

  4. Neuropsychological profile of duchenne muscular dystrophy.

    Science.gov (United States)

    Perumal, Anna Roshini; Rajeswaran, Jamuna; Nalini, Atchayaram

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an inherited myogenic disorder characterized by progressive muscle wasting. DMD is a fatal X-linked recessive disorder with an estimated prevalence of 1 in 3,500 male live births. This disease has long been associated with intellectual impairment. Research has shown that boys with DMD have variable intellectual performance, indicating the presence of specific cognitive deficits. The aim of the study was to use a battery of intelligence, learning, and memory tests to identify a neuropsychological profile in boys with DMD. A total of 22 boys diagnosed with DMD in the age range of 6 to 10 years old were evaluated using the Wechsler Intelligence Scale for Children-Third Edition, Rey's Auditory Verbal Learning Test, and the Memory for Designs Test. The data were interpreted using means, standard deviations, percentages, and percentiles. Normative data were also used for further interpretation. The results showed that boys with DMD had a significantly lower IQ (88.5). Verbal IQ (86.59) was found to be lower than Performance IQ (92.64). There was evidence of impaired performance on the Processing Speed, Freedom From Distractibility, and Verbal Comprehension Indexes. Specific deficits in information processing, complex attention, immediate verbal memory span, verbal working memory, verbal comprehension, vocabulary, visuoconstruction ability, and verbal learning and encoding were observed. However, perceptional organization, general fund of information, abstract reasoning, visual discrimination and acuity, visual learning and memory, and verbal memory were adequate. The neuropsychological findings support the hypothesis that these children have specific cognitive deficits as opposed to a global intellectual deficit. PMID:24279481

  5. Computed tomography in Duchenne type muscular dystrophy

    International Nuclear Information System (INIS)

    The computed tomography (CT) scan was performed on 91 Duchenne type muscular dystrophy (DMD) patients on the following four levels; (1) at the level of L3 vertebra, (2) 2-3cm above the symphysis pubica, (3) midposition of the thigh, (4) largest-diameter section of the lower leg. The CT of muscles common to most of the DMD patients were as follows: 1. Muscle atrophy: Muscle atrophy was shown as a reduction in the cross-sectional area of the muscles. Very mild muscle atrophy could be detected either by the clearly identified muscle border or by scattered low-density areas of so-called ''moth-eaten'' appearance within muscles. 2. Fat infiltration: The decrease in radio-density of muscles was interpreted as infiltration of fatty tissue. This type of density change was further classified into diffuse, streaked, cobblestone and salt-and-pepper patterns according to the spacial distribution of low-density areas. 3. Selectivity pattern: As the chronological sequence of DMD muscle degeneration is usually different among individual muscles, it may be seen, in some stages, that some of the synergistic muscles are still only slightly involved, while the others are quite severely atrophied with evident fat infiltration. In certain stages of the disease, most of the patients show relative preservation of particular muscles although they assumed a rounded shape. The most resistent muscle was musculus gracilis, followed by the musculus sartorius, musculus semitendinosus (and/or musculus semimembranosus) in that order. According to the severity of the CT changes, 86 of the 91 patients were classed into five stages from A1 to A5. Morphological stages (A1-A5) were well correlated to the functional disability stages by Ueda with a correlation factor of r=0.88. (J.P.N.)

  6. Gastrointestinal manifestations in myotonic muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Massimo Bellini; Sonia Biagi; Cristina Stasi; Francesco Costa; Maria Gloria Mumolo; Angelo Ricchiuti; Santino Marchi

    2006-01-01

    Myotonic dystrophy (MD) is characterized by myotonic phenomena and progressive muscular weakness.Involvement of the gastrointestinal tract is frequent and may occur at any level. The clinical manifestations have previously been attributed to motility disorders caused by smooth muscle damage, but histologic evidence of alterations has been scarce and conflicting.A neural factor has also been hypothesized. In the upper digestive tract, dysphagia, heartburn, regurgitation and dyspepsia are the most common complaints, while in the lower tract, abdominal pain, bloating and changes in bowel habits are often reported. Digestive symptoms may be the first sign of dystrophic disease and may precede the musculo-skeletal features. The impairment of gastrointestinal function may be sometimes so gradual that the patients adapt to it with little awareness of symptoms. In such cases routine endoscopic and ultrasonographic evaluations are not sufficient and targeted techniques (electrogastrography, manometry,electromyography, functional ultrasonography,scintigraphy, etc.) are needed. There is a low correlation between the degree of skeletal muscle involvement and the presence and severity of gastrointestinal disturbances whereas a positive correlation with the duration of the skeletal muscle disease has been reported.The drugs recommended for treating the gastrointestinal complaints such as prokinetic, antidyspeptic drugs and laxatives, are mainly aimed at correcting the motility disorders.Gastrointestinal involvement in MD remains a complex and intriguing condition since many important problems are still unsolved. Further studies concentrating on genetic aspects, early diagnostic techniques and the development of new therapeutic strategies are needed to improve our management of the gastrointestinal manifestations of MD.

  7. Duchenne Muscular Dystrophy: From Diagnosis to Therapy

    Directory of Open Access Journals (Sweden)

    Maria Sofia Falzarano

    2015-10-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH, Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options.

  8. Duchenne Muscular Dystrophy: From Diagnosis to Therapy.

    Science.gov (United States)

    Falzarano, Maria Sofia; Scotton, Chiara; Passarelli, Chiara; Ferlini, Alessandra

    2015-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked inherited neuromuscular disorder due to mutations in the dystrophin gene. It is characterized by progressive muscle weakness and wasting due to the absence of dystrophin protein that causes degeneration of skeletal and cardiac muscle. The molecular diagnostic of DMD involves a deletions/duplications analysis performed by quantitative technique such as microarray-based comparative genomic hybridization (array-CGH), Multiple Ligation Probe Assay MLPA. Since traditional methods for detection of point mutations and other sequence variants require high cost and are time consuming, especially for a large gene like dystrophin, the use of next-generation sequencing (NGS) has become a useful tool available for clinical diagnosis. The dystrophin gene is large and finely regulated in terms of tissue expression, and RNA processing and editing includes a variety of fine tuned processes. At present, there are no effective treatments and the steroids are the only fully approved drugs used in DMD therapy able to slow disease progression. In the last years, an increasing variety of strategies have been studied as a possible therapeutic approach aimed to restore dystrophin production and to preserve muscle mass, ameliorating the DMD phenotype. RNA is the most studied target for the development of clinical strategies and Antisense Oligonucleotides (AONs) are the most used molecules for RNA modulation. The identification of delivery system to enhance the efficacy and to reduce the toxicity of AON is the main purpose in this area and nanomaterials are a very promising model as DNA/RNA molecules vectors. Dystrophinopathies therefore represent a pivotal field of investigation, which has opened novel avenues in molecular biology, medical genetics and novel therapeutic options. PMID:26457695

  9. Oncolytic Virotherapy of Canine and Feline Cancer

    Directory of Open Access Journals (Sweden)

    Ivaylo Gentschev

    2014-05-01

    Full Text Available Cancer is the leading cause of disease-related death in companion animals such as dogs and cats. Despite recent progress in the diagnosis and treatment of advanced canine and feline cancer, overall patient treatment outcome has not been substantially improved. Virotherapy using oncolytic viruses is one promising new strategy for cancer therapy. Oncolytic viruses (OVs preferentially infect and lyse cancer cells, without causing excessive damage to surrounding healthy tissue, and initiate tumor-specific immunity. The current review describes the use of different oncolytic viruses for cancer therapy and their application to canine and feline cancer.

  10. Tooth fractures in canine clinical practice

    International Nuclear Information System (INIS)

    Tooth fractures constitute a considerable fraction of all tooth diseases. Out of the 5,370 dogs treated during four years, 492 were presented with dental problems and 28.3 % of the latter were treated for tooth fractures. Canines were the most frequently affected teeth (38.8 %), followed by premolars (33.1 %), incisors (25.9 %), and molars (2.2 %), 55.4 % of the patients with canine and incisor fractures being large breed dogs. Fractures of premolars (mostly of 108, 208) were divided evenly irrespective of breed or body size. Nonsurgical endodontic treatment yielded good therapeutic results in most cases, but repeated treatment was necessary in some patients

  11. A Study of Transmigrated Canine in an Indian Population

    Science.gov (United States)

    Sharma, Gaurav; Nagpal, Archna

    2014-01-01

    Aim. The purpose of this study was to investigate the prevalence of transmigrated canines in a north Indian population and association with gender, side, associated pathologies, and dental anomalies. Subjects and methods. The prospective study consisted of panoramic radiographs of 3000 patients from two dental colleges in north India. The panoramic radiographs were screened for radiographically identified position of the transmigrated tooth, retained canine, and other coexisting dental anomalies. Results. The overall prevalence of transmigrated canines (15 mandibular and 5 maxillary) was 0.66%. The prevalence of mandibular transmigrated canine was 0.5% and maxillary transmigrated canine was 0.16%. All the transmigrated canines were unilateral. The age range was 15–53 years (average age 24.1 years) and there were 12 males (60%) and 8 females (40%). Type 1 mandibular canine transmigration was the commonest type found in our study (10 cases), followed by types 2 and 4 (2 cases each) and 1 case of type 5 transmigration. Conclusion. The prevalence of transmigrated canines in the north Indian population was 0.66% and no gender predilection was evident. The transmigrated canines have a low complication rate (10.0%) and no correlation with other dental anomalies was found. Type 3 canine is the rarest form of mandibular canine transmigration. PMID:27433532

  12. Reflex sympathetic dystrophy: Early treatment and psychological aspects

    NARCIS (Netherlands)

    Geertzen, J.H.B.; De Bruijn, H.; De Bruijn-Kofman, A.T.; Arendzen, J.H.

    1994-01-01

    We report the results of two prospective studies of early treatment and psychological aspects in a series of 26 patients with sympathetic reflex dystrophy of the hand in which treatment was started within 3 months after diagnosis. Ismelin blocks is an often used therapy in sympathetic reflex dystrop

  13. Axillary Brachial Plexus Blockade for the Reflex Sympathetic Dystrophy Syndrome.

    Science.gov (United States)

    Ribbers, G. M.; Geurts, A. C. H.; Rijken, R. A. J.; Kerkkamp, H. E. M.

    1997-01-01

    Reflex sympathetic dystrophy syndrome (RSD) is a neurogenic pain syndrome characterized by pain, vasomotor and dystrophic changes, and often motor impairments. This study evaluated the effectiveness of brachial plexus blockade with local anaesthetic drugs as a treatment for this condition. Three patients responded well; three did not. (DB)

  14. Quantitative assessment of calf circumference in Duchenne muscular dystrophy patients

    NARCIS (Netherlands)

    Beenakker, EAC; de Vries, Joeke; Fock, JM; van Tol, M; Brouwer, OF; Maurits, NM; van der Hoeven, JH

    2002-01-01

    Duchenne muscular dystrophy is clinically characterised by progressive muscle weakness and a gradual increase in the size of some affected muscles, especially calf muscles. The extent of calf enlargement is usually determined by subjective visual assessment. The purpose of this study was to determin

  15. The Child with Muscular Dystrophy in School. Revised.

    Science.gov (United States)

    Schock, Nancy C.

    Practical information on children with muscular dystrophy is intended to help parents and teachers facilitate their inclusion in mainstreamed classrooms. Major topics addressed include the following: transportation arrangements; providing full information to the teacher regarding the child's specific abilities and physical limitations;…

  16. Phosphorylation of intact erythrocytes in human muscular dystrophy

    International Nuclear Information System (INIS)

    The uptake of exogenous 32Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-[32P]ATP, and suggests a possible reinterpretation of those experiments

  17. Population-based incidence and prevalence of facioscapulohumeral dystrophy

    NARCIS (Netherlands)

    Deenen, J.C.W.; Arnts, H.; Maarel, S.M. van der; Padberg, G.W.A.M.; Verschuuren, J.J.; Bakker, E.; Weinreich, S.S.; Verbeek, A.L.M.; Engelen, B.G.M. van

    2014-01-01

    OBJECTIVE: To determine the incidence and prevalence of facioscapulohumeral muscular dystrophy (FSHD) in the Netherlands. METHODS: Using 3-source capture-recapture methodology, we estimated the total yearly number of newly found symptomatic individuals with FSHD, including those not registered in an

  18. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, EM; van der Wouw, PA; Wilde, AAM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; van Essen, AJ; Leschot, NJ; de Visser, M

    1999-01-01

    A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers

  19. Becker′s Muscular Dystrophy-A Case Report

    Directory of Open Access Journals (Sweden)

    Rajendran P

    1998-01-01

    Full Text Available A case of Becker′s Muscular dystrophy (BMD in a 26-year-old male is reported. Muscle biopsy immunohistochemical staining showed absence of labelling for dystrophin along the sacrolemmal membrane in majority of the fibres. Antibodies to adhalin and merosin showed normal localisation along the sacrolemma.

  20. Functional protein networks unifying limb girdle muscular dystrophy

    NARCIS (Netherlands)

    Morrée, Antoine de

    2011-01-01

    Limb Girdle Muscular Dystrophy (LGMD) is a rare progressive heterogeneous disorder that can be caused by mutations in at least 21 different genes. These genes are often widely expressed and encode proteins with highly differing functions. And yet mutations in all of them give rise to a similar clini

  1. Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

    2007-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

  2. Theoretical considerations on germline mosaicism in Duchenne muscular dystrophy.

    OpenAIRE

    Grimm, T; Müller, B.; Müller, C R; Janka, M

    1990-01-01

    A newly formulated mutation selection equilibrium for lethal X linked recessive traits such as Duchenne muscular dystrophy is presented, which allows for both male and female germline mosaicism. Estimates of the additional parameters used are given, thus allowing the incorporation of germline mosaicism into the calculation of genetic risks.

  3. Protriptyline treatment of sleep hypoxaemia in Duchenne muscular dystrophy.

    OpenAIRE

    Smith, P E; Edwards, R H; Calverley, P. M.

    1989-01-01

    Protriptyline 20 mg daily reduced the total time spent in rapid eye movement sleep in an open study in four subjects with Duchenne muscular dystrophy. Sleep related hypoxaemia and episodes of desaturation were reduced. Anticholinergic side effects were prominent, however, in these patients, precluding its use for regular treatment.

  4. Concise Review: Stem Cell Therapy for Muscular Dystrophies

    OpenAIRE

    Wilschut, Karlijn J.; Ling, Vivian B.; Bernstein, Harold S.

    2012-01-01

    Stem cell therapy holds promise as a treatment for muscular dystrophy by providing cells that can both deliver functional muscle proteins and replenish the stem cell pool. This article reviews the current state of research on myogenic stem cells and identifies the important challenges that must be addressed as stem cell therapy is brought to the clinic.

  5. Duchenne muscular dystrophy: CRISPR/Cas9 treatment.

    Science.gov (United States)

    Mendell, Jerry R; Rodino-Klapac, Louise R

    2016-05-01

    A novel approach to gene correction by genome editing shows great promise as a treatment for Duchenne muscular dystrophy (DMD). CRISPR/Cas9 delivered by adeno-associated virus to a mouse model for DMD demonstrated improvement in function and histology. PMID:26926391

  6. Risk of fracture in patients with muscular dystrophies

    NARCIS (Netherlands)

    Pouwels, S.; Boer, A. de; Leufkens, H.G.M.; Weber, W.E.; Cooper, C.; Onzenoort, H.A.W. van; Vries, F de

    2014-01-01

    The aim of the study was to determine fracture risk in incident muscular dystrophy (MD) patients. Patients with MD are at a 1.4-fold increased risk of fracture as compared with population-based control patients. Risk further increased among elderly and female patients and among patients exposed to o

  7. Risk of fracture in patients with muscular dystrophies

    NARCIS (Netherlands)

    Pouwels, S; de Boer, A; Leufkens, H G M; Weber, W E J; Cooper, C; van Onzenoort, H A W; de Vries, F

    2014-01-01

    UNLABELLED: The aim of the study was to determine fracture risk in incident muscular dystrophy (MD) patients. Patients with MD are at a 1.4-fold increased risk of fracture as compared with population-based control patients. Risk further increased among elderly and female patients and among patients

  8. Swallow Characteristics in Patients with Oculopharyngeal Muscular Dystrophy

    Science.gov (United States)

    Palmer, Phyllis M.; Neel, Amy T.; Sprouls, Gwyneth; Morrison, Leslie

    2010-01-01

    Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

  9. Phonological Awareness Skills in Young Boys with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Waring, Phoebe; Woodyatt, Gail

    2011-01-01

    Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

  10. Dasatinib as a treatment for Duchenne muscular dystrophy.

    Science.gov (United States)

    Lipscomb, Leanne; Piggott, Robert W; Emmerson, Tracy; Winder, Steve J

    2016-01-15

    Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy.

  11. Severe paraspinal muscle involvement in facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Dahlqvist, Julia R; Vissing, Christoffer R; Thomsen, Carsten;

    2014-01-01

    OBJECTIVE: In this study, involvement of paraspinal muscles in 50 patients with facioscapulohumeral dystrophy (FSHD) was evaluated using MRI. METHODS: The Dixon MRI technique was used in this observational study to quantify muscle fat content of paraspinal and leg muscles. Muscle strength in the ...

  12. Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

    Science.gov (United States)

    Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-01-01

    Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

  13. Experimental Forelimb Allotransplantation in Canine Model

    Science.gov (United States)

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  14. Seroprevalence of Canine Distemper Virus in Cats

    OpenAIRE

    Ikeda, Yasuhiro; Nakamura, Kazuya; Miyazawa, Takayuki; Chen, Ming-Chu; Kuo, Tzong-Fu; Lin, James A; Mikami, Takeshi; Kai, Chieko; TAKAHASHI, Eiji

    2001-01-01

    A seroepidemiological survey of canine distemper virus (CDV) infection in Asian felids revealed that the prevalence of antibodies varied depending on region and, in some cases, exposure to dogs. The serologic pattern in cats with antibodies indicated that they had likely been exposed to field strains rather than typical CDV vaccine strains.

  15. Canine Distemper Outbreak in Rhesus Monkeys, China

    OpenAIRE

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-01-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  16. Experimental Forelimb Allotransplantation in Canine Model.

    Science.gov (United States)

    Hong, Sa-Hyeok; Eun, Seok-Chan

    2016-01-01

    As reconstructive transplantation is gaining popularity as a viable alternative for upper limb amputees, it is becoming increasingly important for plastic surgeons to renew surgical skills and knowledge of this area. Forelimb allotransplantation research has been performed previously in rodent and swine models. However, preclinical canine forelimb allotransplantation studies are lacking in the literature. The purpose of this paper is to provide an overview of the surgical skills necessary to successfully perform forelimb transplantation in canines as a means to prepare for clinical application. A total of 18 transplantation operations on canines were performed. The recipient limb was shortened at the one-third proximal forearm level. The operation was performed in the following order: bones (two reconstructive plates), muscles and tendons (separately sutured), nerves (median, ulnar, and radial nerve), arteries (two), and veins (two). The total mean time of transplantation was 5 hours ± 30 minutes. All of the animals that received transplantation were treated with FK-506 (tacrolimus, 2 mg/kg) for 7 days after surgery. Most allografts survived with perfect viability without vascular problems during the early postoperative period. The canine forelimb allotransplantation model is well qualified to be a suitable training model for standard transplantation and future research work. PMID:27597952

  17. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F;

    2011-01-01

    is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...

  18. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael;

    2011-01-01

    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  19. Canine notoedric mange: a case report.

    Science.gov (United States)

    Leone, Federico

    2007-04-01

    Notoedric mange is a cutaneous ectoparasitic disease of cats caused by Notoedres cati, a mite belonging to the Sarcoptidae family. The disease occurs in felids, occasionally in other mammals and in humans. The canine form, even if cited by some authors, has never been documented. This report describes for the first time a case of notoedric mange in a dog.

  20. Canine retraction with J hook headgear.

    Science.gov (United States)

    Ayala Perez, C; de Alba, J A; Caputo, A A; Chaconas, S J

    1980-11-01

    Several methods have been described for accomplishing distal movement of canines without losing posterior anchorage. An accepted method in canine retraction is the use of headgear with J hooks. Since it incorporates extraoral anchorage, it is most effective in maximum-anchorage cases. It was the purpose of this study to analyze the distribution of force transmitted to the alveolus and surrounding structures by means of photoelastic visualization, utilizing J hook headgear for maxillary canine retraction. A three-dimensional model representing a human skull was used. This model was constructed with different birefringent materials to simulate bone, teeth, and periodontal membranes. Three different vectors of force were applied representing high-, medium-, and low-pull headgear, which were placed at angles of 40, 20, and 0 degrees to the occlusal plane. The photoelastic analysis was made by means of a circular-transmission polariscope arrangement, and the photoelastic data were recorded photographically. The stress areas created by the three different vectors of force were associated with various degrees of canine tipping. This effect was greater with the low-pull force component than with the medium-pull traction. The high-pull headgear produced the least tipping tendency, being closer to a bodily movemment effect. Further, stresses were transmitted to deeper structures of the simulated facial bones; these regions were the frontozygomatic, zygomaticomaxillary, and zygomaticotemporal sutures.

  1. Revertant fibers in the mdx murine model of Duchenne muscular dystrophy: an age- and muscle-related reappraisal.

    Directory of Open Access Journals (Sweden)

    Sarah R Pigozzo

    Full Text Available Muscles in Duchenne dystrophy patients are characterized by the absence of dystrophin, yet transverse sections show a small percentage of fibers (termed "revertant fibers" positive for dystrophin expression. This phenomenon, whose biological bases have not been fully elucidated, is present also in the murine and canine models of DMD and can confound the evaluation of therapeutic approaches. We analyzed 11 different muscles in a cohort of 40 mdx mice, the most commonly model used in pre-clinical studies, belonging to four age groups; such number of animals allowed us to perform solid ANOVA statistical analysis. We assessed the average number of dystrophin-positive fibers, both absolute and normalized for muscle size, and the correlation between their formation and the ageing process. Our results indicate that various muscles develop different numbers of revertant fibers, with different time trends; besides, they suggest that the biological mechanism(s behind dystrophin re-expression might not be limited to the early development phases but could actually continue during adulthood. Importantly, such finding was seen also in cardiac muscle, a fact that does not fit into the current hypothesis of the clonal origin of "revertant" myonuclei from satellite cells. This work represents the largest, statistically significant analysis of revertant fibers in mdx mice so far, which can now be used as a reference point for improving the evaluation of therapeutic approaches for DMD. At the same time, it provides new clues about the formation of revertant fibers/cardiomyocytes in dystrophic skeletal and cardiac muscle.

  2. Canine visceral leishmaniasis in Sicily.

    Science.gov (United States)

    Orndorff, G R; Cooper, B A; Smith, W; Ryan, J R

    2000-01-01

    The Sicilian province of Catania is an active foci for human visceral leishmaniasis (VL) in the Mediterranean area. Approximately 10 to 15 cases of VL are diagnosed via hospital admissions each year in this community. Recently, an increase in VL case reporting by Sicilian physicians was noted, with 38 and 37 VL cases in 1996 and 1997, respectively. Before 1995, there were no reported VL cases among U.S. military personnel or their family members living in Sicily. However, since 1996, there have been four cases referred to Walter Reed Army Medical Center for diagnosis and treatment, all involving the children of personnel assigned to Naval Air Station Sigonella. Exposure histories for all infected individuals excluded exposure to Leishmania parasites outside of Sicily. All patients lived in areas where vectoring sandflies are present. All had dogs as family pets. To evaluate the level of infection among dogs owned by Navy personnel and their families, U.S. Navy Environmental and Preventive Medicine Unit 7, in a collaborative study with the U.S. Army Veterinary Clinic, Naval Air Station Sigonella, and the Walter Reed Army Institute of Research, performed clinical evaluation and serological testing of 50 dogs residing with U.S. personnel assigned to Naval Air Station Sigonella. The data indicate a high exposure rate to Leishmania (60% of the animals tested had elevated immunoglobulin M antibody levels) in the study population, suggesting that they were infected with Leishmania infantum. Distribution of seropositive dogs by sex was equal. Most of the dogs studied appeared to be in good health. However, inapparent infection of dogs, seen by Italian veterinarians, has been observed throughout all areas of Catania. Sandflies responsible for vectoring L. infantum were trapped in the same locations as the dogs sampled in this study. The level of subclinical infection was 75% among seropositive dogs. The overall level of canine infection observed was higher than expected

  3. Cardiac Niche Influences the Direct Reprogramming of Canine Fibroblasts into Cardiomyocyte-Like Cells

    Directory of Open Access Journals (Sweden)

    Giacomo Palazzolo

    2016-01-01

    Full Text Available The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs. We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C, known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis.

  4. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Parvaneh KARIMZADEH

    2012-03-01

    Full Text Available How to Cite this Article: Karimzadeh P, Ghazavi A. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy. IranianJournal of Child Neurology 2012;6(1:5-12.ObjectiveDuchenne muscular dystrophy (DMD is a degenerative disease that usually becomes clinically detectable in childhood as progressive proximal weakness. No cure is yet available for DMD, but the use of steroids improves muscle strength and function. This study has been carried out to select the best steroid for the management of DMD.Materials & MethodsThis study is a single-blind, randomized clinical trial with a sample volume of 34 DMD patients. Half of these patients were treated with deflazacort (0.9 mg/kg daily and the other half with prednisone (0.75 mg/kg daily for a period of 18 months. The motor function score and excess body weight were registered one year after the start and also at the end of the study and compared between the two groups.ResultsDeflazacort was more effective in the improvement of motor function after one year, but there was no significant difference between the two drugs at the end of the study (18 months after start. Weight gain after one year and at the end of the study was higher in prednisone group and steroid treatment with deflazacort appears to cause fewer side effects than prednisone regarding weight gain.ConclusionDeflazacort seems to be more effective than prednisone in the improvement of motor function causing fewer side effects, particularly weight gain. This medication may be important for the improvement of motor function and could be used as the best steroidal treatment for Duchenne muscular dystrophy. References Lankester BJA, Whitehouse MR, Gargan MF. Duchenne muscular dystrophy. Current Orthopedics 2007;21:298- 300. Wenger DR, Rang M. The art and practice of children’s orthopedics. Philadelphia, PA: Lippincott; Baltimore: Williams and Wilkins; 1993. Sussman M. Duchenne muscular dystrophy. J Am Acad Orthop Surg 2002 Mar

  5. Effects of canine serum collected from dogs at different estrous cycle stages on in vitro nuclear maturation of canine oocytes.

    Science.gov (United States)

    Oh, Hyun Ju; Fibrianto, Yuda Heru; Kim, Min Kyu; Jang, Goo; Hossein, M Shamim; Kim, Hye Jin; Kang, Sung Keun; Lee, Byeong Chun; Hwang, Woo Suk

    2005-08-01

    Canine oocytes are ovulated at prophase of the first meiotic division and undergo maturation in the distal part of the oviduct for at least 48-72 h. Because of these differences from other domestic mammals, the efficiency of in vitro maturation (IVM) of canine oocyte is very low. The present study was conducted to evaluate the effects of canine serum on IVM of canine oocytes recovered from ovaries in various reproductive states (follicular, luteal or anestrous stages). Oocytes were recovered by mincing ovaries from bitches presented for ovariohysterectomy at various stages of the estrous cycle. Heat-inactivated canine serum was prepared with blood taken from dogs at the anestrous, estrous or diestrous stage of the estrous cycle as determined by progesterone concentration and vaginal cytology. Oocytes were cultured for 72 h in tissue culture medium (TCM)-199 supplemented with 10% canine anestrous, estrous or diestrous serum or fetal bovine serum (FBS) (experiment 1), or supplemented with 0 (control), 5%, 10% or 20% canine estrous serum (experiment 2). In experiment 1, IVM of oocytes collected at the follicular stage of the estrous cycle to metaphase II (MII) stage was higher (p < 0.05) with canine estrous serum (14.2%) than with canine anestrous (5.2%) or diestrous serum (6.3%), FBS (2.2%) or in the control (2.2%). In experiment 2, oocytes collected at the follicular stage of the estrous cycle cultured in TCM-199 with 10% canine estrous serum showed a higher maturation rate to MII stage (13.5%, p < 0.05) compared with those cultured with 5% (1.3% MII) or 20% canine estrous serum (5.1% MII) or the control (2.7% MII). In conclusion, our results demonstrate that supplementing culture medium with 10% canine estrous serum improves IVM of canine follicular stage oocytes. PMID:16261767

  6. Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2

    DEFF Research Database (Denmark)

    Kamsteeg, Erik-Jan; Kress, Wolfram; Catalli, Claudio;

    2012-01-01

    Myotonic dystrophy is an autosomal dominant, multisystem disorder that is characterized by myotonic myopathy. The symptoms and severity of myotonic dystrophy type l (DM1) ranges from severe and congenital forms, which frequently result in death because of respiratory deficiency, through to late-o...... molecular testing and reporting is very important for the optimal counseling in myotonic dystrophy. Here, we describe best practice guidelines for clinical molecular genetic analysis and reporting in DM1 and DM2, including presymptomatic and prenatal testing....

  7. New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trials

    OpenAIRE

    Cossu, Giulio; Sampaolesi, Maurilio

    2007-01-01

    Muscular dystrophies primarily affect skeletal muscle. Mutations in a large number of genes, mainly encoding cytoskeletal proteins, cause different forms of dystrophy that compromise patient mobility and quality of life, and in the most severe cases lead to complete paralysis and premature death. Although muscular dystrophies still lack an effective therapy, several novel strategies are entering or are ready to enter clinical trials. Here we review the main experimental strategies, namely dru...

  8. Diagnosis and cell-based therapy for Duchenne muscular dystrophy in humans, mice, and zebrafish

    OpenAIRE

    Kunkel, Louis M; Bachrach, Estanislao; Bennett, Richard R.; Guyon, Jeffrey; Steffen, Leta

    2006-01-01

    The muscular dystrophies are a heterogeneous group of genetically caused muscle degenerative disorders. The Kunkel laboratory has had a longstanding research program into the pathogenesis and treatment of these diseases. Starting with our identification of dystrophin as the defective protein in Duchenne muscular dystrophy (DMD), we have continued our work on normal dystrophin function and how it is altered in muscular dystrophy. Our work has led to the identification of the defective genes in...

  9. Care to child with muscular dystrophies dependent of home technology: mothers´ conception

    OpenAIRE

    Fabíola Sousa de Oliveira; Viviane Mamede Vasconcelos; Mariana Cavalcante Martins; Ingrid Martins Leite Lúcio

    2013-01-01

    It was aimed to understand the mother's conception on care to child with muscular dystrophies dependent on technology. Descriptive study with qualitative approach carried out in a children's hospital of the tertiary net in Fortaleza-Ceará, Brazil, as well as in homes of children with muscular dystrophy assisted by the Home Ventilation Assistance Program. The informants were mothers of children with dystrophy aged between zero and four years old, admitted in the Special Patients Unit and assis...

  10. Merosin-Deficient Congenital Muscular Dystrophy (MDCMD): A Case Report with MRI, MRS and DTI Findings

    OpenAIRE

    Ip, Janice JK; Hui, Peter KT; Chau, MT; Lam, Wendy WM

    2012-01-01

    Congenital muscular dystrophy (CMD) comprises a heterogeneous group of disorders present at birth with muscle weakness, hypotonia and contractures. Congenital muscular dystrophy (CMD) comprises a heterogeneous group of disorders with muscle weakness, hypotonia and contractures present at birth. A particular subset of classic CMD is characterized by a complete absence of merosin. Merosin-deficient congenital muscular dystrophy (MDCMD) is a rare genetic disease involving the central and periphe...

  11. Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice.

    OpenAIRE

    Chapman, V M; Miller, D R; Armstrong, D; Caskey, C. T.

    1989-01-01

    We have used elevated levels of plasma creatine phosphokinase activity to identify muscular dystrophy phenotypes in mice and to screen the progeny of chemical mutagen-treated male mice for X chromosome-linked muscular dystrophy mutations. We were not successful in identifying heterozygous carriers of these induced muscular dystrophy mutations in greater than 8000 progeny. However, we were highly successful in identifying three additional alleles of the characterized mdx locus. These alleles o...

  12. Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco

    OpenAIRE

    Hanane Bellayou; Khalil Hamzi; Mohamed Abdou Rafai; Mehdi Karkouri; Ilham Slassi; Houssine Azeddoug; Sellama Nadifi

    2009-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BM...

  13. Latent TGF-β–binding protein 4 modifies muscular dystrophy in mice

    OpenAIRE

    Heydemann, Ahlke; Ceco, Ermelinda; Lim, Jackie E.; Hadhazy, Michele; Ryder, Pearl; Moran, Jennifer L; Beier, David R.; Palmer, Abraham A.; McNally, Elizabeth M.

    2009-01-01

    Most single-gene diseases, including muscular dystrophy, display a nonuniform phenotype. Phenotypic variability arises, in part, due to the presence of genetic modifiers that enhance or suppress the disease process. We employed an unbiased mapping approach to search for genes that modify muscular dystrophy in mice. In a genome-wide scan, we identified a single strong locus on chromosome 7 that influenced two pathological features of muscular dystrophy, muscle membrane permeability and muscle ...

  14. Genetic polymorphism in muscle biopsies of Duchenne and Becker muscular dystrophy patients.

    OpenAIRE

    Anand A; Prabhakar S; Kaul D

    1999-01-01

    Duchenne muscular dystrophy (DMD), with an incidence of one in 3500 male new borns, and its milder variant, Becker muscular dystrophy (BMD), are allelic X-linked recessive disorders, caused by mutations in the gene coding for dystrophin, a 427 kD cytoskeleton protein. There are no available molecular markers to differentiate these two. The purpose of this study was to study genetic polymorphism in muscular dystrophy and explore its potential in discriminating these two allelic forms of the di...

  15. Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ

    OpenAIRE

    Kay-Marie Lamar; Sasha Bogdanovich; Gardner, Brandon B.; Gao, Quan Q.; Tamari Miller; Earley, Judy U.; Michele Hadhazy; Vo, Andy H.; Lisa Wren; Molkentin, Jeffery D.; McNally, Elizabeth M.

    2016-01-01

    Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular ...

  16. Animal Models for Muscular Dystrophy Show Different Patterns of Sarcolemmal Disruption

    OpenAIRE

    Straub, Volker; Rafael, Jill A.; Jeffrey S. Chamberlain; Campbell, Kevin P.

    1997-01-01

    Genetic defects in a number of components of the dystrophin–glycoprotein complex (DGC) lead to distinct forms of muscular dystrophy. However, little is known about how alterations in the DGC are manifested in the pathophysiology present in dystrophic muscle tissue. One hypothesis is that the DGC protects the sarcolemma from contraction-induced damage. Using tracer molecules, we compared sarcolemmal integrity in animal models for muscular dystrophy and in muscular dystrophy patient samples. Ev...

  17. SIRT1: A Novel Target for the Treatment of Muscular Dystrophies

    OpenAIRE

    Atsushi Kuno; Yoshiyuki Horio

    2016-01-01

    Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and is caused by mutations in the gene that encodes the cytoskeletal protein dystrophin. The treatment for DMD is limited to glucocorticoids, which are associated with multiple side effects. Thus, the identification of novel therapeutic targets is urgently needed. SIRT1 is an NAD+-...

  18. Elimination of Myostatin Does Not Combat Muscular Dystrophy in dy Mice but Increases Postnatal Lethality

    OpenAIRE

    Li, Zhi-fang; Shelton, G Diane; Engvall, Eva

    2005-01-01

    Myostatin is a TGF-β family member and a negative regulator of skeletal muscle growth. It has been proposed that reduction or elimination of myostatin could be a treatment for degenerative muscle diseases such as muscular dystrophy. Laminin-deficient congenital muscular dystrophy is one of the most severe forms of muscular dystrophy. To test the possibility of ameliorating the dystrophic phenotype in laminin deficiency by eliminating myostatin, we crossed dyW laminin α2-deficient and myostati...

  19. Combined orthodontic-surgical management of a transmigrated mandibular canine.

    Science.gov (United States)

    Cavuoti, Serena; Matarese, Giovanni; Isola, Gaetano; Abdolreza, Jamilian; Femiano, Felice; Perillo, Letizia

    2016-07-01

    The presence of an impacted mandibular canine is one of the most difficult challenges that an orthodontist will meet. Orthodontic treatment is planned on an individual basis after thoroughly considering the patient's overall facial and dentoskeletal characteristics; the duration, risks, and costs of treatment; patient preferences; and the orthodontist's experience. This article reports an orthodontic treatment of a boy, age 12.9 years, with an impacted mandibular canine in the permanent dentition that was successfully managed. Radiographic analysis indicated a transmigration of the mandibular right canine. The orthodontic treatment plan included extraction of the deciduous right canine followed by surgical exposure and ligation of the permanent canine. Eruption was properly guided, and the correct position of the tooth was achieved. This challenging treatment approach is described in detail, including the mechanics used to align the impacted canine. PMID:26502299

  20. Na+ Dysregulation Coupled with Ca2+ Entry through NCX1 Promotes Muscular Dystrophy in Mice

    OpenAIRE

    Burr, Adam R.; Millay, Douglas P.; Goonasekera, Sanjeewa A.; Park, Ki Ho; Sargent, Michelle A.; Collins, James; Altamirano, Francisco; Philipson, Kenneth D.; Allen, Paul D.; Ma, Jianjie; López, José Rafael; Molkentin, Jeffery D.

    2014-01-01

    Unregulated Ca2+ entry is thought to underlie muscular dystrophy. Here, we generated skeletal-muscle-specific transgenic (TG) mice expressing the Na+-Ca2+ exchanger 1 (NCX1) to model its identified augmentation during muscular dystrophy. The NCX1 transgene induced dystrophy-like disease in all hind-limb musculature, as well as exacerbated the muscle disease phenotypes in δ-sarcoglycan (Sgcd−/−), Dysf−/−, and mdx mouse models of muscular dystrophy. Antithetically, muscle-specific deletion of t...

  1. Canine oral biofilms: Cultural, molecular, and in vitro studies.

    OpenAIRE

    Elliott, D. R.

    2006-01-01

    The canine oral microbiota is poorly understood compared to that of humans. The aim of this work was to improve understanding of the canine oral microbiota. This was achieved by surveying the canine oral microbiota, determining coaggregation interactions between its members, and developing a laboratory microcosm. Bacteria were isolated from the dental plaque and saliva of dogs, and isolates were identified by comparative 16S rRNA gene sequencing. From 339 isolates, 84 phylotypes belonging to ...

  2. Portrait of a Canine Probiotic – from Gut to Gut

    OpenAIRE

    O'Mahony, D.; Murphy, K. Barry; MacSharry, J.; Boileau, T.; Sunvold, G.; Reinhart, G.; Kiely, B.; Shanahan, F; O'Mahony, L.

    2009-01-01

    Abstract The gastrointestinal environment is a complex interactive system involving the host, ingested dietary components, and numerous microbial species. We hypothesised that isolation and screening of Lactobacilli and Bifidobacteria adherent to healthy canine gastrointestinal tissue would yield strains with commensal activity in canines. The aims of this study were 1) to isolate a bank of commensal organisms from the canine gastrointestinal tract; 2) to screen these novel microbi...

  3. Validation of commercially available automated canine-specific immunoturbidimetric method for measuring canine C-reactive protein

    DEFF Research Database (Denmark)

    Hillström, Anna; Hagman, Ragnvi; Tvedten, Harold;

    2014-01-01

    with a human CRP assay previously validated for canine CRP determination. Samples from 40 healthy dogs were analyzed to establish a reference interval. RESULTS: Total imprecision was ..., there was good agreement between the validated human CRP assay and the new canine-specific assay. Healthy dogs had CRP concentrations that were less than the limit of quantification of the Gentian cCRP method (6.8 mg/L). CONCLUSIONS: The new canine-specific immunoturbidimetric CRP assay is a reliable and rapid......BACKGROUND: Measurement of C-reactive protein (CRP) is used for diagnosing and monitoring systemic inflammatory disease in canine patients. An automated human immunoturbidimetric assay has been validated for measuring canine CRP, but cross-reactivity with canine CRP is unpredictable. OBJECTIVE...

  4. The importance of genetic diagnosis for Duchenne muscular dystrophy

    Science.gov (United States)

    Aartsma-Rus, Annemieke; Ginjaar, Ieke B; Bushby, Kate

    2016-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligible for treatments. This review discusses different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD. PMID:26754139

  5. The importance of genetic diagnosis for Duchenne muscular dystrophy.

    Science.gov (United States)

    Aartsma-Rus, Annemieke; Ginjaar, Ieke B; Bushby, Kate

    2016-03-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligible for treatments. This review discusses different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD. PMID:26754139

  6. Cell transplantation and gene therapy in muscular dystrophy.

    Science.gov (United States)

    Morgan, J E; Partridge, T A

    1992-09-01

    Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births, involves a progressive degeneration of skeletal and cardiac muscle, leading to early death. The protein dystrophin is lacking in DMD and present, but defective, in the allelic, less severe, Becker muscular dystrophy and is also missing in the mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx skeletal muscle leads to the conversion of dystrophin-negative fibres to -positive, with consequent improvement in muscle histology. Direct injection of dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin-positive fibres. Although both appear promising, there are a number of questions to be answered and refinements to be made before either technique could be considered possible as treatments for myopathies in man. PMID:1365921

  7. Muscular dystrophies: key elements for everyday diagnosis and management

    Directory of Open Access Journals (Sweden)

    Alberto Palladino

    2013-12-01

    Full Text Available Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features and dystrophic changes on muscle biopsy, associated with progressive weakness. Weakness may be noted at birth or develop in late adult life. In recent years, cardiac involvement has been observed in a growing number of genetic muscle diseases, and considerable progress has been made in understanding the relationships between disease skeletal muscle and cardiac muscle disease. This review will focus on the skeletal muscle diseases most commonly associated with cardiac complications that can be diagnosed by echocardiography, such as dystrophinopathies including Duchenne (DMD and Becker (BMD muscular dystrophies, cardiomyopathy of DMD/BMD carriers and X-L dilated cardiomyopathy.

  8. Bimaxillary Osteotomy for Jaw Deformity With Facioscapulohumeral Muscular Dystrophy.

    Science.gov (United States)

    Kawasaki, Takako; Ohba, Seigo; Fujimura, Yuji; Asahina, Izumi

    2016-05-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a subtype of muscular dystrophies which reduces the muscle strength, especially the regions of scapular, shoulder, and upper arms, progressively. According to progressive muscle weakness in FSHD, postoperative stability of patient with FSHD after orthognathic surgery is not reliably acquired same as healthy subjects. A 32-year-old woman with FSHD underwent orthodontic and orthognathic surgical treatment due to jaw deformity. She has been followed up more than 3 years after surgery and acquired skeletal stability. This patient is the first report that showed long-term skeletal stability after orthognathic surgery in patient with FSHD. This patient report suggests that it is possible to apply orthognathic surgical treatment to patients with FSHD. PMID:27054436

  9. Satellite Cells in Muscular Dystrophy - Lost in Polarity.

    Science.gov (United States)

    Chang, Natasha C; Chevalier, Fabien P; Rudnicki, Michael A

    2016-06-01

    Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem-cell divisions, and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review we highlight recent research advances in DMD and discuss the current state of treatment and, importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD. PMID:27161598

  10. Creatine monohydrate as a therapeutic aid in muscular dystrophy.

    Science.gov (United States)

    Pearlman, Jared P; Fielding, Roger A

    2006-02-01

    In recent years, dietary supplementation with creatine has been shown to enhance neuromuscular function in several diseases. Recent studies have suggested that creatine can be beneficial in patients with muscular dystrophy and other mitochondrial cytopathies, and may attenuate sarcopenia and facilitate rehabilitation of disuse atrophy. Though the mechanisms are still unknown, creatine has been shown to decrease cytoplasmic Ca2+ levels and increase intramuscular and cerebral phosphocreatine stores, providing potential musculoskeletal and neuroprotective effects. PMID:16536185

  11. Degeneration of Neuromuscular Junction in Age and Dystrophy

    OpenAIRE

    Rudolf, Rüdiger; Khan, Muzamil Majid; Labeit, Siegfried; Deschenes, Michael R.

    2014-01-01

    Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and post-synaptic origin. Consequently, NMJs are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and d...

  12. Degeneration of Neuromuscular Junction in Age and Dystrophy

    OpenAIRE

    Rüdiger eRudolf; Muzamil Majid Khan; Siegfried eLabeit; Deschenes, Michael R.

    2014-01-01

    Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and postsynaptic origin. Consequently, neuromuscular junctions are good indicators of motor health on a systemic level. Indeed, upon sarco...

  13. Motor assessment in patients with Duchenne muscular dystrophy

    OpenAIRE

    Gabriela Palhares Campolina Diniz; Laura Maria de Lima Belizário Facury Lasmar; Juliana Gurgel Giannetti

    2012-01-01

    OBJECTIVE: Evaluate muscle force and motor function in patients with Duchenne muscular dystrophy (DMD) in a period of six months. METHOD: Twenty children and adolescents with diagnosis of DMD were evaluated trough: measurement of the strength of the flexors and extensors of the shoulder, elbow, wrist, knee and ankle through the Medical Research Council (MRC), and application of the Motor Function Measure (MFM). The patients were evaluated twice within a six-month interval. RESULTS: Loss of mu...

  14. Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD)

    OpenAIRE

    Brolin, Camilla; Shiraishi, Takehiko

    2011-01-01

    Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most promising methods for restoration of dystrophin expression. This approach has been tested extensively targeting different exons in numerous models both in vitro and in vivo. During the past 10 years, th...

  15. The role of early diagnosis of muscular dystrophy

    OpenAIRE

    Velickova, Nevenka; Gacova, Marina

    2010-01-01

    Background: Muscular dystrophy (MD) is a genetic disorder that gradually weakens the body's musclesIt's caused by incorrect or missing genetic information that prevents the body from making the proteins needed to build and maintain healthy muscles. This form occurs because of a problem with the gene that makes dystrophin, a protein that helps muscle cells keep their shape and length Girls can carry the gene that causes the disease, but they usually have no symptoms.. Aim: To evaluate t...

  16. GENE AND CELL-MEDIATED THERAPIES FOR MUSCULAR DYSTROPHY

    OpenAIRE

    Konieczny, Patryk; Swiderski, Kristy; Jeffrey S. Chamberlain

    2013-01-01

    Duchenne muscular dystrophy (DMD) is a devastating muscle disorder that affects 1 in 3500 boys. Despite years of research and considerable progress in understanding the molecular mechanism of the disease and advancement of therapeutic approaches, there is no cure for DMD. The current treatment options are limited to physiotherapy and corticosteroids, and although they provide a substantial improvement in affected children, they only slow the course of the disorder. On a more optimistic note, ...

  17. Cell therapy strategies and improvements for muscular dystrophy

    OpenAIRE

    Quattrocelli, Mattia; Cassano, Marco; Crippa, Stefania; Perini, Ilaria; Sampaolesi, Maurilio

    2010-01-01

    Understanding stem cell commitment and differentiation is a critical step towards clinical translation of cell therapies. In past few years, several cell types have been characterized and transplanted in animal models for different diseased tissues, eligible for a cell-mediated regeneration. Skeletal muscle damage is a challenge for cell- and gene-based therapeutical approaches, given the unique architecture of the tissue and the clinical relevance of acute damages or dystrophies. In this rev...

  18. Gene Therapy for Muscular Dystrophies: Progress and Challenges

    OpenAIRE

    Park, Kyung Seok; Oh, Donghoon

    2010-01-01

    Muscular dystrophies are groups of inherited progressive diseases of the muscle caused by mutations of diverse genes related to normal muscle function. Although there is no current effective treatment for these devastating diseases, various molecular strategies have been developed to restore the expressions of the associated defective proteins. In preclinical animal models, both viral and nonviral vectors have been shown to deliver recombinant versions of defective genes. Antisense oligonucle...

  19. Yesterday, today and tomorrow of Duchenne muscular dystrophy

    OpenAIRE

    Zhang, Cheng

    2015-01-01

    The research history of Duchenne muscular dystrophy (DMD) may be roughly divided into 3 phases: clinical describing (1836-1985), molecular diagnosis and exploratory therapy (1985-2020), and the pathogenesis illuminating, gene therapy or treatment against the pathogenesis (2020-). During 1836-1985, doctors described the variation of medical history, clinical signs and symptoms, pathology, biochemistry, and genetic regularity of DMD. During 1985-2020, the scientists set up molecular diagnostic ...

  20. Duchenne muscular dystrophy gene therapy: Lost in translation?

    OpenAIRE

    Dongsheng Duan

    2011-01-01

    Dongsheng DuanDepartment of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USAAbstract: A milestone of molecular medicine is the identification of dystrophin gene mutation as the cause of Duchenne muscular dystrophy (DMD). Over the last 2 decades, major advances in dystrophin biology and gene delivery technology have created an opportunity to treat DMD with gene therapy. Remarkable success has been achieved in treating dystrophic mice. Several...

  1. Congenital Muscular Dystrophies Involving the O-Mannose Pathway

    OpenAIRE

    Martin, Paul T.

    2007-01-01

    A number of forms of congenital muscular dystrophy (CMD) have been identified that involve defects in the glycosylation of dystroglycan with O-mannosyl-linked glycans. There are at least six genes that can affect this type of glycosylation, and defects in these genes give rise to disorders that have many aspects of muscle and brain pathology in common. Overexpression of one gene implicated in CMD, LARGE, was recently shown to increase dystroglycan glycosylation and restore its function in cel...

  2. Duchenne muscular dystrophy with associated growth hormone deficiency

    International Nuclear Information System (INIS)

    A patient with duchenne muscular dystrophy (DMD) and growth hormone (GH) deficiency is described who had no clinical evidence of muscular weakness before initiation of GH replacement therapy. Treatment with human GH resulted in appearance of symptoms of easy fatigability and muscle weakness. Thorough investigations including serum creating phosphokinase (CK) levels in recommended in every patient with GH deficiency before starting GH replacement therapy. (author)

  3. RESPIRATORY DYSFUNCTIONS IN CHILDREN WITH DUCHENNE MUSCULAR DYSTROPHY

    OpenAIRE

    Dhargave Pradnya; Atchayaram Nalini; Meghana Adoor; Raghuram Nagarathna; Raju, Trichur R; Kandhavelu Thennarasu; Sathyaprabha, Talakad N

    2016-01-01

    Aim: The prognosis for Duchenne Muscular Dystrophy (DMD) life depends to a large extent on the respiratory function. Inspiratory and expiratory muscles are affected and respiratory problems occur with or without spinal deformities. It is important to characterize the respiratory function in DMD to facilitate decision of timing of the intervention. Methodology: 124 DMD male children whose parents gave written consent were recruited. The Pulmonary function tests were performed using Spirome...

  4. Stromal cell-derived factors in Duchenne muscular dystrophy

    OpenAIRE

    Abdel-Salam, E.; Ehsan Abdel-Meguid, I.; Shatla, R.; Korraa, S. S.

    2010-01-01

    Duchenne muscular dystrophy (DMD) is characterized by increased muscle damage and an abnormal blood flow after muscle contraction leading to a state of functional ischemia. Abundant evidence suggests that endothelial circulating progenitor cells (EPCs) play an important role in mediating vascular and muscle repair mechanisms and that the stromal cell-derived factor (SDF)-1 α chemokine is responsible for both progenitor cell mobilization from the bone marrow to peripheral blood and homing to t...

  5. Muscle phenotype in patients with myotonic dystrophy type 1

    DEFF Research Database (Denmark)

    Andersen, Anne Grete Kielgast; Orngreen, Mette C; Preisler, Nicolai Rasmus;

    2012-01-01

    Introduction: The pathogenesis of muscle involvement in patients with myotonic dystrophy type 1 (DM1) is not well understood. In this study, we characterized the muscle phenotype in patients with confirmed DM1. Methods: In 38 patients, muscle strength was tested by hand-held dynamometry. Myotonia...... with CTG expansion and that central nuclei are not a prominent feature of proximal muscles in DM1. Muscle Nerve, 2012....

  6. Understanding the impact of genetic testing for inherited retinal dystrophy

    OpenAIRE

    Combs, Ryan; McAllister, Marion; Payne, Katherine; Lowndes, Jo; Devery, Sophie; Webster, Andrew R.; Downes, Susan M; Moore, Anthony T.; Ramsden, Simon; Black, Graeme; Hall, Georgina

    2013-01-01

    The capability of genetic technologies is expanding rapidly in the field of inherited eye disease. New genetic testing approaches will deliver a step change in the ability to diagnose and extend the possibility of targeted treatments. However, evidence is lacking about the benefits of genetic testing to support service planning. Here, we report qualitative data about retinal dystrophy families' experiences of genetic testing in United Kingdom. The data were part of a wider study examining gen...

  7. Cystic dystrophy of heterotopic pancreas in duodenal wall

    OpenAIRE

    Gandhi Minesh B; Panjvani Sahil I; Shah Cherry K; Shah Nailesh R

    2014-01-01

    Cystic dystrophy in heterotopic pancreas is a rare, poorly understood benign disease of gastric and duodenal wall, which was described for the first time by the French authors in 1970, who reported the presence of focal pancreatic disease localized in an area comprising the C-loop of duodenum & the head of pancreas. We report a case of 33 years old male patient with complaint of recurrent abdominal pain with the probable diagnosis of groove pancreatitis on the clinoradiological fi...

  8. Sarcopenia and sarcopenic obesity in patients with muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Luciano eMerlini

    2014-10-01

    Full Text Available Aging sarcopenia and muscular dystrophy are two conditions characterized by lower skeletal muscle quantity, lower muscle strength, and lower physical performance. Aging is associated with a peculiar alteration in body composition called sarcopenic obesity characterized by a decrease in lean body mass and increase in fat mass. To evaluate the presence of sarcopenia and obesity in a cohort of adult patients with muscular dystrophy we have used the measurement techniques considered golden standard for sarcopenia that is for muscle mass dual energy X-ray absorptiometry (DXA, for muscle strength hand held dynamometry, and for physical performance gait speed. The study involved 14 adult patients with different types of muscular dystrophy. We were able to demonstrate that all patient were sarcopenic-obese. We showed in fact that all were sarcopenic based on appendicular lean, fat & bone free, mass index (ALMI. In addition all resulted obese according to the % of body fat determined by DXA in contrast with their body mass index ranging from underweight to obese. Skeletal muscle mass determined by DXA was markedly reduced in all patients and correlated with residual muscle strength determined by hand held dynamometry, and physical performances determined by gait speed and respiratory function. Finally we showed that ALMI was the best linear explicator of muscle strength and physical function. Altogether, our study suggest the relevance of a proper evaluation of body composition in muscular dystrophy and we propose to use, both in research and practice, the measurement techniques that has already been demonstrated effective in aging sarcopenia.

  9. NAD+ biosynthesis ameliorates a zebrafish model of muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Michelle F Goody

    Full Text Available Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction

  10. Poor Facial Affect Recognition Among Boys with Duchenne Muscular Dystrophy

    OpenAIRE

    Hinton, V. J.; Fee, R. J.; Vivo, D.C. De; Goldstein, E.

    2006-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a matching-to-sample test with four types of visual recognition (Object, Face, Affect, and Situation matching) developed by Lucci and Fein. Within-grou...

  11. Functional protein networks unifying limb girdle muscular dystrophy

    OpenAIRE

    de Morrée, Antoine

    2011-01-01

    Limb Girdle Muscular Dystrophy (LGMD) is a rare progressive heterogeneous disorder that can be caused by mutations in at least 21 different genes. These genes are often widely expressed and encode proteins with highly differing functions. And yet mutations in all of them give rise to a similar clinical presentation: adult onset muscle weakness, with muscles of the pelvic and shoulder girdle as predominantly affected muscle groups. This thesis explores a potential molecular mechanism that unif...

  12. RNAseq analysis for the diagnosis of muscular dystrophy

    OpenAIRE

    Gonorazky, Hernan; Liang, Minggao; Cummings, Beryl; Lek, Monkol; Micallef, Johann; Hawkins, Cynthia; Basran, Raveen; Cohn, Ronald; Wilson, Michael D.; MacArthur, Daniel; Marshall, Christian R.; Ray, Peter N.; Dowling, James J.

    2015-01-01

    Abstract The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole‐exome sequencing and next‐generation sequencing‐based gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseq‐based transcriptom...

  13. Therapeutic potential of matrix metalloproteinases in Duchenne muscular dystrophy

    OpenAIRE

    AshokKumar

    2014-01-01

    Matrix metalloproteinases (MMPs) are secreted proteinases that have physiologic roles in degradation and remodeling of extracellular matrix (ECM) in almost all tissues. However, their excessive production in disease conditions leads to many pathological features including tissue breakdown, inflammation, cell death, and fibrosis. Duchenne Muscular dystrophy (DMD) is a devastating genetic muscle disorder caused by partial or complete loss of cytoskeletal protein dystrophin. Progressive muscle w...

  14. Elderly Onset of Weakness in Facioscapulohumeral Muscular Dystrophy

    OpenAIRE

    Fee, Dominic B.

    2012-01-01

    A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent o...

  15. Progress study of the cardiac damage in Duchenne muscular dystrophy

    OpenAIRE

    Zhang, Yao; Tang, Ying; Zhang, Cheng

    2013-01-01

    Duchenne muscular dystrophy (DMD) is a fatal muscular disease with rapid progression in children. Most patients die of respiratory and circulatory failure before the age of 20 if there is no systematic treatment. Now the heart problem in this disease has become increasingly prominent, and is thought to be closely associated with certain dystrophin exon deletion. We would like to review the epidemiology, relevance of dystrophin, pathogenesis, clinical manifestations and pathological features, ...

  16. Corticosteroid Treatment Impact on Spinal Deformity in Duchenne Muscular Dystrophy

    OpenAIRE

    Sanzarello, Ilaria; Merlini, Luciano; Traina, Francesco; Rosa, Michele Attilio; Faldini, Cesare

    2014-01-01

    Duchenne muscular dystrophy is a progressive disease with loss of ambulation at around 9-10 years of age, followed, if untreated, by development of scoliosis, respiratory insufficiency, and death in the second decade of life. This review highlights the natural history of the disease, in particular, with regard to the development of the spinal deformity and how this complication has been modified by surgical interventions and overall by corticosteroid treatment. The beneficial effect of cortic...

  17. The immune system in Duchenne muscular dystrophy: Friend or foe

    OpenAIRE

    Villalta, S. Armando; Rosenberg, Amy S.; Bluestone, Jeffrey A.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutations in the X-linked dystrophin gene, resulting in reduced or absent protein production, subsequently leading to the structural instability of the dystroglycan complex (DGC), muscle degeneration, and early death in males. Thus, current treatments have been targeting the genetic defect either by bypassing the mutation through exon skipping or replacing the defective gene through gene therapy and stem cell approaches. However...

  18. Imatinib attenuates skeletal muscle dystrophy in mdx mice

    OpenAIRE

    HUANG, PING; Zhao, Xinyu S.; Fields, Matthew; Ransohoff, Richard M.; Zhou, Lan

    2009-01-01

    Duchenne-Meryon muscular dystrophy (DMD) is the most common and lethal genetic muscle disease. Ameliorating muscle necrosis, inflammation, and fibrosis represents an important therapeutic approach for DMD. Imatinib, an antineoplastic agent, demonstrated antiinflammatory and antifibrotic effects in liver, kidney, lung, and skin of various animal models. This study tested antiinflammatory and antifibrotic effects of imatinib in mdx mice, a DMD mouse model. We treated mdx mice with intraperitone...

  19. Emery-Dreifuss muscular dystrophy, laminopathies, and other nuclear envelopathies.

    OpenAIRE

    Bonne, Gisèle; Quijano-Roy, Susana

    2013-01-01

    International audience The nuclear envelopathies, more frequently known as laminopathies are a rapidly expanding group of human hereditary diseases caused by mutations of genes that encode proteins of the nuclear envelope. The most frequent and best known form is Emery-Dreifuss muscular dystrophy (EDMD), a skeletal myopathy characterized by progressive muscular weakness, joint contractures, and cardiac disease. EMD gene, encoding emerin, causes the X-linked form of EDMD, while LMNA gene en...

  20. Breed predisposition to canine gastric carcinoma

    DEFF Research Database (Denmark)

    Seim-Wikse, Tonje; Jörundsson, Einar; Nødtvedt, Ane;

    2013-01-01

    Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The ai...... of the study was to retrospectively investigate the proportion and possible breed predisposition to canine gastric carcinoma using the Norwegian Canine Cancer Register for calculations of proportional morbidity ratios (PMRs) for the period 1998-2009.......Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The aim...

  1. Antigenic typing Polish isolates of canine parvovirus

    Energy Technology Data Exchange (ETDEWEB)

    Mizak, B. [National Veterinary Research Institute, Pulawy (Poland); Plucienniczak, A. [Polish Academy ofd Sciences. Microbiology and Virology Center, Lodz (Poland)

    1995-12-31

    Polish strains of canine parvovirus isolated between 1982 and 1993 were examined to determine the extent to which the virus has evolved antigenically and genetically over eleven years. Two CPV isolates obtained in Warsaw in 1982 and Pulawy in 1993, were examined using monoclonal antibody typing, restriction analysis and sequencing VP-2 protein gene. Five other isolates from Warsaw and Pulawy were tested with the panel of monoclonal antibodies specific to CPV-2, CPV-2a and common for canine parvovirus, feline panleukopenia virus and milk enteritis virus. Results of the studies demonstrated that all isolates tested represented CPV-2a antigenic type. Rapid antigenic strain replacement recorded by Parrish and Senda in the U.S.A and Japan was not confirmed in Poland. (author). 30 refs, 2 tabs.

  2. Coryneform bacteria associated with canine otitis externa

    DEFF Research Database (Denmark)

    Aalbæk, Bent; Bemis, David A.; Schjærff, Mette;

    2010-01-01

    This study aims to investigate the occurrence of coryneform bacteria in canine otitis externa. A combined case series and case-control study was carried out to improve the current knowledge on frequency and clinical significance of coryneform bacteria in samples from canine otitis externa. A total...... of 16 cases of otitis externa with involvement of coryneform bacteria were recorded at two referral veterinary hospitals in Denmark and the US, respectively. Coryneform bacteria were identified by partial 16S rRNA gene sequencing. Corynebacterium auriscanis was the most common coryneform species (10...... cases). Small colony variants of this species were also observed. Other coryneform isolates were identified as Corynebacterium amycolatum (3 cases), Corynebacterium freneyi (2 cases) and an Arcanobacterium-like species (1 case). The coryneform bacteria were in all cases isolated together with other...

  3. Extrusion processing : effects on dry canine diets

    OpenAIRE

    Tran, Q.D.

    2008-01-01

    Keywords: Extrusion, Canine diet, Protein, Lysine, Starch gelatinization, Palatability, Drying. Extrusion cooking is a useful and economical tool for processing animal feed. This high temperature, short time processing technology causes chemical and physical changes that alter the nutritional and physical quality of the product. Effects of extrusion on the feed quality for other animals than pets have been well recognized. Our studies investigated to what extent extrusion and/or drying of a c...

  4. Cardiac troponin I levels in canine pyometra

    OpenAIRE

    Hagman Ragnvi; Lagerstedt Anne-Sofie; Fransson Boel A; Bergström Annika; Häggström Jens

    2007-01-01

    Abstract Background Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI) is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS) and to evaluate whether other clinical or laboratory parameter...

  5. Microbiological and histopathological aspects of canine pyometra

    OpenAIRE

    Coggan, Jennifer Anne; Melville, Priscilla Anne; de Oliveira, Clair Motos; Faustino, Marcelo; Moreno, Andréa Micke; Benites, Nilson Roberti

    2008-01-01

    As pyometra is recognized as one of the main causes of disease and death in the bitch the purposes of this study were to evaluate microbiological and histopathological aspects of canine pyometra and to research the virulence factors of the E. coli isolates identifying possible risks to human health. The microbiological isolation from the intrauterine contents of 100 dogs with pyometra was carried out and the virulence factors in the E. coli strains were identified using PCR method. This study...

  6. Remote detection of explosives using trained canines

    International Nuclear Information System (INIS)

    Use of dogs is a search method which combines high probability of detection, speed of search, and low cost. It was concluded that the canine could be used for explosive screening of personnel, but that it was imperative that the dog be in a position remote from employees and employee traffic. A study was made of the design of booths and air flow for this purpose. Results of tests and conclusions are given and discussed

  7. Treatment of canine scabies with milbemycin oxime.

    Science.gov (United States)

    Miller, W H; de Jaham, C; Scott, D W; Cayatte, S M; Bagladi, M S; Buerger, R G

    1996-04-01

    The purpose of this study was to determine the efficacy of orally administered milbemycin oxime in the treatment of canine scabies. Forty dogs were treated. Mean drug dosage for all dogs was approximately 2 mg/kg body weight. Twenty-seven dogs received 3 doses separated by 7 d, and 13 dogs received 2 doses separated by 14 d. All dogs were clinically normal following treatment and no adverse reactions were detected.

  8. Skeletal muscle CT of lower extremities in myotonic dystrophy

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

    We evaluated the leg and thigh muscles of 4 control subjects and 10 patients with myotonic dystrophy using computed tomography. Taking previous reports about the skeletal muscle CT of myotonic dystrophy into account, we concluded that the following 5 features are characteristic of myotonic dystrophy: 1. The main change is the appearance of low-density areas in muscles; these areas reflect fat tissue. In addition, the muscle mass decreases in size. 2. The leg is more severely affected than the thigh. 3. In the thigh, although the m. quadriceps femoris, especially the vastus muscles, tends to be affected, the m. adductor longus and magnus tend to be preserved. 4. In the leg, although the m. tibialis anterior and m. triceps surae tend to be affected, the m. peroneus longus, brevis, and m. tibialis posterior tend to be preserved. 5. Compensatory hypertrophy is often observed in the m. rectus femoris, m. adductor longus, m. adductor magnus, m. peroneus longus, and m. peroneus brevis, accompanied by the involvement of their agonist muscles.

  9. Degeneration of Neuromuscular Junction in Age and Dystrophy

    Directory of Open Access Journals (Sweden)

    Rüdiger eRudolf

    2014-05-01

    Full Text Available Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and postsynaptic origin. Consequently, neuromuscular junctions are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and dystrophy, neuromuscular junctions morphologically deteriorate and exhibit altered characteristics of primary signaling molecules, such as nicotinic acetylcholine receptor and agrin. Since a remarkable reversibility of these changes can be observed by exercise, there is significant interest in understanding the molecular mechanisms underlying synaptic deterioration upon aging and dystrophy and how synapses are reset by the aforementioned treatments. Here, we review the literature that describes the phenomena observed at the neuromuscular junction in sarcopenic and dystrophic muscle as well as to how these alterations can be reversed and to what extent. In a second part, the current information about molecular machineries underlying these processes is reported.

  10. Degeneration of neuromuscular junction in age and dystrophy.

    Science.gov (United States)

    Rudolf, Rüdiger; Khan, Muzamil Majid; Labeit, Siegfried; Deschenes, Michael R

    2014-01-01

    Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and post-synaptic origin. Consequently, NMJs are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and dystrophy, NMJs morphologically deteriorate and exhibit altered characteristics of primary signaling molecules, such as nicotinic acetylcholine receptor and agrin. Since a remarkable reversibility of these changes can be observed by exercise, there is significant interest in understanding the molecular mechanisms underlying synaptic deterioration upon aging and dystrophy and how synapses are reset by the aforementioned treatments. Here, we review the literature that describes the phenomena observed at the NMJ in sarcopenic and dystrophic muscle as well as to how these alterations can be reversed and to what extent. In a second part, the current information about molecular machineries underlying these processes is reported. PMID:24904412

  11. Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Francesca Sciandra

    2015-01-01

    Full Text Available In skeletal muscle, dystroglycan (DG is the central component of the dystrophin-glycoprotein complex (DGC, a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG gene (DAG1 have been recently associated with two forms of muscular dystrophy, one displaying a milder and one a more severe phenotype. This review focuses specifically on the animal (murine and others model systems that have been developed with the aim of directly engineering DAG1 in order to study the DG function in skeletal muscle as well as in other tissues. In the last years, conditional animal models overcoming the embryonic lethality of the DG knock-out in mouse have been generated and helped clarifying the crucial role of DG in skeletal muscle, while an increasing number of studies on knock-in mice are aimed at understanding the contribution of single amino acids to the stability of DG and to the possible development of muscular dystrophy.

  12. Altered cross-bridge properties in skeletal muscle dystrophies

    Directory of Open Access Journals (Sweden)

    Aziz eGuellich

    2014-10-01

    Full Text Available Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal muscle dystrophies and discuss their ultimate impacts on striated muscle function.

  13. Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy.

    Science.gov (United States)

    Paran, Christopher W; Zou, Kai; Ferrara, Patrick J; Song, Haowei; Turk, John; Funai, Katsuhiko

    2015-12-01

    Muscular dystrophy is accompanied by a reduction in activity of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) that contributes to abnormal Ca(2+) homeostasis in sarco/endoplasmic reticulum (SR/ER). Recent findings suggest that skeletal muscle fatty acid synthase (FAS) modulates SERCA activity and muscle function via its effects on SR membrane phospholipids. In this study, we examined muscle's lipid metabolism in mdx mice, a mouse model for Duchenne muscular dystrophy (DMD). De novo lipogenesis was ~50% reduced in mdx muscles compared to wildtype (WT) muscles. Gene expressions of lipogenic and other ER lipid-modifying enzymes were found to be differentially expressed between wildtype (WT) and mdx muscles. A comprehensive examination of muscles' SR phospholipidome revealed elevated phosphatidylcholine (PC) and PC/phosphatidylethanolamine (PE) ratio in mdx compared to WT mice. Studies in primary myocytes suggested that defects in key lipogenic enzymes including FAS, stearoyl-CoA desaturase-1 (SCD1), and Lipin1 are likely contributing to reduced SERCA activity in mdx mice. Triple transgenic expression of FAS, SCD1, and Lipin1 (3TG) in mdx myocytes partly rescued SERCA activity, which coincided with an increase in SR PE that normalized PC/PE ratio. These findings implicate a defect in lipogenesis to be a contributing factor for SERCA dysfunction in muscular dystrophy. Restoration of muscle's lipogenic pathway appears to mitigate SERCA function through its effects on SR membrane composition.

  14. Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy*

    Science.gov (United States)

    Turk, Rolf; Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Pospisil, Tyler C.; Jones, Kayla S.; Campbell, Kevin P.; Wright, Michael E.

    2016-01-01

    Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research. PMID:27099343

  15. Cardiac involvement in Duchenne and Becker muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    Sophie; Mavrogeni; George; Markousis-Mavrogenis; Antigoni; Papavasiliou; Genovefa; Kolovou

    2015-01-01

    Duchenne and Becker muscular dystrophy(DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation,not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction,heart block or malignant arrhythmias. Not only DMD/BMD patients,but also female carriers may present cardiac involvement. Clinically overt heart failure in dystrophinopathies may be delayed or absent,due to relative physical inactivity. The commonest electrocardiographic findings include conduction defects,arrhythmias(supraventricular or ventricular),hypertrophy and evidence of myocardial necrosis. Echocardiography can assess a marked variability of left ventricular dysfunction,independently of age of onset or mutation groups. Cardiovascular magnetic resonance(CMR) has documented a pattern of epicardial fibrosis in both dystrophinopathies’ patients and carriers that can be observed even if overt muscular disease is absent. Recently,new CMR techniques,such as postcontrast myocardial T1 mapping,have been used in Duchenne muscular dystrophy to detect diffuse myocardial fibrosis. A combined approach using clinical assessment and CMR evaluation may motivate early cardioprotective treatment in both patients and asymptomatic carriers and delay the development of serious cardiac complications.

  16. The Effect of Enalapril and Carvedilol on Left Ventricular Dysfunction in Middle Childhood and Adolescent Patients With Muscular Dystrophy

    OpenAIRE

    Kwon, Hye Won; Kwon, Bo Sang; Kim, Gi Beom; Chae, Jong Hee; Park, June Dong; Bae, Eun Jung; Noh, Chung Il

    2012-01-01

    Background and Objectives In Duchenne and Becker muscular dystrophies, cardiac function deteriorates with time resulting in heart failure which is often fatal. We prospectively evaluated the effect of enalapril and carvedilol on left ventricular (LV) dysfunction in middle childhood and adolescent patients with muscular dystrophy. Subjects and Methods Twenty-three patients with LV dysfunction (22 with Duchenne muscular dystrophy, 1 with Becker muscular dystrophy) were enrolled. We prescribed e...

  17. Microbial profile of canine persistent wound infections

    Directory of Open Access Journals (Sweden)

    A. Padhy

    2014-04-01

    Full Text Available Aim: To analyse the microbial profile of canine persistent wound infections. Materials and Methods: The total wound samples (n=172 taken from both traumatic (140 and post-surgical (32 persistent wounds in canines were processed for routine microbial isolation and identification during a period of 15 months. Results: Staphylococcus intermedius was found to be the predominant isolate from all types of wounds under study. It was followed by Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Pasteurella spp., Corynaebacterium spp. and Bacillus spp. From different traumatic wounds of dogs, S. intermedius (92/140=65.7% and from surgical wounds, P. aeruginosa (24/32=75% were found to be the predominant isolates recovered whereas the most commonly isolated bacterial genus in both traumatic and surgical wounds of dogs was Staphylococcus spp. Conclusion: Canine wounds are polymicrobial in nature. Hence proper microbial laboratory diagnosis and presence of multiple organisms in a wound are to be taken into consideration for effective treatment of persistent wound infections in dogs.

  18. Canine kobuviruses in diarrhoeic dogs in Italy.

    Science.gov (United States)

    Di Martino, Barbara; Di Felice, Elisabetta; Ceci, Chiara; Di Profio, Federica; Marsilio, Fulvio

    2013-09-27

    Canine kobuviruses (CaKVs) are newly recognized picornaviruses recently detected in dogs in the US. By molecular analysis of the whole genome, CaKV that appeared genetically closest to the murine kobuvirus (MuKV) and to the human Aichi virus (AiV), may be classified in the Kobuvirus genus as new genotype (CaKV type 1) within the species Aichivirus A. To date, there are no information on the epidemiology of these novel viruses in other continents. In this study, by screening a collection of 256 dog fecal samples either from diarrhoeic or asymptomatic animals, CaKV was identified in six specimens with an overall prevalence of 2.34% (6/256). All the positive dogs presented diarrhea and were found to be infected by CaKV alone or in mixed infections with canine coronavirus (CCoV) and/or canine parvovirus type 2 (CPV-2). By molecular analysis of the partial 3D gene, all the strains detected displayed a close relatedness with the CaKVs recently identified in the US. This study provides evidence that CaKVs circulate in diarrhoeic dogs in Italy and are not geographically restricted to the North American continent, where they were first signaled. PMID:23806200

  19. Cytodiagnostics of canine lymphomas - possibilities and limitations.

    Science.gov (United States)

    Sapierzyński, R; Kliczkowska-Klarowicz, K; Jankowska, U; Jagielski, D

    2016-01-01

    Malignant lymphomas are one of the most common malignant tumours occurring in dogs. The basic method of lymphoma diagnosis in human, as well as in canine oncology is histopathology supported by immunohistochemistry. It was suggested that in veterinary medicine excisional biopsy of lymph node and histopathology should be considered only where the cytologic diagnosis is equivocal or needs to be confirmed. There are at least three basic reasons for which cytological examination ought to be accepted as a sufficient and reliable diagnostic method for lymphoma in dogs. Firstly, most dog owners consider the fine-needle biopsy as an acceptable non-harmful method of sample collection. Secondly, an increasing number of studies recommend cytology as an accurate test for diagnosing and subtyping canine lymphoma. Finally, the vast majority of canine lymphoma subtypes belong to 4-5 categories characterized by a typical cytological picture. Immunocytochemical staining of cytological smears gives new diagnostic possibilities, such as detection of markers better characterizing given growth or a potential goal for target therapy in individual cases (for example inhibitors of platelet-derived growth factor). PMID:27487521

  20. Improving Stem Cell-Based Therapy and Developing a Novel Gene Therapy Approach for Treating Duchenne Muscular Dystrophy (DMD)

    OpenAIRE

    Tabebordbar, Mohammadsharif

    2016-01-01

    Genetic mutations in muscle structural genes can compromise myofiber integrity, causing repeated muscle damage that ultimately exhausts muscle regenerative capacity and results in devastating degenerative conditions such as Duchenne Muscular Dystrophy (DMD), Congenital Muscular Dystrophy (CMD) and different forms of Limb Girdle Muscular Dystrophy (LGMD). Gene supplementation and autologous stem cell transplant have been put forward as promising, though still unproven, therapeutic avenues for ...

  1. Reflex sympathetic dystrophy in a child; Wspolczulna dystrofia odruchowa u dziecka

    Energy Technology Data Exchange (ETDEWEB)

    Napiontek, M.; Krasny, I. [Akademia Medyczna, Poznan (Poland)

    1993-12-31

    A case of reflex sympathetic dystrophy in 11 years old girl was described. The acute pain of the left food was preceded by loss of consciousness of unknown origin. Patchy osteopenia, very rare and non characteristic X-ray changes in children`s reflex sympathetic dystrophy, was observed, mimicking osteomyelitis, bone malignant tumor or Sudeck disease. (author). 5 refs, 2 figs.

  2. Abnormal Polyamine Metabolism in Hereditary Muscular Dystrophies: EFFECT OF HUMAN GROWTH HORMONE

    OpenAIRE

    Rudman, Daniel; Kutner, Michael H.; Chawla, Rajender K.; Goldsmith, Martin A.

    1980-01-01

    Previous studies showed hyperre-sponsiveness to human growth hormone (hGH) in men with myotonic or limb girdle dystrophies (MMD or LGD). Because polyamines may mediate some actions of hGH, we have now investigated polyamine metabolism in these and other dystrophies.

  3. Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication

    Science.gov (United States)

    ... of muscle strength. Mice with a mutant dystrophin gene, which have a muscular dystrophy-like disease, can only hang for about 20 ... suggest that ryanodine-targeting drugs may help improve therapy for children with ... Mouse Models of Duchenne Muscular Dystrophy. Sci Transl Med .13 Dec 2012. 4, 164 ...

  4. Case of early pelviolumeral progressive muscular dystrophy associated with marked heart affection

    International Nuclear Information System (INIS)

    A case of early pelviolumeral progressive muscular dystrophy detected in childhood and associated with marked heart affection is described. Patient underwent multimodality examination, including ECG, ultrasonography, roentgenography. It is shown that patients with progressive muscular dystrophy should receive medical supervision and treatment of both neuropathologist and therapist

  5. Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations

    DEFF Research Database (Denmark)

    Gavassini, Bruno F; Carboni, Nicola; Nielsen, Jørgen E;

    2011-01-01

    In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations.......In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations....

  6. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    S.M. Schade van Westrum; E.M. Hoogerwaard; L. Dekker; T.S. Standaar; E. Bakker; P.F. Ippel; J.C. Oosterwijk; D.F. Majoor-Krakauer; A.J. van Essen; N.J. Leschot; A.A.M. Wilde; R.J. de Haan; M. Visser; A.J. van der Kooi

    2011-01-01

    Objectives: Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities during long-term follow-up is unknown. We describe the long-term follow-up of dilated cardio

  7. Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy

    DEFF Research Database (Denmark)

    Witting, Nanna; Kruuse, Christina; Nyhuus, Bo;

    2014-01-01

    OBJECTIVE: Patients with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy lack neuronal nitric oxide synthase (nNOS). nNOS mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects...

  8. Clinical genetic aspects of Duchenne and Becker muscular dystrophy in the Netherlands

    NARCIS (Netherlands)

    Helderman-van den Enden, Apollonia Theodora Josina Maria

    2012-01-01

    Dystrophinopathies include the well known Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). This thesis is a collection of several clinical and genetic studies on dystrophinopathies with implications for genetic counselling of patients and their families and for future therapy (

  9. Scalpel or Straitjacket: CRISPR/Cas9 Approaches for Muscular Dystrophies.

    Science.gov (United States)

    Himeda, Charis L; Jones, Takako I; Jones, Peter L

    2016-04-01

    Versatility of CRISPR/Cas9-based platforms makes them promising tools for the correction of diverse genetic/epigenetic disorders. Here we contrast the use of these genome editing tools in two myopathies with very different molecular origins: Duchenne muscular dystrophy, a monogenetic disease, and facioscapulohumeral muscular dystrophy, an epigenetic disorder with unique therapeutic challenges. PMID:26917062

  10. Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

    Science.gov (United States)

    Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

    2009-01-01

    Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

  11. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    Science.gov (United States)

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

    2007-01-01

    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  12. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... parvovirus susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood samples...

  13. Stroma and extracellular matrix proteins in canine tumours

    NARCIS (Netherlands)

    Mukaratirwa, Sydney

    2004-01-01

    In this thesis, studies on temporal and spatial changes in stromal cells and extracellular matrix (ECM) molecules in canine gastrointestinal (GIT) tumours and canine transmissible venereal (CTVT) tumours are described. The mechanisms involved in the phenotypic transformation of fibroblasts to myofib

  14. Canine evolution in sabretoothed carnivores: natural selection or sexual selection?

    Science.gov (United States)

    Randau, Marcela; Carbone, Chris; Turvey, Samuel T

    2013-01-01

    The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae), representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids in relation to body size in order to characterize and identify the evolutionary processes driving their development, using the scaling relationships of carnassial teeth in both groups as a control. Carnassials display isometric allometry in both sabretooths and non-sabretooths, supporting their close relationship with meat-slicing, whereas the upper canines of both groups display positive allometry with body size. Whereas there is no statistical difference in allometry of upper canine height between dirk-toothed and scimitar-toothed sabretooth ecomorphs, the significantly stronger positive allometry of upper canine height shown by sabretooths as a whole compared to non-sabretooths reveals that different processes drove canine evolution in these groups. Although sabretoothed canines must still have been effective for prey capture and processing by hypercarnivorous predators, canine morphology in these extinct carnivores was likely to have been driven to a greater extent by sexual selection than in non-sabretooths. Scaling relationships therefore indicate the probable importance of sexual selection in the evolution of the hypertrophied sabretooth anterior dentition. PMID:23951334

  15. Canine evolution in sabretoothed carnivores: natural selection or sexual selection?

    Directory of Open Access Journals (Sweden)

    Marcela Randau

    Full Text Available The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae, representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids in relation to body size in order to characterize and identify the evolutionary processes driving their development, using the scaling relationships of carnassial teeth in both groups as a control. Carnassials display isometric allometry in both sabretooths and non-sabretooths, supporting their close relationship with meat-slicing, whereas the upper canines of both groups display positive allometry with body size. Whereas there is no statistical difference in allometry of upper canine height between dirk-toothed and scimitar-toothed sabretooth ecomorphs, the significantly stronger positive allometry of upper canine height shown by sabretooths as a whole compared to non-sabretooths reveals that different processes drove canine evolution in these groups. Although sabretoothed canines must still have been effective for prey capture and processing by hypercarnivorous predators, canine morphology in these extinct carnivores was likely to have been driven to a greater extent by sexual selection than in non-sabretooths. Scaling relationships therefore indicate the probable importance of sexual selection in the evolution of the hypertrophied sabretooth anterior dentition.

  16. Activation and localization of matrix metalloproteinase-2 and -9 in the skeletal muscle of the muscular dystrophy dog (CXMDJ

    Directory of Open Access Journals (Sweden)

    Takeda Shin'ichi

    2007-06-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are key regulatory molecules in the formation, remodeling and degradation of all extracellular matrix (ECM components in both physiological and pathological processes in various tissues. The aim of this study was to examine the involvement of gelatinase MMP family members, MMP-2 and MMP-9, in dystrophin-deficient skeletal muscle. Towards this aim, we made use of the canine X-linked muscular dystrophy in Japan (CXMDJ model, a suitable animal model for Duchenne muscular dystrophy. Methods We used surgically biopsied tibialis cranialis muscles of normal male dogs (n = 3 and CXMDJ dogs (n = 3 at 4, 5 and 6 months of age. Muscle sections were analyzed by conventional morphological methods and in situ zymography to identify the localization of MMP-2 and MMP-9. MMP-2 and MMP-9 activity was examined by gelatin zymography and the levels of the respective mRNAs in addition to those of regulatory molecules, including MT1-MMP, TIMP-1, TIMP-2, and RECK, were analyzed by semi-quantitative RT-PCR. Results In CXMDJ skeletal muscle, multiple foci of both degenerating and regenerating muscle fibers were associated with gelatinolytic MMP activity derived from MMP-2 and/or MMP-9. In CXMDJ muscle, MMP-9 immunoreactivity localized to degenerated fibers with inflammatory cells. Weak and disconnected immunoreactivity of basal lamina components was seen in MMP-9-immunoreactive necrotic fibers of CXMDJ muscle. Gelatinolytic MMP activity observed in the endomysium of groups of regenerating fibers in CXMDJ did not co-localize with MMP-9 immunoreactivity, suggesting that it was due to the presence of MMP-2. We observed increased activities of pro MMP-2, MMP-2 and pro MMP-9, and levels of the mRNAs encoding MMP-2, MMP-9 and the regulatory molecules, MT1-MMP, TIMP-1, TIMP-2, and RECK in the skeletal muscle of CXMDJ dogs compared to the levels observed in normal controls. Conclusion MMP-2 and MMP-9 are likely involved in the

  17. Care to child with muscular dystrophies dependent of home technology: mothers´ conception

    Directory of Open Access Journals (Sweden)

    Fabíola Sousa de Oliveira

    2013-05-01

    Full Text Available It was aimed to understand the mother's conception on care to child with muscular dystrophies dependent on technology. Descriptive study with qualitative approach carried out in a children's hospital of the tertiary net in Fortaleza-Ceará, Brazil, as well as in homes of children with muscular dystrophy assisted by the Home Ventilation Assistance Program. The informants were mothers of children with dystrophy aged between zero and four years old, admitted in the Special Patients Unit and assisted by this program. We performed semi-structured interviews and after analysis, the following categories emerged: Care of children with muscular dystrophy and Feelings and expectations of mothers of children with muscular dystrophy. We identified that some mothers consider the child's daily life within the normal patterns, and others report difficulties, creating anxiety and fear of death. Thus, we verify the importance of nurses in the training of these mothers for directed care enabling to overcome stressful moments.

  18. Interpretation of "Diagnosis and management of Duchenne muscular dystrophy: a guide for families (2011 version"

    Directory of Open Access Journals (Sweden)

    Xi-hua LI

    2015-05-01

    Full Text Available The guideline "Diagnosis and management of Duchenne muscular dystrophy" was supported by a 3-year-long project guided by US Centers for Disease Control and Prevention (CDC, in collaboration with patient advocacy groups [Muscular Dystrophy Association (MDA, Parent Project Muscular Dystrophy (PPMD and United Parent Projects Muscular Dystrophy (UPPMD] and Translational Research in Europe: Assessment and Treatment of Neuromuscular Disease (TREAT-NMD network. The main document was published in Lancet Neurol in 2010. The recommendations are based on an extensive study by 84 international experts in Duchenne muscular dystrophy (DMD diagnosis and care who were chosen to represent a broad range of specialties. This guideline covers diagnostics, steroid treatment, rehabilitation, orthopedics, pulmonary, cardiac, gastrointestinal, psychosocial, surgical and emergency management of DMD. This guideline is recommended as the first choice by TREAT- NMD for DMD diagnosis and care. DOI: 10.3969/j.issn.1672-6731.2015.05.003

  19. Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

    DEFF Research Database (Denmark)

    Guo, L T; Zhang, X U; Kuang, W;

    2003-01-01

    Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal...... substantially prevented the muscular dystrophy in these mice. However, dy(W)/dy(W) mice, expressing the human laminin alpha2 under the control of the striated muscle-specific portion of the desmin promoter, still developed muscular dystrophy. This failure to rescue is apparently because of insufficient...... production of laminin alpha2. This study provides additional evidence that the amount of laminin alpha2 is most critical for the prevention of muscular dystrophy. These data may thus be of significance for attempts to treat congenital muscular dystrophy in human patients....

  20. Apicotomy: surgical management of maxillary dilacerated or ankylosed canines.

    Science.gov (United States)

    Araújo, Eustáquio A; Araújo, Cristiana V; Tanaka, Orlando M

    2013-12-01

    This clinical article reports a technique, apicotomy, for managing dilacerated or ankylosed canines. The records of 3 patients successfully treated with apicotomy are presented. Orthodontists observe clinically significant incidences of impacted maxillary canines in their daily practices. Several procedures have been described to bring an ankylosed, impacted tooth into occlusion. Luxation is the most widely used solution, but there are risks involved with that approach, and the success rate is low. Surgical repositioning has also been used, but morbidity is high, and the aggressiveness of the procedure might also contraindicate it. Ankylosis might be related to the anatomic position of the canine's root apex and its adjacent anatomic structures. Apicotomy is a guided fracture of a canine root apex, followed by its orthodontic traction. It is a conservative surgical alternative for treating impacted canines with dilacerations or apical root ankylosis. PMID:24286914

  1. Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas.

    Science.gov (United States)

    Mikiewicz, M; Otrocka-Domagała, I; Paździor-Czapula, K; Gesek, M

    2016-01-01

    The aim of the study was the evaluation of morphology and immunophenotype of canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours, located in skin, oral cavity and spleen were surgically excised, fixed and processed for histopathology and immunohistochemistry (CD79α, CD18, proliferating cell nuclear antigen, metallothionein). Histologically, tumours were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin, or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression of CD79α antigen. The expression of CD18 was observed in canine cutaneous and splenic tumours. In canine tumours expression of metallothionein was low to moderate, while in feline plasmacytomas - absent or low. In canine tumours, the mitotic index and proliferating cell nuclear antigen index were positively correlated with the expression of metallothionein. In feline tumours no correlation between mitotic index, proliferating cell nuclear antigen and metallothionein was found. This is the first study describing expression of metallothionein in canine and feline extramedullary plasmacytoma. PMID:27487508

  2. Ullrich Congenital Muscular Dystrophy (UCMD: Clinical and Genetic Correlations

    Directory of Open Access Journals (Sweden)

    Bita BOZORGMEHR

    2013-08-01

    Full Text Available How to Cite This Article: Bozorgmehr B, Kariminejad A, Nafissi Sh, Jebelli B, Andoni U, Gartioux C, Ledeuil C, Allamand Y, Richard P, Kariminejad MH. Ullrich Congenital Muscular Dystrophy (UCMD:Clinical and Genetic Correlations. Iran J Child Neurol. 2013 Summer; 7(3: 15-22.  Objective:Ullrich congenital muscular dystrophy (UCMD corresponds to the severe end of the clinical spectrum of neuromuscular disorders caused by mutations in the genes encoding collagen VI (COL VI. We studied four unrelated families with six affected children that had typical UCMD with dominant and recessive inheritance.Materials & MethodsFour unrelated Iranian families with six affected children with typical UCMD were analyzed for COLVI secretion in skin fibroblast culture and the secretion of COLVI in skin fibroblast culture using quantitative RT–PCR (Q-RT-PCR, and mutation identification was performed by sequencing of complementary DNA.ResultsCOL VI secretion was altered in all studied fibroblast cultures. Two affected sibs carried a homozygous nonsense mutation in exon 12 of COL6A2, while another patient had a large heterozygous deletion in exon 5-8 of COL6A2. The two other affected sibs had homozygote mutation in exon 24 of COL6A2, and the last one was homozygote in COL6A1.ConclusionIn this study, we found out variability in clinical findings and genetic inheritance among UCMD patients, so that the patient with complete absence of COLVI was severely affected and had a large heterozygous deletion in COL6A2. In contrast, the patients with homozygous deletion had mild to moderate decrease in the secretion of COL VI and were mildly tomoderately affected.References1. Voit T. Congenital Muscular Dystrophies Brain Dev 1998;20(2: 65-74.2. Ullrich OZ Ges. Scleroatonic Muscular Dystrophy. NeurolPsychiatr 1930;126:171-201.3. Ullrich O. Monatsschr. Kinderheilkd 1930;47:502-10.4. Mercuri E, Yuva Y, Brown SC, Brockington M, Kinali M, Jungbluth H, et al. Collagen VI involvement in

  3. Extraglandular and intraglandular vascularization of canine prostate.

    Science.gov (United States)

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism.

  4. Enzyme-linked immunosorbent Assay for detecting of antibody to canine distemper virus

    OpenAIRE

    Sudarisman

    2006-01-01

    Serum neutralisation test (SNT) has been established for evaluating canine distemper vaccination, but until now SNT was rarely used due to the need for continuous tissue culture facilities and requires 3 days to perform. For detecting antibody to canine distemper virus, an enzyme-linked immunosorbent assay (ELISA) is relatively simple and rapid seroassay. ELISA for canine immunoglobulin (Ig) G antibodies to canine distemper virus (CDV) was developed by using Onderstepoort strain of canine dis...

  5. Creation of distal canine limb lymphedema

    Energy Technology Data Exchange (ETDEWEB)

    Chen, H.C.; Pribaz, J.J.; O' Brien, B.M.; Knight, K.R.; Morrison, W.A.

    1989-06-01

    A canine model of distal limb lymphedema was established in order to study the treatment of this condition by lymph node transfer. This model was more difficult to establish than whole-limb lymphedema. Significant edema was achieved by a combination of preoperative irradiation and circumferential removal of skin from the irradiated areas followed by removal of the contents of the popliteal fossa. Despite these measures, it was not possible to produce lymphedema in every case, possibly because of the presence of lymphaticovenous shunts and panvascular compensation mechanisms.

  6. Lactoferrin in canine sera: a pyometra study.

    Science.gov (United States)

    Bartoskova, A; Adlerova, L; Kudlackova, H; Leva, L; Vitasek, R; Faldyna, M

    2009-07-01

    The concentration of lactoferrin was measured in canine sera from groups of healthy male dogs as well as pregnant and non-pregnant female dogs and was compared with that of bitches with pyometra. Lactoferrin concentrations were higher in bitches with pyometra. The role of elevated lactoferrin concentrations in the suppression of lymphocyte activity was examined in sera from bitches with pyometra in a series of investigations. Although the sera from bitches with pyometra were capable of suppressing lymphocyte activity, lactoferrin was not found to be involved in this action. PMID:19754566

  7. Definition, Classification, and Pathophysiology of Canine Glaucoma.

    Science.gov (United States)

    Pizzirani, Stefano

    2015-11-01

    Glaucoma is a common ocular condition in humans and dogs leading to optic nerve degeneration and irreversible blindness. Primary glaucoma is a group of spontaneous heterogeneous diseases. Multiple factors are involved in its pathogenesis and these factors vary across human ethnic groups and canine breeds, so the clinical phenotypes are numerous and their classification can be challenging and remain superficial. Aging and oxidative stress are major triggers for the manifestation of disease. Multiple, intertwined inflammatory and biochemical cascades eventually alter cellular and extracellular physiology in the optic nerve and trabecular meshwork and lead to vision loss. PMID:26456751

  8. New aspects on patients affected by dysferlin deficient muscular dystrophy

    Science.gov (United States)

    Klinge, Lars; Aboumousa, Ahmed; Eagle, Michelle; Hudson, Judith; Sarkozy, Anna; Vita, Gianluca; Charlton, Richard; Roberts, Mark; Straub, Volker; Barresi, Rita; Lochmüller, Hanns

    2009-01-01

    Mutations in the dysferlin gene lead to limb girdle muscular dystrophy 2B, Miyoshi myopathy and distal anterior compartment myopathy. A cohort of 36 patients affected by dysferlinopathy is described, in the first UK study of clinical, genetic, pathological and biochemical data. The diagnosis was established by reduction of dysferlin in the muscle biopsy and subsequent mutational analysis of the dysferlin gene. Seventeen mutations were novel; the majority of mutations were small deletions/insertions, and no mutational hotspots were identified. Sixty-one per cent of patients (22 patients) initially presented with limb girdle muscular dystrophy 2B, 31% (11 patients) with a Miyoshi phenotype, one patient with proximodistal mode of onset, one patient with muscle stiffness after exercise and one patient as a symptomatic carrier. A wider range of age of onset was noted than previously reported, with 25% of patients having first symptoms before the age of 13 years. Independent of the initial mode of presentation, in our cohort of patients the gastrocnemius muscle was the most severely affected muscle leading to an inability to stand on tiptoes, and lower limbs were affected more severely than upper limbs. As previous anecdotal evidence on patients affected by dysferlinopathy suggests good muscle prowess before onset of symptoms, we also investigated pre-symptomatic fitness levels of the patients. Fifty-three per cent of the patients were very active and sporty before the onset of symptoms which makes the clinical course of dysferlinopathy unusual within the different forms of muscular dystrophy and provides a challenge to understanding the underlying pathomechanisms in this disease. PMID:19528035

  9. Red-Green Color Vision Impairment in Duchenne Muscular Dystrophy

    OpenAIRE

    Costa, Marcelo Fernandes; Oliveira, Andre Gustavo Fernandes; Feitosa-Santana, Claudia; Zatz, Mayana; Ventura, Dora Fix

    2008-01-01

    The present study evaluated the color vision of 44 patients with Duchenne muscular dystrophy (DMD) (mean age 14.8 years; SD 4.9) who were submitted to a battery of four different color tests: Cambridge Colour Test (CCT), Neitz Anomaloscope, Ishihara, and American Optical Hardy-Rand-Rittler (AO H-R-R). Patients were divided into two groups according to the region of deletion in the dystrophin gene: upstream of exon 30 (n=12) and downstream of exon 30 (n=32). The control group was composed of 7...

  10. Magnetic resonance imaging of children with Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Eight children representing a spectrum of clinical states of biopsy-proven Duchenne muscular dystrophy (DMD) underwent magnetic resonance (MR) scans to assess the degree of muscular involvement and disease progression. Five muscle groups (neck, shoulder girdle, pelvic girdle, thigh and calf) were evaluated. In each case, involved muscles were clearly demarcated. Image estimates of disease severity by degree of muscle involvement correlated well with clinical staging. In our experience MR is useful for assessment of disease stage, selection of appropriate muscles for biopsy and planning for courses of physical and rehabilitation therapy. (orig.)

  11. Duchenne muscular dystrophy: normal ATP turnover in cultured cells

    International Nuclear Information System (INIS)

    This paper examines ATP metabolism in cultured muscle cells and fibroblasts from patients with Duchenne dystrophy. ATP and ADP levels were the same in cultured cells from normal subjects and patients and there was no difference in ATP synthesis or degradation. The ATP synthesis was measured by the incorporation of C 14-U-adenine into aTP and ADP. although there was a significant decrease in radioactively labelled ATP after incubation with deoxyglucose in Duchenne muscle cells, there was no difference in ATP concentration of ADP metabolism

  12. The pyrophosphate heart scintigram in children with progressive muscular dystrophy

    International Nuclear Information System (INIS)

    A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index. (orig.)

  13. Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD).

    Science.gov (United States)

    Brolin, Camilla; Shiraishi, Takehiko

    2011-01-01

    Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most promising methods for restoration of dystrophin expression. This approach has been tested extensively targeting different exons in numerous models both in vitro and in vivo. During the past 10 years, there has been a considerable progress by using DMD animal models involving three types of antisense oligonucleotides (2'-O-methyl phosphorothioate (2OME-PS), phosphorodiamidate morpholino oligomer (PMO)) and peptide nucleic acid (PNA). PMID:21686247

  14. Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD)

    DEFF Research Database (Denmark)

    Brolin, Camilla; Shiraishi, Takehiko

    2011-01-01

    Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most...... promising methods for restoration of dystrophin expression. This approach has been tested extensively targeting different exons in numerous models both in vitro and in vivo. During the past 10 years, there has been a considerable progress by using DMD animal models involving three types of antisense...

  15. Progress study of the cardiac damage in Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    ZHANG Yao

    2013-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is a fatal muscular disease with rapid progression in children. Most patients die of respiratory and circulatory failure before the age of 20 if there is no systematic treatment. Now the heart problem in this disease has become increasingly prominent, and is thought to be closely associated with certain dystrophin exon deletion. We would like to review the epidemiology, relevance of dystrophin, pathogenesis, clinical manifestations and pathological features, as well as early prevention and treatment of DMD.

  16. Functional muscle ischemia in Duchenne and Becker muscular dystrophy

    OpenAIRE

    GailDThomas

    2013-01-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) comprise a spectrum of devastating X-linked muscle wasting disease for which there is no treatment. DMD/BMD is caused by mutations in the gene encoding dystrophin, a cytoskeletal protein that stabilizes the muscle membrane and also targets other proteins to the sarcolemma. Among these is the muscle-specific isoform of neuronal nitric oxide synthase (nNOSµ) which binds spectrin-like repeats within dystrophin’s rod domain and the adaptor pro...

  17. Merosin-negative congenital muscular dystrophy: Report of five cases

    OpenAIRE

    Faruk Incecik; Ozlem M Herguner; Serdar Ceylaner; Sakir Altunbasak

    2015-01-01

    Context: Congenital muscular dystrophy type 1A (MDC1A) is caused by mutations in the laminin α-2 gene encoding laminin-a2. Aims: The purpose of this study is to determine clinical and genetic results in five Turkish patients with MDC1A. Setting and Designs: Five children with MDC1A were retrospectively analyzed. Results: Three (60%) were boys, and 2 (40%) were girls. Parental consanguinity was found in all the families. In all the patients, hypotonia, weakness, delayed motor milestones, marke...

  18. A genetic study of Duchenne muscular dystrophy in West Midlands.

    OpenAIRE

    Bundey, S

    1981-01-01

    A study of Duchenne muscular dystrophy has shown an approximate prevalence of the disease among schoolboys to be 1 in 4000. Fifty-four families were available for genetic studies. In 19 families there were further affected cases and in 34 families the index patients was an isolated case. The proportion of affected brothers was 0.22 (11 of 50). There were 142 female relatives who had a risk of 1 in 10 or worse of being carriers: 66 of these were aged under 16. As genetic counselling is being i...

  19. Cell and gene therapy in Duchenne muscular dystrophy.

    Science.gov (United States)

    Morgan, J E

    1994-02-01

    Experiments in mice have supported the idea of treating Duchenne muscular dystrophy (DMD) by implanting normal muscle precursor cells into dystrophin-deficient muscles. However, similar experiments on DMD patients have had little success. Gene therapy for DMD, by introducing dystrophin constructs via retroviral or adenoviral vectors, has been shown to be possible in the mouse, but the efficiency and safety aspects of this technique will have to be carefully examined before similar experiments can be attempted in man. Direct injection of dystrophin cDNA constructs into mdx muscles has given rise to very low levels of dystrophin and this may be a possibility for the treatment of heart muscle. PMID:7514447

  20. Cone beam computed tomography findings of impacted upper canines

    Energy Technology Data Exchange (ETDEWEB)

    Da Silva Santos, Ludmilla Mota [Dept. of Endodontics, Aracatuba Dental School, Paulista State University, Aracatuba(Brazil); Bastos, Luana Costa; Da Silva, Silvio Jose Albergaria; Campos, Paulo Sergio Flores [School of Dentistry, Federal University of Bahia, Salvador (Brazil); Oliveira Santos, Christiano [Dept. of Stomatology, Oral Public Health, and Forensic Dentistry, School of Dentistry, University of Sao Paulo, Ribeirao Preto (Brazil); Neves, Frederico Sampaio [Dept. of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Piracicaba (Brazil)

    2014-12-15

    To describe the features of impacted upper canines and their relationship with adjacent structures through three-dimensional cone-beam computed tomography (CBCT) images. Using the CBCT scans of 79 upper impacted canines, we evaluated the following parameters: gender, unilateral/bilateral occurrence, location, presence and degree of root resorption of adjacent teeth (mild, moderate, or severe), root dilaceration, dental follicle width, and presence of other associated local conditions. Most of the impacted canines were observed in females (56 cases), unilaterally (51 cases), and at a palatine location (53 cases). Root resorption in adjacent teeth and root dilaceration were observed in 55 and 47 impacted canines, respectively. In most of the cases, the width of the dental follicle of the canine was normal; it was abnormally wide in 20 cases. A statistically significant association was observed for all variables, except for root dilaceration (p=0.115) and the side of impaction (p=0.260). Root resorption of adjacent teeth was present in most cases of canine impaction, mostly affecting adjacent lateral incisors to a mild degree. A wide dental follicle of impacted canines was not associated with a higher incidence of external root resorption of adjacent teeth.

  1. Cone beam computed tomography findings of impacted upper canines

    International Nuclear Information System (INIS)

    To describe the features of impacted upper canines and their relationship with adjacent structures through three-dimensional cone-beam computed tomography (CBCT) images. Using the CBCT scans of 79 upper impacted canines, we evaluated the following parameters: gender, unilateral/bilateral occurrence, location, presence and degree of root resorption of adjacent teeth (mild, moderate, or severe), root dilaceration, dental follicle width, and presence of other associated local conditions. Most of the impacted canines were observed in females (56 cases), unilaterally (51 cases), and at a palatine location (53 cases). Root resorption in adjacent teeth and root dilaceration were observed in 55 and 47 impacted canines, respectively. In most of the cases, the width of the dental follicle of the canine was normal; it was abnormally wide in 20 cases. A statistically significant association was observed for all variables, except for root dilaceration (p=0.115) and the side of impaction (p=0.260). Root resorption of adjacent teeth was present in most cases of canine impaction, mostly affecting adjacent lateral incisors to a mild degree. A wide dental follicle of impacted canines was not associated with a higher incidence of external root resorption of adjacent teeth.

  2. Cardiac involvement in myotonic muscular dystrophy (Steinert's disease): a prospective study of 25 patients

    International Nuclear Information System (INIS)

    The presence, degree and frequency of disorders of cardiac conduction and rhythm and of regional or global myocardial dystrophy or myotonia have not previously been studied prospectively and systematically in the same population of patients with myotonic dystrophy. Accordingly, 25 adults with classic Steinert's disease underwent electrocardiography, 24-hour ambulatory electrocardiography, vectorcardiography, chest x-rays, echocardiography, electrophysiologic studies, and technetium-99m angiography. Clinically important cardiac manifestations of myotonic dystrophy reside in specialized tissues rather than in myocardium. Involvement is relatively specific, primarily assigned to the His-Purkinje system. The cardiac muscle disorder takes the form of dystrophy rather than myotonia, and is not selective, appearing with approximately equal distribution in all 4 chambers. Myocardial dystrophy seldom results in clinically overt ventricular failure, but may be responsible for atrial and ventricular arrhythmias. Since myotonic dystrophy is genetically transmitted, a primary biochemical defect has been proposed with complete expression of the gene toward striated muscle tissue, whether skeletal or cardiac. Specialized cardiac tissue and myocardium have close, if not identical, embryologic origins, so it is not surprising that the genetic marker affects both. Cardiac involvement is therefore an integral part of myotonic dystrophy, targeting particularly the infranodal conduction system, to a lesser extent the sinus node, and still less specifically, the myocardium

  3. Establishment of a sensitized canine model for kidney transplantation

    Institute of Scientific and Technical Information of China (English)

    XIE Sen; XIA Sui-sheng; TANG Li-gong; CHENG Jun; CHEN Zhi-shui; ZHENG Shan-gen

    2005-01-01

    Objective:To establish a sensitized canine model for kidney transplantation. Methods:12 male dogs were averagely grouped as donors and recipients. A small number of donor canine lymphocytes was infused into different anatomic locations of a paired canine recipient for each time and which was repeated weekly. Specific immune sensitization was monitored by means of Complement Dependent Cytotoxicity (CDC) and Mixed Lymphocyte Culture (MLC) test. When CDC test conversed to be positive and MLC test showed a significant proliferation of reactive lymphocytes of canine recipients, the right kidneys of the paired dogs were excised and transplanted to each other concurrently. Injury of renal allograft function was scheduled determined by ECT dynamic kidney photography and pathologic investigation. Results :CDC test usually conversed to be positive and reactive lymphocytes of canine recipients were also observed to be proliferated significantly in MLC test after 3 to 4 times of canine donor lymphocyte infusions. Renal allograft function deterioration occurred 4 d post-operatively in 4 of 6 canine recipients, in contrast to none in control dogs. Pathologic changes suggested antibody-mediated rejection (delayed) or acute rejection in 3 excised renal allograft of sensitized dogs. Seven days after operation, all sensitized dogs had lost graft function, pathologic changes of which showed that the renal allografts were seriously rejected. 2 of 3 dogs in control group were also acutely rejected. Conclusion:A convenient method by means of repeated stimulation of canine lymphocyte may induce specific immune sensitization in canine recipients. Renal allografts in sensitized dogs will be earlier rejected and result in a more deteriorated graft function.

  4. Detection of canine echinococcosis by coproantigen ELISA

    Institute of Scientific and Technical Information of China (English)

    DeS; PanD; BeraAK; SreevatsavaV; DasSK; DasS; RanaT; BandyopadhyayS; BhattacharyaD

    2010-01-01

    Objective:To study the canine echinococcosis by coproantigen ELISA method. Methods:During the present investigation experimental infection was established using evaginated worms of Echinococcus granulosus (E. granulosus). To check cross reactivity two pups were infected with Taenia hydatigena(T. hydatigena). In order to detect the presence of antigen, hyperimmune sera were raised against excretory-secretory products of adult worms E. chinococcus granulosus. Faecal sample collected either from experimentally infected pups or from other sources were heated at 70℃to detect heat stable soluble antigen. Results:Pups harbouring less than 104 worms showed negative results. Samples collected from 14 days onwards from experimentally infected animals harbouring more than 104 worms showed positive value. The maximum positive samples were detected in samples collected from in and around slaughter house and the least number of samples were detected positive maintained by dog squad. Conclusions:The affinity purified IgG exhibited promising results for detection of canine echinococcosis by indirect ELISA.

  5. Seroepidemiology of Canine parvovirus infection in dogs

    Directory of Open Access Journals (Sweden)

    Indrawati Sendow

    2004-10-01

    Full Text Available Canine parvovirus is an acute and fatal viral disease in dogs. A total of 209 local, cross breed and breed dogs sera from Kodya Bogor, Kabupaten Bogor, Sukabumi, and Jakarta, had been tested using Haemagglutination Inhibition Test (HI with pig red blood cells. A total of 64 breed and cross breed dogs from Sukabumi and Kodya Bogor, were used as a sentinel dogs to study the epidemiology of Canine parvovirus (CPV infection and its immunological responses caused by vaccination. The results indicated that 78% (95 breed and cross bred dogs and 59% (51 local dogs had antibody to CPV. Sentinel dogs results indicated that dogs had been vaccinated showed antibody response with the varied titre dependant upon prevaccination titre. Low prevaccinated titre gave better response than protective level titre. From 19 puppies observed, Maternal antibodi were still detected until 5 weeks old puppies. First vaccination given at less than 3 months old, should be boosted after 3 months old puppied. Antibodi titre produced by natural infection will keep untill 2 years. These data concluded that the dog condition and time of vaccination will affect the optimum antibody response.

  6. Limb-girdle muscular dystrophy subtypes First-reported cohort from northeastern China*

    Institute of Scientific and Technical Information of China (English)

    Omar Abdulmonem Mahmood; Xinmei Jiang; Qi Zhang

    2013-01-01

    The relative frequencies of different subtypes of limb-girdle muscular dystrophies vary widely among different populations. We estimated the percentage of limb-girdle muscular dystrophy sub-types in Chinese people based on 68 patients with limb-girdle muscular dystrophy from the Myology Clinic, Neurology Department, First Hospital of Jilin University, China. A diagnosis of calpainopathy was made in 12 cases (17%), and dysferlin deficiency in 10 cases (15%). Two biopsies revealedα-sarcoglycan deficiency (3%), and two others revealed a lack of caveolin-3 (3%). A diagnosis of unclassified limb-girdle muscular dystrophy was made in the remaining patients (62%). The ap-pearances of calpain 3-and dysferlin-deficient biopsies were similar, though rimmed vacuoles were unique to dysferlinopathy, while inflammatory infiltrates were present in both these limb-girdle muscular dystrophy type 2D biopsies. Macrophages were detected in seven dysferlinopathy biop-sies. The results of this study suggest that the distribution of limb-girdle muscular dystrophy sub-types in the Han Chinese population is similar to that reported in the West. The less necrotic, re-generating and inflammatory appearance of limb-girdle muscular dystrophy type 2A, but with more lobulated fibers, supports the idea that calpainopathy is a less active, but more chronic disease than dysferlinopathy. Unusual features indicated an extended limb-girdle muscular dystrophy disease spectrum. The use of acid phosphatase stain should be considered in suspected dysferlinopathies. To the best of our knowledge, this is the first report to define the relative proportions of the various forms of limb-girdle muscular dystrophy in China, based on protein testing.

  7. A custom made jig for individual canine retraction

    Directory of Open Access Journals (Sweden)

    Vipul Kumar Sharma

    2016-01-01

    Full Text Available We face difficulty in individual canine retraction in the bracket system lacking power arms on the canines. When orthodontic force is applied through the center of resistance (CR, then, tooth translation ensues. Forces applied at a distance from the CR create a moment that tends to rotate and tip the tooth. The tendency of tipping is increased in the bracket system lacking power arm, since, force is applied more occlusally. Hence, we have designed a chair side custom made jig to retract the canines individually.

  8. Canine pluripotent stem cells: Are they ready for clinical applications?

    Directory of Open Access Journals (Sweden)

    Dean Harvey Betts

    2015-10-01

    Full Text Available The derivation of canine embryonic stem cells and generation of canine induced pluripotent stem cells are significant achievements that have unlocked the potential for developing novel cell-based disease models, drug discovery platforms and transplantation therapies in the dog. A progression from concept to cure in this clinically relevant companion animal will not only help our canine patients but also help advance human regenerative medicine. Nevertheless, many issues remain to be resolved before pluripotent cells can be used clinically in a safe and reproducible manner.

  9. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

    Directory of Open Access Journals (Sweden)

    Reiner Ulrich

    Full Text Available Canine distemper virus (CDV-induced demyelinating leukoencephalitis in dogs (Canis familiaris is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy

  10. Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy.

    Science.gov (United States)

    De Arcangelis, Valeria; Strimpakos, Georgios; Gabanella, Francesca; Corbi, Nicoletta; Luvisetto, Siro; Magrelli, Armando; Onori, Annalisa; Passananti, Claudio; Pisani, Cinzia; Rome, Sophie; Severini, Cinzia; Naro, Fabio; Mattei, Elisabetta; Di Certo, Maria Grazia; Monaco, Lucia

    2016-01-01

    Numerous therapeutic approaches for Duchenne and Becker Muscular Dystrophy (DMD and BMD), the most common X-linked muscle degenerative disease, have been proposed. So far, the only one showing a clear beneficial effect is the use of corticosteroids. Recent evidence indicates an improvement of dystrophic cardiac and skeletal muscles in the presence of sustained cGMP levels secondary to a blocking of their degradation by phosphodiesterase five (PDE5). Due to these data, we performed a study to investigate the effect of the specific PDE5 inhibitor, tadalafil, on dystrophic skeletal muscle function. Chronic pharmacological treatment with tadalafil has been carried out in mdx mice. Behavioral and physiological tests, as well as histological and biochemical analyses, confirmed the efficacy of the therapy. We then performed a microarray-based genomic analysis to assess the pattern of gene expression in muscle samples obtained from the different cohorts of animals treated with tadalafil. This scrutiny allowed us to identify several classes of modulated genes. Our results show that PDE5 inhibition can ameliorate dystrophy by acting at different levels. Tadalafil can lead to (1) increased lipid metabolism; (2) a switch towards slow oxidative fibers driven by the up-regulation of PGC-1α; (3) an increased protein synthesis efficiency; (4) a better actin network organization at Z-disk. PMID:26097015

  11. Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. (Penn State College of Medicine, Hershey, PA (United States)); Shokeir, M. (Univ. Hospital, Saskatchewan (Canada))

    1992-09-01

    In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

  12. Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Melinda F. Davis

    2010-10-01

    Full Text Available Medical investigations use a wide variety of outcome indicators that are often not comparable. It can be challenging to integrate results across multiple studies that do not share a common metric. Some conditions such as Duchenne and Becker muscular dystrophy have a predictable course of disease progression. Severity can be inferred from a patient's medical history. This paper describes the development of a disease severity measure using common markers of disease progression. Rasch modeling was used to estimate severity using dichotomous events that indicate disease progression. Caregivers of 34 young men with Duchenne or Becker muscular dystrophy completed structured interviews about their care and medical history. Interview questions included surgeries (tendon release, scoliosis, tracheostomy, respiratory equipment (assisted ventilation, cough assist devices, and the use of other medical equipment (e.g., braces, walkers, wheelchairs, transfer boards, hospital beds. The resulting measure had a reliability of .83. The correlation between the severity measure and the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS was .68. Preliminary results and item calibrations are provided for the severity measure that can be estimated from caregiver reports or administrative data. DOI: 10.2458/azu_jmmss.v1i1.76

  13. Drugs in development and dietary approach for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Angelini C

    2015-08-01

    Full Text Available Corrado Angelini, Elisabetta Tasca Neuromuscular Laboratory, Fondazione San Camillo Hospital IRCCS, Venice, Italy Abstract: Therapeutic trials studying Duchenne muscular dystrophy (DMD in Europe and the USA have been done using a protocol that includes manual muscle testing and functional testing, and have shown the efficacy of steroid drugs in various doses and regimens. Further, drisapersen and eteplirsen (exon skipping drugs and ataluren (a drug to overcome stop codon mutations have achieved some clinical improvement. Cardioprotective drugs are efficacious in DMD, and eplerenone, an aldosterone inhibitor and diuretic, is now being used to treat the disease. The dietary approach should be used in wheelchair-bound DMD children in combination with respiratory assistance. The importance of some of the treatments proposed is that they might also be useful in other genetic disorders where stop codon mutations are present; moreover, it is possible that these new treatments will improve quality of life for many patients. Keywords: Duchenne muscular dystrophy, steroids, ataluren, drisapersen, eplerenone, eteplirsen

  14. Understanding the impact of genetic testing for inherited retinal dystrophy.

    Science.gov (United States)

    Combs, Ryan; McAllister, Marion; Payne, Katherine; Lowndes, Jo; Devery, Sophie; Webster, Andrew R; Downes, Susan M; Moore, Anthony T; Ramsden, Simon; Black, Graeme; Hall, Georgina

    2013-11-01

    The capability of genetic technologies is expanding rapidly in the field of inherited eye disease. New genetic testing approaches will deliver a step change in the ability to diagnose and extend the possibility of targeted treatments. However, evidence is lacking about the benefits of genetic testing to support service planning. Here, we report qualitative data about retinal dystrophy families' experiences of genetic testing in United Kingdom. The data were part of a wider study examining genetic eye service provision. Twenty interviewees from families in which a causative mutation had been identified by a genetic eye clinic were recruited to the study. Fourteen interviewees had chosen to have a genetic test and five had not; one was uncertain. In-depth telephone interviews were conducted allowing a thorough exploration of interviewees' views and experiences of the benefits of genetic counselling and testing. Transcripts were analysed using thematic analysis. Both affected and unaffected interviewees expressed mainly positive views about genetic testing, highlighting benefits such as diagnostic confirmation, risk information, and better preparation for the future. Negative consequences included the burden of knowledge, moral dilemmas around reproduction, and potential impact on insurance. The offer of genetic testing was often taken up, but was felt unnecessary in some cases. Interviewees in the study reported many benefits, suggesting genetic testing should be available to this patient group. The benefits and risks identified will inform future evaluation of models of service delivery. This research was part of a wider study exploring experiences of families with retinal dystrophy. PMID:23403902

  15. Depression in Myotonic Dystrophy type 1: clinical and neuronal correlates

    Directory of Open Access Journals (Sweden)

    Samuelsson Lena

    2010-05-01

    Full Text Available Abstract Background This study was designed to investigate the prevalence and correlates of depression in Myotonic dystrophy type 1 (DM1. Methods Thirty-one patients with DM1 and 47 subjects in a clinical contrast group, consisting of other neuromuscular disorders, including Spinal muscular atrophy, Limb girdle muscle atrophy and Facioscapulohumeral dystrophy, completed Beck Depression Inventory (BDI. We aimed to establish whether different factors associated with DM1 correlated with ratings in the BDI. Results Signs of a clinical depression were prevalent in 32% of the patients with DM1, which was comparable with ratings in the clinical contrast group. The depressive condition was mild to moderate in both groups. In DM1, a longer duration of clinical symptoms was associated with lower scores on the BDI and higher educational levels were correlated with higher scores on depression. We also found a negative association with brain white matter lesions. Conclusions Findings indicate significantly more DM1 patients than normative collectives showing signs of a clinical depression. The depressive condition is however mild to moderate and data indicate that the need for intervention is at hand preferentially early during the disease process.

  16. Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy

    OpenAIRE

    Mahadevan, Mani S.; Yadava, Ramesh S; Yu, Qing; Balijepalli, Sadguna; Frenzel-McCardell, Carla D; Bourne, T. David; Phillips, Lawrence H

    2006-01-01

    Myotonic dystrophy (DM1), the most common muscular dystrophy in adults, is caused by an expanded (CTG)n tract in the 3′ UTR of the gene encoding myotonic dystrophy protein kinase (DMPK)1, which results in nuclear entrapment of the ‘toxic’ mutant RNA and interacting RNA-binding proteins (such as MBNL1) in ribonuclear inclusions2. It is unclear if therapy aimed at eliminating the toxin would be beneficial. To address this, we generated transgenic mice expressing the DMPK 3′ UTR as part of an in...

  17. Anti-gravity training improves walking capacity and postural balance in patients with muscular dystrophy

    DEFF Research Database (Denmark)

    Berthelsen, Martin Peter; Husu, Edith; Christensen, Sofie Bouschinger;

    2014-01-01

    of their weakness. We investigated the functional effects of combined aerobic and strength training in patients with Becker and limb-girdle muscular dystrophies with knee muscle strength levels as low as 3% of normal strength. Eight patients performed 10weeks of aerobic and strength training on an anti...... affected patients with Becker and limb-girdle muscular dystrophies.......Recent studies in patients with muscular dystrophies suggest positive effects of aerobic and strength training. These studies focused training on using bicycle ergometers and conventional strength training, which precludes more severely affected patients from participating, because...

  18. Clinical and serological response of wild dogs (Lycaon pictus to vaccination against canine distemper, canine parvovirus infection and rabies

    Directory of Open Access Journals (Sweden)

    J. Van Heerden

    2002-07-01

    Full Text Available Wild dogs Lycaon pictus (n = 8 were vaccinated 4 times against canine distemper (n = 8 (initially with inactivated and subsequently with live attenuated strains of canine distemper and canine parvovirus infection (n = 8 over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

  19. Case Report: Canine Fossa Abscess; A Rare Etiological Factor: The Lower Canine Tooth

    OpenAIRE

    Agacayak, K. Serkan; Atılgan, S. Serhat; GORGUN, Belgin; Yaman, Ferhan; Ucan, M. Can; Atalay, Yusuf

    2013-01-01

    Odontogenic infection may be dangerous; especially when life-threatening complications occur. Infection spreads through the bone and periosteum toward nearby or more distant structures and spaces. Canine fossa abscess is an odontogenic infection that can lead to life-threatening complications. Successful treatment requires early recognition, determination of etiological factors, and proper medical and surgical management. The aim of this paper is to emphasize different and rare etiological fa...

  20. Emerging perspectives on hereditary glomerulopathies in canines

    Directory of Open Access Journals (Sweden)

    Littman MP

    2015-04-01

    Full Text Available Meryl P LittmanDepartment of Clinical Studies – Philadelphia, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USAAbstract: Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immune-complex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1 glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked, and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive; and 2 glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to non-synonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic

  1. Death of a wild wolf from canine parvovirus enteritis

    Science.gov (United States)

    Mech, L.D.; Kurtz, H.J.; Goyal, S.

    1997-01-01

    A 9-mo-old female wolf (Canis lupus) in the Superior National Forest of Minnesota (USA) died from a canine parvovirus (CPV) infection. This is the first direct evidence that this infection effects free-ranging wild wolves.

  2. Canine index – A tool for sex determination

    Directory of Open Access Journals (Sweden)

    Shankar M. Bakkannavar

    2015-12-01

    Full Text Available Teeth are most useful tools in victim identification in the living as well as the dead in the field of forensic investigations. Their ability to survive in situations like mass disasters makes them constructive devices. Many authors have measured crowns of teeth in both males and females and found certain variations. Canines, reported to survive in air crash and hurricane disasters, are perhaps the most stable teeth in the oral cavity because of the labiolingual thickness of the crown and the root anchorage in the alveolar process of jaws. Measurement of mesiodistal width of the mandibular canines and inter-canine distance of the mandible provides good evidence of sex identification due to dimorphism. This study was undertaken to evaluate the effectiveness of canine index (CI in the determination of sex.

  3. Periodontal ligament distraction: A simplified approach for rapid canine retraction

    Directory of Open Access Journals (Sweden)

    K C Prabhat

    2012-01-01

    Full Text Available Distraction osteogenesis is a method of inducing new bone formation by applying mechanical strains on preexisting bone. The process of osteogenesis in the periodontal ligament during orthodontic tooth movement is similar to the osteogenesis in the midpalatal suture during rapid palatal expansion. A new concept of "distracting the periodontal ligament" is proposed to elicit rapid canine retraction in two weeks. At the time of first premolar extraction, the interseptal bone distal to the canine was undermined with a bone bur, grooving vertically inside the extraction socket along the buccal and lingual sides and extending obliquely toward the socket base. Then, a tooth-borne, custom-made, intraoral distraction device was placed to distract the canine distally into the extraction space. It was activated 0.5 mm/day, immediately after the extraction. Canine was distracted 6.5 mm into the extraction space within two weeks.

  4. Severe canine distemper outbreak in unvaccinated dogs in Mozambique

    Directory of Open Access Journals (Sweden)

    Julieta Zacarias

    2016-02-01

    Full Text Available Although significant animal suffering caused by preventable diseases is frequently seen in developing countries, reports of this are scarce. This report describes avoidable animal suffering owing to a suspected canine distemper (CD outbreak in unvaccinated dogs owned by low-income families in Mozambique that killed approximately 200 animals. Affected dogs exhibited clinical signs, and gross and microscopic lesions compatible with CD. Immunohistochemical staining confirmed the presence of canine distemper virus (CDV in the kidney of one dog from the cohort. This brief communication again illustrates that large outbreaks of CDV in unvaccinated dogs occur and that large-scale avoidable suffering and threats to the health of dogs and wild canines continue. Mass vaccination supported by government and non-government organisations is recommended.Keywords: Canine distemper; dogs; outbreak; animal welfare; Mozambique

  5. Phenotypic Spectrum of Granular Corneal Dystrophy Type II in Two Italian Families Presenting an Unusual Granular Corneal Dystrophy Type I Clinical Appearance

    Directory of Open Access Journals (Sweden)

    Cosimo Mazzotta

    2015-01-01

    Full Text Available Clinical, instrumental, and genetic findings are reported in Italian families with Type II Granular Corneal Dystrophies (GCD2 presenting an initial unusual presentation of a Granular Corneal Dystrophy Type I (GCD1 phenotypic spectrum in female descendants. Slit-lamp examinations showed the typical phenotypic features of GCD2 in both mothers and a phenotypic appearance of GCD1 in both daughters. Despite the different phenotypic onset, the genetic diagnostic testing revealed the presence of a mutation in the TGFB-I gene, typical of GCD2 in both cases, excluding GCD1. Patients who were clinically suspected of corneal dystrophy need a genetic confirmatory testing for certain diagnosis. Genetic test may help to find the specific mutation distinguishing between different phenotypic spectra with relative diagnostic and prognostic implications. The study demonstrates that the phenotypic spectrum of genetically confirmed granular corneal dystrophies in patients may change over time. Since the R124H mutation has also been described in clinically asymptomatic individuals prior to LASIK, who then develop dramatic deposition, suggesting that this particular mutation and phenotype may be sensitive to, precipitated, or modified by central cornea trauma, a careful familial anamnesis excluding cornel dystrophies and specific preoperative genetic test are recommended prior to LASIK.

  6. Canine distemper virus in Lake Baikal seals (Phoca sibirica).

    OpenAIRE

    Mamaev, L.V.; Visser, Ilona; Belikov, S.I.; Denikina, N.N.; Harder, Timm; Goatley, L.; Rima, B.; Edginton, B.; Osterhaus, Albert; Barrett, Thomas,

    1996-01-01

    textabstractThe virus epizootic which resulted in significant mortality in Siberian seals (Phoca sibirica) in Lake Baikal during 1987/88 was caused by canine distemper virus. Sequence analysis of the virus glycoprotein genes revealed that it was most closely related to recent European field isolates of canine distemper virus. This paper presents evidence that the same virus continued to circulate in seals in Lake Baikal after the initial epizootic. Three out of 45 brain tissue samples collect...

  7. Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus

    OpenAIRE

    Otávio Valério Carvalho; Clarisse Vieira Botelho; Caroline Gracielle Torres Ferreira; Paulo Oldemar Scherer; Jamária Adriana Pinheiro Soares-Martins; Márcia Rogéria de Almeida; Abelardo Silva Júnior

    2012-01-01

    Canine distemper is a highly contagious viral disease caused by the canine distemper virus (CDV), which is a member of the Morbillivirus genus, Paramyxoviridae family. Animals that most commonly suffer from this disease belong to the Canidae family; however, the spectrum of natural hosts for CDV also includes several other families of the order Carnivora. The infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availabilit...

  8. Characterization of a Canine Homolog of Human Aichivirus▿

    OpenAIRE

    Kapoor, A; Simmonds, P.; Dubovi, E J; Qaisar, N.; Henriquez, J. A.; J. Medina; S Shields; Lipkin, W. I.

    2011-01-01

    Many of our fatal "civilization" infectious diseases have arisen from domesticated animals. Although picornaviruses infect most mammals, infection of a companion animal is not known. Here we describe the identification and genomic characterization of the first canine picornavirus. Canine kobuvirus (CKoV), identified in stool samples from dogs with diarrhea, has a genomic organization typical of a picornavirus and encodes a 2,469-amino-acid polyprotein flanked by 5' and 3' untranslated regions...

  9. Permanent Maxillary Canine Agenesis: A Rare Case Report

    OpenAIRE

    Halaswamy V Kambalimath; Jain, Somya; Patil, Raju Umaji; Asokan, Alexander; Kambalimath, Deepashri

    2015-01-01

    ABSTRACT Congenitally missing teeth (CMT) are among one of the commonly known dental anomalies. The most frequently missing teeth in the permanent dentition, excluding the third molars, are mandibular second premolars and maxillary lateral incisors. Exclusive agenesis of both maxillary canines is an extremely rare occurrence and only a few cases have been reported. Previous studies showed that the prevalence of maxillary canine agenesis varies between 0.07 and 0.13%. In recent studies on Indi...

  10. Genomic instability and telomere fusion of canine osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Junko Maeda

    Full Text Available Canine osteosarcoma (OSA is known to present with highly variable and chaotic karyotypes, including hypodiploidy, hyperdiploidy, and increased numbers of metacentric chromosomes. The spectrum of genomic instabilities in canine OSA has significantly augmented the difficulty in clearly defining the biological and clinical significance of the observed cytogenetic abnormalities. In this study, eight canine OSA cell lines were used to investigate telomere fusions by fluorescence in situ hybridization (FISH using a peptide nucleotide acid probe. We characterized each cell line by classical cytogenetic studies and cellular phenotypes including telomere associated factors and then evaluated correlations from this data. All eight canine OSA cell lines displayed increased abnormal metacentric chromosomes and exhibited numerous telomere fusions and interstitial telomeric signals. Also, as evidence of unstable telomeres, colocalization of γ-H2AX and telomere signals in interphase cells was observed. Each cell line was characterized by a combination of data representing cellular doubling time, DNA content, chromosome number, metacentric chromosome frequency, telomere signal level, cellular radiosensitivity, and DNA-PKcs protein expression level. We have also studied primary cultures from 10 spontaneous canine OSAs. Based on the observation of telomere aberrations in those primary cell cultures, we are reasonably certain that our observations in cell lines are not an artifact of prolonged culture. A correlation between telomere fusions and the other characteristics analyzed in our study could not be identified. However, it is important to note that all of the canine OSA samples exhibiting telomere fusion utilized in our study were telomerase positive. Pending further research regarding telomerase negative canine OSA cell lines, our findings may suggest telomere fusions can potentially serve as a novel marker for canine OSA.

  11. Canine Evolution in Sabretoothed Carnivores: Natural Selection or Sexual Selection?

    OpenAIRE

    Marcela Randau; Chris Carbone; Turvey, Samuel T.

    2013-01-01

    The remarkable elongated upper canines of extinct sabretoothed carnivorous mammals have been the subject of considerable speculation on their adaptive function, but the absence of living analogues prevents any direct inference about their evolution. We analysed scaling relationships of the upper canines of 20 sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae), representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33 non-sabretoothed felids...

  12. Recent epidemiological status of canine viral enteric infections and Giardia infection in Japan.

    Science.gov (United States)

    Mochizuki, M; Hashimoto, M; Ishida, T

    2001-05-01

    Epidemiology of canine enteric infections was studied. Rectal swabs collected from 95 dogs presented at animal hospitals during a period from January to June of 2000 were examined for enteric pathogens, including viruses and Giardia lamblia (G. lamblia). Most frequently detected in both diarrheal and normal feces were canine coronavirus (55.4%) and G. lamblia (48.2%). Canine parvovirus type 2 (CPV-2) was specifically associated with diarrheal cases and CPV-2b was the predominant antigenic type. Although canine rotavirus, canine adenovirus, and canine distemper virus were also detected in a small number of diarrheal cases, no evidence for calicivirus infection was obtained. PMID:11411507

  13. Transmigration of mandibular canine: report of four cases and review of literature.

    Science.gov (United States)

    Sharma, Gaurav; Nagpal, Archna

    2011-01-01

    Transmigration of canine is a rare phenomenon. The prevalence of transmigration of mandibular canine has been found to be only 0.14%-0.31%. The treatment of impacted transmigrated canine is very complicated if it is diagnosed at a later stage. We report 4 cases of transmigration of mandibular canine and review the literature regarding the etiology and treatment. Panoramic radiograph should be taken during the mixed dentition period if the mandibular canine has not erupted from more than one year from its normal chronological age of eruption as intraoral periapical radiograph examination will not always detect an impacted or transmigrated canine. PMID:22570797

  14. Transmigration of Mandibular Canine: Report of Four Cases and Review of Literature

    Directory of Open Access Journals (Sweden)

    Gaurav Sharma

    2011-01-01

    Full Text Available Transmigration of canine is a rare phenomenon. The prevalence of transmigration of mandibular canine has been found to be only 0.14%–0.31%. The treatment of impacted transmigrated canine is very complicated if it is diagnosed at a later stage. We report 4 cases of transmigration of mandibular canine and review the literature regarding the etiology and treatment. Panoramic radiograph should be taken during the mixed dentition period if the mandibular canine has not erupted from more than one year from its normal chronological age of eruption as intraoral periapical radiograph examination will not always detect an impacted or transmigrated canine.

  15. [Reflex dystrophy following so-called whiplash injury of the cervical spine].

    Science.gov (United States)

    Bühring, M

    1984-01-01

    In bad cases of whiplash injury of the cervical spine the post-accidental course is complicated by pain, vegetative dysfunctional syndromes and by psychic and psychiatric disorders over many years. There is no satisfactory concept to understand the pathophysiology of these processes. The paper deals with the possibility of a reflex dystrophy. Sympathetic reflex dystrophy syndromes are seen principally in patients with joint, tendon or vascular lesions. In case of whiplash injury, it would concern the cervical spine itself as well as visceral organs including the central nervous system. For the CNS the lymphostatic encephalopathy is a well defined entity. Above all, a reflex dystrophy develops on the basis of a special personality structure. In case of psychic and psychiatric complaints after whiplash injury patients with a so called Sudeck-personality should not be suspected to aggravate; in contrast, especially in these patients complications by reflex dystrophy are credible. Consequences for the assessment and for rehabilitation are discussed. PMID:6475217

  16. 反射性交感神经营养不良%Reflex sympathetic dystrophy

    Institute of Scientific and Technical Information of China (English)

    马抒音; 张丽苓

    2002-01-01

    @@ Background: Reflex sympathetic dystrophy (RSD),also known as complex regional pain syndrome (CRPS), is a nervous system disorder that often results in severe chronic and burning pain and other symptoms.

  17. Stakeholder cooperation to overcome challenges in orphan medicine development: the example of Duchenne muscular dystrophy.

    Science.gov (United States)

    Straub, Volker; Balabanov, Pavel; Bushby, Kate; Ensini, Monica; Goemans, Nathalie; De Luca, Annamaria; Pereda, Alejandra; Hemmings, Robert; Campion, Giles; Kaye, Edward; Arechavala-Gomeza, Virginia; Goyenvalle, Aurelie; Niks, Erik; Veldhuizen, Olav; Furlong, Pat; Stoyanova-Beninska, Violeta; Wood, Matthew J; Johnson, Alex; Mercuri, Eugenio; Muntoni, Francesco; Sepodes, Bruno; Haas, Manuel; Vroom, Elizabeth; Aartsma-Rus, Annemieke

    2016-07-01

    Duchenne muscular dystrophy is a rare, progressive, muscle-wasting disease leading to severe disability and premature death. Treatment is currently symptomatic, but several experimental therapies are in development. Implemented care standards, validated outcome measures correlating with clinical benefit, and comprehensive information about the natural history of the disease are essential for regulatory approval of any treatment. However, for Duchenne muscular dystrophy and other rare diseases, these requirements are not always in place when potential therapies enter the clinical trial phase. A cooperative effort of stakeholders in Duchenne muscular dystrophy-including representatives from patients' groups, academia, industry, and regulatory agencies-is aimed at addressing this shortfall by identifying strategies to overcome challenges, developing the tools needed, and collecting relevant data. An open and constructive dialogue among European stakeholders has positively affected development of treatments for Duchenne muscular dystrophy; this approach could serve as a paradigm for development of treatments for rare diseases in general. PMID:27302365

  18. Defective [U-14 C] palmitic acid oxidation in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased [U-14 C] palmitic acid oxidation. [1-14 C] palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation

  19. Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.

    Directory of Open Access Journals (Sweden)

    Kazunari Momma

    Full Text Available Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

  20. Upper Extremity Kinematics and Muscle Activation Patterns in Subjects With Facioscapulohumeral Dystrophy

    NARCIS (Netherlands)

    Bergsma, Arjen; Murgia, Alessio; Cup, Edith H.; Verstegen, Paul P.; Meijer, Kenneth; de Groot, Imelda J.

    2014-01-01

    Objective: To compare the kinematics and muscle activity of subjects with facioscapulohumeral dystrophy (FSHD) and healthy control subjects during the performance of standardized upper extremity tasks. Design: Exploratory case-control study. Setting: A movement laboratory. Participants: Subjects (N=

  1. Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

    Directory of Open Access Journals (Sweden)

    Ana Cotta

    2014-09-01

    Full Text Available Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.

  2. Pattern Dystrophy of the Macula in a Case of Steinert Disease

    Directory of Open Access Journals (Sweden)

    Filipe Esteves

    2013-09-01

    Full Text Available Introduction: Myotonic dystrophies are typically associated with ocular complications like ptosis, weakness of the ocular muscle and cataracts, but also with less recognized retinal changes. Case Report: A 41-year-old female with type 1 myotonic dystrophy complained of progressive vision loss. Slit lamp examination revealed the presence of typical bilateral polychromatic cataract with posterior subcapsular component. Dilated fundus examination was remarkable for bilateral macular depigmented changes. Multimodal imaging analysis of the macula suggested the presence of a butterfly-shaped pattern dystrophy. Discussion: In cases of myotonic dystrophies it is of great relevance to analyze the presence of retinal changes that might limit the visual improvement following cataract extraction.

  3. Glycosaminoglycan modifications in Duchenne muscular dystrophy: specific remodeling of chondroitin sulfate/dermatan sulfate

    NARCIS (Netherlands)

    Negroni, E.; Henault, E.; Chevalier, F.; Gilbert-Sirieix, M.; Kuppevelt, T.H. van; Papy-Garcia, D.; Uzan, G.; Albanese, P.

    2014-01-01

    Widespread skeletal muscle degeneration and impaired regeneration lead to progressive muscle weakness and premature death in patients with Duchenne muscular dystrophy (DMD). Dystrophic muscles are progressively replaced by nonfunctional tissue because of exhaustion of muscle precursor cells and exce

  4. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy

    DEFF Research Database (Denmark)

    Vissing, John; Barresi, Rita; Witting, Nanna;

    2016-01-01

    Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation...... creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did...... affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings in 10 families, our study indicates that a dominantly inherited pattern of calpainopathy exists, and should be considered...

  5. Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.

    Science.gov (United States)

    Momma, Kazunari; Noguchi, Satoru; Malicdan, May Christine V; Hayashi, Yukiko K; Minami, Narihiro; Kamakura, Keiko; Nonaka, Ikuya; Nishino, Ichizo

    2012-01-01

    Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

  6. Canine vector-borne diseases in Brazil

    Directory of Open Access Journals (Sweden)

    Dantas-Torres Filipe

    2008-08-01

    Full Text Available Abstract Canine vector-borne diseases (CVBDs are highly prevalent in Brazil and represent a challenge to veterinarians and public health workers, since some diseases are of great zoonotic potential. Dogs are affected by many protozoa (e.g., Babesia vogeli, Leishmania infantum, and Trypanosoma cruzi, bacteria (e.g., Anaplasma platys and Ehrlichia canis, and helminths (e.g., Dirofilaria immitis and Dipylidium caninum that are transmitted by a diverse range of arthropod vectors, including ticks, fleas, lice, triatomines, mosquitoes, tabanids, and phlebotomine sand flies. This article focuses on several aspects (etiology, transmission, distribution, prevalence, risk factors, diagnosis, control, prevention, and public health significance of CVBDs in Brazil and discusses research gaps to be addressed in future studies.

  7. Canine distemper in endangered Ethiopian wolves.

    Science.gov (United States)

    Gordon, Christopher H; Banyard, Ashley C; Hussein, Alo; Laurenson, M Karen; Malcolm, James R; Marino, Jorgelina; Regassa, Fekede; Stewart, Anne-Marie E; Fooks, Anthony R; Sillero-Zubiri, Claudio

    2015-05-01

    The Ethiopian wolf (Canis simensis) is the world's rarest canid; ≈500 wolves remain. The largest population is found within the Bale Mountains National Park (BMNP) in southeastern Ethiopia, where conservation efforts have demonstrated the negative effect of rabies virus on wolf populations. We describe previously unreported infections with canine distemper virus (CDV) among these wolves during 2005-2006 and 2010. Death rates ranged from 43% to 68% in affected subpopulations and were higher for subadult than adult wolves (83%-87% vs. 34%-39%). The 2010 CDV outbreak started 20 months after a rabies outbreak, before the population had fully recovered, and led to the eradication of several focal packs in BMNP's Web Valley. The combined effect of rabies and CDV increases the chance of pack extinction, exacerbating the typically slow recovery of wolf populations, and represents a key extinction threat to populations of this highly endangered carnivore. PMID:25898177

  8. European surveillance for pantropic canine coronavirus.

    Science.gov (United States)

    Decaro, Nicola; Cordonnier, Nathalie; Demeter, Zoltan; Egberink, Herman; Elia, Gabriella; Grellet, Aurélien; Le Poder, Sophie; Mari, Viviana; Martella, Vito; Ntafis, Vasileios; von Reitzenstein, Marcela; Rottier, Peter J; Rusvai, Miklos; Shields, Shelly; Xylouri, Eftychia; Xu, Zach; Buonavoglia, Canio

    2013-01-01

    Highly virulent pantropic canine coronavirus (CCoV) strains belonging to subtype IIa were recently identified in dogs. To assess the distribution of such strains in Europe, tissue samples were collected from 354 dogs that had died after displaying systemic disease in France (n = 92), Hungary (n = 75), Italy (n = 69), Greece (n = 87), The Netherlands (n = 27), Belgium (n = 4), and Bulgaria (n = 1). A total of 124 animals tested positive for CCoV, with 33 of them displaying the virus in extraintestinal tissues. Twenty-four CCoV strains (19.35% of the CCoV-positive dogs) detected in internal organs were characterized as subtype IIa and consequently assumed to be pantropic CCoVs. Sequence and phylogenetic analyses of the 5' end of the spike protein gene showed that pantropic CCoV strains are closely related to each other, with the exception of two divergent French viruses that clustered with enteric strains. PMID:23100349

  9. A canine model of multiple portosystemic shunting.

    Science.gov (United States)

    Howe, L M; Boothe, H W; Miller, M W; Boothe, D M

    2000-01-01

    The objective of this study was to develop and describe an experimental canine model of multiple acquired portosystemic shunts (PSS) similar in nature to spontaneously occurring PSS. Sixteen dogs were used and were divided into a control (n = 6) and a diseased group (n = 10). Dogs of the diseased group were administered dimethylnitrosamine (2 mg/kg of body weight, po) twice weekly, and clinicopathologic, ultrasonographic, and hepatic scintigraphic findings were recorded during the development of hepatic disease and PSS. Surgery was then performed to permit visual verification of multiple shunts, catheter placement for portography examination, and biopsy of the liver. All diseased dogs developed severe hepatic disease and multiple PSS as documented visually at surgery and on portography. Based on this study, dimethylnitrosamine-induced portosystemic shunting appears to be an appropriate model for spontaneously occurring multiple PSS secondary to portal hypertension. PMID:10741951

  10. Why segment the maxilla between laterals and canines?

    Directory of Open Access Journals (Sweden)

    Lucas Senhorinho Esteves

    2016-02-01

    Full Text Available Introduction: Maxillary surgery on a bone segment enables movement in the sagittal and vertical planes. When performed on multiple segments, it further provides movement in the transverse plane. Typical sites for interdental osteotomies are between laterals and canines, premolars and canines, or between incisors. Additionally, osteotomies can be bilateral, unilateral or asymmetric. The ability to control intercanine width, buccolingual angulation of incisors, and correct Bolton discrepancy are some of the advantages of maxillary segmentation between laterals and canines. Objective: This article describes important features to be considered in making a clinical decision to segment the maxilla between laterals and canines when treating a dentoskeletal deformity. It further discusses the history of this surgical approach, the indications for its clinical use, the technique used to implement it, as well as its advantages, disadvantages, complications and stability. It is therefore hoped that this paper will contribute to disseminate information on this topic, which will inform the decision-making process of those professionals who wish to make use of this procedure in their clinical practice. Conclusions: Segmental maxillary osteotomy between laterals and canines is a versatile technique with several indications. Furthermore, it offers a host of advantages compared with single-piece osteotomy, or between canines and premolars.

  11. Consequences of crown shortening canine teeth in Greenland sled dogs

    DEFF Research Database (Denmark)

    Kortegaard, H E; Anthony Knudsen, T; Dahl, S;

    2015-01-01

    OBJECTIVES: To evaluate the consequences of crown shortening, focusing on the prevalence of pulp exposure and periapical pathology in Greenland sled dogs that had had their canine crowns shortened at an early age. METHODS: Five cadaver heads and 54 sled dogs underwent an oral examination for dental...... fractures and pulp exposure of canines. All canines were radiographed and evaluated for periapical pathology. RESULTS: The prevalence of canine pulp exposure in 12 (5 heads and 7 dogs) crown shortened dogs was 91 · 7%, and 21 · 3% in 47 not-crown shortened dogs. A significant (P ... exposure of the canines in the crown shortened group compared to the not-crown shortened group was seen with a relative risk of 4 · 3 on a dog basis and a relative risk of 12 · 2 on a tooth basis. In dogs with pulp exposure of canines (n = 51) the prevalence of periapical pathology was 82 · 4%, but only 0...

  12. Chlamydia in canine or feline coronary arteriosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Grabarevic Zeljko

    2011-09-01

    Full Text Available Abstract Background There are numerous reports linking Chlamydia infection to human coronary atherosclerosis. However, there is a lack of data regarding this correlation in dogs and cats, and there are no reports investigating coronary arteriosclerosis and Chlamydia in these species. The aim of the present study was to examine whether there is a correlation between canine and feline spontaneous atherosclerosis or arteriosclerosis and the presence of Chlamydia. Archived histopathological samples of dogs (n = 16 and cats (n = 13 with findings of atherosclerosis or arteriosclerosis in heart tissue were examined for the presence of Chlamydiaceae using real-time PCR, ArrayTube Microarray and immunohistochemistry. Additionally, arteriosclerotic lesions of all cases were histologically classified and graded. Results Both canine atherosclerotic cases, and all 14 canine arteriosclerotic cases were negative for Chlamydia. Only one of the 13 arteriosclerotic feline cases was positive for Chlamydia by real-time PCR, revealing C. abortus by ArrayTube Microarray. To our knowledge, this is the first description of C. abortus in a cat. Overall, the type and grade of canine and feline arteriosclerotic lesions revealed similarities, and were predominantly moderate and hyperplastic. Conclusions These findings suggest that there is no obvious correlation between canine and feline coronary arteriosclerosis and the presence of Chlamydia. In order to draw final conclusions about the correlation between Chlamydia and canine atherosclerosis, examination of more samples is required.

  13. Current and emerging treatment strategies for Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Mah JK

    2016-07-01

    Full Text Available Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments

  14. The Intriguing Regulators of Muscle Mass in Sarcopenia and Muscular Dystrophy

    OpenAIRE

    Sakuma, Kunihiro; AOI, WATARU; Yamaguchi, Akihiko

    2014-01-01

    Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This revie...

  15. Respiratory function and the mechanism of cough in Duchenne Muscular Dystrophy

    OpenAIRE

    Ingrid de Castro Bolina Faria; Renata Menezes Dalmonch

    2009-01-01

    Objective: To describe the relationship between the inefficiency of the mechanism of cough and the degradation of respiratory function in patients with Duchenne Muscular Dystrophy (DMD). Methods: A documentary study carried out from the following databases: Pubmed, Cochrane and Scielo. The terms “Duchenne muscular Dystrophy”, “Respiratory Function” and “Peak Cough Flow” were used as descriptors, individually or in association. Articles that addressed other types of muscular dystrophy or were ...

  16. Transgenic Overexpression of ADAM12 Suppresses Muscle Regeneration and Aggravates Dystrophy in Aged mdx Mice

    OpenAIRE

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M.; Schrøder, Henrik Daa

    2007-01-01

    Muscular dystrophies are characterized by insufficient restoration and gradual replacement of the skeletal muscle by fat and connective tissue. ADAM12 has previously been shown to alleviate the pathology of young dystrophin-deficient mdx mice, a model for Duchenne muscular dystrophy. The observed effect of ADAM12 was suggested to be mediated via a membrane-stabilizing up-regulation of utrophin, α7B integrin, and dystroglycans. Ectopic ADAM12 expression in normal mouse skeletal muscle also imp...

  17. Myostatin inhibition by a follistatin-derived peptide ameliorates the pathophysiology of muscular dystrophy model mice

    OpenAIRE

    Tsuchida, K.

    2008-01-01

    Gene-targeted therapies, such as adeno-associated viral vector (AAV)-mediated gene therapy and cell-mediated therapy using myogenic stem cells, are hopeful molecular strategies for muscular dystrophy. In addition, drug therapies based on the pathophysiology of muscular dystrophy patients are desirable. Multidisciplinary approaches to drug design would offer promising therapeutic strategies. Myostatin, a member of the transforming growth factor-β superfamily, is predominantly produced by skele...

  18. Skeletal muscle homeostasis in Duchenne muscular dystrophy : modulating autophagy as a promising therapeutic strategy

    OpenAIRE

    Clara De Palma; Emilio Clementi; Davide Cervia

    2014-01-01

    Muscular dystrophies are a group of genetic and heterogeneous neuromuscular disorders characterized by the primary wasting of skeletal muscle. In Duchenne muscular dystrophy (DMD), the most severe form of these diseases, the mutations in the dystrophin gene lead to muscle weakness and wasting, exhaustion of muscular regenerative capacity, and chronic local inflammation leading to substitution of myofibers by connective and adipose tissue. DMD patients suffer from continuous and progressive sk...

  19. Enhancement of plasmid-mediated gene therapy for muscular dystrophy by directed plasmid integration

    OpenAIRE

    Bertoni, Carmen; Jarrahian, Sohail; Wheeler, Thurman M.; LI, YINING; Olivares, Eric C.; Michele P Calos; Rando, Thomas A.

    2005-01-01

    Plasmid-mediated gene therapy can restore dystrophin expression in skeletal muscle in the mdx mouse, a model of Duchenne muscular dystrophy. However, sufficient long-term expression and distribution of dystrophin remain a hurdle for translating this technology into a viable treatment for Duchenne muscular dystrophy. To improve plasmid-mediated gene therapy for muscle diseases, we studied the effects of targeted plasmid integration using a phage integrase (φC31) that can mediate the integratio...

  20. Progress in muscular dystrophy research with special emphasis on gene therapy

    OpenAIRE

    SUGITA, Hideo; Takeda, Shin’ichi

    2010-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful mar...

  1. Flt-1 haploinsufficiency ameliorates muscular dystrophy phenotype by developmentally increased vasculature in mdx mice

    OpenAIRE

    Verma, Mayank; Asakura, Yoko; Hirai, Hiroyuki; Watanabe, Shuichi; Tastad, Christopher; Fong, Guo-Hua; Ema, Masatsugu; Call, Jarrod A.; Lowe, Dawn A.; Asakura, Atsushi

    2010-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease caused by mutations in the gene coding for the protein dystrophin. Recent work demonstrates that dystrophin is also found in the vasculature and its absence results in vascular deficiency and abnormal blood flow. This induces a state of ischemia further aggravating the muscular dystrophy pathogenesis. For an effective form of therapy of DMD, both the muscle and the vasculature need to be addressed. To reveal the develo...

  2. RNAi-based Gene Therapy for Dominant Limb Girdle Muscular Dystrophies

    OpenAIRE

    Liu, Jian; Harper, Scott Q.

    2012-01-01

    Limb Girdle Muscular Dystrophy (LGMD) refers to a group of 25 genetic diseases linked by common clinical features, including wasting of muscles supporting the pelvic and shoulder girdles. Cardiac involvement may also occur. Like other muscular dystrophies, LGMDs are currently incurable, but prospective gene replacement therapies targeting recessive forms have shown promise in pre-clinical and clinical studies. In contrast, little attention has been paid to developing gene therapy approaches f...

  3. Effect of Cellular Therapy in Progression of Becker’s Muscular Dystrophy: A Case Study

    OpenAIRE

    Alok Sharma; Hemangi Sane; Nandini Gokulchandra; Rishabh Sharan; Amruta Paranjape; Pooja Kulkarni; Jayanti Yadav; Prerna Badhe

    2016-01-01

    Becker muscular dystrophy (BMD) is an inherited disorder due to deletions of the dystrophin gene that leads to muscle weakness. Effects of bone marrow mononuclear cell (BMMNC) transplantation in Muscular Dystrophy have shown to be safe and beneficial. We treated a 20-year-old male suffering from BMD with autologous BMMNC transplantation followed by multidisciplinary rehabilitation. He presented with muscle weakness and had difficulty in performing his activities. The BMMNCs were transplanted ...

  4. Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases

    OpenAIRE

    Consalvi, Silvia; Saccone, Valentina; Giordani, Lorenzo; Minetti, Giulia; Mozzetta, Chiara; Puri, Pier Lorenzo

    2011-01-01

    Histone deacetylases inhibitors (HDACi) include a growing number of drugs that share the ability to inhibit the enzymatic activity of some or all the HDACs. Experimental and preclinical evidence indicates that these epigenetic drugs not only can be effective in the treatment of malignancies, inflammatory diseases and degenerative disorders, but also in the treatment of genetic diseases, such as muscular dystrophies. The ability of HDACi to counter the progression of muscular dystrophies point...

  5. 1H and 31P nuclear magnetic resonance spectroscopy of erythrocyte extracts in myotonic muscular dystrophy

    International Nuclear Information System (INIS)

    Extracts freshly prepared from erythrocytes of patients with myotonic muscular dystrophy, their unaffected siblings, and normal control subjects were examined with both 1H and 31P nuclear magnetic resonance spectroscopy. A moderate variability was found in the relative amounts of various nonphosphorylated compounds among patients and control subjects; however, no significant differences were found between the groups. As for the phosphorylated compounds, the sum of ADP+ATP was found significantly elevated in the myotonic muscular dystrophy patients

  6. Oculopharyngeal muscular dystrophy as a rare differential diagnosis for unexplained dysphagia: a case report

    OpenAIRE

    Bumm, Klaus; Zenker, Martin; Bozzato, Alessandro

    2009-01-01

    Introduction We wish to report on a rare cause of dysphagia; oculopharyngeal muscular dystrophy (OPMD). It is a late adult onset autosomal dominant form of muscular dystrophy that constitutes as a rare diagnosis for any place outside of Canada and first case in southern Germany. Case presentation We report the medical odyssey of a 57-year old male Caucasian patient. He was referred at our hospital for further clarification of a progressive dysphagia, which, at first view, was thought to be tu...

  7. Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular dystrophy and prospective therapy with cyclosporins

    OpenAIRE

    Angelin, Alessia; Tiepolo, Tania; Sabatelli, Patrizia; Grumati, Paolo; Bergamin, Natascha; Golfieri, Cristina; Mattioli, Elisabetta; Gualandi, Francesca; Ferlini, Alessandra; Merlini, Luciano; Maraldi, Nadir M.; Bonaldo, Paolo; Bernardi, Paolo

    2007-01-01

    Ullrich congenital muscular dystrophy is a severe genetically and clinically heterogeneous muscle disorder linked to collagen VI deficiency. The pathogenesis of the disease is unknown. To assess the potential role of mitochondrial dysfunction in the onset of muscle fiber death in this form of dystrophy, we studied biopsies and myoblast cultures obtained from patients with different genetic defects of collagen VI and variable clinical presentations of the disease. We identified a latent mitoch...

  8. Analysis of calpain-3 protein in muscle biopsies of different muscular dystrophies from India

    OpenAIRE

    Renjini, R.; Gayathri, N.; A Nalini; Bharath, M.M. Srinivas

    2012-01-01

    Background & objectives: Calpain-3, a Ca2+-dependent protease has been implicated in the pathology of neuromuscular disorders (NMDs). The current study aimed to analyze calpain-3 expression in cases diagnosed as muscular dystrophy from the Indian population. Methods: Calpain-3 Western blot analysis in muscle biopsies of immunohistochemically confirmed cases of Duchenne muscular dystrophy (DMD) (n=10), dysferlinopathy (n=30) and sarcoglycanopathy (n=8) was carried out. Calpain-3 Western blotti...

  9. A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings

    OpenAIRE

    Suneja, B; Suneja, ES; Adlakha, VK; Chandna, P

    2015-01-01

    ABSTRACT Duchenne muscular dystrophy (DMD) is an recessive X-linked mediated, musculoskeletal disorder that affects only males. It is the most common and severe form of muscular dystrophy where there is failure to manufacture dystrophin. Clinically, it is characterized by progressive muscle wasting eventually leading to premature death. This case report describes the genetic, oral and systemic findings in two cases of DMD in male siblings. How to cite this article: Suneja B, Suneja ES, Adlakh...

  10. The clinical and molecular genetic approach to Duchenne and Becker muscular dystrophy: an updated protocol

    OpenAIRE

    Essen, van, A.M.; Kneppers, A.L.J.; Hout, van, H.P.J.; Scheffer, H; Ginjaarl, B.; Kate, L.P. ten; van Ommen, G. J. B.; Buys, C.H.C.M.; Bakker, E

    1997-01-01

    Detection of large rearrangements in the dystrophin gene in Duchenne and Becker muscular dystrophy is possible in about 65-70% of patients by Southern blotting or multiplex PCR. Subsequently, carrier detection is possible by assessing the intensity of relevant bands, but preferably by a non-quantitative test method. Detection of microlesions in Duchenne and Becker muscular dystrophy is currently under way. Single strand conformational analysis, heteroduplex analysis, and the protein truncatio...

  11. Fukuyama-type congenital muscular dystrophy and defective glycosylation of α-dystroglycan

    OpenAIRE

    Saito Fumiaki; Matsumura Kiichiro

    2011-01-01

    Abstract Fukuyama-type congenital muscular dystrophy (FCMD) is a severe form of muscular dystrophy accompanied by abnormalities in the eye and brain. The incidence of FCMD is particularly high in the Japanese population. Mutations in the fukutin gene have been identified in patients with FCMD. Fukutin is predicted to be a Golgi apparatus resident protein and to be involved in the post-translational modification of cell-surface proteins. Recently, progress has been made in our understanding of...

  12. A population study of adult onset limb-girdle muscular dystrophy.

    OpenAIRE

    Yates, J R; Emery, A E

    1985-01-01

    Complete ascertainment of adult onset limb-girdle muscular dystrophy in the Lothian Region of Scotland was attempted. Ten index cases were identified giving a prevalence of 1.3 per 100 000 (0.9 per 100 000 for cases where the diagnosis of muscular dystrophy was supported by both electromyographic and muscle biopsy findings). In these 10 sibships there had been 11 affected subjects, significantly less than the 16.5 cases expected for autosomal recessive inheritance. Excluding cases suspected o...

  13. Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A

    Energy Technology Data Exchange (ETDEWEB)

    Speer, M.C.; Yamaoka, L.H.; Stajich, J.; Lewis, K. [and others

    1995-08-28

    The Bethlem myopathy, an autosomal-dominant myopathy, shows a distribution of proximal muscle weakness similar to that observed in dominant limb-girdle muscular dystrophy (LGMD). Yet the Bethlem myopathy differs from most limb-girdle dystrophies in two important regards. First, the Bethlem myopathy presents with joint contractures most commonly observed at the elbows, ankles, and neck. Secondly, disease onset in the Bethlem myopathy is in early childhood, while most dominant LGMDs present with adult onset. 6 refs., 1 fig.

  14. Dissecting muscle and neuronal disorders in a Drosophila model of muscular dystrophy.

    OpenAIRE

    Shcherbata, H.; Yatsenko, A.; Patterson, L; Sood, V.; Nudel, U; Yaffe, D; Baker, D.; Ruohola-Baker, H

    2007-01-01

    Perturbation in the Dystroglycan (Dg)–Dystrophin (Dys) complex results in muscular dystrophies and brain abnormalities in human. Here we report that Drosophila is an excellent genetically tractable model to study muscular dystrophies and neuronal abnormalities caused by defects in this complex. Using a fluorescence polarization assay, we show a high conservation in Dg–Dys interaction between human and Drosophila. Genetic and RNAi-induced perturbations of Dg and Dys in Drosophila cause cell po...

  15. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy

    OpenAIRE

    Millay, Douglas P.; Sargent, Michelle A.; Osinska, Hanna; Baines, Christopher P.; Barton, Elisabeth R; Vuagniaux, Grégoire; Sweeney, H. Lee; Robbins, Jeffrey; Molkentin, Jeffery D.

    2008-01-01

    Muscular dystrophies comprise a diverse group of genetic disorders that lead to muscle wasting and, in many instances, premature death1. Many mutations that cause muscular dystrophy compromise the support network that connects myofilament proteins within the cell to the basal lamina outside the cell, rendering the sarcolemma more permeable or leaky. Here we show that deletion of the gene encoding cyclophilin D (Ppif) rendered mitochondria largely insensitive to the calcium overload–induced sw...

  16. The intriguing regulators of muscle mass in sarcopenia and muscular dystrophy

    OpenAIRE

    Kunihiro Sakuma; wataru Aoi; Akihiko Yamaguchi

    2014-01-01

    Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mTOR, serum response factor, atrogin-1, myostatin, etc) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This review provides an overview of ...

  17. Corticosteroid Treatments in Males With Duchenne Muscular Dystrophy: Treatment Duration and Time to Loss of Ambulation

    OpenAIRE

    Kim, Sunkyung; Campbell, Kimberly A.; Fox, Deborah J.; Matthews, Dennis J.; Valdez, Rodolfo

    2014-01-01

    This population-based study examines the association between corticosteroid treatment and time to loss of ambulation, stratifying by treatment duration (short: 0.25–3 years, long: >3 years), among 477 Duchenne muscular dystrophy cases identified by the Muscular Dystrophy Surveillance Tracking and Research Network (MDSTARnet). Those cases who received short-term corticosteroid treatment had a time to loss of ambulation that was 0.8 years shorter (t test) and an annual risk of losing ambulation...

  18. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    OpenAIRE

    Marshall, JL; Kwok, Y; McMorran, BJ; Baum, LG; Crosbie-Watson, RH

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a...

  19. Unusual respiratory manifestations in two young adults with Duchenne muscular dystrophy

    OpenAIRE

    Julie Lemay; Frédéric Sériès; Mario Sénéchal; Bruno Maranda; François Maltais

    2012-01-01

    Adult respirologists are often involved in the evaluation and treatment of young adult patients with Duchenne muscular dystrophy. In this context, the most frequent respiratory complication is nocturnal and daytime hypoventilation related to respiratory muscle weakness. The present article describes cases of Duchenne muscular dystrophy involving two brothers, 17 and 19 years of age, respectively, who presented with less frequently reported respiratory complications of their disease: obstructi...

  20. Sleep-Wake Cycle and Daytime Sleepiness in the Myotonic Dystrophies

    Directory of Open Access Journals (Sweden)

    A. Romigi

    2013-01-01

    Full Text Available Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterized by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified, myotonic dystrophy type 1 (DM1 or Steinert’s Disease and myotonic dystrophy type 2 (DM2. Myotonic dystrophies are strongly associated with sleep dysfunction. Sleep disturbances in DM1 are common and include sleep-disordered breathing (SDB, periodic limb movements (PLMS, central hypersomnia, and REM sleep dysregulation (high REM density and narcoleptic-like phenotype. Interestingly, drowsiness in DM1 seems to be due to a central dysfunction of sleep-wake regulation more than SDB. To date, little is known regarding the occurrence of sleep disorders in DM2. SDB (obstructive and central apnoea, REM sleep without atonia, and restless legs syndrome have been described. Further polysomnographic, controlled studies are strongly needed, particularly in DM2, in order to clarify the role of sleep disorders in the myotonic dystrophies.