Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging.

Science.gov (United States)

Song, Hongxin; Rossi, Ethan A; Stone, Edwin; Latchney, Lisa; Williams, David; Dubra, Alfredo; Chung, Mina

2018-01-01

Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the GUCA1A gene. Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in GUCA1A segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in GUCA1A . This finding suggests that a mutation in GUCA1A does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cone-rod dystrophy and amelogenesis imperfecta (Jalili syndrome): phenotypes and environs.

Science.gov (United States)

Jalili, I K

2010-11-01

To report a new phenotype with additional data on the oculo-dental syndrome of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) caused by mutations on CNNM4, a metal transporter, with linkage at achromatopsia locus 2q11 (Jalili syndrome). Three siblings aged 5, 6, and 10 years from a six-generation Arab family in Gaza City underwent full systemic, ophthalmic, and dental examinations, investigations and detailed genealogy. Subjects presented at early childhood with visual impairment and abnormal dentition together with photophobia and fine nystagmus increasing under photopic conditions, in the presence of normal fundi. Electrophysiologically, photopic flicker responses were impaired; scotopic responses were extinguished at the age of 10 years. Anterior open bite accompanied AI in all siblings. The syndrome formed 83% of CRD cases in the Gaza Strip, which has a prevalence of 1 : 10,000. On the basis of clinical features and electrophysiology, two phenotypes exist: an infancy onset form with progressive macular lesion and an early childhood onset form with normal fundi. More prevalent than previously thought, Jalili syndrome presents a model of the effect of different mutations of the same genetic defect, observations of the same phenotype at different stages of the natural history of the disease, and the influence of epigenetic and tissue-specific factors as causes of phenotypic variability. The paper calls for action to tackle consanguinity in endogamous communities, addresses the possible role of high fluoride levels in groundwater as a trigger for genetic mutations, and the use of red-tinted filter in cone disorders.

Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response

DEFF Research Database (Denmark)

Wissinger, Bernd; Schaich, Simone; Baumann, Britta

2011-01-01

KCNV2 gene and one also includes the adjacent VLDLR gene. Furthermore, we investigated N-terminal amino acid substitution mutations for its effect on interaction with Kv2.1 using yeast two-hybrid technology. We found that these mutations dramatically reduce or abolish this interaction suggesting a lack......Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very rare autosomal recessive retinal disorder. CDSRR is associated with mutations in KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage-gated potassium channel. In this study, we found that KCNV2 mutations...... are present in a substantial fraction (2.2-4.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR is underdiagnosed and more common than previously thought. In total, we identified 20 different KCNV2 mutations; 15 of them are novel...

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

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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. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan

OpenAIRE

KOHYAMA, Moeko; TADA, Naomi; MITSUI, Hiroko; TOMIOKA, Hitomi; TSUTSUI, Toshihiko; YABUKI, Akira; RAHMAN, Mohammad Mahbubur; KUSHIDA, Kazuya; MIZUKAMI, Keijiro; YAMATO, Osamu

2015-01-01

Canine progressive rod-cone degeneration (PRCD) is a middle- to late-onset, autosomal recessive, inherited retinal disorder caused by a substitution (c.5G>A) in the canine PRCD gene that has been identified in 29 or more purebred dogs. In the present study, a TaqMan probe-based real-time PCR assay was developed and evaluated for rapid genotyping and large-scale screening of the mutation. Furthermore, a genotyping survey was carried out in a population of the three most popular breeds in Japan...

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

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Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido; Ben-Yosef, Tamar

2015-01-01

To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. 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. 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 complete exon 22 skipping. A novel

Clinical results from low-level laser therapy in patients with autosomal dominant cone-rod dystrophy

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Koev, K.; Avramov, L.; Borissova, E.

2018-03-01

The objective of this study is to examine long-term effects of low-level laser therapy (LLLT) in patients with autosomal dominant cone-rod dystrophy (CRDs). A He-Ne Laser with continuous emission at 633 nm (01 mW/cm2) was used on five patients with autosomal dominant pedigree of Romani origin with non-syndromic CRDs. The laser radiation was applied transpupillary to the macula six times for three minutes every other day. The experiment was conducted for a period of three years. The clinical evaluation included best corrected visual acuity determination, funduscopy, Humphrey perimetry, Farnsworth Hue-28 color testing, fluorescein angiography, and full-field electroretinogram (ERG). All affected individuals presented reduced visual acuity (0.01 – 0.4) and photophobia. The funduscopic examination and fluorescein angiography revealed advanced changes including bone spicule-like pigment deposits in the midperiphery and the macular area, along with retinal atrophy, narrowing of the vessels, and waxy optic discs. The visual fields demonstrated central scotoma. The electrophysiologic examination of the patients detected an abnormal cone-rod ERG (20 – 30 μV) with photopic amplitudes more markedly reduced than the scotopic. Flicker responses were missing and Farnsworth Hue-28 test found protanopia. There was a statistically significant increase in the visual acuity (p<0.001, end of study versus baseline) for CRDs patients for the period of three years after the treatment with LLLT. Following the LLLT, the central absolute scotoma in CRDs was reduced, as was the prevalence of metamorphopsia in CRDs. This study shows that LLLT may prove be a novel long-lasting therapeutic option for both forms of CRDs. It is a highly effective treatment resulting in a long-term improvement of the visual acuity.

Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

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Maugeri, A; Klevering, B J; Rohrschneider, K; Blankenagel, A; Brunner, H G; Deutman, A F; Hoyng, C B; Cremers, F P

2000-10-01

The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

Alteration of rod and cone function in children with Usher syndrome.

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Malm, Eva; Ponjavic, Vesna; Möller, Claes; Kimberling, William J; Stone, Edwin S; Andréasson, Sten

2011-01-01

To evaluate the retinal function, with emphasis on phenotype and rate of progression, in infants and children with different genotypes of Usher syndrome. Fourteen children (2-10 years of age) with retinitis pigmentosa and hearing impairment were examined with full-field electroretinography (ERG) during general anesthesia, ophthalmologic examination, and genetic analysis. Five children were repeatedly examined (follow-up 5-10 years) with full-field ERG under local anesthesia and in 2 children multifocal ERG and optical coherence tomography (OCT) were performed. These results were compared to full-field ERG data from 58 children without retinal eye disorder. Six children were genotyped as Usher 1B, 2A, and 3A. Full-field ERG demonstrated early alterations corresponding to a rod-cone dystrophy in all children. A remaining rod function could be verified in the majority of the children up to 4 years of age. After 4 years of age, there was a further deterioration of the rod function; the progress was severe in Usher types 1 and 2 and moderate in Usher type 3. In all children, the cone function was moderately reduced, in a few cases almost normal. The results from the 58 children without retinal disorder confirm that full-field ERG during general anesthesia is reliable. Multifocal ERG confirmed a preserved central cone function and in OCT there were discrete structural alterations. Full-field ERG during general anesthesia in children with Usher syndrome demonstrates variable phenotypes and different degrees in rate of progression during childhood.

CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family.

Science.gov (United States)

Kubota, Daiki; Gocho, Kiyoko; Kikuchi, Sachiko; Akeo, Keiichiro; Miura, Masahiro; Yamaki, Kunihiko; Takahashi, Hiroshi; Kameya, Shuhei

2018-05-02

CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins. C-Nap1 has been reported to be expressed in the photoreceptor cilia and is known to interact with other ciliary proteins. Mutations of CEP250 cause atypical Usher syndrome which is characterized by early-onset sensorineural hearing loss (SNHL) and a relatively mild retinitis pigmentosa. This study tested the hypothesis that the mild cone-rod dystrophy (CRD) and SNHL in a non-consanguineous Japanese family was caused by CEP250 mutations. Detailed ophthalmic and auditory examinations were performed on the proband and her family members. Whole exome sequencing (WES) was used on the DNA obtained from the proband. Electrophysiological analysis revealed a mild CRD in two family members. Adaptive optics (AO) imaging showed reduced cone density around the fovea. Auditory examinations showed a slight SNHL in both patients. WES of the proband identified compound heterozygous variants c.361C>T, p.R121*, and c.562C>T, p.R188* in CEP250. The variants were found to co-segregate with the disease in five members of the family. The variants of CEP250 are both null variants and according to American College of Medical Genetics and Genomics (ACMG) standards and guideline, these variants are classified into the very strong category (PVS1). The criteria for both alleles will be pathogenic. Our data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients. Because the ophthalmological phenotypes were very mild, high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP250-associated disease.

Association of a homozygous nonsense mutation in the ABCA4 (ABCR) gene with cone-rod dystrophy phenotype in an Italian family.

Science.gov (United States)

Simonelli, Francesca; Testa, Francesco; Zernant, Jana; Nesti, Anna; Rossi, Settimio; Rinaldi, Ernesto; Allikmets, Rando

2004-01-01

Genetic variation in the ABCA4 (ABCR) gene has been associated with several distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), retinitis pigmentosa (RP) and age-related macular degeneration. The current model of genotype/phenotype association suggests that patients harboring deleterious mutations in both ABCR alleles would develop RP-like retinal pathology. Here we describe ABCA4-associated phenotypes, including a proband with a homozygous nonsense mutation in a family from Southern Italy. The proband had been originally diagnosed with STGD. Ophthalmologic examination included kinetic perimetry, electrophysiological studies and fluorescein angiography. DNA of the affected individual and family members was analyzed for variants in all 50 exons of the ABCA4 gene by screening on the ABCR400 microarray. A homozygous nonsense mutation 2971G>T (G991X) was detected in a patient initially diagnosed with STGD based on funduscopic evidence, including bull's eye depigmentation of the fovea and flecks at the posterior pole extending to the mid-peripheral retina. Since this novel nucleotide substitution results in a truncated, nonfunctional, ABCA4 protein, the patient was examined in-depth for the severity of the disease phenotype. Indeed, subsequent electrophysiological studies determined severely reduced cone amplitude as compared to the rod amplitude, suggesting the diagnosis of CRD. ABCR400 microarray is an efficient tool for determining causal genetic variation, including new mutations. A homozygous protein-truncating mutation in ABCA4 can cause a phenotype ranging from STGD to CRD as diagnosed at an early stage of the disease. Only a combination of comprehensive genotype/phenotype correlation studies will determine the proper diagnosis and prognosis of ABCA4-associated pathology. Copyright 2004 S. Karger AG, Basel

Tokay gecko photoreceptors achieve rod-like physiology with cone-like proteins.

Science.gov (United States)

Zhang, Xue; Wensel, Theodore G; Yuan, Ching

2006-01-01

The retinal photoreceptors of the nocturnal Tokay gecko (Gekko gekko) consist exclusively of rods by the criteria of morphology and key features of their light responses. Unlike cones, they display robust photoresponses and have relatively slow recovery times. Nonetheless, the major and minor visual pigments identified in gecko rods are of the cone type by sequence and spectroscopic behavior. In the ongoing search for the molecular bases for the physiological differences between cones and rods, we have characterized the molecular biology and biochemistry of the gecko rod phototransduction cascade. We have cloned cDNAs encoding all or part of major protein components of the phototransduction cascade by RT-PCR with degenerate oligonucleotides designed to amplify cone- or rod-like sequences. For all proteins examined we obtained only cone-like and never rod-like sequences. The proteins identified include transducin alpha (Galphat), phosphodiesterase (PDE6) catalytic and inhibitory subunits, cyclic nucleotide-gated channel (CNGalpha) and arrestin. We also cloned cDNA encoding gecko RGS9-1 (Regulator of G Protein Signaling 9, splice variant 1), which is expressed in both rods and cones of all species studied but is typically found at 10-fold higher concentrations in cones, and found that gecko rods contain slightly lower RGS9-1 levels than mammalian rods. Furthermore, we found that the levels of GTPase accelerating protein (GAP) activity and cyclic GMP (cGMP) phosphodiesterase activity were similar in gecko and mammalian rods. These results place substantial constraints on the critical changes needed to convert a cone into a rod in the course of evolution: The many features of phototransduction molecules conserved between those expressed in gecko rods and those expressed in cones cannot explain the physiological differences, whereas the higher levels of RGS9-1 and GAP activity in cones are likely among the essential requirements for the rapid photoresponses of cones.

Muscular dystrophy in a dog resembling human becker muscular dystrophy.

Science.gov (United States)

Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

2014-05-01

A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man. Copyright © 2014 Elsevier Ltd. All rights reserved.

Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan.

Science.gov (United States)

Kohyama, Moeko; Tada, Naomi; Mitsui, Hiroko; Tomioka, Hitomi; Tsutsui, Toshihiko; Yabuki, Akira; Rahman, Mohammad Mahbubur; Kushida, Kazuya; Mizukami, Keijiro; Yamato, Osamu

2016-03-01

Canine progressive rod-cone degeneration (PRCD) is a middle- to late-onset, autosomal recessive, inherited retinal disorder caused by a substitution (c.5G>A) in the canine PRCD gene that has been identified in 29 or more purebred dogs. In the present study, a TaqMan probe-based real-time PCR assay was developed and evaluated for rapid genotyping and large-scale screening of the mutation. Furthermore, a genotyping survey was carried out in a population of the three most popular breeds in Japan (Toy Poodles, Chihuahuas and Miniature Dachshunds) to determine the current mutant allele frequency. The assay separated all the genotypes of canine PRCD rapidly, indicating its suitability for large-scale surveys. The results of the survey showed that the mutant allele frequency in Toy Poodles was high enough (approximately 0.09) to allow the establishment of measures for the prevention and control of this disorder in breeding kennels. The mutant allele was detected in Chihuahuas for the first time, but the frequency was lower (approximately 0.02) than that in Toy Poodles. The mutant allele was not detected in Miniature Dachshunds. This assay will allow the selective breeding of dogs from the two most popular breeds (Toy Poodle and Chihuahua) in Japan and effective prevention or control of the disorder.

Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

NARCIS (Netherlands)

Klevering, B.J.; Blankenagel, A.; Maugeri, A.; Cremers, F.P.M.; Hoyng, C.B.; Rohrschneider, K.

2002-01-01

PURPOSE: To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. METHODS: The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were

Correlated cone noise decreases rod signal contributions to the post-receptoral pathways.

Science.gov (United States)

Hathibelagal, Amithavikram R; Feigl, Beatrix; Zele, Andrew J

2018-04-01

This study investigated how invisible extrinsic temporal white noise that correlates with the activity of one of the three [magnocellular (MC), parvocellular (PC), or koniocellular (KC)] post-receptoral pathways alters mesopic rod signaling. A four-primary photostimulator provided independent control of the rod and three cone photoreceptor excitations. The rod contributions to the three post-receptoral pathways were estimated by perceptually matching a 20% contrast rod pulse by independently varying the LMS (MC pathway), +L-M (PC pathway), and S-cone (KC pathway) excitations. We show that extrinsic cone noise caused a predominant decrease in the overall magnitude and ratio of the rod contributions to each pathway. Thus, the relative cone activity in the post-receptoral pathways determines the relative mesopic rod inputs to each pathway.

Analysis of macular cone photoreceptors in a case of occult macular dystrophy

Directory of Open Access Journals (Sweden)

Tojo N

2013-05-01

Full Text Available Naoki Tojo Tomoko Nakamura Hironori Ozaki Miyako Oka Toshihiko Oiwake Atsushi HayashiDepartment of Ophthalmology, University of Toyama, Toyama, JapanPurpose: To investigate changes in cone photoreceptors with adaptive optics (AO fundus imaging and spectral domain optical coherence tomography (SD-OCT in a case of occult macular dystrophy (OMD.Patient and methods: Both eyes of a 42-year-old woman diagnosed with OMD were examined. We used an AO fundus camera to obtain images of cone photoreceptors in the macula of the OMD subject and five healthy control subjects. Correlations between the AO images and the SD-OCT images were examined. Cone photoreceptors in eight areas in the macula of OMD and healthy control subjects were analyzed and compared.Results: SD-OCT showed a loss of the cone outer-segment tips line outside of the fovea in both eyes of the subject with OMD. The left eye with decreased visual acuity showed a discontinuous photoreceptor inner-segment and outer-segment line and cone outer-segment tips line at the fovea in SD-OCT and loss of cone mosaics as a dark spot in the AO image. In panoramic AO images and cone-density maps, less cone density was observed in a ring-like region outside the fovea than in the peripheral retina. In most of the areas examined, the cone densities were lower in the OMD eyes than in the healthy control eyes.Conclusions: Cone densities in the macula of the OMD patient were greatly decreased. AO images were found to be useful to evaluate morphologic changes in cone photoreceptors in patients with OMD.Keywords: occult macular dystrophy, adaptive optics, cone photoreceptor, cone analysis, optical coherence tomography

Inherited Retinal Degenerative Disease Registry

Science.gov (United States)

2017-09-13

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

Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision.

Science.gov (United States)

Seeliger, Mathias W; Brombas, Arne; Weiler, Reto; Humphries, Peter; Knop, Gabriel; Tanimoto, Naoyuki; Müller, Frank

2011-11-08

Retinal photoreceptors permit visual perception over a wide range of lighting conditions. Rods work best in dim, and cones in bright environments, with considerable functional overlap at intermediate (mesopic) light levels. At many sites in the outer and inner retina where rod and cone signals interact, gap junctions, particularly those containing Connexin36, have been identified. However, little is known about the dynamic processes associated with the convergence of rod and cone system signals into ON- and OFF-pathways. Here we show that proper cone vision under mesopic conditions requires rapid adaptational feedback modulation of rod output via hyperpolarization-activated and cyclic nucleotide-gated channels 1. When these channels are absent, sustained rod responses following bright light exposure saturate the retinal network, resulting in a loss of downstream cone signalling. By specific genetic and pharmacological ablation of key signal processing components, regular cone signalling can be restored, thereby identifying the sites involved in functional rod-cone interactions.

Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

Science.gov (United States)

Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin

2017-01-01

Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754

Cone visual pigments are present in gecko rod cells.

Science.gov (United States)

Kojima, D; Okano, T; Fukada, Y; Shichida, Y; Yoshizawa, T; Ebrey, T G

1992-08-01

The Tokay gecko (Gekko gekko), a nocturnal lizard, has two kinds of visual pigments, P467 and P521. In spite of the pure-rod morphology of the photoreceptor cells, the biochemical properties of P521 and P467 resemble those of iodopsin (the chicken red-sensitive cone visual pigment) and rhodopsin, respectively. We have found that the amino acid sequence of P521 deduced from the cDNA was very similar to that of iodopsin. In addition, P467 has the highest homology with the chicken green-sensitive cone visual pigment, although it also has a relatively high homology with rhodopsins. These results give additional strength to the transmutation theory of Walls [Walls, G. L. (1934) Am. J. Ophthalmol. 17, 892-915], who proposed that the rod-shaped photoreceptor cells of lizards have been derived from ancestral cone-like photoreceptors. Apparently amino acid sequences of visual pigments are less changeable than the morphology of the photoreceptor cells in the course of evolution.

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.

Cone beam computed tomography findings of impacted upper canines

International Nuclear Information System (INIS)

Da Silva Santos, Ludmilla Mota; Bastos, Luana Costa; Da Silva, Silvio Jose Albergaria; Campos, Paulo Sergio Flores; Oliveira Santos, Christiano; Neves, Frederico Sampaio

2014-01-01

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.

Spatiotemporal regulation of ATP and Ca2+ dynamics in vertebrate rod and cone ribbon synapses.

Science.gov (United States)

Johnson, Jerry E; Perkins, Guy A; Giddabasappa, Anand; Chaney, Shawntay; Xiao, Weimin; White, Andrew D; Brown, Joshua M; Waggoner, Jenna; Ellisman, Mark H; Fox, Donald A

2007-06-15

In conventional neurons, Ca2+ enters presynaptic terminals during an action potential and its increased local concentration triggers transient exocytosis. In contrast, vertebrate photoreceptors are nonspiking neurons that maintain sustained depolarization and neurotransmitter release from ribbon synapses in darkness and produce light-dependent graded hyperpolarizing responses. Rods transmit single photon responses with high fidelity, whereas cones are less sensitive and exhibit faster response kinetics. These differences are likely due to variations in presynaptic Ca2+ dynamics. Metabolic coupling and cross-talk between mitochondria, endoplasmic reticulum (ER), plasma membrane Ca2+ ATPase (PMCA), and Na+-Ca2+ exchanger (NCX) coordinately control presynaptic ATP production and Ca2+ dynamics. The goal of our structural and functional studies was to determine the spatiotemporal regulation of ATP and Ca2+ dynamics in rod spherules and cone pedicles. Central retina tissue from C57BL/6 mice was used. Laser scanning confocal microscopy (LSCM) experiments were conducted on fixed-frozen vertical sections. Primary antibodies were selected for their tissue/cellular specificity and ability to recognize single, multiple or all splice variants of selected isoforms. Electron microscopy (EM) and 3-D electron tomography (ET) studies used our standard procedures on thin- and thick-sectioned retinas, respectively. Calibrated fluo-3-Ca2+ imaging experiments of dark- and light-adapted rod and cone terminals in retinal slices were conducted. Confocal microscopy showed that mitochondria, ER, PMCA, and NCX1 exhibited distinct retinal lamination patterns and differential distribution in photoreceptor synapses. Antibodies for three distinct mitochondrial compartments differentially labeled retinal areas with high metabolic demand: rod and cone inner segments, previously undescribed cone juxtanuclear mitochondria and the two plexiform layers. Rod spherule membranes uniformly and intensely

Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

KAUST Repository

Busserolles, Fanny de

2017-11-09

Most vertebrates have a duplex retina comprising two photoreceptor types, rods for dim-light (scotopic) vision and cones for bright-light (photopic) and color vision. However, deep-sea fishes are only active in dim-light conditions; hence, most species have lost their cones in favor of a simplex retina composed exclusively of rods. Although the pearlsides, Maurolicus spp., have such a pure rod retina, their behavior is at odds with this simplex visual system. Contrary to other deep-sea fishes, pearlsides are mostly active during dusk and dawn close to the surface, where light levels are intermediate (twilight or mesopic) and require the use of both rod and cone photoreceptors. This study elucidates this paradox by demonstrating that the pearlside retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone phototransduction cascade to form a unique photoreceptor type, a rod-like cone, specifically tuned to the light conditions of the pearlsides\\' habitat (blue-shifted light at mesopic intensities). Combining properties of both rods and cones into a single cell type, instead of using two photoreceptor types that do not function at their full potential under mesopic conditions, is likely to be the most efficient and economical solution to optimize visual performance. These results challenge the standing paradigm of the function and evolution of the vertebrate duplex retina and emphasize the need for a more comprehensive evaluation of visual systems in general.

Pushing the limits of photoreception in twilight conditions: The rod-like cone retina of the deep-sea pearlsides

KAUST Repository

Busserolles, Fanny de; Cortesi, Fabio; Helvik, Jon Vidar; Davies, Wayne I. L.; Templin, Rachel M.; Sullivan, Robert K. P.; Michell, Craig T.; Mountford, Jessica K.; Collin, Shaun P.; Irigoien, Xabier; Kaartvedt, Stein; Marshall, Justin

2017-01-01

retina does not have rod photoreceptors only; instead, it is composed almost exclusively of transmuted cone photoreceptors. These transmuted cells combine the morphological characteristics of a rod photoreceptor with a cone opsin and a cone

Rod and cone interactions in the retina [version 1; referees: 4 approved

Directory of Open Access Journals (Sweden)

Gordon Fain

2018-05-01

Full Text Available We have long known that rod and cone signals interact within the retina and can even contribute to color vision, but the extent of these influences has remained unclear. New results with more powerful methods of RNA expression profiling, specific cell labeling, and single-cell recording have provided greater clarity and are showing that rod and cone signals can mix at virtually every level of signal processing. These interactions influence the integration of retinal signals and make an important contribution to visual perception.

Morphology of palatally impacted canines: A case-controlled cone-beam volumetric tomography study.

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Hettiarachchi, Pilana Vithanage Kalani Shihanika; Olive, Richard John; Monsour, Paul

2017-02-01

The aim of this study was to investigate the relationships between an apical curvature or a hook and the crown/root ratio in subjects with and without palatally impacted maxillary canines. An experimental group of 44 patients (17 boys, 27 girls; mean age, 13.6 years) with 59 palatally impacted maxillary canines was selected from the records of patients referred to a radiology practice for cone-beam imaging. If a patient had bilateral palatally impacted canines, 1 canine was randomly selected for analysis. The palatally impacted canine group was matched for age and sex with 49 normal subjects (25 boys, 24 girls; mean age, 13.2 years) with 98 canines. Cone-beam DICOM files were imported into In Vivo imaging software (version 5.3; Anatomage, San Jose, Calif) for analysis. The angulations and linear variables of the maxillary canines were measured by using the software measurement tools. Chi-square and independent t tests were used to test for differences between the groups. The presence of a hook at the apical third and other root curvature were significantly different between the 2 groups (P <0.001 and P <0.05, respectively). Of the 44 palatally impacted canines, 16 (36.4%) had an apical hook and only 1 canine in the control group had an apical hook (1.0%). The mean root length of the palatally impacted canines was 2.66 mm shorter (P <0.001), and the mean crown/root ratio was significantly greater for the palatally impacted canines compared with the nonimpacted group (P <0.001). Palatally impacted canines have a greater tendency to develop apical hooks and are less likely to develop other root curvatures than are nonimpacted canines. Also, they have shorter roots resulting in larger crown/root ratios compared with the control group. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Aerobic Glycolysis Is Essential for Normal Rod Function and Controls Secondary Cone Death in Retinitis Pigmentosa.

Science.gov (United States)

Petit, Lolita; Ma, Shan; Cipi, Joris; Cheng, Shun-Yun; Zieger, Marina; Hay, Nissim; Punzo, Claudio

2018-05-29

Aerobic glycolysis accounts for ∼80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic stress conditions such as those encountered in retinitis pigmentosa, where the loss of rods causes a nutrient shortage in cones. The data support a model where aerobic glycolysis in PRs is not a necessity but rather a metabolic choice that maximizes PR function and adaptability to nutrient stress conditions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Duchenne Muscular Dystrophy Gene Therapy in the Canine Model

Science.gov (United States)

2015-01-01

Abstract 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

X linked progressive cone dystrophy. Localisation of the gene locus to Xp21-p11.1 by linkage analysis

NARCIS (Netherlands)

Meire, F. M.; Bergen, A. A.; de Rouck, A.; Leys, M.; Delleman, J. W.

1994-01-01

Six affected males, three female carriers, and two possible carriers were evaluated from a three generation pedigree with X linked progressive cone dystrophy. The affected males presented with progressive decrease of visual acuity, impairment of colour vision, and deterioration of electroretinogram,

Cone and Rod Loss in Stargardt Disease Revealed by Adaptive Optics Scanning Light Ophthalmoscopy

Science.gov (United States)

Song, Hongxin; Rossi, Ethan A.; Latchney, Lisa; Bessette, Angela; Stone, Edwin; Hunter, Jennifer J.; Williams, David R.; Chung, Mina

2015-01-01

Importance Stargardt disease (STGD1) is characterized by macular atrophy and flecks in the retinal pigment epithelium. The causative ABCA4 gene encodes a protein localizing to photoreceptor outer segments. The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pigment epithelium changes remain unclear. We investigated early STGD1 using adaptive optics scanning light ophthalmoscopy. Observations Adaptive optics scanning light ophthalmoscopy imaging of 2 brothers with early STGD1 and their unaffected parents was compared with conventional imaging. Cone and rod spacing were increased in both patients (P optics scanning light ophthalmoscopy reveals increased cone and rod spacing in areas that appear normal in conventional images, suggesting that photoreceptor loss precedes clinically detectable retinal pigment epithelial disease in STGD1. PMID:26247787

Multiple rod–cone and cone–rod photoreceptor transmutations in snakes: Evidence from visual opsin gene expression

Science.gov (United States)

Simoe, Bruno F; Sampaio, Filipa L.; Loew, Ellis R.; Sanders, Kate L.; Fisher, Robert N.; Hart, Nathan S.; Hunt, David M.; Partridge, Julian C.; Gower, David J.

2016-01-01

In 1934, Gordon Walls forwarded his radical theory of retinal photoreceptor ‘transmutation’. This proposed that rods and cones used for scotopic and photopic vision, respectively, were not fixed but could evolve into each other via a series of morphologically distinguishable intermediates. Walls' prime evidence came from series of diurnal and nocturnal geckos and snakes that appeared to have pure-cone or pure-rod retinas (in forms that Walls believed evolved from ancestors with the reverse complement) or which possessed intermediate photoreceptor cells. Walls was limited in testing his theory because the precise identity of visual pigments present in photoreceptors was then unknown. Subsequent molecular research has hitherto neglected this topic but presents new opportunities. We identify three visual opsin genes, rh1, sws1 and lws, in retinal mRNA of an ecologically and taxonomically diverse sample of snakes central to Walls' theory. We conclude that photoreceptors with superficially rod- or cone-like morphology are not limited to containing scotopic or photopic opsins, respectively. Walls' theory is essentially correct, and more research is needed to identify the patterns, processes and functional implications of transmutation. Future research will help to clarify the fundamental properties and physiology of photoreceptors adapted to function in different light levels.

Three-dimensional localization of impacted canines and root resorption assessment using cone beam computed tomography.

Science.gov (United States)

Almuhtaseb, Eyad; Mao, Jing; Mahony, Derek; Bader, Rawan; Zhang, Zhi-xing

2014-06-01

The purpose of this study was to develop a new way to localize the impacted canines from three dimensions and to investigate the root resorption of the adjacent teeth by using cone beam computed tomography (CBCT). Forty-six patients undergoing orthodontic treatments and having impacted canines in Tongji Hospital were examined. The images of CBCT scans were obtained from KaVo 3D exam vision. Angular and linear measurements of the cusp tip and root apex according to the three planes (mid-sagittal, occlusal and frontal) have been taken using the cephalometric tool of the InVivo Dental Anatomage Version 5.1.10. The measurements of the angular and linear coordinates of the maxillary and mandibular canines were obtained. Using this technique the operators could envision the location of the impacted canine according to the three clinical planes. Adjacent teeth root resorption of 28.26 % was in the upper lateral incisors while 17.39% in upper central incisors, but no lower root resorption was found in our samples. Accurate and reliable localization of the impacted canines could be obtained from the novel analysis system, which offers a better surgical and orthodontic treatment for the patients with impacted canines.

Evaluating the Amount of Tooth Movement and Root Resorption during Canine Retraction with Friction versus Frictionless Mechanics Using Cone Beam Computed Tomography.

Science.gov (United States)

Makhlouf, Mohamed; Aboul-Ezz, Amr; Fayed, Mona Salah; Hafez, Hend

2018-02-15

The current study was carried out to compare the amount of tooth movement during canine retraction comparing two different retraction mechanics; friction mechanics represented by a NiTi closed coil spring versus frictionless mechanics represented by T - loop, and their effect on root resorption using Cone Beam Computed Tomography (CBCT). Ten patients were selected in a split-mouth study design that had a malocclusion that necessitates the extraction of maxillary first premolars and retraction of maxillary canines. The right maxillary canines were retracted using T - loops fabricated from 0.017 X 0.025 TMA wires. The left maxillary canines received NiTi coil spring with 150 gm of retraction force. Pre retraction and post retraction Cone Beam Computed Tomography were taken to evaluate the amount of tooth movement and root resorption using three-dimensional planes. T - loop side showed statistically significant higher mean anteroposterior measurement than NiTi coil spring side, indicating a lower amount of canine movement pre and post a canine retraction. Concerning the root resorption, there was no statistically significant change in the mean measurements of canine root length post retraction. The NiTi coil spring side showed more distal movement more than the T-loop side. Both retraction mechanics with controlled retraction force, do not cause root resorption.

Evaluation of cone function by a handheld non-mydriatic flicker electroretinogram device

Directory of Open Access Journals (Sweden)

Nakamura N

2016-06-01

Full Text Available Natsuko Nakamura,1 Kaoru Fujinami,1 Yoshinobu Mizuno,2 Toru Noda,2 Kazushige Tsunoda11Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, 2Department of Ophthalmology, National Hospital Organization, National Tokyo Medical Center, Tokyo, JapanPurpose: Full-field electroretinograms (ERGs are used to evaluate retinal function in patients with various types of hereditary and acquired retinal diseases. However, ERG recordings require relatively invasive procedures, including pupillary dilation and the use of contact lens electrodes. Thus, it would be helpful to have a simpler and noninvasive screening method. The purpose of this study was to determine whether a new, handheld, portable ERG device, RETeval™, can be used to screen patients for cone dysfunction.Patients and methods: Thirty-five eyes of 35 patients who had reduced cone responses ascertained by a conventional ERG system using contact lens electrodes were studied. The causative diseases included achromatopsia, cone dystrophy, cone-rod dystrophy, retinitis pigmentosa, choroidal dystrophy, autoimmune retinopathy, and Stargardt disease. The flicker ERGs were recorded with the RETeval™ under undilated conditions with skin electrodes (stimulus strength, 3.0 cd·s/m2; frequency, 28.3 Hz, and the responses were compared to that of 50 healthy eyes. The amplitudes and implicit times of the fundamental component of the flicker ERGs were analyzed in three age groups: Group A, ≤20 years; Group B, 21–40 years; and Group C, ≥41 years.Results: In all of the age groups, the amplitudes of the ERGs were significantly smaller and the implicit times significantly longer in patients with cone dysfunction than in the control eyes. All but one of the patients had flicker amplitudes lower than the mean −2.0 standard deviation of control eyes.Conclusion: The RETeval™ has a potential of being used to screen for cone dysfunction. The entire examination

Volumetric imaging of rod and cone photoreceptor structure with a combined adaptive optics-optical coherence tomography-scanning laser ophthalmoscope

Science.gov (United States)

Wells-Gray, Elaine M.; Choi, Stacey S.; Zawadzki, Robert J.; Finn, Susanna C.; Greiner, Cherry; Werner, John S.; Doble, Nathan

2018-03-01

We have designed and implemented a dual-mode adaptive optics (AO) imaging system that combines spectral domain optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) for in vivo imaging of the human retina. The system simultaneously acquires SLO frames and OCT B-scans at 60 Hz with an OCT volume acquisition time of 4.2 s. Transverse eye motion measured from the SLO is used to register the OCT B-scans to generate three-dimensional (3-D) volumes. Key optical design considerations include: minimizing system aberrations through the use of off-axis relay telescopes, conjugate pupil plane requirements, and the use of dichroic beam splitters to separate and recombine the OCT and SLO beams around the nonshared horizontal scanning mirrors. To demonstrate system performance, AO-OCT-SLO images and measurements are taken from three normal human subjects ranging in retinal eccentricity from the fovea out to 15-deg temporal and 20-deg superior. Also presented are en face OCT projections generated from the registered 3-D volumes. The ability to acquire high-resolution 3-D images of the human retina in the midperiphery and beyond has clinical importance in diseases, such as retinitis pigmentosa and cone-rod dystrophy.

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...

[Clinical features of patients with Becker muscular dystrophy and deletions of the rod domain of dystrophin gene].

Science.gov (United States)

Wang, Yanyun; Zhu, Yuling; Yang, Juan; Li, Yaqin; Sun, Jiangwen; Zhan, Yixin; Zhang, Cheng

2018-02-10

OBJECTIVE To explore the clinical features of patients carrying deletions of the rod domain of the dystrophin gene. METHODS Clinical data of 12 Chinese patients with Becker muscular dystrophy (BMD) and such deletions was reviewed. RESULTS Most patients complained of muscle weakness of lower limbs. Two patients had muscle cramps, one had increased creatine kinase (CK) level, and one had dilated cardiomyopathy. CONCLUSION Compared with DMD, the clinical features of BMD are much more variable, particularly for those carrying deletions of the rod domain of the dystrophin gene. Muscular weakness may not be the sole complaint of BMD. The diagnosis of BMD cannot be excluded by moderately elevated CK. For male patients with dilated cardiomyopathy, the possibility of BMD should be considered.

MRI-based quantification of Duchenne muscular dystrophy in a canine model

Science.gov (United States)

Wang, Jiahui; Fan, Zheng; Kornegay, Joe N.; Styner, Martin A.

2011-03-01

Duchenne muscular dystrophy (DMD) is a progressive and fatal X-linked disease caused by mutations in the DMD gene. Magnetic resonance imaging (MRI) has shown potential to provide non-invasive and objective biomarkers for monitoring disease progression and therapeutic effect in DMD. In this paper, we propose a semi-automated scheme to quantify MRI features of golden retriever muscular dystrophy (GRMD), a canine model of DMD. Our method was applied to a natural history data set and a hydrodynamic limb perfusion data set. The scheme is composed of three modules: pre-processing, muscle segmentation, and feature analysis. The pre-processing module includes: calculation of T2 maps, spatial registration of T2 weighted (T2WI) images, T2 weighted fat suppressed (T2FS) images, and T2 maps, and intensity calibration of T2WI and T2FS images. We then manually segment six pelvic limb muscles. For each of the segmented muscles, we finally automatically measure volume and intensity statistics of the T2FS images and T2 maps. For the natural history study, our results showed that four of six muscles in affected dogs had smaller volumes and all had higher mean intensities in T2 maps as compared to normal dogs. For the perfusion study, the muscle volumes and mean intensities in T2FS were increased in the post-perfusion MRI scans as compared to pre-perfusion MRI scans, as predicted. We conclude that our scheme successfully performs quantitative analysis of muscle MRI features of GRMD.

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.

Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.

Directory of Open Access Journals (Sweden)

Hong Hao

Full Text Available A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.

Overexpression of retinal degeneration slow (RDS protein adversely affects rods in the rd7 model of enhanced S-cone syndrome.

Directory of Open Access Journals (Sweden)

Dibyendu Chakraborty

Full Text Available The nuclear receptor NR2E3 promotes expression of rod photoreceptor genes while repressing cone genes. Mice lacking NR2E3 (Nr2e3(rd7/rd7 referred to here as rd7 are a model for enhanced S-cone syndrome, a disease associated with increased sensitivity to blue light and night blindness. Rd7 retinas have reduced levels of the outer segment (OS structural protein retinal degeneration slow (RDS. We test the hypothesis that increasing RDS levels would improve the Rd7 phenotype. Transgenic mice over-expressing normal mouse peripherin/RDS (NMP in rods and cones were crossed onto the rd7 background. Disease phenotypes were assessed in NMP/rd7 eyes and compared to wild-type (WT and rd7 eyes at postnatal day 30. NMP/rd7 retinas expressed total RDS (transgenic and endogenous message at WT levels, and NMP protein was correctly localized to the OS. NMP/rd7 retinas have shorter OSs compared to rd7 and WT and significantly reduced number of rosettes. NMP/rd7 mice also exhibited significant deficits in scotopic ERG amplitudes compared to rd7 while photopic amplitudes remained unaffected. Protein levels of rhodopsin, RDS, and the RDS homologue ROM-1 were significantly reduced in the NMP/rd7 retinas compared to rd7. We show that correcting the levels of RDS gene expression does not improve the phenotype of the rd7 suggesting that RDS deficiency is not responsible for the defect in this model. We suggest that the specific rod defect in the NMP/rd7 is likely associated with ongoing problems in the rd7 that are related to the expression of cone genes in rod cells, a characteristic of the model.

Retinal pigment epithelial dystrophy in Briard dogs.

Science.gov (United States)

Lightfoot, R M; Cabral, L; Gooch, L; Bedford, P G; Boulton, M E

1996-01-01

The eyes of normal Briard dogs, Briards affected with inherited retinal pigment epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were examined and the histopathology of RPED in the Briard was compared with the histopathological features of ageing in the normal canine retina. RPED was characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions in the retinal pigment epithelium (RPE), which initially involved only non-pigmented RPE cells overlying the tapetum but subsequently spread to all pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a gradual loss of the outer nuclear layer and the subsequent atrophy and degeneration of the inner retina. The loss of primary photoreceptors in the peripheral retina was accompanied by the migration of photoreceptor nuclei and appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled leucine was used to examine the rate of turnover of the outer segments of the rods in some Briards, but no significant variations were found. The activity of acid phosphatase in RPE was assayed in vitro and showed comparable regional variations in Briard and crossbred dogs. The results suggest that RPED in the Briard is unlikely to be due either to an increased rate of turnover of rod outer segments (and thus an increased phagocytic load) or to a primary insufficiency of lysosomal enzyme.

Distrofias retinianas da infância: análise retrospectiva Retinal dystrophies in childhood: retrospective analysis

Directory of Open Access Journals (Sweden)

Heloisa Andrade Maestrini

2004-12-01

distrofias retinianas da infância são um grupo heterogêneo de doenças que se manifestam por meio de sintomas inespecíficos. Uma análise cuidadosa dos sintomas, o exame oftalmológico completo e os exames complementares, principalmente ERG, testes de visão de cores e campo visual, podem ser úteis em seu diagnóstico.PURPOSE: To describe the clinical features and the results of diagnostic methods in all patients with diagnosis of one of the following retinal dystrophies: Leber congenital amaurosis (LCA, achromatopsia, cone distrophy or cone-rod distrophy, examined at the Low Vision Department of the Federal University of Minas Gerais, in the period of 1992 to 2003. METHODS: Retrospective analysis of charts of 40 patients. Ten had LCA, 17 had achromatopsia, 6 had cone distrophy and 7 had cone-rod distrophy. RESULTS: Visual acuity was extremely low in patients with LCA, ranging from 20/710 to light perception. The mean value for achromatopsia was 20/200, 20/280 for cone distrophy and 20/260 for cone-rod distrophy. High hyperopia was the most common refractional error in LCA patients. Hyperopia was more frequent in cases of achromatopsia and cone distrophy, while in cone-rod distrophy myopia predominated. Fundoscopy was altered in most cases of LCA, cone distrophy and rod-cone distrophy, and normal in most cases of achromatopsia. Oculodigital sign and enophtalmus were found only in LCA patients while photofobia and color vision defects prevailed in other groups. Nistagmus and strabismus were frequent findings in all groups. There was a high incidence of delayed neuro-psycho-motor development in LCA patients. Two of them had also associated genetic syndromes. Patients presented symptoms very early in life in LCA and achromatopsia, while in cone and cone-rod distrophies symptoms appeared later, but never after the age of 10. Consanguinity and positive familial history were strongly associated in all groups. The ERG was extinct in LCA, showed reduced photopic response in

Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.

LENUS (Irish Health Repository)

Bhatt, Lavinia

2010-01-01

PURPOSE: The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal of trophic factors is used as a model system to investigate the effects of stress in the retina. The aims were to determine if both rod and cone photoreceptor cells produce ROS when they are deprived of trophic factor support and to demonstrate if the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes are responsible for this ROS production. METHODS: Retinas were explanted from mice aged between postnatal days 8-10 and cultured overnight. The following morning, confocal microscopy combined with various fluorescent probes was used to detect the production of ROS. Each time peanut agglutinin (PNA), a cone photoreceptor marker, was used to facilitate orientation of the retina. Dihydroethidium and dihydrorhodamine 123 (DHR123) were used to determine which cells produce ROS. Subsequently, western blots of retinal serial sections were used to detect the presence of Noxs in the different retinal layers. The Nox inhibitor apocynin was then tested to determine if it altered the production of ROS within these cells. RESULTS: Live retinal explants, viewed at high magnifications using confocal microscopy, displayed an increase in the fluorescent products of dihydroethidium and DHR123 upon serum removal when compared to controls. DHR123 fluorescence, once oxidized, localized to mitochondria and was found in the same focal plane as the PNA staining. This showed that cones and rods produced ROS when stressed. Retinal serial sectioning established that the photoreceptor layer expressed Nox4, dual oxidase (Duox) 1, and Duox2 at varying levels. Finally, the Nox inhibitor apocynin decreased the burst stimulated by the stress of serum removal. CONCLUSIONS: Confocal microscopy and PNA staining allowed differentiation of cell types within the outermost layers of the retina, demonstrating

A computerized MRI biomarker quantification scheme for a canine model of Duchenne muscular dystrophy.

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Wang, Jiahui; Fan, Zheng; Vandenborne, Krista; Walter, Glenn; Shiloh-Malawsky, Yael; An, Hongyu; Kornegay, Joe N; Styner, Martin A

2013-09-01

Golden retriever muscular dystrophy (GRMD) is a widely used canine model of Duchenne muscular dystrophy (DMD). Recent studies have shown that magnetic resonance imaging (MRI) can be used to non-invasively detect consistent changes in both DMD and GRMD. In this paper, we propose a semiautomated system to quantify MRI biomarkers of GRMD. Our system was applied to a database of 45 MRI scans from 8 normal and 10 GRMD dogs in a longitudinal natural history study. We first segmented six proximal pelvic limb muscles using a semiautomated full muscle segmentation method. We then performed preprocessing, including intensity inhomogeneity correction, spatial registration of different image sequences, intensity calibration of T2-weighted and T2-weighted fat-suppressed images, and calculation of MRI biomarker maps. Finally, for each of the segmented muscles, we automatically measured MRI biomarkers of muscle volume, intensity statistics over MRI biomarker maps, and statistical image texture features. The muscle volume and the mean intensities in T2 value, fat, and water maps showed group differences between normal and GRMD dogs. For the statistical texture biomarkers, both the histogram and run-length matrix features showed obvious group differences between normal and GRMD dogs. The full muscle segmentation showed significantly less error and variability in the proposed biomarkers when compared to the standard, limited muscle range segmentation. The experimental results demonstrated that this quantification tool could reliably quantify MRI biomarkers in GRMD dogs, suggesting that it would also be useful for quantifying disease progression and measuring therapeutic effect in DMD patients.

Dog as a model in studies on human hereditary diseases and their gene therapy.

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Switonski, Marek

2014-03-01

During the last 15 years spectacular progress has been achieved in knowledge on the dog genome organization and the molecular background of hereditary diseases in this species. A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important large animal model in human biomedicine. Among canine monogenic diseases with known causative gene mutations there are two large groups classified as retinal dystrophies and lysosomal storage diseases. Specific types of these diseases are usually diagnosed in a single or several breeds. A well known disorder, restricted to a single breed, is congenital stationary night blindness described in Briards. This disease is a counterpart of Leber amaurosis in children. On the other hand, one of the most common monogenic human diseases (Duchenne muscular dystrophy), has its canine counterparts in several breeds (e.g., the Golden retriever, Beagle and German short-haired pointer). For some of the canine diseases gene therapy strategy was successfully applied, e.g., for congenital stationary night blindness, rod-cone dystrophy and muccopolysaccharydoses type I, IIIB and VII. Since phenotypic variability between the breeds is exceptionally high, the dog is an interesting model to study the molecular background of congenital malformations (e.g., dwarfism and osteoporosis imperfecta). Also disorders of sexual development (DSD), especially testicular or ovotesticular DSD (78,XX; SRY-negative), which is widely distributed across dozens of breeds, are of particular interest. Studies on the genetic background of canine cancers, a major health problem in this species, are also quite advanced. On the other hand, genetic studies on canine counterparts of major human complex diseases (e.g., obesity, the metabolic syndrome and diabetes mellitus) are still in their infancy. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish

A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.

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Audo, Isabelle; Bujakowska, Kinga; Mohand-Saïd, Saddek; Tronche, Sophie; Lancelot, Marie-Elise; Antonio, Aline; Germain, Aurore; Lonjou, Christine; Carpentier, Wassila; Sahel, José-Alain; Bhattacharya, Shomi; Zeitz, Christina

2011-01-01

To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition. A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing. The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment. We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2.

Integrity of the cone photoreceptor mosaic in oligocone trichromacy

DEFF Research Database (Denmark)

Michaelides, Michel; Rha, Jungtae; Dees, Elise W

2011-01-01

Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these......Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed...

Reconstruction-of-difference (RoD) imaging for cone-beam CT neuro-angiography

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Wu, P.; Stayman, J. W.; Mow, M.; Zbijewski, W.; Sisniega, A.; Aygun, N.; Stevens, R.; Foos, D.; Wang, X.; Siewerdsen, J. H.

2018-06-01

Timely evaluation of neurovasculature via CT angiography (CTA) is critical to the detection of pathology such as ischemic stroke. Cone-beam CTA (CBCT-A) systems provide potential advantages in the timely use at the point-of-care, although challenges of a relatively slow gantry rotation speed introduce tradeoffs among image quality, data consistency and data sparsity. This work describes and evaluates a new reconstruction-of-difference (RoD) approach that is robust to such challenges. A fast digital simulation framework was developed to test the performance of the RoD over standard reference reconstruction methods such as filtered back-projection (FBP) and penalized likelihood (PL) over a broad range of imaging conditions, grouped into three scenarios to test the trade-off between data consistency, data sparsity and peak contrast. Two experiments were also conducted using a CBCT prototype and an anthropomorphic neurovascular phantom to test the simulation findings in real data. Performance was evaluated primarily in terms of normalized root mean square error (NRMSE) in comparison to truth, with reconstruction parameters chosen to optimize performance in each case to ensure fair comparison. The RoD approach reduced NRMSE in reconstructed images by up to 50%–53% compared to FBP and up to 29%–31% compared to PL for each scenario. Scan protocols well suited to the RoD approach were identified that balance tradeoffs among data consistency, sparsity and peak contrast—for example, a CBCT-A scan with 128 projections acquired in 8.5 s over a 180°  +  fan angle half-scan for a time attenuation curve with ~8.5 s time-to-peak and 600 HU peak contrast. With imaging conditions such as the simulation scenarios of fixed data sparsity (i.e. varying levels of data consistency and peak contrast), the experiments confirmed the reduction of NRMSE by 34% and 17% compared to FBP and PL, respectively. The RoD approach demonstrated superior performance in 3D angiography

Clinical features and endodontic treatment of two-rooted mandibular canines: Report of four cases

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Stojanac Igor

2014-01-01

Full Text Available Introduction. Predictable endodontic treatment depends on the dentist’s knowledge about root canal morphology and its possible anatomic variations. The majority of mandibular canines have one root and root canal, but 15% may have two canals and a smaller number may have two distinct roots. The following clinical reports describe endodontic treatment of mandibular canines with two roots and two root canals. Outline of Cases. Four clinical case reports are presented to exemplify anatomical variation in the human mandibular canine. Detailed analysis of the preoperative radiographs and careful examination of the pulp chamber floor detected the presence of two root canal orifices in all canines. Working length was determined with an electronic apex locator and biomechanical preparation was carried out by using engine driven BioRaCe Ni-Ti rotary instruments in a crown-down manner, followed by copious irrigation with 1% sodium hypochlorite. Definitive obturation was performed using cold lateral condensation with gutta-percha cones and Top Seal paste. The treatment outcome was evaluated using postoperative radiographs. Conclusion. Endodontists should be aware of anatomical variations of the treated teeth, and should never presume that canal systems are simple. [Projekat Ministarstva nauke Republike Srbije, br. 174005: Viscoelasticity of fractional type and optimization of shape in rod theory

Amyloid precursor protein is required for normal function of the rod and cone pathways in the mouse retina.

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Tracy Ho

Full Text Available Amyloid precursor protein (APP is a transmembrane glycoprotein frequently studied for its role in Alzheimer's disease. Our recent study in APP knockout (KO mice identified an important role for APP in modulating normal neuronal development in the retina. However the role APP plays in the adult retina and whether it is required for vision is unknown. In this study we evaluated the role of APP in retinal function and morphology comparing adult wildtype (WT and APP-KO mice. APP was expressed on neuronal cells of the inner retina, including horizontal, cone bipolar, amacrine and ganglion cells in WT mice. The function of the retina was assessed using the electroretinogram and although the rod photoreceptor responses were similar in APP-KO and WT mice, the post-photoreceptor, inner retinal responses of both the rod and cone pathways were reduced in APP-KO mice. These changes in inner retinal function did not translate to a substantial change in visual acuity as assessed using the optokinetic response or to changes in the gross cellular structure of the retina. These findings indicate that APP is not required for basic visual function, but that it is involved in modulating inner retinal circuitry.

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

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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.

Muscular dystrophy in a family of Labrador Retrievers with no muscle dystrophin and a mild phenotype.

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Vieira, Natassia M; Guo, Ling T; Estrela, Elicia; Kunkel, Louis M; Zatz, Mayana; Shelton, G Diane

2015-05-01

Animal models of dystrophin deficient muscular dystrophy, most notably canine X-linked muscular dystrophy, play an important role in developing new therapies for human Duchenne muscular dystrophy. Although the canine disease is a model of the human disease, the variable severity of clinical presentations in the canine may be problematic for pre-clinical trials, but also informative. Here we describe a family of Labrador Retrievers with three generations of male dogs having markedly increased serum creatine kinase activity, absence of membrane dystrophin, but with undetectable clinical signs of muscle weakness. Clinically normal young male Labrador Retriever puppies were evaluated prior to surgical neuter by screening laboratory blood work, including serum creatine kinase activity. Serum creatine kinase activities were markedly increased in the absence of clinical signs of muscle weakness. Evaluation of muscle biopsies confirmed a dystrophic phenotype with both degeneration and regeneration. Further evaluations by immunofluorescence and western blot analysis confirmed the absence of muscle dystrophin. Although dystrophin was not identified in the muscles, we did not find any detectable deletions or duplications in the dystrophin gene. Sequencing is now ongoing to search for point mutations. Our findings in this family of Labrador Retriever dogs lend support to the hypothesis that, in exceptional situations, muscle with no dystrophin may be functional. Unlocking the secrets that protect these dogs from a severe clinical myopathy is a great challenge which may have important implications for future treatment of human muscular dystrophies. Copyright © 2015 Elsevier B.V. All rights reserved.

Dual AAV Gene Therapy for Duchenne Muscular Dystrophy with a 7-kb Mini-Dystrophin Gene in the Canine Model.

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Kodippili, Kasun; Hakim, Chady H; Pan, Xiufang; Yang, Hsiao T; Yue, Yongping; Zhang, Yadong; Shin, Jin-Hong; Yang, N Nora; Duan, Dongsheng

2018-03-01

Dual adeno-associated virus (AAV) technology was developed in 2000 to double the packaging capacity of the AAV vector. The proof of principle has been demonstrated in various mouse models. Yet, pivotal evidence is lacking in large animal models of human diseases. Here we report expression of a 7-kb canine ΔH2-R15 mini-dystrophin gene using a pair of dual AAV vectors in the canine model of Duchenne muscular dystrophy (DMD). The ΔH2-R15 minigene is by far the most potent synthetic dystrophin gene engineered for DMD gene therapy. We packaged minigene dual vectors in Y731F tyrosine-modified AAV-9 and delivered to the extensor carpi ulnaris muscle of a 12-month-old affected dog at the dose of 2 × 10 13 viral genome particles/vector/muscle. Widespread mini-dystrophin expression was observed 2 months after gene transfer. The missing dystrophin-associated glycoprotein complex was restored. Treatment also reduced muscle degeneration and fibrosis and improved myofiber size distribution. Importantly, dual AAV therapy greatly protected the muscle from eccentric contraction-induced force loss. Our data provide the first clear evidence that dual AAV therapy can be translated to a diseased large mammal. Further development of dual AAV technology may lead to effective therapies for DMD and many other diseases in human patients.

Brain perfusion imaging using a Reconstruction-of-Difference (RoD) approach for cone-beam computed tomography

Science.gov (United States)

Mow, M.; Zbijewski, W.; Sisniega, A.; Xu, J.; Dang, H.; Stayman, J. W.; Wang, X.; Foos, D. H.; Koliatsos, V.; Aygun, N.; Siewerdsen, J. H.

2017-03-01

Purpose: To improve the timely detection and treatment of intracranial hemorrhage or ischemic stroke, recent efforts include the development of cone-beam CT (CBCT) systems for perfusion imaging and new approaches to estimate perfusion parameters despite slow rotation speeds compared to multi-detector CT (MDCT) systems. This work describes development of a brain perfusion CBCT method using a reconstruction of difference (RoD) approach to enable perfusion imaging on a newly developed CBCT head scanner prototype. Methods: A new reconstruction approach using RoD with a penalized-likelihood framework was developed to image the temporal dynamics of vascular enhancement. A digital perfusion simulation was developed to give a realistic representation of brain anatomy, artifacts, noise, scanner characteristics, and hemo-dynamic properties. This simulation includes a digital brain phantom, time-attenuation curves and noise parameters, a novel forward projection method for improved computational efficiency, and perfusion parameter calculation. Results: Our results show the feasibility of estimating perfusion parameters from a set of images reconstructed from slow scans, sparse data sets, and arc length scans as short as 60 degrees. The RoD framework significantly reduces noise and time-varying artifacts from inconsistent projections. Proper regularization and the use of overlapping reconstructed arcs can potentially further decrease bias and increase temporal resolution, respectively. Conclusions: A digital brain perfusion simulation with RoD imaging approach has been developed and supports the feasibility of using a CBCT head scanner for perfusion imaging. Future work will include testing with data acquired using a 3D-printed perfusion phantom currently and translation to preclinical and clinical studies.

Pupillometer-based objective chromatic perimetry in normal eyes and patients with retinal photoreceptor dystrophies.

Science.gov (United States)

Skaat, Alon; Sher, Ifat; Kolker, Andrew; Elyasiv, Sivan; Rosenfeld, Elkana; Mhajna, Mohamad; Melamed, Shlomo; Belkin, Michael; Rotenstreich, Ygal

2013-04-17

To evaluate a novel objective perimetry using multifocal chromatic pupil light reflex in normal participants and patients with photoreceptor dysfunction, and to relate this new technique with subjective dark-adapted chromatic Goldmann perimetry. Thirty-two eyes of 17 retinitis pigmentosa (RP) or cone-rod dystrophy patients and 20 eyes of 12 healthy individuals were tested. A computerized infrared video pupillometer was used to record changes in pupil diameter in response to short- and long-wavelength stimuli (peak 485 and 640 nm, respectively; light intensity 40 cd/m(2)) at 13 different points of the 30° visual field (VF), under background illumination of 2.7 cd/m(2). The pupillary response (PR) of patients was compared with PR obtained from normal control participants. In 11 patients, the pupillary responses were also compared with their findings on dark-adapted chromatic Goldmann perimetry. Significantly reduced pupillary responses were obtained in RP patients in response to the short-wavelength stimulus in nearly all perimetric locations (P chromatic Goldmann perimetry. In all patients that were tested by the chromatic Goldmann, minimal PR was recorded in areas that were nondetected in the chromatic Goldmann perimetry. This study demonstrates the potential feasibility of using pupillometer-based chromatic perimetry for objectively assessing VF defects and retinal function in patients with retinal dystrophies. (ClinicalTrials.gov number, NCT01021982.).

Genetics Home Reference: Mainzer-Saldino syndrome

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... The most common rod-cone dystrophy is called retinitis pigmentosa , and the vision problems in Mainzer-Saldino syndrome ... deposits of pigment in the retina from which retinitis pigmentosa gets its name are often not found in ...

Case of Unilateral Peripheral Cone Dysfunction

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Yujin Mochizuki

2012-05-01

Full Text Available Purpose: Peripheral cone dystrophy is a subgroup of cone dystrophy, and only 4 cases have been reported. We present a patient with unilateral peripheral cone dysfunction and report the functional changes determined by electrophysiological tests and ultrastructural changes determined by spectral domain optical coherence tomography (SD-OCT. Case: A 34-year-old woman complained of blurred vision in both eyes. Our examination showed that her visual acuity was 0.05 OD and 0.2 OS. A relative afferent pupillary defect was present in her right eye. The results of slit-lamp examination, ophthalmoscopy, and fluorescein angiography were normal except for pallor of the right optic disc. SD-OCT showed a diffuse thinning of the retina in the posterior pole of the right eye. A severe constriction of the visual fields was found in both eyes but more in the right eye. The photopic full-field electroretinograms (ERGs were reduced in the right eye but normal in the left eye. The multifocal ERGs were severely reduced throughout the visual field except in the central area of the right eye. The multifocal ERGs from the left eye were normal. The pattern visual evoked responses were within the normal range in both eyes. She had a 5-year history of sniffing paint thinner. Results: Although the visual dysfunction was initially suspected to be due to psychological problems from the results of subjective tests, objective tests indicated a peripheral cone dysfunction in the right eye. The pathophysiological mechanism and the relationship with thinner sniffing were not determined. Conclusions: Our findings indicate that peripheral cone dysfunction can occur unilaterally. Electrophysiology and SD-OCT are valuable tests to perform to determine the pathogenesis of unusual ocular findings objectively.

Expanded clinical spectrum of enhanced S-cone syndrome

NARCIS (Netherlands)

Yzer, Suzanne; Barbazetto, Irene; Allikmets, Rando; van Schooneveld, Mary J.; Bergen, Arthur; Tsang, Stephen H.; Jacobson, Samuel G.; Yannuzzi, Lawrence A.

2013-01-01

New funduscopic findings in patients with enhanced S-cone syndrome (ESCS) may help clinicians in diagnosing this rare autosomal recessive retinal dystrophy. To expand the clinical spectrum of ESCS due to mutations in the NR2E3 gene. Retrospective, noncomparative case series of 31 patients examined

Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ: electrocardiographic, echocardiographic, and morphologic studies

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Machida Noboru

2006-12-01

Full Text Available Abstract Background Cardiac mortality in Duchenne muscular dystrophy (DMD has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ and examined the cardiac involvement. Methods The cardiac phenotypes of eight CXMDJ and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations. Results Increases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMDJ dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMDJ dogs. In the echocardiogram, one of eight of CXMDJ dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMDJ dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMDJ dogs by 21 months of age. Conclusion Cardiac involvement in CXMDJ dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and

Clinical Characteristics and Current Therapies for Inherited Retinal Degenerations

Science.gov (United States)

Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2015-01-01

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307–316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod–cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone–rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

Genotyping microarray (gene chip) for the ABCR (ABCA4) gene.

NARCIS (Netherlands)

Jaakson, K.; Zernant, J.; Kulm, M.; Hutchinson, A.; Tonisson, N.; Glavac, D.; Ravnik-Glavac, M.; Hawlina, M.; Meltzer, M.R.; Caruso, R.C.; Testa, F.; Maugeri, A.; Hoyng, C.B.; Gouras, P.; Simonelli, F.; Lewis, R.A.; Lupski, J.R.; Cremers, F.P.M.; Allikmets, R.

2003-01-01

Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of ABCR variation and diagnostics

Retinal cone photoreceptors of the deer mouse Peromyscus maniculatus: development, topography, opsin expression and spectral tuning.

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Patrick Arbogast

Full Text Available A quantitative analysis of photoreceptor properties was performed in the retina of the nocturnal deer mouse, Peromyscus maniculatus, using pigmented (wildtype and albino animals. The aim was to establish whether the deer mouse is a more suitable model species than the house mouse for photoreceptor studies, and whether oculocutaneous albinism affects its photoreceptor properties. In retinal flatmounts, cone photoreceptors were identified by opsin immunostaining, and their numbers, spectral types, and distributions across the retina were determined. Rod photoreceptors were counted using differential interference contrast microscopy. Pigmented P. maniculatus have a rod-dominated retina with rod densities of about 450.000/mm(2 and cone densities of 3000-6500/mm(2. Two cone opsins, shortwave sensitive (S and middle-to-longwave sensitive (M, are present and expressed in distinct cone types. Partial sequencing of the S opsin gene strongly supports UV sensitivity of the S cone visual pigment. The S cones constitute a 5-15% minority of the cones. Different from house mouse, S and M cone distributions do not have dorsoventral gradients, and coexpression of both opsins in single cones is exceptional (<2% of the cones. In albino P. maniculatus, rod densities are reduced by approximately 40% (270.000/mm(2. Overall, cone density and the density of cones exclusively expressing S opsin are not significantly different from pigmented P. maniculatus. However, in albino retinas S opsin is coexpressed with M opsin in 60-90% of the cones and therefore the population of cones expressing only M opsin is significantly reduced to 5-25%. In conclusion, deer mouse cone properties largely conform to the general mammalian pattern, hence the deer mouse may be better suited than the house mouse for the study of certain basic cone properties, including the effects of albinism on cone opsin expression.

Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking

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Chizzolini, Marzio; Galan, Alessandro; Milan, Elisabeth; Sebastiani, Adolfo; Costagliola, Ciro; Parmeggiani, Francesco

2011-01-01

Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals first experience night-blindness and/or visual field constriction (secondary to rod dysfunctions), followed by variable alterations of the central vision (due to cone damages). On the other hand, during the atypical form of RP (cone-rod dystrophy), the cone’s functionalities are prevalently disrupted in comparison with the rod’s ones. The basic diagnosis of RP relies upon the documentation of unremitting loss in photoreceptor activity by electroretinogram and/or visual field testing. The prevalence of all RP typologies is variably reported in about one case for each 3000-5000 individuals, with a total of about two millions of affected persons worldwide. The inherited retinal dystrophies are sometimes the epiphenomenon of a complex framework (syndromic RP), but more often they represent an isolated disorder (about 85-90 % of cases). Although 200 causative RP mutations have been hitherto detected in more than 100 different genes, the molecular defect is identifiable in just about the 50% of the analyzed patients with RP. Not only the RP genotypes are very heterogeneous, but also the patients with the same mutation can be affected by different phenotypic manifestations. RP can be inherited as autosomal dominant, autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in patients with no affected relatives. Dissecting the clinico-genetic complexity of RP has become an attainable objective by means of large-scale research projects, in which the collaboration

Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis

DEFF Research Database (Denmark)

Siemiatkowska, Anna M; van den Born, L Ingeborgh; van Genderen, Maria M

2014-01-01

, were screened in 532 additional patients with retinal dystrophies. This cohort encompassed 108 persons with isolated or autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well as 104 persons with LCA...... and associated phenotypes in different types of inherited retinal dystrophies. METHODS: DNA samples of 161 patients with LCA without genetic diagnosis were analyzed for variants in NMNAT1 using Sanger sequencing. Variants in exon 5 of NMNAT1, which harbors the majority of the previously identified mutations...

Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.

Science.gov (United States)

Schonthaler, Helia B; Lampert, Johanna M; Isken, Andrea; Rinner, Oliver; Mader, Andreas; Gesemann, Matthias; Oberhauser, Vitus; Golczak, Marcin; Biehlmaier, Oliver; Palczewski, Krzysztof; Neuhauss, Stephan C F; von Lintig, Johannes

2007-10-01

An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.

Salamander blue-sensitive cones lost during metamorphosis.

NARCIS (Netherlands)

Chen, Y.; Znoiko, S.; Grip, W.J. de; Crouch, R.K.; Ma, J.X.

2008-01-01

The tiger salamander lives in shallow water with bright light in the aquatic phase, and in dim tunnels or caves in the terrestrial phase. In the aquatic phase, there are five types of photoreceptors--two types of rods and three types of cones. Our previous studies showed that the green rods and

Morphology and function of the retina in children and young adults with Stargardt dystrophy

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Martina Jarc Vidmar

2012-06-01

Conclusions: In young patients with Stargardt dystrophy central retinal atrophy was shown by OCT and AF. The shift of fixation to the PRL was seen in all the patients. MfERG showed central cone dysfunction in all the patients.

Integrity of the cone photoreceptor mosaic in oligocone trichromacy

DEFF Research Database (Denmark)

Michaelides, Michel; Rha, Jungtae; Dees, Elise W

2011-01-01

Oligocone trichromacy (OT) is an unusual cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, reduced amplitude of the cone electroretinogram with normal rod responses, normal fundus appearance, and normal or near-normal color vision. It has been proposed that these...... that these patients have a reduced number of normal functioning cones (oligocone). This paper has sought to evaluate the integrity of the cone photoreceptor mosaic in four patients previously described as having OT....

Non-syndromic retinitis pigmentosa

NARCIS (Netherlands)

Verbakel, S.K. (Sanne K.); R.A.C. van Huet (Ramon A. C.); C.J.F. Boon (Camiel); A.I. Hollander (Anneke); R.W.J. Collin (Rob); C.C.W. Klaver (Caroline); C. Hoyng (Carel); R. Roepman (Ronald); B.J. Klevering (Jeroen)

2018-01-01

textabstractRetinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by the primary degeneration of rod and cone photoreceptors. RP is a leading cause of visual disability, with a worldwide prevalence of 1:4000. Although the majority of RP cases are non-syndromic,

Molecular evolution of the cone visual pigments in the pure rod-retina of the nocturnal gecko, Gekko gekko.

Science.gov (United States)

Yokoyama, S; Blow, N S

2001-10-03

We have isolated a full-length cDNA encoding a putative ultraviolet (UV)-sensitive visual pigment of the Tokay gecko (Gekko gekko). This clone has 57 and 59% sequence similarities to the gecko RH2 and MWS pigment genes, respectively, but it shows 87% similarity to the UV pigment gene of the American chameleon (Anolis carolinensis). The evolutionary rates of amino acid replacement are significantly higher in the three gecko pigments than in the corresponding chameleon pigments. The accelerated evolutionary rates reflect not only the transition from cones to rods in the retina but also the blue-shift in the absorption spectra of the gecko pigments.

Functional Optical Coherence Tomography Enables In Vivo Physiological Assessment of Retinal Rod and Cone Photoreceptors

Science.gov (United States)

Zhang, Qiuxiang; Lu, Rongwen; Wang, Benquan; Messinger, Jeffrey D.; Curcio, Christine A.; Yao, Xincheng

2015-04-01

Transient intrinsic optical signal (IOS) changes have been observed in retinal photoreceptors, suggesting a unique biomarker for eye disease detection. However, clinical deployment of IOS imaging is challenging due to unclear IOS sources and limited signal-to-noise ratios (SNRs). Here, by developing high spatiotemporal resolution optical coherence tomography (OCT) and applying an adaptive algorithm for IOS processing, we were able to record robust IOSs from single-pass measurements. Transient IOSs, which might reflect an early stage of light phototransduction, are consistently observed in the photoreceptor outer segment almost immediately (retinal stimulation. Comparative studies of dark- and light-adapted retinas have demonstrated the feasibility of functional OCT mapping of rod and cone photoreceptors, promising a new method for early disease detection and improved treatment of diseases such as age-related macular degeneration (AMD) and other eye diseases that can cause photoreceptor damage.

Noninvasive imaging of the human rod photoreceptor mosaic using a confocal adaptive optics scanning ophthalmoscope

Science.gov (United States)

Dubra, Alfredo; Sulai, Yusufu; Norris, Jennifer L.; Cooper, Robert F.; Dubis, Adam M.; Williams, David R.; Carroll, Joseph

2011-01-01

The rod photoreceptors are implicated in a number of devastating retinal diseases. However, routine imaging of these cells has remained elusive, even with the advent of adaptive optics imaging. Here, we present the first in vivo images of the contiguous rod photoreceptor mosaic in nine healthy human subjects. The images were collected with three different confocal adaptive optics scanning ophthalmoscopes at two different institutions, using 680 and 775 nm superluminescent diodes for illumination. Estimates of photoreceptor density and rod:cone ratios in the 5°–15° retinal eccentricity range are consistent with histological findings, confirming our ability to resolve the rod mosaic by averaging multiple registered images, without the need for additional image processing. In one subject, we were able to identify the emergence of the first rods at approximately 190 μm from the foveal center, in agreement with previous histological studies. The rod and cone photoreceptor mosaics appear in focus at different retinal depths, with the rod mosaic best focus (i.e., brightest and sharpest) being at least 10 μm shallower than the cones at retinal eccentricities larger than 8°. This study represents an important step in bringing high-resolution imaging to bear on the study of rod disorders. PMID:21750765

X-linked dominant cone-rod degeneration: linkage mapping of a new locus for retinitis pigmentosa (RP 15) to Xp22.13-p22.11.

OpenAIRE

McGuire, R E; Sullivan, L S; Blanton, S H; Church, M W; Heckenlively, J R; Daiger, S P

1995-01-01

Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and excluded all mapped autosomal loci. However, a marker from ...

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa

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Clérin Emmanuelle

2011-12-01

Full Text Available Abstract Background Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. Methods An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. Results The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. Conclusion The automated

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa.

Science.gov (United States)

Clérin, Emmanuelle; Wicker, Nicolas; Mohand-Saïd, Saddek; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry

2011-12-20

Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. The automated platform ℮-conome used here for retinal disease is a tool that

Low Vision Rehabilitation of Retinitis Pigmentosa. Practice Report

Science.gov (United States)

Rundquist, John

2004-01-01

Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…

A theoretically exact reconstruction algorithm for helical cone-beam differential phase-contrast computed tomography

International Nuclear Information System (INIS)

Li Jing; Sun Yi; Zhu Peiping

2013-01-01

Differential phase-contrast computed tomography (DPC-CT) reconstruction problems are usually solved by using parallel-, fan- or cone-beam algorithms. For rod-shaped objects, the x-ray beams cannot recover all the slices of the sample at the same time. Thus, if a rod-shaped sample is required to be reconstructed by the above algorithms, one should alternately perform translation and rotation on this sample, which leads to lower efficiency. The helical cone-beam CT may significantly improve scanning efficiency for rod-shaped objects over other algorithms. In this paper, we propose a theoretically exact filter-backprojection algorithm for helical cone-beam DPC-CT, which can be applied to reconstruct the refractive index decrement distribution of the samples directly from two-dimensional differential phase-contrast images. Numerical simulations are conducted to verify the proposed algorithm. Our work provides a potential solution for inspecting the rod-shaped samples using DPC-CT, which may be applicable with the evolution of DPC-CT equipments. (paper)

Neuroaxonal Dystrophy and Cavitating Leukoencephalopathy of Chihuahua Dogs.

Science.gov (United States)

Degl'Innocenti, Sara; Asiag, Nimrod; Zeira, Offer; Falzone, Cristian; Cantile, Carlo

2017-09-01

A novel form of neuroaxonal dystrophy is described in 3 Chihuahua pups, 2 of which were from the same litter. It was characterized not only by accumulation of numerous and widely distributed axonal swellings (spheroids) but also by a severe cavitating leukoencephalopathy. The dogs presented with progressive neurological signs, including gait abnormalities and postural reaction deficits. Magnetic resonance images and gross examination at necropsy revealed dilation of lateral ventricles and cerebral atrophy, accompanied by cavitation of the subcortical white matter. Histopathologically, severe axonal degeneration with formation of large spheroids was found in the cerebral and cerebellar white matter, thalamus, and brainstem nuclei. Small-caliber spheroids were observed in the cerebral and cerebellar gray matter. The telencephalic white matter had severe myelin loss and cavitation with relative sparing of the U-fibers. Different from previously reported cases of canine neuroaxonal dystrophy, in these Chihuahuas the spheroid distribution predominantly involved the white matter with secondary severe leukoencephalopathy.

Rod and cone function in patients with KCNV2 retinopathy.

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Ditta Zobor

Full Text Available BACKGROUND: To investigate rod and cone function and disease mechanisms in patients with KCNV2 retinopathy. METHODOLOGY/PRINCIPAL FINDINGS: Psychophysical examinations as well as detailed electrophysiological examinations with Ganzfeld and multifocal electroretinogram (ERG were performed to study response dynamics. Additionally, fundus photography, autofluorescence imaging and spectral domain OCTs were carried out for morphological characterization. Molecular genetic analysis revealed compound heterozygosity in five patients and homozygosity for the KCNV2 gene in one patient. The mutations resulted in complete absence of Kv8.2 subunits in three patients (no protein group, NOP, while the other three patients expressed mutant Kv8.2 subunits resulting in altered Kv2.1/Kv8.2 heteromeric or residual Kv2.1 homomeric potassium channel function (altered protein group, ALP. Although more advanced morphological changes were visible in the NOP group, a clear functional difference between the two groups could not be observed. All patients showed characteristic dynamics of the b-wave intensity-response function, however, scotopic b-wave response amplitudes were within normal limits. We also observed severely reduced oscillatory potentials. CONCLUSIONS/SIGNIFICANCE: A specific genotype-phenotype correlation in retinal function could not be demonstrated. KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K(+-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged. The reduced oscillatory potentials further suggest an altered function of the inner retina. Besides the characteristically steep amplitude-versus-intensity relationship, flicker responses at intermediate frequencies (5-15 Hz are significantly reduced and shifted in phase.

Spectrum of ABCA4 (ABCR) gene mutations in Spanish patients with autosomal recessive macular dystrophies.

Science.gov (United States)

Paloma, E; Martínez-Mir, A; Vilageliu, L; Gonzàlez-Duarte, R; Balcells, S

2001-06-01

The ABCA4 gene has been involved in several forms of inherited macular dystrophy. In order to further characterize the complex genotype-phenotype relationships involving this gene, we have performed a mutation analysis of ABCA4 in 14 Spanish patients comprising eight STGD (Stargardt), four FFM (fundus flavimaculatus), and two CRD (Cone-rod dystrophy) patients. SSCP (single-strand conformation polymorphism) analysis and DNA sequencing of the coding and 5' upstream regions of this gene allowed the identification of 16 putatively pathogenic alterations, nine of which are novel. Most of these were missense changes, and no patient was found to carry two null alleles. Overall, the new data agree with a working model relating the different pathogenic phenotypes to the severity of the mutations. When considering the information presented here together with that of previous reports, a picture of the geographic distribution of three particular mutations emerges. The R212C change has been found in French, Italian, Dutch, German, and Spanish but not in British patients. In the Spanish collection, R212C was found in a CRD patient, indicating that it may be a rather severe change. In contrast, c.2588G>C, a very common mild allele in the Dutch population, is rarely found in Southern Europe. Interestingly, the c.2588G>C mutation has been found in a double mutant allele together with the missense R1055W. Finally, the newly described L1940P was found in two unrelated Spanish patients, and may be a moderate to severe allele. Copyright 2001 Wiley-Liss, Inc.

A neuroanatomical and physiological study of the non-image forming visual system of the cone-rod homeobox gene (Crx) knock out mouse

DEFF Research Database (Denmark)

Rovsing, Louise; Rath, Martin F; Lund-Andersen, Casper

2010-01-01

The anatomy and physiology of the non-image forming visual system was investigated in a visually blind cone-rod homeobox gene (Crx) knock-out mouse (Crx(-)(/)(-)), which lacks the outer segments of the photoreceptors. We show that the suprachiasmatic nuclei (SCN) in the Crx(-/-) mouse exhibit...... melanopsin neurons or the SCN may be necessary for a normal function of the non-image forming system of the mouse. However, a change in the SCN of the Crx(-/-) mouse might also explain the observed circadian differences between the knock out mouse and wild type mouse....

Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision.

Science.gov (United States)

Cao, Yan; Sarria, Ignacio; Fehlhaber, Katherine E; Kamasawa, Naomi; Orlandi, Cesare; James, Kiely N; Hazen, Jennifer L; Gardner, Matthew R; Farzan, Michael; Lee, Amy; Baker, Sheila; Baldwin, Kristin; Sampath, Alapakkam P; Martemyanov, Kirill A

2015-09-23

In the retina, rod and cone photoreceptors form distinct connections with different classes of downstream bipolar cells. However, the molecular mechanisms responsible for their selective connectivity are unknown. Here we identify a cell-adhesion protein, ELFN1, to be essential for the formation of synapses between rods and rod ON-bipolar cells in the primary rod pathway. ELFN1 is expressed selectively in rods where it is targeted to the axonal terminals by the synaptic release machinery. At the synapse, ELFN1 binds in trans to mGluR6, the postsynaptic receptor on rod ON-bipolar cells. Elimination of ELFN1 in mice prevents the formation of synaptic contacts involving rods, but not cones, allowing a dissection of the contributions of primary and secondary rod pathways to retinal circuit function and vision. We conclude that ELFN1 is necessary for the selective wiring of rods into the primary rod pathway and is required for high sensitivity of vision. Copyright © 2015 Elsevier Inc. All rights reserved.

Bcl-xL-mediated remodeling of rod and cone synaptic mitochondria after postnatal lead exposure: electron microscopy, tomography and oxygen consumption.

Science.gov (United States)

Perkins, Guy A; Scott, Ray; Perez, Alex; Ellisman, Mark H; Johnson, Jerry E; Fox, Donald A

2012-01-01

Postnatal lead exposure produces rod-selective and Bax-mediated apoptosis, decreased scotopic electroretinograms (ERGs), and scotopic and mesopic vision deficits in humans and/or experimental animals. Rod, but not cone, inner segment mitochondria were considered the primary site of action. However, photoreceptor synaptic mitochondria were not examined. Thus, our experiments investigated the structural and functional effects of environmentally relevant postnatal lead exposure on rod spherule and cone pedicle mitochondria and whether Bcl-xL overexpression provided neuroprotection. C57BL/6N mice pups were exposed to lead only during lactation via dams drinking water containing lead acetate. The blood [Pb] at weaning was 20.6±4.7 µg/dl, which decreased to the control value by 2 months. To assess synaptic mitochondrial structural differences and vulnerability to lead exposure, wild-type and transgenic mice overexpressing Bcl-xL in photoreceptors were used. Electron microscopy, three-dimensional electron tomography, and retinal and photoreceptor synaptic terminal oxygen consumption (QO(2)) studies were conducted in adult control, Bcl-xL, lead, and Bcl-xL/lead mice. The spherule and pedicle mitochondria in lead-treated mice were swollen, and the cristae structure was markedly changed. In the lead-treated mice, the mitochondrial cristae surface area and volume (abundance: measure correlated with ATP (ATP) synthesis) were decreased in the spherules and increased in the pedicles. Pedicles also had an increased number of crista segments per volume. In the lead-treated mice, the number of segments/crista and fraction of cristae with multiple segments (branching) similarly increased in spherule and pedicle mitochondria. Lead-induced remodeling of spherule mitochondria produced smaller cristae with more branching, whereas pedicle mitochondria had larger cristae with more branching and increased crista junction (CJ) diameter. Lead decreased dark- and light-adapted photoreceptor

Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis.

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Masaya Tsuboi

Full Text Available Whole exome sequencing (WES has become a common tool for identifying genetic causes of human inherited disorders, and it has also recently been applied to canine genome research. We conducted WES analysis of neuroaxonal dystrophy (NAD, a neurodegenerative disease that sporadically occurs worldwide in Papillon dogs. The disease is considered an autosomal recessive monogenic disease, which is histopathologically characterized by severe axonal swelling, known as "spheroids," throughout the nervous system. By sequencing all eleven DNA samples from one NAD-affected Papillon dog and her parents, two unrelated NAD-affected Papillon dogs, and six unaffected control Papillon dogs, we identified 10 candidate mutations. Among them, three candidates were determined to be "deleterious" by in silico pathogenesis evaluation. By subsequent massive screening by TaqMan genotyping analysis, only the PLA2G6 c.1579G>A mutation had an association with the presence or absence of the disease, suggesting that it may be a causal mutation of canine NAD. As a human homologue of this gene is a causative gene for infantile neuroaxonal dystrophy, this canine phenotype may serve as a good animal model for human disease. The results of this study also indicate that WES analysis is a powerful tool for exploring canine hereditary diseases, especially in rare monogenic hereditary diseases.

Transmigration of mandibular canine – case report

International Nuclear Information System (INIS)

Gruszka, Katarzyna; Różyło, T. Katarzyna; Różyło-Kalinowska, Ingrid; Denkiewicz, Katarzyna; Masłowska, Klaudia

2014-01-01

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

Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk.

Science.gov (United States)

Vollrath, D; Feng, W; Duncan, J L; Yasumura, D; D'Cruz, P M; Chappelow, A; Matthes, M T; Kay, M A; LaVail, M M

2001-10-23

The Royal College of Surgeons (RCS) rat is a widely studied animal model of retinal degeneration in which the inability of the retinal pigment epithelium (RPE) to phagocytize shed photoreceptor outer segments leads to a progressive loss of rod and cone photoreceptors. We recently used positional cloning to demonstrate that the gene Mertk likely corresponds to the retinal dystrophy (rdy) locus of the RCS rat. In the present study, we sought to determine whether gene transfer of Mertk to a RCS rat retina would result in correction of the RPE phagocytosis defect and preservation of photoreceptors. We used subretinal injection of a recombinant replication-deficient adenovirus encoding rat Mertk to deliver the gene to the eyes of young RCS rats. Electrophysiological assessment of animals 30 days after injection revealed an increased sensitivity of treated eyes to low-intensity light. Histologic and ultrastructural assessment demonstrated substantial sparing of photoreceptors, preservation of outer segment structure, and correction of the RPE phagocytosis defect in areas surrounding the injection site. Our results provide definitive evidence that mutation of Mertk underlies the RCS retinal dystrophy phenotype, and that the phenotype can be corrected by treatment of juvenile animals. To our knowledge, this is the first demonstration of complementation of both a functional cellular defect (phagocytosis) and a photoreceptor degeneration by gene transfer to the RPE. These results, together with the recent discovery of MERTK mutations in individuals with retinitis pigmentosa, emphasize the importance of the RCS rat as a model for gene therapy of diseases that arise from RPE dysfunction.

Blue cone monochromatism in a female due to skewed X-inactivation

DEFF Research Database (Denmark)

Frederiksen, Anja Lisbeth; Duno, Morten; Welinder, Lotte G

2012-01-01

Blue cone monochromatism (BCM) is a rare cone dystrophy with recessive X-linked inheritance and therefore diagnosed in males whereas females are clinically unaffected. We present a female with clinically manifested BCM. The diagnosis was genetically verified with the identification of one single...... red-green OPN1LW/MW hybrid gene harboring a point mutation c.607C>G, p.Cys203Arg that associates with BCM and in addition a completely biased X-inactivation in DNA isolated from full blood and buccal mucosa. The present case illustrates that females may develop symptoms of recessive X-linked eye...

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy?

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Onder Ayyildiz

Full Text Available ABSTRACT Purpose: The aim of the present study was to use enhanced depth imaging optical coherence tomography (EDI-OCT to investigate choroidal changes in patients with cone dystrophy (CD and to correlate these findings with clinical and electroretinography (ERG findings. Methods: This case-control study included 40 eyes of 20 patients with CD and 40 eyes of 40 age- and refraction-matched healthy individuals. Choroidal thickness (CT measurements were obtained under the foveal center and at 500 and 1,500 μm from the nasal and temporal regions to the center of the fovea, respectively. EDI-OCT and ERG data were analyzed, and the correlations of CT with the best-corrected visual acuity (BCVA and the central foveal thickness (CFT were evaluated. Results: The mean subfoveal CTs in the CD and control groups were 240.70 ± 70.78 and 356.18 ± 48.55 μm, respectively. The subfoveal CT was significantly thinner in patients with CD than in the controls (p<0.001. The patients with CD also had significantly thinner choroids than the controls at each measurement location relative to the fovea (p<0.001. The subfoveal CT in the CD group correlated with CFT (p=0.012, but no significant correlation was found between the subfoveal CT and BCVA or photopic ERG responses. Conclusions: The present study demonstrated a significant thinning of the choroid in patients with CD. EDI-OCT is a useful technique for describing the choroidal changes occurring in CD. Future studies investigating the association between choroidal changes and outer retinal destruction or the disease stage may provide a better understanding of the pathophysiology of CD.

Is there a relationship between outer retinal destruction and choroidal changes in cone dystrophy?

Science.gov (United States)

Ayyildiz, Onder; Ozge, Gokhan; Kucukevcilioglu, Murat; Ozgonul, Cem; Mumcuoglu, Tarkan; Durukan, Ali Hakan; Mutlu, Fatih Mehmet

2016-01-01

The aim of the present study was to use enhanced depth imaging optical coherence tomography (EDI-OCT) to investigate choroidal changes in patients with cone dystrophy (CD) and to correlate these findings with clinical and electroretinography (ERG) findings. This case-control study included 40 eyes of 20 patients with CD and 40 eyes of 40 age- and refraction-matched healthy individuals. Choroidal thickness (CT) measurements were obtained under the foveal center and at 500 and 1,500 μm from the nasal and temporal regions to the center of the fovea, respectively. EDI-OCT and ERG data were analyzed, and the correlations of CT with the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) were evaluated. The mean subfoveal CTs in the CD and control groups were 240.70 ± 70.78 and 356.18 ± 48.55 μm, respectively. The subfoveal CT was significantly thinner in patients with CD than in the controls (p<0.001). The patients with CD also had significantly thinner choroids than the controls at each measurement location relative to the fovea (p<0.001). The subfoveal CT in the CD group correlated with CFT (p=0.012), but no significant correlation was found between the subfoveal CT and BCVA or photopic ERG responses. The present study demonstrated a significant thinning of the choroid in patients with CD. EDI-OCT is a useful technique for describing the choroidal changes occurring in CD. Future studies investigating the association between choroidal changes and outer retinal destruction or the disease stage may provide a better understanding of the pathophysiology of CD.

[ERG diagnosis and differential diagnosis: results of examination over 6 years].

Science.gov (United States)

Stemeyer, G; Stähli, P

1996-05-01

This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement

Health of periodontal tissues and resorption status after orthodontic treatment of impacted maxillary canines.

Science.gov (United States)

Oz, A Z; Ciger, S

2018-03-01

The aim of the present study was to evaluate the changes of incisor root resorption associated with impacted maxillary canines and health of periodontal tissues around maxillary canines erupted with orthodontic treatment. Twenty patients with a unilateral palatally impacted maxillary canine were included in the study. Cone-beam computed tomography images taken before and after orthodontic treatment were compared with the contralateral canines serving as control teeth. Root resorption was present in 10% of central and 40% of lateral incisors before treatment. After treatment, the incidence of resorption decreased. The thickness of the buccal bone surrounding the impacted canines was similar to that surrounding the contralateral canines, except in the apical area. Periodontal pocket depth and alveolar bone loss were greater for the impacted canine teeth than for the contralateral canines. Incisor root resorption associated with impacted canine teeth showed signs of repair after orthodontic treatment. Slight differences related to periodontal health were found between the previously impacted teeth and contralateral canine teeth.

Functional muscle ischemia in Duchenne and Becker muscular dystrophy

OpenAIRE

Thomas, Gail D.

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...

Myotonic Muscular Dystrophy

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Correlated and uncorrelated invisible temporal white noise alters mesopic rod signaling.

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Hathibelagal, Amithavikram R; Feigl, Beatrix; Kremers, Jan; Zele, Andrew J

2016-03-01

We determined how rod signaling at mesopic light levels is altered by extrinsic temporal white noise that is correlated or uncorrelated with the activity of one (magnocellular, parvocellular, or koniocellular) postreceptoral pathway. Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. Psychometric (Weibull) functions were measured for incremental rod pulses (50 to 250 ms) in the presence (or absence; control) of perceptually invisible subthreshold extrinsic noise. Uncorrelated (rod) noise facilitates rod detection. Correlated postreceptoral pathway noise produces differential changes in rod detection thresholds and decreases the slope of the psychometric functions. We demonstrate that invisible extrinsic noise changes rod-signaling characteristics within the three retinogeniculate pathways at mesopic illumination depending on the temporal profile of the rod stimulus and the extrinsic noise type.

Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

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Marta Corton

Full Text Available Retinal dystrophies (RD are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context.We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

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

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

2014-07-09

Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin. 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 DMD. 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 simultaneously targeted two exons in the rat Dmd gene, which resulted in the absence of Dystrophin expression in the F0 generation. Dmd-mutated rats exhibited a decline in muscle strength, and the emergence of degenerative/regenerative phenotypes in the skeletal muscle, heart, and diaphragm. These mutations were heritable by the next generation, and F1 male rats exhibited similar phenotypes in their skeletal muscles. These model rats should prove to be useful for developing therapeutic methods to treat DMD.

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

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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. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Alstr?m Syndrome: Genetics and Clinical Overview

OpenAIRE

Marshall, Jan D; Maffei, Pietro; Collin, Gayle B; Naggert, J?rgen K

2011-01-01

Alstr?m syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinic...

The prenyl-binding protein PrBP/δ: a chaperone participating in intracellular trafficking.

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Zhang, Houbin; Constantine, Ryan; Frederick, Jeanne M; Baehr, Wolfgang

2012-12-15

Expressed ubiquitously, PrBP/δ functions as chaperone/co-factor in the transport of a subset of prenylated proteins. PrBP/δ features an immunoglobulin-like β-sandwich fold for lipid binding, and interacts with diverse partners. PrBP/δ binds both C-terminal C15 and C20 prenyl side chains of phototransduction polypeptides and small GTP-binding (G) proteins of the Ras superfamily. PrBP/δ also interacts with the small GTPases, ARL2 and ARL3, which act as release factors (GDFs) for prenylated cargo. Targeted deletion of the mouse Pde6d gene encoding PrBP/δ resulted in impeded trafficking to the outer segments of GRK1 and cone PDE6 which are predicted to be farnesylated and geranylgeranylated, respectively. Rod and cone transducin trafficking was largely unaffected. These trafficking defects produce progressive cone-rod dystrophy in the Pde6d(-/-) mouse. Copyright © 2012 Elsevier Ltd. All rights reserved.

A rare case of canine anomaly - a possible algorithm for treating it.

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Vaida, Ligia; Todor, Bianca Ioana; Corega, Claudia; Băciuţ, Mihaela; Băciuţ, Grigore

2014-01-01

Canine transmigration is a very rare dental anomaly in which an unerupted mandibular canine migrates, crossing the mandibular midline. This unusual condition is most often diagnosed by chance during a routine X-ray examination. The most common clinical signs announcing the presence of this anomaly are over-retention of the deciduous canine and the absence of permanent canine from the dental arch after its physiological period of eruption. In this paper, we present a clinical case, 10-year-old boy, who was diagnosed with mandibular right canine transmigration at three years after the start of orthodontic treatment, during which we were expecting the eruption of mandibular canines. The orthopantomograph revealed the mandibular right canine to be in a horizontal position under the apices of the incisors - type 2 transmigration pattern classified by Mupparapu (2002). Based on cone-beam computer tomography examination, we recommended a surgical exposure of the canine and orthodontic alignment. Due to the risk of root resorption of the mandibular right lateral incisor during orthodontic movement phase of canine transmigrated to the dental arch, we decided to align the mandibular right canine in a transposition, between the two mandibular right incisors. Then we resorted to adapting the mandibular right lateral incisor coronary morphology to simulate a canine and also to reshaping the canine coronary morphology to resemble a lateral incisor. This therapeutic approach allowed us to restore morphologically and functionally the mandibular dento-alveolar arch, preserving the entire dental system.

Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa

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Murakami, Y; Ikeda, Y; Nakatake, S; Tachibana, T; Fujiwara, K; Yoshida, N; Notomi, S; Nakao, S; Hisatomi, T; Miller, J W; Vavvas, DG; Sonoda, KH; Ishibashi, T

2015-01-01

Retinitis pigmentosa (RP) refers to a group of inherited retinal degenerations resulting form rod and cone photoreceptor cell death. The rod cell death due to deleterious genetic mutations has been shown to occur mainly through apoptosis, whereas the mechanisms and features of the secondary cone cell death have not been fully elucidated. Our previous study showed that the cone cell death in rd10 mice, an animal model of RP, involves necrotic features and is partly mediated by the receptor interacting protein kinase. However, the relevancy of necrotic cone cell death in human RP patients remains unknown. In the present study, we showed that dying cone cells in rd10 mice exhibited cellular enlargement, along with necrotic changes such as cellular swelling and mitochondrial rupture. In human eyes, live imaging of cone cells by adaptive optics scanning laser ophthalmoscopy revealed significantly increased percentages of enlarged cone cells in the RP patients compared with the control subjects. The vitreous of the RP patients contained significantly higher levels of high-mobility group box-1, which is released extracellularly associated with necrotic cell death. These findings suggest that necrotic enlargement of cone cells is involved in the process of cone degeneration, and that necrosis may be a novel target to prevent or delay the loss of cone-mediated central vision in RP. PMID:27551484

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

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Fishman, G A; Stone, E M; Grover, S; Derlacki, D J; Haines, H L; Hockey, R R

1999-04-01

To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of

Feeding ecology and morphology of the upper canines in bears (carnivora: Ursidae).

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Christiansen, Per

2008-07-01

The morphology and mechanical strength of the upper canines in all eight extant species of ursids is analyzed, and the findings are discussed in relation to feeding ecology. Ursids have proportionally smaller canines than other large carnivores with a specialized feeding ecology, such as large felids, and the upper canine morphology is both canid-like and felid-like. The giant panda is the most divergent species, and its short, blunt, and cone-like canines appear well adapted for tearing into bamboo. The almost equally herbivorous spectacled bear has a less derived canine morphology. The large canines of the sun bear are divergent from other ursine ursids, and may be an adaptation for tearing open tree trunks in search of insects. Discriminant Analysis is successful in separating ursid species on the basis of canine morphology, but the canines of ursine ursids, and also of the spectacled bear, show greater resemblance among the species than the marked differences in feeding ecology would suggest. This could be in part due to a short evolutionary history, and in part due to canines not having been subjected to much evolutionary selection as has been the case among other large carnivores, such as large felids. Ursids are probably evolutionarily and ecologically successful due to physical size and strength rather than a derived craniodental anatomy. Copyright 2008 Wiley-Liss, Inc.

Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment.

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Schietroma, Cataldo; Parain, Karine; Estivalet, Amrit; Aghaie, Asadollah; Boutet de Monvel, Jacques; Picaud, Serge; Sahel, José-Alain; Perron, Muriel; El-Amraoui, Aziz; Petit, Christine

2017-06-05

Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis , these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23 , encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15-containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. © 2017 Schietroma et al.

Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment

Science.gov (United States)

Parain, Karine; Aghaie, Asadollah; Picaud, Serge

2017-01-01

Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal. PMID:28495838

Limb-Girdle Muscular Dystrophy (LGMD)

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Relationship between the maxillary transverse dimension and palatally displaced canines: A cone-beam computed tomographic study.

Science.gov (United States)

Hong, Wei-Hsin; Radfar, Rebecca; Chung, Chun-Hsi

2015-05-01

To examine the relationship between palatally displaced maxillary canines (PDC) and the maxillary transverse dimension using cone-beam computed tomography (CBCT). Thirty-three patients (11 males and 22 females, mean age 18.2 years) with PDC were matched to 66 patients (22 males and 44 females, mean age 18.1 years) without PDC (control) by gender, age, and posterior occlusion. A CBCT image was taken on all the patients prior to any orthodontic treatment. For each patient the maxillary basal bone widths and interdental widths at the maxillary first molars and first and second premolars were measured on axial and coronal sections of CBCT images. In addition, the presence of permanent tooth agenesis and the widths of maxillary incisors were recorded. Similar maxillary transverse dimensions, both skeletally and dentally, were found between the PDC and control groups. In the PDC group, the number of patients with permanent tooth agenesis was six times higher than in the control group. In addition, the maxillary lateral incisors on PDC-affected sides were smaller than those of control group (P transverse dimension, both skeletally and dentally, had no effect on the occurrence of PDC. The higher prevalence of permanent tooth agenesis was found in the PDC group. Moreover, the mean mesiodistal width of maxillary lateral incisors in the PDC group was significantly smaller than in the control group (P < .05).

Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes.

Science.gov (United States)

Fu, Jinling; Nagashima, Mikiko; Guo, Chuanyu; Raymond, Pamela A; Wei, Xiangyun

2018-01-01

Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion. We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts. Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors. These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.

Canine Models of Duchenne Muscular Dystrophy and Their Use in Therapeutic Strategies

Science.gov (United States)

Kornegay, Joe N.; Bogan, Janet R.; Bogan, Daniel J.; Childers, Martin K.; Li, Juan; Nghiem, Peter; Detwiler, David A.; Larsen, C. Aaron; Grange, Robert W.; Bhavaraju-Sanka, Ratna K.; Tou, Sandra; Keene, Bruce P.; Howard, James F.; Wang, Jiahui; Fan, Zheng; Schatzberg, Scott J.; Styner, Martin A.; Flanigan, Kevin M.; Xiao, Xiao; Hoffman, Eric P.

2013-01-01

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. We and others have developed various phenotypic tests to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. While some of these studies have largely provided general proof-of-concept for the treatment under study, others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. While confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified. PMID:22218699

Increased expression of MERTK is associated with a unique form of canine retinopathy.

Directory of Open Access Journals (Sweden)

Saija J Ahonen

Full Text Available Progressive retinal degenerations are among the most common causes of blindness both in human and in dogs. Canine progressive retinal atrophy (PRA resembles human retinitis pigmentosa (RP and is typically characterized by a progressive loss of rod photoreceptors followed by a loss of cone function. The disease gradually progress from the loss of night and day vision to a complete blindness. We have recently described a unique form of retinopathy characterized by the multifocal gray/brown discoloration and thinning of the retina in the Swedish Vallhund (SV breed. We aimed to identify the genetic cause by performing a genome wide association analysis in a cohort of 18 affected and 10 healthy control dogs using Illumina's canine 22k SNP array. We mapped the disease to canine chromosome 17 (p = 7.7×10(-5 and found a 6.1 Mb shared homozygous region in the affected dogs. A combined analysis of the GWAS and replication data with additional 60 dogs confirmed the association (p = 4.3×10(-8, OR = 11.2 for homozygosity. A targeted resequencing of the entire associated region in four cases and four controls with opposite risk haplotypes identified several variants in the coding region of functional candidate genes, such as a known retinopathy gene, MERTK. However, none of the identified coding variants followed a compelling case- or breed-specific segregation pattern. The expression analyses of four candidate genes in the region, MERTK, NPHP1, ANAPC1 and KRCC1, revealed specific upregulation of MERTK in the retina of the affected dogs. Collectively, these results indicate that the retinopathy is associated with overexpression of MERTK, however further investigation is needed to discover the regulatory mutation for the better understanding of the disease pathogenesis. Our study establishes a novel gain-of-function model for the MERTK biology and provides a therapy model for retinopathy MERTK inhibitors. Meanwhile, a marker-based genetic

Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

OpenAIRE

Ma, Hongwei; Thapa, Arjun; Morris, Lynsie; Redmond, T. Michael; Baehr, Wolfgang; Ding, Xi-Qin

2014-01-01

Photoreceptors degenerate in a wide array of hereditary retinal diseases and age-related macular degeneration. There is currently no treatment available for retinal degenerations. While outnumbered roughly 20:1 by rods in the human retina, it is the cones that mediate color vision and visual acuity, and their survival is critical for vision. In this communication, we investigate whether thyroid hormone (TH) signaling affects cone viability in retinal degeneration mouse models. TH signaling is...

Loss and gain of cone types in vertebrate ciliary photoreceptor evolution.

Science.gov (United States)

Musser, Jacob M; Arendt, Detlev

2017-11-01

Ciliary photoreceptors are a diverse cell type family that comprises the rods and cones of the retina and other related cell types such as pineal photoreceptors. Ciliary photoreceptor evolution has been dynamic during vertebrate evolution with numerous gains and losses of opsin and phototransduction genes, and changes in their expression. For example, early mammals lost all but two cone opsins, indicating loss of cone receptor types in response to nocturnal lifestyle. Our review focuses on the comparison of specifying transcription factors and cell type-specific transcriptome data in vertebrate retinae to build and test hypotheses on ciliary photoreceptor evolution. Regarding cones, recent data reveal that a combination of factors specific for long-wavelength sensitive opsin (Lws)- cones in non-mammalian vertebrates (Thrb and Rxrg) is found across all differentiating cone photoreceptors in mice. This suggests that mammalian ancestors lost all but one ancestral cone type, the Lws-cone. We test this hypothesis by a correlation analysis of cone transcriptomes in mouse and chick, and find that, indeed, transcriptomes of all mouse cones are most highly correlated to avian Lws-cones. These findings underscore the importance of specifying transcription factors in tracking cell type evolution, and shed new light on the mechanisms of cell type loss and gain in retina evolution. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Histopathologic Evolution of Cardiomyopathy in a Canine Model of Duchenne Muscular Dystrophy

Directory of Open Access Journals (Sweden)

Lygia M.M. Malvestio

2015-07-01

Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked disorder characterized for mutation in dystrophin gene and manifested by progressive degeneration and necrosis of skeletal and cardiac muscle with replacement leading to generalized muscular weakness and atrophy. The dog Golden Retriever Muscular Dystrophy (GRMD is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. The objective of this study was to evaluate the pathological progression of myocardial lesions from GRMD dogs in different ages in order to clarify the pathogenesis of Duchenne´s cardiomyopathy. Fragments of left and right ventricle and interventricular septum, from 18 GRMD dogs between 6 to 51 months were collected, fixed, dehydrated, clarified, and finally embedded in paraffin. Five micrometer thick serial sections were obtained and stained with Hematoxylin-Eosin (HE, Picrosirius red, and Von Kossa. Histological analyses were performed at the light microscopy. Myocardial lesions were observed in all GRMD dogs and the sequence of cardiac lesion classified according to according to the age included: abnormal calcium accumulation, myofibrillar necrosis, proliferation of granulation tissue, endomysial and perimysial fibrosis, and finally myocardial fatty infiltration. Interestingly, several Anitschkow cells, the hallmark of rheumatic carditis, were detected in inflammatory infiltrate present at granulation tissue. Our results demonstrate the sequence of cardiac lesions that determine the cardiomyopathy in Golden Retriever dogs affected by DMD and exhibit, for the first time, the Anitschkow cells in the histological findings of this cardiomyopathy. These results are relevant for to clarify the pathogenesis of cardiomyopathy in dogs and humans affected by DMD.

Diaphragm remodeling and compensatory respiratory mechanics in a canine model of Duchenne muscular dystrophy.

Science.gov (United States)

Mead, A F; Petrov, M; Malik, A S; Mitchell, M A; Childers, M K; Bogan, J R; Seidner, G; Kornegay, J N; Stedman, H H

2014-04-01

Ventilatory insufficiency remains the leading cause of death and late stage morbidity in Duchenne muscular dystrophy (DMD). To address critical gaps in our knowledge of the pathobiology of respiratory functional decline, we used an integrative approach to study respiratory mechanics in a translational model of DMD. In studies of individual dogs with the Golden Retriever muscular dystrophy (GRMD) mutation, we found evidence of rapidly progressive loss of ventilatory capacity in association with dramatic morphometric remodeling of the diaphragm. Within the first year of life, the mechanics of breathing at rest, and especially during pharmacological stimulation of respiratory control pathways in the carotid bodies, shift such that the primary role of the diaphragm becomes the passive elastic storage of energy transferred from abdominal wall muscles, thereby permitting the expiratory musculature to share in the generation of inspiratory pressure and flow. In the diaphragm, this physiological shift is associated with the loss of sarcomeres in series (∼ 60%) and an increase in muscle stiffness (∼ 900%) compared with those of the nondystrophic diaphragm, as studied during perfusion ex vivo. In addition to providing much needed endpoint measures for assessing the efficacy of therapeutics, we expect these findings to be a starting point for a more precise understanding of respiratory failure in DMD.

Feasibility of using cone penetrometer truck (CPT) to install time domain reflectometry (TDR) and fiber optic slope failure detectors in pavement structures.

Science.gov (United States)

2011-02-01

A new method of cable installation using a heavy-duty Cone Penetration Test : (CPT) truck was developed and practiced successfully in this study. The coaxial and fiber : optic cables were pushed along with the cone rods by the hydraulic system integr...

ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

Science.gov (United States)

Nair, Archana A; Marmor, Michael F

2017-06-01

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.

Science.gov (United States)

Briggs, C E; Rucinski, D; Rosenfeld, P J; Hirose, T; Berson, E L; Dryja, T P

2001-09-01

To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD). One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified. The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes. This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.

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)

The Study of Factors Influencing on Orthodontic Treatment Difficulty of Impacted Maxillary Canine with Cone Beam Computed Tomography

Directory of Open Access Journals (Sweden)

A.F. Miresmaeili

2012-10-01

Full Text Available Introduction & Objective: Maxillary canines are esthetically and functionally important, but patients with impacted maxillary canines are perceived to be more difficult and time-consuming to treat than the average orthodontic patient. The aim of this study was to define orthodontic Treatment Difficulty Index (TDI of impacted maxillary canine with CBCT according to experts' opinions.Materials & Methods: In this cross sectional study, nine variables in CBCT of thirty six consecutive patients with 50 impacted maxillary canines were measured using Dolphin 3D. The related 3D and 2D pictures and the measured data were uploaded on a website. Ten orthodontists were asked to judge the difficulty of bringing the impacted canine to occlusal plane from 1 to 10 (1 = easy, 10 = extremely difficult.Then, they were also asked to evaluate the effect of each variable on treatment from 1 to 5 (1= very low, 5= very high. Random effect linear regression was used in exploration stage and then simple linear regression was used for the application of the model.Results: The patients mean age was 19.08 ± 5.8 years. Mean clinical experience of examiners was 22.7 ±12.02 years. Three variables were deleted at exploration stage and two other in model application stage. Vertical distance to the occlusal plane (P=0.000, overlap in frontal view (P=0.000, angulations of the canine to the occlusal plan (P=0.029, dilacerations (P=0.000, and rotation (P=0.029 had a significant relationship with TDI.Conclusion: Treatment difficulty of impacted maxillary canines could be predicted quantitatively by measuring variables in CBCT.(Sci J Hamadan Univ Med Sci 2012;19(3:30-35

Granular corneal dystrophy Groenouw type I (GrI) and Reis-Bücklers' corneal dystrophy (R-B). One entity?

Science.gov (United States)

Møller, H U

1989-12-01

This paper maintains that Reis-Bücklers' corneal dystrophy and granular corneal dystrophy Groenouw type I are one and the same disease. Included are some of the technically best photographs of Reis-Bücklers' dystrophy found in the literature, and these are compared with photographs from patients with granular corneal dystrophy examined by the author. It is argued that most of the histological and ultrastructural findings on Reis Bücklers' dystrophy described in the literature are either congruent with what is found in granular corneal dystrophy or unspecific.

Effects of ionizing radiation on the light sensing elements of the retina. [Structural and physiological effects of carbon, helium, and neon ions on rods and cones of salamanders and mice

Energy Technology Data Exchange (ETDEWEB)

Malachowski, M.J.

1978-07-01

This investigation was undertaken to quantitate possible morphological and physiological effects of particles of high linear energy transfer on the retina, in comparison with x-ray effects. The particles used were accelerated atomic nuclei of helium, carbon, and neon at kinetic energies of several hundred MeV/nucleon. For morphological studies, scanning and transmission electron microscopy and light microscopy were used. Physiological studies consisted of autoradiographic data of the rate of incorporation of labeled protein in the structures (opsin) of the outer segment of visual cells. Structural changes were found in the nuclei, as well as the inner and outer segments of visual cells, rods and cones. At a low dose of 10 rad, x rays and helium had no statistically significant morphological effects, but carbon and neon beams did cause significant degeneration of individual cells, pointing to the existence of a linear dose--effect relationship. At high doses of several hundred rads, a Pathologic Index determined the relative biological effectiveness of neon against alpha particles to have a value of greater than 6. The severity of effects per particle increased with atomic number. Labeling studies demonstrated a decreased rate of incorporation of labeled proteins in the structural organization of the outer segments of visual rods. The rate of self-renewal of visual rod discs was punctuated by irradiation and the structures themselves were depleted of amino acids. A model of rod discs (metabolic and catabolic) was postulated for correlated early and late effects to high and low doses.

The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy

NARCIS (Netherlands)

de Visser, M.; de Voogt, W. G.; la Rivière, G. V.

1992-01-01

We report a study, assessing involvement of the heart in 33 familial cases of Becker muscular dystrophy (BMD), 31 familiar cases of facioscapulohumeral (FSH) dystrophy, and 27 familial cases of Bethlem myopathy. In the patients with BMD, correlations of myocardial involvement with age and extent of

Multiple cone pathways are involved in photic regulation of retinal dopamine.

Science.gov (United States)

Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

2016-06-30

Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

Rhabdomyolysis featuring muscular dystrophies.

Science.gov (United States)

Lahoria, Rajat; Milone, Margherita

2016-02-15

Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18 years (range, 2-47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2 years. Fukutin-related protein (FKRP) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200 IU/L; range, 600-3600). Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

Self-cleaning threaded rod spinneret for high-efficiency needleless electrospinning

Science.gov (United States)

Zheng, Gaofeng; Jiang, Jiaxin; Wang, Xiang; Li, Wenwang; Zhong, Weizheng; Guo, Shumin

2018-07-01

High-efficiency production of nanofibers is the key to the application of electrospinning technology. This work focuses on multi-jet electrospinning, in which a threaded rod electrode is utilized as the needless spinneret to achieve high-efficiency production of nanofibers. A slipper block, which fits into and moves through the threaded rod, is designed to transfer polymer solution evenly to the surface of the rod spinneret. The relative motion between the slipper block and the threaded rod electrode promotes the instable fluctuation of the solution surface, thus the rotation of threaded rod electrode decreases the critical voltage for the initial multi-jet ejection and the diameter of nanofibers. The residual solution on the surface of threaded rod is cleaned up by the moving slipper block, showing a great self-cleaning ability, which ensures the stable multi-jet ejection and increases the productivity of nanofibers. Each thread of the threaded rod electrode serves as an independent spinneret, which enhances the electric field strength and constrains the position of the Taylor cone, resulting in high productivity of uniform nanofibers. The diameter of nanofibers decreases with the increase of threaded rod rotation speed, and the productivity increases with the solution flow rate. The rotation of electrode provides an excess force for the ejection of charged jets, which also contributes to the high-efficiency production of nanofibers. The maximum productivity of nanofibers from the threaded rod spinneret is 5-6 g/h, about 250-300 times as high as that from the single-needle spinneret. The self-cleaning threaded rod spinneret is an effective way to realize continuous multi-jet electrospinning, which promotes industrial applications of uniform nanofibrous membrane.

Genetics Home Reference: Fukuyama congenital muscular dystrophy

Science.gov (United States)

... with mental retardation Muscular dystrophy, congenital, Fukuyama type Muscular dystrophy, congenital, with central nervous system involvement Polymicrogyria with muscular dystrophy Related Information How ...

Orocaecal transit time in Duchenne muscular dystrophy.

OpenAIRE

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

Retinitis pigmentosa

Directory of Open Access Journals (Sweden)

Hamel Christian

2006-10-01

Full Text Available Abstract Retinitis pigmentosa (RP is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms. Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema, and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis.

Progressive rod-cone degeneration (PRCD) in selected dog breeds and variability in its phenotypic expression

Czech Academy of Sciences Publication Activity Database

Dostál, Jaromír; Hrdlicová, Anna; Horák, Pavel

2011-01-01

Roč. 56, č. 5 (2011), s. 243-247 ISSN 0375-8427 Institutional research plan: CEZ:AV0Z50450515 Keywords : canine * retinitis pigmentosa * autosomal Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.748, year: 2011

Genetics Home Reference: Duchenne and Becker muscular dystrophy

Science.gov (United States)

... Conditions Duchenne and Becker muscular dystrophy Duchenne and Becker muscular dystrophy Printable PDF Open All Close All Enable Javascript ... dystrophy occur almost exclusively in males. Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused ...

Achondroplasia and Macular Coloboma.

Science.gov (United States)

Ahoor, M H; Amizadeh, Y; Sorkhabi, R

2015-01-01

Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

Science.gov (United States)

Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

2017-02-10

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment.

Directory of Open Access Journals (Sweden)

Naoto Tanaka

Full Text Available Cyclic nucleotide-gated (CNG ion channels are key mediators underlying signal transduction in retinal and olfactory receptors. Genetic defects in CNGA3 and CNGB3, encoding two structurally related subunits of cone CNG channels, lead to achromatopsia (ACHM. ACHM is a congenital, autosomal recessive retinal disorder that manifests by cone photoreceptor dysfunction, severely reduced visual acuity, impaired or complete color blindness and photophobia. Here, we report the first canine models for CNGA3-associated channelopathy caused by R424W or V644del mutations in the canine CNGA3 ortholog that accurately mimic the clinical and molecular features of human CNGA3-associated ACHM. These two spontaneous mutations exposed CNGA3 residues essential for the preservation of channel function and biogenesis. The CNGA3-R424W results in complete loss of cone function in vivo and channel activity confirmed by in vitro electrophysiology. Structural modeling and molecular dynamics (MD simulations revealed R424-E306 salt bridge formation and its disruption with the R424W mutant. Reversal of charges in a CNGA3-R424E-E306R double mutant channel rescued cGMP-activated currents uncovering new insights into channel gating. The CNGA3-V644del affects the C-terminal leucine zipper (CLZ domain destabilizing intersubunit interactions of the coiled-coil complex in the MD simulations; the in vitro experiments showed incompetent trimeric CNGA3 subunit assembly consistent with abnormal biogenesis of in vivo channels. These newly characterized large animal models not only provide a valuable system for studying cone-specific CNG channel function in health and disease, but also represent prime candidates for proof-of-concept studies of CNGA3 gene replacement therapy for ACHM patients.

How far is the root apex of a unilateral impacted canine from the root apices' arch form?

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Kim, Sung-Hun; Kim, You-Min; Oh, Sewoong; Kim, Seong-Sik; Park, Soo-Byung; Son, Woo-Sung; Kim, Yong-Il

2017-02-01

The purpose of this study was to determine the arch form of the root apices of normally erupting teeth and then determine the differences in the location of the apex of impacted canines relative to normally erupting canines. In addition, we sought to determine whether the labiopalatal position of the impacted canines influences the position of the apices. The study included 21 patients with unerupted canines that subsequently had a normal eruption, 21 patients with palatally impacted canines, 27 patients with labially impacted canines, and 17 patients with midalveolus impacted canines. Images were obtained using cone beam computed tomography, and the x, y, and z coordinates of the root apices were determined using Ondemand3D software (Cybermed Co., Seoul, Korea). Two-dimensional coordinates were converted from acquired 3-dimensional coordinates via projection on a palatal plane, and the Procrustes method was used to process the converted 2-dimensional coordinates and to draw the arch forms of the root apices. Finally, we measured the extent of root apex deviation from the arch forms of the root apices. Normally erupting canines showed that even though calcifications may be immature, their positions were aligned with a normal arch form. The root apices of the impacted canines were an average of 6.572 mm away from the root apices' arch form, whereas those of the contralateral nonimpacted canines were an average distance of 2.221 mm away, a statistically significant difference. The palatally impacted canines' root apices distribution tended toward the first premolar root apices. Incompletely calcified, unerupted teeth with a subsequent normal eruption showed a normal arch form of the root apices. The root apices of impacted canines were farther from the arch forms than were the nonimpacted canines. Also, the root apices of impacted canines in the palatal area showed distributions different from those of the other impacted canine groups. Copyright © 2017 American

Rayleigh-Love model of longitudinal vibrations of conical and exponential rods: Exact solutions and numerical simulation by the method of lines

CSIR Research Space (South Africa)

Shatalov, M

2011-07-01

Full Text Available of conical surface of the rod is described by equation ( ) ( )pr x k x x kx= ? = , where px is coordinate of the pole of the cone, px x x= ? , then ( ) 2 2S x k xpi= , ( ) 4 4 2pI x k xpi= and equation (2) is rewritten as follows: ( ) ( ) ( ) ( ) ( ) 2... rod in accordance with the classi- cal theory, and 2 k c ? ?? = is the wavenumber of the conical rod which has dimension 1m? . Introducing new dimensionless variable z x?= , considering new function ( ) zV z U ? ? ? = ? ?? ? ( )W z z...

Learning about Duchenne Muscular Dystrophy

Science.gov (United States)

... protein. Often these boys are classified as having Becker muscular dystrophy. Genetic testing (looking at the body's genetic instructions) ... National Library of Medicine Web site Duchenne and Becker muscular dystrophy [ghr.nlm.nih.gov] From Genetics Home Reference ...

A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

Science.gov (United States)

Yamada, Yuka; Kawakami, Michiyuki; Wada, Ayako; Otsuka, Tomoyoshi; Muraoka, Kaori; Liu, Meigen

2018-06-01

Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

Scanning laser densitometry and color perimetry demonstrate reduced photopigment density and sensitivity in two patients with retinal degeneration.

Science.gov (United States)

Tornow, R P; Stilling, R; Zrenner, E

1999-10-01

To test the feasibility of scanning laser densitometry with a modified Rodenstock scanning laser ophthalmoscope (SLO) to measure the rod and cone photopigment distribution in patients with retinal diseases. Scanning laser densitometry was performed using a modified Rodenstock scanning laser ophthalmoscope. The distribution of the photopigments was calculated from dark adapted and bleached images taken with the 514 nm laser of the SLO. This wavelength is absorbed by rod and cone photopigments. Discrimination is possible due to their different spatial distribution. Additionally, to measure retinal sensitivity profiles, dark adapted two color static perimetry with a Tübinger manual perimeter was performed along the horizontal meridian with 1 degree spacing. A patient with retinitis pigmentosa had slightly reduced photopigment density within the central +/- 5 degrees but no detectable photopigment for eccentricities beyond 5 degrees. A patient with cone dystrophy had nearly normal pigment density beyond +/- 5 degrees, but considerably reduced photopigment density within the central +/- 5 degrees. Within the central +/- 5 degrees, the patient with retinitis pigmentosa had normal sensitivity for the red stimulus and reduced sensitivity for the green stimulus. There was no measurable function beyond 7 degrees. The patient with cone dystrophy had normal sensitivity for the green stimulus outside the foveal center and reduced sensitivity for the red stimulus at the foveal center. The results of color perimetry for this patient with a central scotoma were probably influenced by eccentric fixation. Scanning laser densitometry with a modified Rodenstock SLO is a useful method to assess the human photopigment distribution. Densitometry results were confirmed by dark adapted two color static perimetry. Photopigment distribution and retinal sensitivity profiles can be measured with high spatial resolution. This may help to measure exactly the temporal development of retinal

Prevalence of generalized retinal dystrophy in Denmark

DEFF Research Database (Denmark)

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

2014-01-01

of this study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in the Danish population. METHODS: A population-based cross-sectional study with data from the Danish Retinitis Pigmentosa Registry that comprises all patients in Denmark with generalized retinal......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...... and chorioretinal dystrophies from the 19th century to the present. Among 3076 registered cases, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Demographic data on the Danish population were retrieved from Statistics Denmark...

Morphological and ultrastructural evaluation of the golden retriever muscular dystrophy trachea, lungs, and diaphragm muscle.

Science.gov (United States)

Lessa, Thais Borges; de Abreu, Dilayla Kelly; Rodrigues, Márcio Nogueira; Brólio, Marina Pandolphi; Miglino, Maria Angélica; Ambrósio, Carlos Eduardo

2014-11-01

Duchenne muscular dystrophy (DMD) is a genetic disease, characterized by atrophy and muscle weakness. The respiratory failure is a common cause of early death in patients with DMD. Golden retriever muscular dystrophy (GRMD) is a canine model which has been extensively used for many advances in therapeutics applications. As the patients with DMD, the GRMD frequently died from cardiac and respiratory failure. Observing the respiratory failure in DMD is one of the major causes of mortality we aimed to describe the morphological and ultrastructural data of trachea, lungs (conductive and respiratory portion of the system), and diaphragm muscle using histological and ultrastructural analysis. The diaphragm muscle showed discontinuous fibers architecture, with different diameter; a robust perimysium inflammatory infiltrate and some muscle cells displayed central nuclei. GRMD trachea and lungs presented collagen fibers and in addition, the GRMD lungs showed higher of levels collagen fibers that could limit the alveolar ducts and alveoli distension. Therefore, the most features observed were the collagen areas and fibrosis. We suggested in this study that the collagen remodeling in the trachea, lungs, and diaphragm muscle may increase fibrosis and affect the trachea, lungs, and diaphragm muscle function that can be a major cause of respiratory failure that occur in patients with DMD. © 2014 Wiley Periodicals, Inc.

The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

Science.gov (United States)

Wang, Feng-Yu; Fu, Wen-Chun; Wang, I-Li; Yan, Hong Young; Wang, Tzi-Yuan

2014-01-01

Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2) revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292) and four putative (S124, V189, V286, I290) tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

Root length and alveolar bone level of impacted canines and adjacent teeth after orthodontic traction: a long-term evaluation

Science.gov (United States)

da SILVA, Aldir Cordeiro; CAPISTRANO, Anderson; de ALMEIDA-PEDRIN, Renata Rodrigues; CARDOSO, Maurício de Almeida; CONTI, Ana Cláudia de Castro Ferreira; CAPELOZZA, Leopoldino

2017-01-01

Abstract Objective The aim of this retrospective study was to evaluate the long-term effects of orthodontic traction on root length and alveolar bone level in impacted canines and adjacent teeth. Material and Methods Sample consisted of 16 patients (nine males and seven females), mean initial age 11 years and 8 months presenting with unilaterally maxillary impacted canines, palatally displaced, treated with the same surgical and orthodontic approach. Teeth from the impacted-canine side were assigned as Group I (GI), and contralateral teeth as control, Group II (GII). The mean age of patients at the end of orthodontic treatment was 14 years and 2 months and the mean post-treatment time was 5 years and 11 months. Both contralateral erupted maxillary canines and adjacent teeth served as control. Root length and alveolar bone level (buccal and palatal) were evaluated on cone-beam computed tomography (CBCT) images. The comparison of root length and alveolar bone level changes between groups were assessed by applying paired t-test, at a significance level of 5% (p<0.05). Results There were no statistically significant differences in root length and buccal and palatal bone levels of canines and adjacent teeth among groups. Conclusions Impacted canine treatment by closed-eruption technique associated with canine crown perforation, has a minimal effect on root length and buccal and palatal alveolar bone level in both canine and adjacent teeth, demonstrating that this treatment protocol has a good long-term prognosis. PMID:28198979

Occult Macular Dystrophy

Directory of Open Access Journals (Sweden)

Işıl Sayman Muslubaş

2016-04-01

Full Text Available Occult macular dystrophy is an inherited macular dystrophy characterized by a progressive decline of bilateral visual acuity with normal fundus appearance, fluorescein angiogram and full-field electroretinogram. This case report presents a 20-year-old female patient with bilateral progressive decline of visual acuity for six years. Her visual acuity was 3-4/10 in both eyes. Anterior segment and fundus examination, fluorescein angiogram and full-field electroretinogram were normal. She could read all Ishihara pseudoisochromatic plates. Fundus autofluorescence imaging was normal. There was a mild central hyporeflectance on fundus infrared reflectance imaging in both eyes. Reduced foveal thickness and alterations of the photoreceptor inner and outer segment junction were observed by optical coherence tomography in both eyes. Central scotoma was also found by microperimetry and reduced central response was revealed by multifocal electroretinogram in both eyes. These findings are consistent with the clinical characteristics of occult macular dystrophy

Comparison of panoramic radiography and cone-beam computed tomography for qualitative and quantitative measurements regarding localization of permanent impacted maxillary canines

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Çiğdem Sarıkır

2017-01-01

Full Text Available Objective: The purpose of this retrospective study was to compare the correlation between digital panoramic radiography (DPR and cone-beam computed tomography (CBCT evaluations for localization of impacted permanent maxillary canines (IPMCs and for other qualitative and quantitative parameters. Materials and Method: DPR and CBCT images of 60 patients (17 men and 43 women were examined independently by two observers. Correlations between DPR and CBCT images were evaluated regarding qualitative (bucco-palatal positioning of IPMCs, morphology and presence of root resorption of adjacent permanent lateral incisors, and contact relationship between IPMCs and adjacent permanent lateral incisors and quantitative (angle measurements variables. All evaluations were repeated 1 month later by each observer. Chi-square and t-tests were used for statistical analysis. Kappa statistics were used to assess intra- and interobserver agreement (Cohen’s κ. Results: No correlation was observed for determination of bucco-palatal positioning of IPMCs between DPR and CBCT images (p>0.05. Correlations were observed for other qualitative variables (p<0.05. Differences between DPR and CBCT images were seen for all examined quantitative variables (p<0.01. Intra- and interobserver agreements were substantial to almost-perfect. Conclusion: No significant correlation was found between DPR and CBCT images for determination of bucco-palatal positioning of IPMCs. All quantitative measurements performed on DPR and CBCT images significantly differed from each other.

3-Methylhistidine excretion in myotonic dystrophy

Energy Technology Data Exchange (ETDEWEB)

Griggs, R.C.; Moxley, R.T. III; Forbes, G.B.

1980-12-01

3-Methylhistidine (3-MH) excretion reflects the rate of muscle protein catabolism, since 3-MH occurs almost exclusively in muscle actin and myosin and is not reutilized or catabolized. We studied 3-MH excretion in 9 patients with myotonic dystrophy, 8 normals, and 10 disease controls with Duchenne dystrophy and other disorders. 3-MH excretion was expressed relative to muscle mass as determined by both urinary creatinine and total body potassium (/sup 40/K method). Absolute 3-MH excretion was decreased in myotonic dystrophy patients but was normal when related to muscle mass. The finding of normal 3-MH excretion in myotonic dystrophy suggests that the muscle wasting in this disorder results from impaired anabolic processes rather than accelerated muscle destruction.

3-Methylhistidine excretion in myotonic dystrophy

International Nuclear Information System (INIS)

Griggs, R.C.; Moxley, R.T. III; Forbes, G.B.

1980-01-01

3-Methylhistidine (3-MH) excretion reflects the rate of muscle protein catabolism, since 3-MH occurs almost exclusively in muscle actin and myosin and is not reutilized or catabolized. We studied 3-MH excretion in 9 patients with myotonic dystrophy, 8 normals, and 10 disease controls with Duchenne dystrophy and other disorders. 3-MH excretion was expressed relative to muscle mass as determined by both urinary creatinine and total body potassium ( 40 K method). Absolute 3-MH excretion was decreased in myotonic dystrophy patients but was normal when related to muscle mass. The finding of normal 3-MH excretion in myotonic dystrophy suggests that the muscle wasting in this disorder results from impaired anabolic processes rather than accelerated muscle destruction

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...

Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy.

Science.gov (United States)

Matsuzaka, Yasunari; Kishi, Soichiro; Aoki, Yoshitsugu; Komaki, Hirofumi; Oya, Yasushi; Takeda, Shin-Ichi; Hashido, Kazuo

2014-11-01

Muscular dystrophies are a clinically and genetically heterogeneous group of inherited myogenic disorders. In clinical tests for these diseases, creatine kinase (CK) is generally used as diagnostic blood-based biomarker. However, because CK levels can be altered by various other factors, such as vigorous exercise, etc., false positive is observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dystrophy (DMD). However, no alternative biomarkers have been established for the other muscular dystrophies. We, therefore, evaluated whether these miR-1, miR-133a, and miR-206 can be used as powerful biomarkers using the serum from muscular dystrophy patients including DMD, myotonic dystrophy 1 (DM1), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), becker muscular dystrophy (BMD), and distal myopathy with rimmed vacuoles (DMRV) by qualitative polymerase chain reaction (PCR) amplification assay. Statistical analysis indicated that all these miRNA levels in serum represented no significant differences between all muscle disorders examined in this study and controls by Bonferroni correction. However, some of these indicated significant differences without correction for testing multiple diseases (P < 0.05). The median values of miR-1 levels in the serum of patients with LGMD, FSHD, and BMD were approximately 5.5, 3.3 and 1.7 compared to that in controls, 0.68, respectively. Similarly, those of miR-133a and miR-206 levels in the serum of BMD patients were about 2.5 and 2.1 compared to those in controls, 1.03 and 1.32, respectively. Taken together, our data demonstrate that levels of miR-1, miR-133a, and miR-206 in serum of BMD and miR-1 in sera of LGMD and FSHD patients showed no significant differences compared with those of controls by Bonferroni correction. However, the results might need increase in sample sizes to evaluate these three miRNAs as

[Encopresis revealing myotonic dystrophy in 2 children].

Science.gov (United States)

Avez-Couturier, J; Michaud, L; Cuisset, J-M; Lamblin, M-D; Dolhem, P; Turck, D; Vallée, L; Gottrand, F

2009-05-01

Gastrointestinal symptoms are very frequent in myotonic dystrophy but largely unrecognized. They can be the revealing factors of the disease. We report 2 cases of 10 and 17-year-old children with persistent encopresis starting at the age of 3 and 5 years in spite of laxative treatment. Neurological examination and anorectal manometry provided the diagnosis of myotonic dystrophy. Procainamide treatment was introduced and the digestive symptoms improved. Any child with encopresis should have complete evaluation to rule out the diagnosis of myotonic dystrophy and physicians should look for upper and/or lower gastrointestinal symptoms in every patient with myotonic dystrophy.

Process and equipment for locating defective fuel rods of a reactor fuel element

International Nuclear Information System (INIS)

Jester, A.; Honig, H.

1977-01-01

By this equipment, well-known processes for determining defective fuel rods of a reactor fuel element are improved in such a fashion that defective fuel rods can be located individually, so that it is possible to replace them. The equipment consists of a cylindrical test vessel open above, which accommodates the element to be tested, so that an annular space is left between the latter's external circumference and the wall of the vessel, and so that the fuel rods project above the vessel. A bell in the shape of a frustrum of a cone is inverted over the test vessel, which has an infra-red measuring equipment at a certain distance above the tops of the fuel rods. The fuel element to be tested together with the test vessel and hood are immersed in a basin full of water, which displaces water by means of gas from the hood. The post-shutdown heat increases the temperature in the water space of the test vessel, which is stabilised at 100 0 C. In each defective fuel rod the water which has penetrated the defective fuel rod previously, or does so now, starts to boil. The steam rising in the fuel rod raises the temperature of the defective fuel rod compared to all the sound ones. The subsequent measurement easily determines this. Where one can expect interference with the measurement by appreciable amounts of gamma rays, the measuring equipment is removed from the path of radiation by mirror deflection in a suitably shaped measuring hood. (FW) [de

Infrastructure for Clinical Trials in Duchenne Dystrophy

Science.gov (United States)

2010-09-13

A Zimmerman, T Duong, J Florence and the CINRG Investigators. Pulmonary Function Characteristics of Boys with Duchenne and Becker Muscular Dystrophy ...designated CINRG site staff 1. Has the participant been clinically diagnosed with Limb-Girdle or Becker muscular dystrophy ? LGMD BMD 2. Was...Number: W81XWH-09-1-0592 TITLE: CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy PRINCIPAL INVESTIGATOR: Avital Cnaan, PhD

The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

Directory of Open Access Journals (Sweden)

Feng-Yu Wang

Full Text Available Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2 revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292 and four putative (S124, V189, V286, I290 tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

Rapid Retinal Release from a Cone Visual Pigment Following Photoactivation*

Science.gov (United States)

Chen, Min-Hsuan; Kuemmel, Colleen; Birge, Robert R.; Knox, Barry E.

2012-01-01

As part of the visual cycle, the retinal chromophore in both rod and cone visual pigments undergoes reversible Schiff base hydrolysis and dissociation following photobleaching. We characterized light-activated retinal release from a short-wavelength sensitive cone pigment (VCOP) in 0.1% dodecyl maltoside using fluorescence spectroscopy. The half-time (t1/2) of retinal release from VCOP was 7.1 s, 250-fold faster than rhodopsin. VCOP exhibited pH-dependent release kinetics, with the t1/2 decreasing from 23 s to 4 s with pH 4.1 to 8, respectively. However, the Arrhenius activation energy (Ea) for VCOP derived from kinetic measurements between 4° and 20°C was 17.4 kcal/mol, similar to 18.5 kcal/mol for rhodopsin. There was a small kinetic isotope (D2O) effect in VCOP, but less than that observed in rhodopsin. Mutation of the primary Schiff base counterion (VCOPD108A) produced a pigment with an unprotonated chromophore (⌊max = 360 nm) and dramatically slowed (t1/2 ~ 6.8 min) light-dependent retinal release. Using homology modeling, a VCOP mutant with two substitutions (S85D/ D108A) was designed to move the counterion one alpha helical turn into the transmembrane region from the native position. This double mutant had a UV-visible absorption spectrum consistent with a protonated Schiff base (⌊max = 420 nm). Moreover, VCOPS85D/D108A mutant had retinal release kinetics (t1/2 = 7 s) and Ea (18 kcal/mol) similar to the native pigment exhibiting no pH-dependence. By contrast, the single mutant VCOPS85D had a ~3-fold decrease in retinal release rate compared to the native pigment. Photoactivated VCOPD108A had kinetics comparable to a rhodopsin counterion mutant, RhoE113Q, both requiring hydroxylamine to fully release retinal. These results demonstrate that the primary counterion of cone visual pigments is necessary for efficient Schiff base hydrolysis. We discuss how the large differences in retinal release rates between rod and cone visual pigments arise, not from

Muscular dystrophy

Science.gov (United States)

... are no known cures for the various muscular dystrophies. The goal of treatment is to control symptoms. Physical therapy may help maintain muscle strength and function. Leg braces and a wheelchair ...

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.

Emerging strategies for cell and gene therapy of the muscular dystrophies

OpenAIRE

Muir, Lindsey A.; Chamberlain, Jeffrey S.

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 ...

Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.

Science.gov (United States)

Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J; Davis, Brian W; Kornegay, Joe N

2016-08-22

Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.

Cone beam computed tomography and intraoral radiography for diagnosis of dental abnormalities in dogs and cats

International Nuclear Information System (INIS)

Roza, Marcello R.; Fioravanti, Maria Clorinda S.; Silva, Luiz Antonio F.; Barriviera, Mauricio; Januario, Alessandro L.; Bezerra, Ana Cristina B.

2011-01-01

The development of veterinary dentistry has substantially improved the ability to diagnose canine and feline dental abnormalities. Consequently, examinations previously performed only on humans are now available for small animals, thus improving the diagnostic quality. This has increased the need for technical qualification of veterinary professionals and increased technological investments. This study evaluated the use of cone beam computed tomography and intraoral radiography as complementary exams for diagnosing dental abnormalities in dogs and cats. Cone beam computed tomography was provided faster image acquisition with high image quality, was associated with low ionizing radiation levels, enabled image editing, and reduced the exam duration. Our results showed that radiography was an effective method for dental radiographic examination with low cost and fast execution times, and can be performed during surgical procedures

Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function.

Science.gov (United States)

Nishiguchi, Koji M; Friedman, James S; Sandberg, Michael A; Swaroop, Anand; Berson, Eliot L; Dryja, Thaddeus P

2004-12-21

Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL.

Evaluation of the morphology of the canalis sinuous using cone-beam computed tomography in patients with maxillary impacted canines

Energy Technology Data Exchange (ETDEWEB)

Gurler, Gokhan; Delilbsi, Cagri; Ogut, Emine Esen [Istanbul Medipol University School of Dentistry, Istanbul (Turkmenistan); Sakul, Ufuk [Dept. of Anatomy, Istanbul Medipol University School of Medicine, Istanbul (Turkmenistan)

2017-06-15

The nasopalatine canal is a well-known, important anatomical structure in the anterior maxilla, but this region contains many accessory canals. The canalis sinuosus (CS) is one of these canals; it contains the anterior superior alveolar nerve, along with veins and arteries. The purpose of this study was to evaluate the CS using conebeam computed tomography (CBCT) in patients with maxillary impacted canines. A total of 111 patients admitted to the Istanbul Medipol University School of Dentistry for the exposure, orthodontic treatment, and/or extraction of an impacted canine were included in this study. CBCT images were obtained for these patients under standard conditions. Axial, coronal, and sagittal sections were evaluated to assess the prevalence of CS, the direction and diameter of the canal, its relation with the impacted canine, and its distance from the alveolar crest. Further, possible correlations with patient gender and age were analyzed. The CS could be detected bilaterally in all the evaluated tomography images. The mean canal diameter was significantly larger in males than in females (P=.001). The CS ran significantly closer to the impacted canine when the canal was located horizontally (P=.03). Variations of the canal, such as accessory canals, were identified in 6 patients. CS is an anatomical entity that may resemble periapical lesions and other anatomical structures. Evaluation with CBCT prior to surgical procedures in the anterior maxilla will help to prevent overlooking such anatomical structures and to decrease possible surgical complications.

Evaluation of the morphology of the canalis sinuous using cone-beam computed tomography in patients with maxillary impacted canines

International Nuclear Information System (INIS)

Gurler, Gokhan; Delilbsi, Cagri; Ogut, Emine Esen; Sakul, Ufuk

2017-01-01

The nasopalatine canal is a well-known, important anatomical structure in the anterior maxilla, but this region contains many accessory canals. The canalis sinuosus (CS) is one of these canals; it contains the anterior superior alveolar nerve, along with veins and arteries. The purpose of this study was to evaluate the CS using conebeam computed tomography (CBCT) in patients with maxillary impacted canines. A total of 111 patients admitted to the Istanbul Medipol University School of Dentistry for the exposure, orthodontic treatment, and/or extraction of an impacted canine were included in this study. CBCT images were obtained for these patients under standard conditions. Axial, coronal, and sagittal sections were evaluated to assess the prevalence of CS, the direction and diameter of the canal, its relation with the impacted canine, and its distance from the alveolar crest. Further, possible correlations with patient gender and age were analyzed. The CS could be detected bilaterally in all the evaluated tomography images. The mean canal diameter was significantly larger in males than in females (P=.001). The CS ran significantly closer to the impacted canine when the canal was located horizontally (P=.03). Variations of the canal, such as accessory canals, were identified in 6 patients. CS is an anatomical entity that may resemble periapical lesions and other anatomical structures. Evaluation with CBCT prior to surgical procedures in the anterior maxilla will help to prevent overlooking such anatomical structures and to decrease possible surgical complications

Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

Directory of Open Access Journals (Sweden)

Oriana del Rocío Cruz Guzmán

2012-01-01

Full Text Available Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

Samd7 is a cell type-specific PRC1 component essential for establishing retinal rod photoreceptor identity.

Science.gov (United States)

Omori, Yoshihiro; Kubo, Shun; Kon, Tetsuo; Furuhashi, Mayu; Narita, Hirotaka; Kominami, Taro; Ueno, Akiko; Tsutsumi, Ryotaro; Chaya, Taro; Yamamoto, Haruka; Suetake, Isao; Ueno, Shinji; Koseki, Haruhiko; Nakagawa, Atsushi; Furukawa, Takahisa

2017-09-26

Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells. Samd7- null mutant mice showed ectopic expression of nonrod genes including S-opsin in rod photoreceptor cells and rod photoreceptor cell dysfunction. Samd7 physically interacts with Polyhomeotic homologs (Phc proteins), components of the Polycomb repressive complex 1 (PRC1), and colocalizes with Phc2 and Ring1B in Polycomb bodies. ChIP assays showed a significant decrease of H3K27me3 in the genes up-regulated in the Samd7 -deficient retina, showing that Samd7 deficiency causes the derepression of nonrod gene expression in rod photoreceptor cells. The current study suggests that Samd7 is a cell type-specific PRC1 component epigenetically defining rod photoreceptor cell identity.

The dual rod system of amphibians supports colour discrimination at the absolute visual threshold.

Science.gov (United States)

Yovanovich, Carola A M; Koskela, Sanna M; Nevala, Noora; Kondrashev, Sergei L; Kelber, Almut; Donner, Kristian

2017-04-05

The presence of two spectrally different kinds of rod photoreceptors in amphibians has been hypothesized to enable purely rod-based colour vision at very low light levels. The hypothesis has never been properly tested, so we performed three behavioural experiments at different light intensities with toads ( Bufo ) and frogs ( Rana ) to determine the thresholds for colour discrimination. The thresholds of toads were different in mate choice and prey-catching tasks, suggesting that the differential sensitivities of different spectral cone types as well as task-specific factors set limits for the use of colour in these behavioural contexts. In neither task was there any indication of rod-based colour discrimination. By contrast, frogs performing phototactic jumping were able to distinguish blue from green light down to the absolute visual threshold, where vision relies only on rod signals. The remarkable sensitivity of this mechanism comparing signals from the two spectrally different rod types approaches theoretical limits set by photon fluctuations and intrinsic noise. Together, the results indicate that different pathways are involved in processing colour cues depending on the ecological relevance of this information for each task.This article is part of the themed issue 'Vision in dim light'. © 2017 The Authors.

Prominent Optic Disc Featured in Inherited Retinopathy.

Science.gov (United States)

Todorova, M G; Bojinova, R I; Valmaggia, C; Schorderet, D F

2017-04-01

Background We investigated the relationship between prominent optic disc (POD) and inherited retinal dystrophy (IRD). Patients and Methods A cross-sectional consecutive study was performed in 10 children and 11 adults of 7 non-related families. We performed clinical phenotyping, including a detailed examination, fundus autofluorescence, and colour fundus and OCT imaging. Genetic testing was subsequently performed for all family members presenting retinal pathology. Results In 4 members of a 3-generation family, hyperfluorescent deposits on the surface of POD were related to a p.(L224M) heterozygous mutation in BEST1 . In the second family, one member presented deposits located on the surface on hyperaemic OD and a compound p.(R141H);(A195V) mutation in BEST1 . In the third family, POD was observed in father and child with early onset cone-rod dystrophy and a novel autosomal recessive p.(W31*) homozygous mutation in ABCA4 . In the fourth family, POD with "mulberry-like" deposits and attenuated vessels were observed in a 7-year old girl, with a mutation in USH1A , and with early onset rod-cone dystrophy, associated with hearing loss. In the fifth family, blurry OD with tortuous vessels was observed in 4 consanguineous female carriers and a hemizygous boy with a p.(R200H) mutation in the X-linked retinoschisis RS1 . In the sixth family, a mother and her son were both affected with POD and attenuated peripapillary vessels, and presented with a p.(Y836C) heterozygous mutation in TOPORS , thus confirming autosomal dominant RP. In the seventh family, in 3 family members with POD, compound p.(L541P;A1038 V);(G1961E) mutations in ABCA4 confirmed the diagnosis of Stargardt disease. Conclusions A variety of OD findings are found in a genetically heterogeneous group of IRDs. In the presence of POD, an inherited progressive photoreceptor disease should be ruled out. Georg Thieme Verlag KG Stuttgart · New York.

Muscular Dystrophy

Science.gov (United States)

... Surveillance Tracking and Research Network , known as MD STAR net . Learn more about CDC’s other muscular dystrophy ... for Disease Control and Prevention Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

Effect of clear aligner therapy on the buccolingual inclination of mandibular canines and the intercanine distance.

Science.gov (United States)

Grünheid, Thorsten; Gaalaas, Sara; Hamdan, Hani; Larson, Brent E

2016-01-01

To compare the changes in buccolinugal inclination of mandibular canines and intercanine distance in patients treated with clear aligners to those treated with preadjusted edgewise appliances. The buccolingual inclination of mandibular canines and the intercanine distance were measured on pre- and posttreatment cone-beam computed tomograms of 30 patients who had been treated with clear aligners and 30 patients who had been treated with fixed preadjusted edgewise appliances. Differences between the aligner and fixed appliance groups and between pre- and posttreatment measurements were tested for statistical significance. In both groups, most of the mandibular canines had positive buccolingual inclinations (ie, their crowns were positioned lateral to their roots) both before and after treatment. While there was no difference between the groups pretreatment, the posttreatment buccolingual inclination was significantly greater in the aligner group. In the fixed appliance group, the canines became more upright with treatment, while the buccolingual inclination did not change significantly in the clear aligner group. The intercanine distance did not differ between the groups either before or after treatment. However, it increased significantly over the course of treatment in the aligner group, whereas it did not change significantly in the fixed appliance group. Orthodontic treatment with clear aligners tends to increase the mandibular intercanine distance with little change in inclination in contrast to treatment with fixed appliances, which leaves the intercanine distance unchanged but leads to more upright mandibular canines.

Radiographic features of Golden Retriever muscular dystrophy.

Science.gov (United States)

Brumitt, Jason W; Essman, Stephanie C; Kornegay, Joe N; Graham, John P; Weber, William J; Berry, Clifford R

2006-01-01

Golden Retriever muscular dystrophy is an inherited, degenerative myopathy due to the absence of dystrophin and is used as a model of Duchenne muscular dystrophy of young boys. This report describes the radiographic abnormalities of Golden Retriever muscular dystrophy in 26 dogs. The thoracic abnormalities included diaphragmatic asymmetry (18/26), diaphragmatic undulation (18/26), and gastro-esophageal hiatal hernia (6/26). Pelvic abnormalities included narrowing of the body of the ilia (14/19), ventral deviation and curvature of the tuber ischii (14/19), elongation of the obturator foramen with a decrease in opacity of the surrounding bone (12/19), and lateral flaring of the wings of the ilia (12/19). Abdominal abnormalities consisted of hepatomegaly (14/22) and poor serosal detail (12/22). The unique thoracic abnormalities were a consistent finding in affected Golden Retriever muscular dystrophy dogs. The diagnosis of muscular dystrophy should be included in the differential list if the combination of diaphragm undulation and asymmetry, and gastro-esophageal hiatal hernia are identified. These diaphragmatic abnormalities are related to hypertrophy and hyperplasia of the diaphragm. Additionally, the skeletal changes of pelvic tilt, elongation of the pelvis, widening of the obturator foramina and thinning of the ischiatic tables appear to be specific to Golden Retriever muscular dystrophy in dogs. These pelvic abnormalities are most likely secondary to bone remodeling associated with the progressive skeletal myopathy and subsequent contracture/fibrosis.

Control rod

International Nuclear Information System (INIS)

Kawakami, Kazuo; Shimoshige, Takanori; Nishimura, Akira

1979-01-01

Purpose: A control rod has been developed, which provided a plurality of through-holes in the vicinity of the sheath fitting position, in order to flatten burn-up, of fuel rods in positions confronting a control rod. Thereby to facilitate the manufacture of the control rods and prevent fuel rod failures. Constitution: A plurality of through-holes are formed in the vicinity of the sheath fitting position of a central support rod to which a sheath for the control rod is fitted. These through-holes are arranged in the axial direction of the central support rod. Accordingly, burn-up of fuel rods confronting the control rods can be reduced by through-holes and fuel rod failures can be prevented. (Yoshino, Y.)

Translational Research for Muscular Dystrophy

Science.gov (United States)

2012-05-01

muscle dystrophy with abnormal waddling gait at 4 weeks of age. At 10 weeks of age, double mutants exhibit skeletal muscle degeneration, necrosis... dystrophy (MCMD). Homozygous dyW mice are passive, small, and emaciated, and demonstrate partial hindleg weakness and clasping. Their muscles contain...was statistically significant for both single- treatment groups. Figure 4. Effect of GW and AICAR on body mass, muscle mass, and behavioral

What Are the Types of Muscular Dystrophy?

Science.gov (United States)

... muscular dystrophy? There are more than 30 forms of muscular dystrophy (MD), with information on the primary types included in the table below. 1 Duchenne (DMD) What It Is Common Symptoms How It ...

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case definition in surveillance for childhood-onset Duchenne/Becker muscular dystrophy.

Science.gov (United States)

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

2010-09-01

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 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

Clinical aspects, molecular pathomechanisms and management of myotonic dystrophies

OpenAIRE

Meola, G.

2013-01-01

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP....

Mitochondrial disorders in progressive muscular dystrophies

Directory of Open Access Journals (Sweden)

D. A. Kharlamov

2014-01-01

Full Text Available The literature review gives data on the role of mitochondrial disorders in the pathogenesis of different progressive muscular dystrophies. It describes changes in Duchenne, limb-girdle, facial scapulohumeral (Landuzi—Degerina muscular dystrophies. The review is based on both clinical and experimental animal studies. Along with the implication of mitochondria in the pathogenesis of the diseases, it describes muscular dystrophy treatment options compensating for energy disorders and overcoming oxidative stress and mitochondrial dysfunction. Mitochondrial studies in different muscle diseases hand physicians treatment modalities that fail to lead to recovery, but compensate for disorders caused by mutations in the genetic apparatus. 

Computerized tomography in myotonic dystrophy

International Nuclear Information System (INIS)

Gellerich, I.; Mueller, D.; Koch, R.D.

1986-01-01

Besides clinical symptoms, progress and electromyography computerized tomography improves the diagnostics of myotonic dystrophy. Even small changes in muscular structure are detectable and especially the musculus soleus exhibits early and pronounced alterations. By means of density distribution pattern an improved characterization of the disease is possible. Additional information is obtained by cerebral computerized tomography. Atrophy of brain tissue is to be expected in all patients with myotonic dystrophy. (author)

Becker muscular dystrophy: an unusual presentation.

OpenAIRE

Thakker, P B; Sharma, A

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.

One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus, and canine kobuvirus.

Science.gov (United States)

Liu, Dafei; Liu, Fei; Guo, Dongchun; Hu, Xiaoliang; Li, Zhijie; Li, Zhigang; Ma, Jianzhang; Liu, Chunguo

2018-01-23

To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was developed, with detection limits of 10 2.1 TCID 50 for CDV, 10 1.9 TCID 50 for CPV and 10 3 copies for CaKoV. This method did not amplify nonspecific DNA or RNA from other canine viruses. Therefore, the assay provides a sensitive tool for the rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV in dogs.

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)....

Evaluation of the Root and Canal Morphology of Mandibular Permanent Anterior Teeth in an Iranian Population by Cone-Beam Computed Tomography

Directory of Open Access Journals (Sweden)

Mohsen Aminsobhani

2013-01-01

Full Text Available Objective: To evaluate differences in the root and canal configurations of mandibular permanent anterior incisors and canines in an Iranian population by means of Cone Beam CT (CBCT images.Materials and Methods: Four hundred CBCT images of mandibular permanent incisors and canines that met the inclusion criteria were evaluated. Vertucci´s classification was used to evaluate the number of roots, number of root canals, root lengths, root curvatures and canal types.Results: Totally 632 central incisors, 614 lateral incisors and 608 canines were evaluated. The average length of the mandibular central, lateral incisors and canines was 21.3±0.10, 21.9± 0.13 and 25.1± 0.11 mm, respectively. All of the mandibular central and lateral incisors had one root, but the incidence of single-rooted mandibular canines and two-rooted mandibular canines was 96.3% and 4.7%, respectively. The majority of mandibular central, lateral incisors and canines had one canal (72.7%, 70.6% and 71.8%, respectively. Five types of Vertucci canal configurations were seen in the evaluated teeth. Type 1 Vertucci configuration was the most prevalent configuration (72.3%, 70.6% and 71.8% for the central, lateral incisors and canines, respectively, and type 5 Vertucci canal configuration was the least prevalent type seen (3.3%, 3.2% and 2.3% for the central, lateral incisors and canines, respectively. The most frequent root curvatures in these teeth were distally and buccally. No significant difference was seen between male and female patients regarding any of the parameters evaluated in this study (p>0.05.Conclusion: More attention should be given to the detection of additional canals and the recognition of canal curvature in Iranian patients.

Respiratory function in facioscapulohumeral muscular dystrophy 1

NARCIS (Netherlands)

Wohlgemuth, M.; Horlings, G.C.; Kooi, E.L. van der; Gilhuis, H.J.; Hendriks, J.C.M.; Maarel, S.M. van der; Engelen, B.G.M. van; Heijdra, Y.F.; Padberg, G.W.A.M.

2017-01-01

To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory

Genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies.

Science.gov (United States)

Hightower, Rylie M; Alexander, Matthew S

2018-01-01

Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes, including age of loss of ambulation, steroid responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. This review highlights recent findings on genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. Muscle Nerve 57: 6-15, 2018. © 2017 Wiley Periodicals, Inc.

Morphologic imaging in muscular dystrophies and inflammatory myopathies

International Nuclear Information System (INIS)

Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick; Morillon, David; Cotten, Anne; Stojkovic, Tanya

2010-01-01

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.)

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.)

CT findings of muscular dystrophy

International Nuclear Information System (INIS)

Saitoh, Hiroshi

1991-01-01

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)

CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy

Science.gov (United States)

2013-09-01

monitoring visit to monitor this study, the PITT0908 clinical trial, a study on facioscapulohumeral muscular dystrophy (FSHD), and PITT0112 Becker natural...height findings manuscript are currently in working stage and circulating among co-authors for editing. 2.3.6 Becker Muscular Dystrophy – A Natural...participants with Becker muscular dystrophy . The study period is 36 months per patient. This project is primarily funded by the National Institutes of

Cone Algorithm of Spinning Vehicles under Dynamic Coning Environment

Directory of Open Access Journals (Sweden)

Shuang-biao Zhang

2015-01-01

Full Text Available Due to the fact that attitude error of vehicles has an intense trend of divergence when vehicles undergo worsening coning environment, in this paper, the model of dynamic coning environment is derived firstly. Then, through investigation of the effect on Euler attitude algorithm for the equivalency of traditional attitude algorithm, it is found that attitude error is actually the roll angle error including drifting error and oscillating error, which is induced directly by dynamic coning environment and further affects the pitch angle and yaw angle through transferring. Based on definition of the cone frame and cone attitude, a cone algorithm is proposed by rotation relationship to calculate cone attitude, and the relationship between cone attitude and Euler attitude of spinning vehicle is established. Through numerical simulations with different conditions of dynamic coning environment, it is shown that the induced error of Euler attitude fluctuates by the variation of precession and nutation, especially by that of nutation, and the oscillating frequency of roll angle error is twice that of pitch angle error and yaw angle error. In addition, the rotation angle is more competent to describe the spinning process of vehicles under coning environment than Euler angle gamma, and the real pitch angle and yaw angle are calculated finally.

Cyclooxygenase expression in canine platelets and Madin-Darby canine kidney cells.

Science.gov (United States)

Kay-Mugford, P A; Benn, S J; LaMarre, J; Conlon, P D

2000-12-01

To examine cyclooxygenase (COX) expression in canine platelets and Madin-Darby canine kidney (MDCK) cells in culture. Canine platelets and MDCK cells. Total RNA was recovered from isolated canine platelets and MDCK cells. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), using complementary DNA probes and primers designed from the human COX sequences, were used to determine COX-1 and -2 (cyclooxygenase isoforms 1 and 2) messenger RNA (mRNA) expression. Following northern blot analysis, canine platelets were found to express only the 2.8-kb COX-1 transcript; COX-2 was not detected. Canine MDCK cells expressed the 4.5-kb COX-2 transcript, in addition to the 2.8-kb COX-1 transcript. A single DNA band of 270 base pairs was identified following gel electrophoresis of the product obtained from RT-PCR of mRNA from canine platelets. Sequencing revealed that this PCR product was 90% homologous to a portion of the human COX-1 gene (Genbank M59979). Detection of COX-1 by RT-PCR of RNA obtained from canine platelets is a novel finding. The 90% homology of the PCR product with the human sequence suggests strong conservation between the canine and human COX-1 gene. Cloning and sequencing of the canine gene will be required to fully characterize homologous regions. Because of the importance of COX in the inflammatory process and as a potential target of currently available nonsteroidal anti-inflammatory drugs (NSAID), a better understanding of canine COX may improve our ability to use NSAID appropriately, achieve efficacy, and avoid potential adverse drug effects in dogs.

Root Length and Anatomy of Impacted Maxillary Canines in Patients with Unilateral Maxillary Canine Impaction

Directory of Open Access Journals (Sweden)

Mostfa Shahabi

2017-09-01

Full Text Available Introduction: Canine impaction is a common occurrence. In this study, we sought to investigate the root anatomy and length of impacted canines and lateral incisor adjacent to impacted maxillary canine. Materials and Methods: In this retrospective study, three-dimensional tomographic imaging was performed on 26 patients with unilateral maxillary canine impaction. In this study, we evaluated root length and anatomy of impacted canines, in terms of resorption intensity and curvature, with Planmeca Romexis Viewer 4.0. Furthermore, crown shape as well as root length and anatomy of the lateral incisors adjacent to impacted canines were investigated and compared with the other side on the dental arch, where canine eruption was normal. Results: Root length of impacted canines was significantly lower than that of normal canines (P=0.011. There were no significant differences between root length of lateral incisors adjacent to impacted canines and root length of lateral incisors adjacent to normal canines (P=0.221. Moreover, the resorption intensity of the adjacent lateral incisors was higher than that of the impacted canines. No significant differences were noted in root resorption intensity between the lateral incisors adjacent to the imacted canines and the lateral incisors adjacent to normal canines (P=0.36. In addition, resorption intensity was significantly higher in impacted canines than in normal canines (P=0.024. Root anatomy of impacted canines was not significantly different from that of normal canines (P=0.055. The crown shape of the lateral incisors adjacent to impacted canines was not significantly different from that of the lateral incisors adjacent to normal canines (P=0.052. Conclusion: Impaction can probably affect root length and canine resorption severity. However, root and crown shape of lateral incisors cannot always be associated with canine impaction.

Outcome of ABCA4 disease-associated alleles in autosomal recessive retinal dystrophies: retrospective analysis in 420 Spanish families.

Science.gov (United States)

Riveiro-Alvarez, Rosa; Lopez-Martinez, Miguel-Angel; Zernant, Jana; Aguirre-Lamban, Jana; Cantalapiedra, Diego; Avila-Fernandez, Almudena; Gimenez, Ascension; Lopez-Molina, Maria-Isabel; Garcia-Sandoval, Blanca; Blanco-Kelly, Fiona; Corton, Marta; Tatu, Sorina; Fernandez-San Jose, Patricia; Trujillo-Tiebas, Maria-Jose; Ramos, Carmen; Allikmets, Rando; Ayuso, Carmen

2013-11-01

To provide a comprehensive overview of all detected mutations in the ABCA4 gene in Spanish families with autosomal recessive retinal disorders, including Stargardt's disease (arSTGD), cone-rod dystrophy (arCRD), and retinitis pigmentosa (arRP), and to assess genotype-phenotype correlation and disease progression in 10 years by considering the type of variants and age at onset. Case series. A total of 420 unrelated Spanish families: 259 arSTGD, 86 arCRD, and 75 arRP. Spanish families were analyzed through a combination of ABCR400 genotyping microarray, denaturing high-performance liquid chromatography, and high-resolution melting scanning. Direct sequencing was used as a confirmation technique for the identified variants. Screening by multiple ligation probe analysis was used to detect possible large deletions or insertions in the ABCA4 gene. Selected families were analyzed further by next generation sequencing. DNA sequence variants, mutation detection rates, haplotypes, age at onset, central or peripheral vision loss, and night blindness. Overall, we detected 70.5% and 36.6% of all expected ABCA4 mutations in arSTGD and arCRD patient cohorts, respectively. In the fraction of the cohort where the ABCA4 gene was sequenced completely, the detection rates reached 73.6% for arSTGD and 66.7% for arCRD. However, the frequency of possibly pathogenic ABCA4 alleles in arRP families was only slightly higher than that in the general population. Moreover, in some families, mutations in other known arRP genes segregated with the disease phenotype. An increasing understanding of causal ABCA4 alleles in arSTGD and arCRD facilitates disease diagnosis and prognosis and also is paramount in selecting patients for emerging clinical trials of therapeutic interventions. Because ABCA4-associated diseases are evolving retinal dystrophies, assessment of age at onset, accurate clinical diagnosis, and genetic testing are crucial. We suggest that ABCA4 mutations may be associated with a

Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I.

NARCIS (Netherlands)

Kalkman, J.S.; Schillings, M.L.; Zwarts, M.J.; Engelen, B.G.M. van; Bleijenberg, G.

2007-01-01

OBJECTIVES: To study the presence of psychiatric comorbidity assessed by the use of a structured clinical interview and self-reported questionnaires in a large sample of patients with adult-onset myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and hereditary motor and sensory

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, Marianne

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

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

NARCIS (Netherlands)

Hoogerwaard, E. M.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; Leschot, N. J.; van Essen, A. J.; Brunner, H. G.; van der Wouw, P. A.; Wilde, A. A.; 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

Cold knife cone biopsy

Science.gov (United States)

... biopsy; Pap smear - cone biopsy; HPV - cone biopsy; Human papilloma virus - cone biopsy; Cervix - cone biopsy; Colposcopy - cone biopsy Images Female reproductive anatomy Cold cone biopsy Cold cone removal References Baggish ...

Increased proliferation of late-born retinal progenitor cells by gestational lead exposure delays rod and bipolar cell differentiation.

Science.gov (United States)

Chaney, Shawnta Y; Mukherjee, Shradha; Giddabasappa, Anand; Rueda, Elda M; Hamilton, W Ryan; Johnson, Jerry E; Fox, Donald A

2016-01-01

Studies of neuronal development in the retina often examine the stages of proliferation, differentiation, and synaptic development, albeit independently. Our goal was to determine if a known neurotoxicant insult to a population of retinal progenitor cells (RPCs) would affect their eventual differentiation and synaptic development. To that end, we used our previously published human equivalent murine model of low-level gestational lead exposure (GLE). Children and animals with GLE exhibit increased scotopic electroretinogram a- and b-waves. Adult mice with GLE exhibit an increased number of late-born RPCs, a prolonged period of RPC proliferation, and an increased number of late-born rod photoreceptors and rod and cone bipolar cells (BCs), with no change in the number of late-born Müller glial cells or early-born neurons. The specific aims of this study were to determine whether increased and prolonged RPC proliferation alters the spatiotemporal differentiation and synaptic development of rods and BCs in early postnatal GLE retinas compared to control retinas. C57BL/6N mouse pups were exposed to lead acetate via drinking water throughout gestation and until postnatal day 10, which is equivalent to the human gestation period for retinal neurogenesis. RT-qPCR, immunohistochemical analysis, and western blots of well-characterized, cell-specific genes and proteins were performed at embryonic and early postnatal ages to assess rod and cone photoreceptor differentiation, rod and BC differentiation and synaptic development, and Müller glial cell differentiation. Real-time quantitative PCR (RT-qPCR) with the rod-specific transcription factors Nrl , Nr2e3 , and Crx and the rod-specific functional gene Rho , along with central retinal confocal studies with anti-recoverin and anti-rhodopsin antibodies, revealed a two-day delay in the differentiation of rod photoreceptors in GLE retinas. Rhodopsin immunoblots supported this conclusion. No changes in glutamine synthetase gene

Muscular Dystrophy

Science.gov (United States)

... sets of muscles and cause different degrees of muscle weakness. Duchenne muscular dystrophy is the most common and the most severe ... can walk independently. Prednisone If a child has Duchenne muscular ... to help slow the rate of muscle deterioration. By doing so, the child may be ...

Muscular Dystrophy (MD)

Science.gov (United States)

... patients may need assisted ventilation to treat respiratory muscle weakness and a pacemaker for cardiac abnormalities. View Full Treatment Information Definition The muscular dystrophies (MD) are a group of more than 30 ...

Rod rotation and differential rod contouring followed by direct vertebral rotation for treatment of adolescent idiopathic scoliosis: effect on thoracic and thoracolumbar or lumbar curves assessed with intraoperative computed tomography.

Science.gov (United States)

Seki, Shoji; Kawaguchi, Yoshiharu; Nakano, Masato; Makino, Hiroto; Mine, Hayato; Kimura, Tomoatsu

2016-03-01

Although direct vertebral rotation (DVR) is now used worldwide for the surgical treatment of adolescent idiopathic scoliosis (AIS), the benefit of DVR in reducing vertebral body rotation in these patients has not been determined. We investigated a possible additive effect of DVR on further reduction of vertebral body rotation in the axial plane following intraoperative rod rotation or differential rod contouring in patients undergoing surgical treatment for AIS. The study was a prospective computed tomography (CT) image analysis. We analyzed the results of the two intraoperative procedures in 30 consecutive patients undergoing surgery for AIS (Lenke type I or II: 15; Lenke type V: 15). The angle of reduction of vertebral body rotation taken by intraoperative CT scan was measured and analyzed. Pre- and postoperative responses to the Scoliosis Research Society 22 Questionnaire (SRS-22) were also analyzed. To analyze the reduction of vertebral body rotation with rod rotation or DVR, intraoperative cone-beam CT scans of the three apical vertebrae of the major curve of the scoliosis (90 vertebrae) were taken pre-rod rotation (baseline), post-rod rotation with differential rod contouring, and post-DVR in all patients. The angle of vertebral body rotation in these apical vertebrae was measured and analyzed for statistical significance. Additionally, differences between thoracic curve scoliosis (Lenke type I or II; 45 vertebrae) and thoracolumbar or lumbar curve scoliosis (Lenke type V; 45 vertebrae) were analyzed. Pre- and postoperative SRS-22 scores were evaluated in all patients. The mean (90 vertebrae) vertebral body rotation angles at baseline, post-rod rotation or differential rod contouring, and post-rod rotation or differential rod contouring or post-DVR were 17.3°, 11.1°, and 6.9°, respectively. The mean reduction in vertebral body rotation with the rod rotation technique was 6.8° for thoracic curves and 5.7° for thoracolumbar or lumbar curves (pself

Control rod

International Nuclear Information System (INIS)

Igarashi, Takao; Sugawara, Satoshi; Yoshimoto, Yuichiro; Saito, Shozo; Fukumoto, Takashi.

1987-01-01

Purpose: To reduce the weight and thereby obtain satisfactory operationability of control rods by combining absorbing nuclear chain type neutron absorbers and conventional type neutron absorbers in the axial direction of blades. Constitution: Neutron absorber rods and long life type neutron absorber rods are disposed in a tie rod and a sheath. The neutron absorber rod comprises a poison tube made of stainless steels and packed with B 4 C powder. The long life type neutron absorber rod is prepared by packing B-10 enriched boron carbide powder into a hafnium metal rod, hafnium pipe, europium and stainless made poison tube. Since the long life type absorber rod uses HF as the absorbing nuclear chain type neutron absorber, it absorbs neutrons to form new neutron absorbers to increase the nuclear life. (Yoshino, Y.)

Control rods

International Nuclear Information System (INIS)

Maruyama, Hiromi.

1984-01-01

Purpose: To realize effective utilization, cost reduction and weight reduction in neutron absorbing materials. Constitution: Residual amount of neutron absorbing material is averaged between the top end region and other regions of a control rod upon reaching to the control rod working life, by using a single kind of neutron absorbing material and increasing the amount of the neutron absorber material at the top end region of the control rod as compared with that in the other regions. Further, in a case of a control rod having control rod blades such as in a cross-like control rod, the amount of the neutron absorbing material is decreased in the middle portion than in the both end portions of the control rod blade along the transversal direction of the rod, so that the residual amount of the neutron absorbing material is balanced between the central region and both end regions upon reaching the working life of the control rod. (Yoshihara, H.)

Molecular mechanisms of muscle atrophy in myotonic dystrophies

OpenAIRE

Timchenko, Lubov

2013-01-01

Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystemic diseases that primarily affect skeletal muscle, causing myotonia, muscle atrophy, and muscle weakness. DM1 and DM2 pathologies are caused by expansion of CTG and CCTG repeats in non-coding regions of the genes encoding myotonic dystrophy protein kinase (DMPK) and Zinc finger protein 9 (ZNF9) respectively. These expansions cause DM pathologies through accumulation of mutant RNAs that alter RNA metabolism in p...

A novel method for objective vision testing in canine models of inherited retinal disease.

Science.gov (United States)

Gearhart, Patricia M; Gearhart, Chris C; Petersen-Jones, Simon M

2008-08-01

The use of canine models of retinal disease in the development of therapeutic strategies for inherited retinal disorders is a growing area of research. To evaluate accurately the success of potential vision-enhancing treatments, reliable methods for objectively assessing visual function in canine models is necessary. A simple vision-testing device was constructed that consisted of a junction box with four exit tunnels. Dogs were placed in the junction box and given one vision-based choice for exit. The first-choice tunnel and time to exit were recorded and analyzed. Two canine models of retinal disease with distinct molecular defects, a null mutation in the gene encoding the alpha subunit of rod cyclic GMP phosphodiesterase (PDE6A), and a null mutation in the gene encoding a retinal pigment epithelium-specific protein (RPE65) were tested and compared to those in unaffected dogs. With the use of bright light versus dim red light, the test differentiated between unaffected dogs and dogs affected with either mutation with a high degree of certainty. The white-light intensity series showed a significantly different performance between the unaffected and affected dogs. A significant difference in performance was detected between the dogs with each mutation. The results indicate that this novel canine vision-testing method is an accurate and sensitive means of distinguishing between unaffected dogs and dogs affected with two different forms of inherited retinal disease and should be useful as a means of assessing response to therapy in future studies.

Genetics Home Reference: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Science.gov (United States)

... Facebook Twitter Home Health Conditions APECED Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Printable PDF Open All Close All ... view the expand/collapse boxes. Description Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( APECED ) is an inherited condition that ...

Control rod calibration including the rod coupling effect

International Nuclear Information System (INIS)

Szilard, R.; Nelson, G.W.

1984-01-01

In a reactor containing more than one control rod, which includes all reactors licensed in the United States, there will be a 'coupling' or 'shadowing' of control rod flux at the location of a control rod as a result of the flux depression caused by another control rod. It was decided to investigate this phenomenon further, and eventually to put calibration table data or formulae in a small computer in the control room, so once could insert the positions of the three control rods and receive the excess reactivity without referring to separate tables. For this to be accomplished, a 'three control- rod reactivity function' would be used which would include the flux coupling between the rods. The function is design and measured data was fitted into it to determine the calibration constants. The input data for fitting the trial functions consisted of 254 data points, each consisting of the position of the reg, shim, and transient rods, and the total excess reactivity. (About 200 of these points were 'critical balance points', that is the rod positions for which reactor was critical, and the remainder were determined by positive period measurements.) Although this may be unrealistic from a physical viewpoint, the function derived gave a very accurate recalculation of the input data, and thus would faithfully give the excess reactivity for any possible combination of the locations of the three control rods. The next step, incorporation of the three-rod function into the minicomputer, will be pursued in the summer and fall of 1984

CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

Energy Technology Data Exchange (ETDEWEB)

Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi (Kumamoto Univ. (Japan). School of Medicine); Kawasaki, Shoichiro; Imamura, Shigehiro

1983-06-01

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 ..gamma..-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, ..gamma..-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.

CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

International Nuclear Information System (INIS)

Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi; Kawasaki, Shoichiro; Imamura, Shigehiro.

1983-01-01

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)

Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

NARCIS (Netherlands)

Renkema, Anne-Marie; Renkema, Alianne; Bronkhorst, Ewald; Katsaros, Christos

Introduction: The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the

Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

NARCIS (Netherlands)

Renkema, A.M.; Bronkhorst, E.M.; Katsaros, C.

2011-01-01

INTRODUCTION: The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the

Prevalence of muscular dystrophy in patients with muscular disorders in Tehran, Iran

Directory of Open Access Journals (Sweden)

Khadijeh Hajinaghi Tehrani

2018-05-01

Full Text Available Muscular dystrophy is a group of diseases that is characterized by progressive muscle wasting and the weakness of variable distribution and severity. On the basis of the distribution of predominant muscle weakness, there are many different kinds of muscular dystrophy. Some dystrophies are especially frequent in certain populations. There are no studies on the prevalence of muscular dystrophy in Iran. This study was aimed to survey the prevalence of muscular dystrophy among Iranian patients with muscular disorders. This analytical cross-sectional study was conducted on 1000 patients with musculoskeletal disorders who visited the dystrophy association of Bou-Ali Hospital (Tehran from June 2014 to June 2016. Patients’ data were extracted using a checklist that included age, gender, age of onset, family history, findings from clinical diagnostic tests and types of muscular dystrophy. The clinical findings were the results of genetic tests; EMG-NCV; para-clinical findings, including LDH and CPK; and pathological findings. All data were analyzed by SPSS V.22 (IBM Inc., NY with Chi Square and One way ANOVA tests. All analyses were performed with P = 0.05 considered as the threshold of statistical significant. Out of the 337 patients studied, 262 (77.7% were male and 75 (22.3% were female. Subjects had a mean (± SD age of 26.08 (± 11.86 years with an age range of 3 to 59 years. The most common types of muscular dystrophy were found to be Duchenne dystrophy (131 cases, 38.9%, limb-girdle dystrophy (91 cases, 27%, Becker dystrophy (58 cases, 17.2%, FSHD dystrophy (31 cases, 9.2%, and SMA (26 cases, 7.7%, respectively. The results showed that a statistically significant relationship between dystrophy types and gender, age, family history, age of diagnosis, CPK and LDH levels (P < 0.001. There were no statistical relationship between dystrophy types and pathological findings (P = 0.57, EMG-NCV test results (P = 0.062, and genetic findings (P = 0

Survey of Canadian Myotonic Dystrophy Patients' Access to Computer Technology.

Science.gov (United States)

Climans, Seth A; Piechowicz, Christine; Koopman, Wilma J; Venance, Shannon L

2017-09-01

Myotonic dystrophy type 1 is an autosomal dominant condition affecting distal hand strength, energy, and cognition. Increasingly, patients and families are seeking information online. An online neuromuscular patient portal under development can help patients access resources and interact with each other regardless of location. It is unknown how individuals living with myotonic dystrophy interact with technology and whether barriers to access exist. We aimed to characterize technology use among participants with myotonic dystrophy and to determine whether there is interest in a patient portal. Surveys were mailed to 156 participants with myotonic dystrophy type 1 registered with the Canadian Neuromuscular Disease Registry. Seventy-five participants (60% female) responded; almost half were younger than 46 years. Most (84%) used the internet; almost half of the responders (47%) used social media. The complexity and cost of technology were commonly cited reasons not to use technology. The majority of responders (76%) were interested in a myotonic dystrophy patient portal. Patients in a Canada-wide registry of myotonic dystrophy have access to and use technology such as computers and mobile phones. These patients expressed interest in a portal that would provide them with an opportunity to network with others with myotonic dystrophy and to access information about the disease.

National standards and code compliance for electrical equipment and instruments installed in hazardous locations for the cone penetrometer

International Nuclear Information System (INIS)

Bussell, J.H.

1996-03-01

The cone penetrometer is designed to measure the material properties of waste tank contents at the Hanford Site. The penetrometer system consists of a skid-mounted assembly, a penetrometer assembly (composed of a guide tube and a push rod), an active neutron moisture measurement probe, decontamination unit, and a support trailer containing a diesel-engine-driven hydraulic pump and a generator. The skid-mounted assembly is about 8 feet wide by 23 feet long and 15 feet high. Its nominal weight is about 40,000 pounds with the provisions to add up to 54,500 pounds of additional ballast. This document describes the cone penetrometer electrical instruments and how it complies with national standards

Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA.

Science.gov (United States)

Ritelli, Marco; Morlino, Silvia; Giacopuzzi, Edoardo; Carini, Giulia; Cinquina, Valeria; Chiarelli, Nicola; Majore, Silvia; Colombi, Marina; Castori, Marco

2017-01-01

Filamin A is an X-linked, ubiquitous actin-binding protein whose mutations are associated to multiple disorders with limited genotype-phenotype correlations. While gain-of-function mutations cause various bone dysplasias, loss-of-function variants are the most common cause of periventricular nodular heterotopias with variable soft connective tissue involvement, as well as X-linked cardiac valvular dystrophy (XCVD). The term "Ehlers-Danlos syndrome (EDS) with periventricular heterotopias" has been used in females with neurological, cardiovascular, integument and joint manifestations, but this nosology is still a matter of debate. We report the clinical and molecular update of an Italian family with an X-linked recessive soft connective tissue disorder and which was described, in 1975, as the first example of EDS type V of the Berlin nosology. The cutaneous phenotype of the index patient was close to classical EDS and all males died for a lethal cardiac valvular dystrophy. Whole exome sequencing identified the novel c.1829-1G>C splice variation in FLNA in two affected cousins. The nucleotide change was predicted to abolish the canonical splice acceptor site of exon 13 and to activate a cryptic acceptor site 15 bp downstream, leading to in frame deletion of five amino acid residues (p.Phe611_Gly615del). The predicted in frame deletion clusters with all the mutations previously identified in XCVD and falls within the N-terminus rod 1 domain of filamin A. Our findings expand the male-specific phenotype of FLNA mutations that now includes classical-like EDS with lethal cardiac valvular dystrophy, and offer further insights for the genotype-phenotype correlations within this spectrum. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Confirmation of linkage of Best`s macular dystrophy to 11q13, and evidence for genetic heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Mansergh, F.C.; Kenna, P.F.; Farrar, G.J. [Trinity College, Dublin (United Kingdom)] [and others

1994-09-01

Best`s macular dystrophy, also known as vitelliform macular degeneration, is an autosomal dominant, early onset form of macular degeneration. The disease is characterized by a roughly circular deposit of lipofuscin beneath the pigment epithelium of the retinal macula. Linkage studies were performed in two families, one Irish and one German, segregating typical Best`s macular dystrophy. In the Irish family (BTMD1), linkage analysis mapped the disease causing gene to chromosome 11q13, in a 10 cM region between the microsatellite markers PYGM and D11S871. Both markers showed different recombinants with the disease phenotype. This is a region that has previously shown linkage in families affected with Best`s macular dystrophy. Lod scores of 9.63, 9.12, 6.92, and 6.83 at zero recombination, were obtained with markers D11S1344, D11S1361, D11S1357 and D11S903, respectively. This data places the disease locus definitvely within the region between PYGM and D11S871. Linkage has been significantly excluded in this region in the German family (FamE), thereby providing evidence for genetic heterogeneity in this disease. The retinal specific gene, rod outer membrane protein 1 (ROM1), which maps to this region, has been screened for mutations in family BTMD1 by SSCPE analysis and by direct sequencing. Some of the promoter region, the three exons, and both introns have been sequenced; however, no mutations were found. It is likely that a gene other than ROM1 within this region may be responsible for causing the disease phenotype.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

Directory of Open Access Journals (Sweden)

Rosa Dolz-Marco

2014-01-01

Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

Science.gov (United States)

Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

2014-01-01

Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

Facioscapulohumeral muscular dystrophy

Science.gov (United States)

... There is no known cure for facioscapulohumeral muscular dystrophy. Treatments are given to control symptoms and improve quality of life. Activity is encouraged. Inactivity such as bedrest can make the muscle disease worse. Physical therapy may help maintain muscle ...

Retinitis pigmentosa inversa with unilateral high myopia with fellow eye optic disc pitting.

Science.gov (United States)

Sheth, Saumil; Rush, Ryan; Narayanan, Raja

2011-01-01

To report a possible rare association of bilateral retinitis pigmentosa inversa (RPI) with unilateral high myopia with fellow eye optic disc pitting. A 55-year-old man with a history of reduced vision in the right eye since childhood presented with gradually decreasing vision in the left eye. On examination, a -23.00 diopter refractive error and diffuse chorioretinal atrophy consistent with pathologic myopia was found in the right eye. An optic disc pit with posterior pole pigmentary alterations thought to be consequent to a previous neurosensory detachment was found in the left eye. Though the retinal arteriolar attenuation seen in both eyes with an inconsistent history of night blindness since childhood pointed towards the possibility of a concurrently existing rod or rod-cone dystrophy, the posterior pole pigmentary alterations characteristic of RPI were clearly masked by the above pathologies. Optical coherence tomography demonstrated prominent foveal atrophy and an optic disc pit in the left eye. Electroretinography (ERG) demonstrated moderately attenuated amplitudes with prolonged implicit times of rod and cone responses bilaterally. The patient was diagnosed with bilateral RPI and anisometropic amblyopia in the right eye. This report documents a unique constellation of findings which include bilateral RPI and unilateral high myopia with an optic disc pit in the fellow eye. An ERG confirmation of a dystrophic etiology should be sought in suspicious cases, especially when findings are masked by the concurrent presence of other pathologies.

Central areolar choroidal dystrophy with associated dominant drusen

Directory of Open Access Journals (Sweden)

Julie Rodman

2013-04-01

Conclusion: Central areolar choroidal dystrophy normally presents without drusen. However, in patients manifesting a specific mutation, central areolar choridal dystrophy may present in conjunction with drusen. It appears that the Arg142Trp mutation is one of the factors predisposing to drusen formation.

Control rod drives

International Nuclear Information System (INIS)

Nakamura, Akira.

1984-01-01

Purpose: To enable to monitor the coupling state between a control rod and a control rod drive. Constitution: After the completion of a control rod withdrawal, a coolant pressure is applied to a control rod drive being adjusted so as to raise only the control rod drive and, in a case where the coupling between the control rod drive and the control rod is detached, the former is elevated till it contacts the control rod and then stopped. The actual stopping position is detected by an actual position detection circuit and compared with a predetermined position stored in a predetermined position detection circuit. If both of the positions are not aligned with each other, it is judged by a judging circuit that the control rod and the control rod drives are not combined. (Sekiya, K.)

Petaloid-pattern pigmentary retinopathy: a novel case report.

Science.gov (United States)

Padhi, Tapas Ranjan; Jalali, Subhadra; Panda, Krushna Gopal; Mukherjee, Sujoy; Mohan, Neha; Agroiya, Pushpalata; Das, Taraprasad

2014-10-01

We report the case of a 6-year-old girl with an unusual petaloid-pattern pigmentary retinopathy associated with nyctalopia and reduction of vision which had been invariably static over the past 5 years. We performed a comprehensive ophthalmic examination including fundoscopy, autofluorescent imaging, electroretinography and optical coherence tomography. There were diffuse retinal pigment epithelium (RPE) washout areas with blotches of pigment distributed in the pattern of a petal with marked chorioretinal atrophy and scar at the fovea. The arterial caliber was normal. Investigations ruled out intrauterine and neonatal infection. Systemically, she was healthy with normal intellect but with 3-month delayed milestones of development. She had used valproic acid for seizure disorder (without any organic central nervous system lesion) from 2-5 years of age. Electroretinography showed extinguished scotopic responses with slight reduction in cone responses. Optical coherence tomography showed a scar with attenuated RPE-choriocapillary complex at the macula. Her clinical profile did not fully match with any previously described pigmentary retinopathies except rod-cone dystrophy and choroidal dystrophy to a certain extent. The pigmentary retinopathy reported here is a combination of a petaloid pattern of pigmentary disturbance, stationary reduction of vision, nyctalopia, normal intellect and marginal delayed milestones. In the absence of such a description in the literature we named this disorder as petaloid-pattern pigmentary retinopathy.

Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

Science.gov (United States)

Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

2015-10-01

Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of Duchenne muscular dystrophy. © The Author(s) 2015.

Control rod assembly

International Nuclear Information System (INIS)

Takahashi, Akio.

1982-01-01

Purpose: To enable reliable insertion and drops of control rods, as well as insure a sufficient flow rate of coolants flowing through the control rods for attaining satisfactory cooling thereof to enable relexation of thermal stress resulted to rectifying mechanisms or the likes. Constitution: To the outer circumference of a control rod contained vertically movably within a control rod guide tube, resistive members are retractably provided in such a way as to project to close the gap between outer circumference of the control rod and the inner surface of the control rod guide tube upon engagement of a gripper of control rod drives, and retract upon release of the engagement of the gripper. Thus, since the resistive members project to provide a greater resistance to the coolants flowing between them and the control rod guide tube in the normal operation where the gripper is engaged to drive the control rod by the control rod drives, a major part of the coolant flowing into the control rod guide tube flows into the control rod. This enables to cool the control rod effectively and make the temperature distribution uniform for the coolant flowing from the upper end of the control rod guide tube to thereby attain the relaxation of the thermal stress resulted in the rectifying mechanisms or the likes. (Moriyama, K.)

Device for coupling a control rod and control rod drive

International Nuclear Information System (INIS)

Nishioka, Kazuya.

1975-01-01

Object: To obtain simple and reliable coupling between a control rod and control rod drive by equipping the lower end of the control rod with an extension provided with lateral protuberances and forming the upper end of an index tube with a recess provided with lateral holes. Structure: The tapering central extension of the control rod is inserted into the recess by lowering the control rod, and then it is further inserted by causing frictional movement of the inclined surfaces of lateral protuberances in frictional contact with guide surfaces. When the lateral protuberances are brought into contact with a stepped portion, the control rod is rotated to fit the lateral protuberances into the lateral holes. In this way, the control rod is coupled to the index tube of the control rod drive. (Yoshino, Y.)

Posterior amorphous corneal dystrophy: case report

OpenAIRE

Oliveira, Lauro Augusto de [UNIFESP; Vieira, Luiz Antônio [UNIFESP; Freitas, Denise de [UNIFESP; Sousa, Luciene Barbosa de [UNIFESP

2006-01-01

O objetivo deste trabalho é alertar o oftalmologista da possibilidade de se deparar com casos raros de distrofias corneanas. Neste caso correlacionamos os achados clínicos da distrofia amorfa posterior com refração, topografia e biomicroscopia ultra-sônica.The purpose of this paper is to warn the ophthalmologist about the possibility of facing rare cases of corneal dystrophies. Clinical findings of a case of posterior amorphous dystrophy were correlated with refraction, topography, and ultras...

Acute flaccid paraparesis (cauda equina syndrome) in a patient with Bardet–Biedl syndrome

Science.gov (United States)

Viswanathan, Vibhu Krishnan; Kanna, Rishi Mugesh; Shetty, Ajoy Prasad; Rajasekaran, S

2017-01-01

Bardet–Biedl syndrome (BBS) is a rare, autosomal-recessive, debilitating genetic disorder, which can present with multitudinous systemic clinical features including rod-cone dystrophy, polydactyly, Frohlich-like central obesity, mental retardation, hypogonadism, and renal anomalies. Diverse neuromuscular manifestations in patients afflicted by this heterogeneous disorder include ataxia, cervical, and thoracic canal stenoses, presenting as spastic quadriparesis and other gait disturbances. We report a young patient with BBS, who had presented with acute flaccid paraparesis due to severe primary lumbar canal stenosis. She underwent immediate lumbar decompression and discectomy following which she recovered significantly. Acute cauda equina syndrome due to primary lumbar canal stenosis has not been reported as a clinical feature of BBS previously. PMID:28566787

Stem cell transplantation for treating Duchenne muscular dystrophy

Science.gov (United States)

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 indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011. RESULTS: A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation

Control rod displacement

International Nuclear Information System (INIS)

Nakazato, S.

1987-01-01

This patent describes a nuclear reactor including a core, cylindrical control rods, a single support means supporting the control rods from their upper ends in spaced apart positions and movable for displacing the control rods in their longitudinal direction between a first end position in which the control rods are fully inserted into the core and a second end position in which the control rods are retracted from the core, and guide means contacting discrete regions of the outer surface of each control rod at least when the control rods are in the vicinity of the second end position. The control rods are supported by the support means for longitudinal movement without rotation into and out of the core relative to the guide means to thereby cause the outer surface of the control rods to experience wear as a result of sliding contact with the guide means. The support means are so arranged with respect to the core and the guide means that it is incapable of rotation relative to the guide means. The improvement comprises displacement means being operatively coupled to a respective one of the control rods for periodically rotating the control rod in a single angular direction through an angle selected to change the locations on the outer surfaces of the control rods at which the control rods are contacted by the guide means during subsequent longitudinal movement of the control rods

The role of 11-cis-retinyl esters in vertebrate cone vision.

Science.gov (United States)

Babino, Darwin; Perkins, Brian D; Kindermann, Aljoscha; Oberhauser, Vitus; von Lintig, Johannes

2015-01-01

A cycle of cis-to-trans isomerization of the chromophore is intrinsic to vertebrate vision where rod and cone photoreceptors mediate dim- and bright-light vision, respectively. Daylight illumination can greatly exceed the rate at which the photoproduct can be recycled back to the chromophore by the canonical visual cycle. Thus, an additional supply pathway(s) must exist to sustain cone-dependent vision. Two-photon microscopy revealed that the eyes of the zebrafish (Danio rerio) contain high levels of 11-cis-retinyl esters (11-REs) within the retinal pigment epithelium. HPLC analyses demonstrate that 11-REs are bleached by bright light and regenerated in the dark. Pharmacologic treatment with all-trans-retinylamine (Ret-NH2), a potent and specific inhibitor of the trans-to-cis reisomerization reaction of the canonical visual cycle, impeded the regeneration of 11-REs. Intervention with 11-cis-retinol restored the regeneration of 11-REs in the presence of all-trans-Ret-NH2. We used the XOPS:mCFP transgenic zebrafish line with a functional cone-only retina to directly demonstrate that this 11-RE cycle is critical to maintain vision under bright-light conditions. Thus, our analyses reveal that a dark-generated pool of 11-REs helps to supply photoreceptors with the chromophore under the varying light conditions present in natural environments. © FASEB.

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy

Science.gov (United States)

Martin, Elizabeth A.; Barresi, Rita; Byrne, Barry J.; Tsimerinov, Evgeny I.; Scott, Bryan L.; Walker, Ashley E.; Gurudevan, Swaminatha V.; Anene, Francine; Elashoff, Robert M.; Thomas, Gail D.; Victor, Ronald G.

2013-01-01

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin’s rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived nitric oxide (NO) attenuates local α-adrenergic vasoconstriction thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective—causing functional muscle ischemia—in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. Here, we report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled cross-over trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation fully restored in the muscles of men with BMD by boosting NO-cGMP signaling with a single dose of the drug tadalafil, a phosphodiesterase (PDE5A) inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD. PMID:23197572

Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.

Science.gov (United States)

Martin, Elizabeth A; Barresi, Rita; Byrne, Barry J; Tsimerinov, Evgeny I; Scott, Bryan L; Walker, Ashley E; Gurudevan, Swaminatha V; Anene, Francine; Elashoff, Robert M; Thomas, Gail D; Victor, Ronald G

2012-11-28

Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.

Morphoelastic rods. Part I: A single growing elastic rod

KAUST Repository

Moulton, D.E.

2013-02-01

A theory for the dynamics and statics of growing elastic rods is presented. First, a single growing rod is considered and the formalism of three-dimensional multiplicative decomposition of morphoelasticity is used to describe the bulk growth of Kirchhoff elastic rods. Possible constitutive laws for growth are discussed and analysed. Second, a rod constrained or glued to a rigid substrate is considered, with the mismatch between the attachment site and the growing rod inducing stress. This stress can eventually lead to instability, bifurcation, and buckling. © 2012 Elsevier Ltd. All rights reserved.

Morphoelastic rods. Part I: A single growing elastic rod

KAUST Repository

Moulton, D.E.; Lessinnes, T.; Goriely, A.

2013-01-01

A theory for the dynamics and statics of growing elastic rods is presented. First, a single growing rod is considered and the formalism of three-dimensional multiplicative decomposition of morphoelasticity is used to describe the bulk growth of Kirchhoff elastic rods. Possible constitutive laws for growth are discussed and analysed. Second, a rod constrained or glued to a rigid substrate is considered, with the mismatch between the attachment site and the growing rod inducing stress. This stress can eventually lead to instability, bifurcation, and buckling. © 2012 Elsevier Ltd. All rights reserved.

[Ocular findings in patients with Steinert myotonic dystrophy].

Science.gov (United States)

Markowska, Elzbieta; Zalewska, Renata; Mariak, Zofia; Wojnar, Małgorzata

2006-01-01

The authors present one of many myotonic dystrophies: Steinert myotonic dystrophy (Steinert disease), which is a disease occuring seldom, and causing a lot of problems during the diagnostic and treatment process. Genetic factors, results of the histopathology tests, main clinical symptoms, particularly ophtalmic manifestation are described in this article.

The golden retriever model of Duchenne muscular dystrophy.

Science.gov (United States)

Kornegay, Joe N

2017-05-19

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in the DMD gene and loss of the protein dystrophin. The absence of dystrophin leads to myofiber membrane fragility and necrosis, with eventual muscle atrophy and contractures. Affected boys typically die in their second or third decade due to either respiratory failure or cardiomyopathy. Despite extensive attempts to develop definitive therapies for DMD, the standard of care remains prednisone, which has only palliative benefits. Animal models, mainly the mdx mouse and golden retriever muscular dystrophy (GRMD) dog, have played a key role in studies of DMD pathogenesis and treatment development. Because the GRMD clinical syndrome is more severe than in mice, better aligning with the progressive course of DMD, canine studies may translate better to humans. The original founder dog for all GRMD colonies worldwide was identified in the early 1980s before the discovery of the DMD gene and dystrophin. Accordingly, analogies to DMD were initially drawn based on similar clinical features, ranging from the X-linked pattern of inheritance to overlapping histopathologic lesions. Confirmation of genetic homology between DMD and GRMD came with identification of the underlying GRMD mutation, a single nucleotide change that leads to exon skipping and an out-of-frame DMD transcript. GRMD colonies have subsequently been established to conduct pathogenetic and preclinical treatment studies. Simultaneous with the onset of GRMD treatment trials, phenotypic biomarkers were developed, allowing definitive characterization of treatment effect. Importantly, GRMD studies have not always substantiated findings from mdx mice and have sometimes identified serious treatment side effects. While the GRMD model may be more clinically relevant than the mdx mouse, usage has been limited by practical considerations related to expense and the number of dogs available. This further complicates ongoing broader concerns about

Control rod drive

International Nuclear Information System (INIS)

Hawke, B.C.

1986-01-01

A reactor core, one or more control rods, and a control rod drive are described for selectively inserting and withdrawing the one or more control rods into and from the reactor core, which consists of: a support structure secured beneath the reactor core; control rod positioning means supported by the support structure for movably supporting the control rod for movement between a lower position wherein the control rod is located substantially beneath the reactor core and an upper position wherein at least an upper portion of the control rod extends into the reactor core; transmission means; primary drive means connected with the control rod positioning means by the transmission means for positioning the control rod under normal operating conditions; emergency drive means for moving the control rod from the lower position to the upper position under emergency conditions, the emergency drive means including a weight movable between an upper and a lower position, means for movably supporting the weight, and means for transmitting gravitational force exerted on the weight to the control rod positioning means to move the control rod upwardly when the weight is pulled downwardly by gravity; the transmission means connecting the control rod positioning means with the emergency drive means so that the primary drive means effects movement of the weight and the control rod in opposite directions under normal conditions, thus providing counterbalancing to reduce the force required for upward movement of the control rod under normal conditions; and restraint means for restraining the fall of the weight under normal operating conditions and disengaging the primary drive means to release the weight under emergency conditions

CONGENITAL MYOTONIC DYSTROPHY – CASE REPORT

Directory of Open Access Journals (Sweden)

David Neubauer

2001-07-01

Full Text Available Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized by myotonia, myopathy of voluntary and involuntary muscles, frontal baldness in men, cardiac conduction abnormalities, catharacts, intellectual deterioration and endocrinopathy. Men with this disorder have often gonadal atrophy and infertility. On the other hand women are generally fertile. During pregnancy their myopathy worsens, often causing severe obstetrical complications. Their children may develop congenital form of the disease with signs of myopathy in utero and have great difficulties in maintaining life functions after birth, together with other characteristical signs of this form: bilateral facial weakness, severe hypotonia, feeding difficulties, talipes equinovarus and mental retardation. The authors present a female newborn with such congenital form of myotonic dystrophy.Conclusions. The authors have emphasized the importance of medical history, regular updating of all the cases of neuromuscular diseases in the region and clinical characteristics for the recognition of congenital form of myotonic dystrophy because of possible prenatal diagnostics and better antenatal and postantal care.

Root Length and Anatomy of Impacted Maxillary Canines in Patients with Unilateral Maxillary Canine Impaction

OpenAIRE

Mostfa Shahabi; Maryam Omidkhoda; Seyedeh Haniyeh Omidi; Seyed Hosein Hoseini Zarch

2017-01-01

Introduction: Canine impaction is a common occurrence. In this study, we sought to investigate the root anatomy and length of impacted canines and lateral incisor adjacent to impacted maxillary canine. Materials and Methods: In this retrospective study, three-dimensional tomographic imaging was performed on 26 patients with unilateral maxillary canine impaction. In this study, we evaluated root length and anatomy of impacted canines, in terms of resorption intensity and curvature, with Planme...

Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy.

Science.gov (United States)

Bianco, Bianca; Christofolini, Denise Maria; Conceição, Gabriel Seixas; Barbosa, Caio Parente

2017-01-01

Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy.

Median nail dystrophy involving the thumb nail

Directory of Open Access Journals (Sweden)

Rahulkrishna Kota

2016-01-01

Full Text Available Median canaliform dystrophy of Heller is a rare entity characterized by a midline or a paramedian ridge or split and canal formation in nail plate of one or both the thumb nails. It is an acquired condition resulting from a temporary defect in the matrix that interferes with nail formation. Habitual picking of the nail base may be responsible for some cases. Histopathology classically shows parakeratosis, accumulation of melanin within and between the nail bed keratinocytes. Treatment of median nail dystrophy includes injectable triamcinalone acetonide, topical 0.1% tacrolimus, and tazarotene 0.05%, which is many a times challenging for a dermatologist. Psychiatric opinion should be taken when associated with the depressive, obsessive-compulsive, or impulse-control disorder. We report a case of 19-year-old male diagnosed as median nail dystrophy.

[Posterior polymorphous dystrophy, case report and literature review].

Science.gov (United States)

Mendoza-Adam, G; Hernandez-Camarena, J C; Valdez-García, J E

2015-09-01

Posterior Polymorphous Dystrophy (DPP) is a rare posterior corneal dystrophy that is genetically transmitted as autosomal dominant. Corneal structures affected in this dystrophy are Descemet membrane and the endothelium. A case is presented on a 47 years old woman with no relevant history, with typical findings of DPP (vesicular and band lesions at the endothelium and posterior Descemet). To our knowledge there are no reported cases of DPP in Latin-American patients in the literature. The clinical manifestations in our patient were found to be very similar to the cases reported in other populations. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Replacement rod

International Nuclear Information System (INIS)

Hatfield, S.C.

1989-01-01

This patent describes in an elongated replacement rod for use with fuel assemblies of the type having two end fittings connected by guide tubes with a plurality of rod and guide tube cell defining spacer grids containing rod support features and mixing vanes. The grids secured to the guide tubes in register between the end fittings at spaced intervals. The fuel rod comprising: an asymmetrically beveled tip; a shank portion having a straight centerline; and a permanently diverging portion between the tip and the shank portion

Geomorphometric variability of "monogenetic" volcanic cones: Evidence from Mauna Kea, Lanzarote and experimental cones

Science.gov (United States)

Kervyn, M.; Ernst, G. G. J.; Carracedo, J.-C.; Jacobs, P.

2012-01-01

Volcanic cones are the most common volcanic constructs on Earth. Their shape can be quantified using two morphometric ratios: the crater/cone base ratio (W cr/W co) and the cone height/width ratio (H co/W co). The average values for these ratios obtained over entire cone fields have been explained by the repose angle of loose granular material (i.e. scoria) controlling cone slopes. The observed variability in these ratios between individual cones has been attributed to the effect of erosional processes or contrasting eruptive conditions on cone morphometry. Using a GIS-based approach, high spatial resolution Digital Elevation Models and airphotos, two new geomorphometry datasets for cone fields at Mauna Kea (Hawaii, USA) and Lanzarote (Canary Islands, Spain) are extracted and analyzed here. The key observation in these datasets is the great variability in morphometric ratios, even for simple-shape and well-preserved cones. Simple analog experiments are presented to analyze factors influencing the morphometric ratios. The formation of a crater is simulated within an analog cone (i.e. a sand pile) by opening a drainage conduit at the cone base. Results from experiments show that variability in the morphometric ratios can be attributed to variations in the width, height and horizontal offset of the drainage point relative to the cone symmetry axis, to the dip of the underlying slope or to the influence of a small proportion of fine cohesive material. GIS analysis and analog experiments, together with specific examples of cones documented in the field, suggest that the morphometric ratios for well-preserved volcanic cones are controlled by a combination of 1) the intrinsic cone material properties, 2) time-dependent eruption conditions, 3) the local setting, and 4) the method used to estimate the cone height. Implications for interpreting cone morphometry solely as either an age or as an eruption condition indicator are highlighted.

An experimental study of BIGH3 gene mutations in the patients with corneal dystrophies

International Nuclear Information System (INIS)

Jin Tao; Zou Liuhe; Yang Ling

2004-01-01

Objective: To evaluate BIGH3 gene mutations in Chinese patents with corneal dystrophies. Methods: 2ml peripheral venous blood was collected from 15 patients with granular corneal dystrophies and 5 normal subjects. Leucocytes DNA was extracted with standard method. With two pairs of oligonucleotide primers, exon 4 and exon 12 of the BIGH3 gene were amplified using the polymerase chain reaction. Amplified DNA fragments were purified and sequenced directly. Results: Mutations in BIGH3 gene were detected in all the patients with corneal dystrophies. BIGH3 gene mutations were not found in normal subjects. 12 patients with Avellino corneal dystrophy had the missense mutation R124H in the BIGH3 gene. 3 patients with granular corneal dystrophy had the missense mutation R555W in the BIGH3 gene. Conclusion: R124H and R555W mutations in BIGH3 gene were also found in the Chinese patients with Avellino and granular corneal dystrophies. In China, Avellino corneal dystrophy associated with the R124H mutation is the most common form in the corneal dystrophies resulted by BIGH3 gene mutions. Condon 124 and 555 are also the hot spots for the mutations in the BIGH3 gene in the Chinese patients with corneal dystrophies. Molecular genetic analysis may be repuired for proper diagnosis and subclassification of corneal dystrophies. (authors)

Upper limb function in adults with Duchenne muscular dystrophy

NARCIS (Netherlands)

B. Bartels (Bart); R.F. Pangalila (Robert); 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

Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

Science.gov (United States)

Marcos, S; Tornow, R P; Elsner, A E; Navarro, R

1997-07-01

Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

Water rod

International Nuclear Information System (INIS)

Kashiwai, Shin-ichi; Yokomizo, Osamu; Orii, Akihito.

1992-01-01

In a reactor core of a BWR type reactor, the area of a flow channel in a lower portion of a downcoming pipe for downwardly releasing steams present at the top portion in a water rod is increased. Further, a third coolant flow channel (an inner water rod) is disposed in an uprising having an exit opened near the inlet of the water rod and an inlet opened at the outside near the top portion of the water and having an increase flow channel area in the upper portion. The downcoming pipe in the water rod is filled with steams, and the void ratio is increased by so much as the flow channel area of the downcoming pipe is increased. Since the pressure difference between the inlet and the exit of the inner water rod is greater than the pressure difference between the inlet and the exit of the water rod, most of water flown into the inner water rod is discharged out of the exit in the form of water as it is. Since the area of the flow channel is increased in the portion of the inner water rod, void efficiency in the upper portion of the reactor core is decreased by so much. Since the void ratio is thus increased in the lower portion and the void efficiency is decreased in the upper portion of the reactor core, axial void distribution can be flattened. (N.H.)

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

2015-01-01

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

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. © 2015. Published by The Company of Biologists Ltd.

Guidelines for the Perianesthesia Care of the Duchenne Muscular Dystrophy/Becker Muscular Dystrophy Patient.

Science.gov (United States)

Alliod, Barbara A; Ash, Rebecca A

2016-12-01

More patients suffering with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are presenting to perianesthesia settings for emergent and nonemergent treatment and care. A group of collaborative health care providers at Rush University Medical Center in Chicago developed a multidisciplinary DMD/BMD Task Force to study this disorder and create a set of guidelines to aid those engaging in the planning, execution of care, and recovery of this unique population in the perianesthesia setting. Attention to detail, well-executed preplanning, meticulous awareness of the patient, and prearranged implementation and intervention has proven to offset potential problems and complications and is the key to a successful perianesthesia period. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.

Science.gov (United States)

Fuerst, Nicole M; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Maguire, Albert M; Leroy, Bart P; Kim, Benjamin J; Aleman, Tomas S

2016-12-01

To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin ® ; Genentech/Roche). A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.

Sleep disturbances in myotonic dystrophy type 2

OpenAIRE

Shepard, Paul; Lam, Erek M.; St. Louis, Erik K.; Dominik, Jacob

2012-01-01

Sleep disorders in myotonic dystrophy type 1 (DM1) are common and include sleep disordered breathing (SDB), hypersomnia, and fatigue. Little is known regarding the occurrence of sleep disturbance in myotonic dystrophy type 2 (DM2). We hypothesized that DM2 patients may frequently harbor sleep disorders. We reviewed medical records of all genetically confirmed cases of DM2 seen at our sleep center between 1997 and 2010 for demographic, laboratory, overnight oximetry, and polysomnography (PSG) ...

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. PMID:27757431

Control rod

International Nuclear Information System (INIS)

Igarashi, Takao; Yoshimoto, Yuichiro; Sugawara, Satoshi; Fukumoto, Takashi; Endo, Zen-ichiro; Saito, Shozo; Shinpo, Katsutoshi; Nishimura, Akira; Ozawa, Michihiro

1988-01-01

Purpose: To provide a sufficient shutdown margin upon reactor shutdown, prevent sheath deformation without decreasing neutron absorbents and prevent impact shocks exerted to structural materials. Constitution: The control rod of the present invention comprises a neutron absorption region, a sheath deformation means attached to the side wall and means for restricting and supporting axial movement of the neutron absorbent rod. Then, the amount of absorptive nuclei chained absorbents in the lower region is reduced than that in the upper region. In this way, effective neutron absorbing performance can be obtained relative to the neutron importance distribution during reactor shutdown. In addition, since the operationability is improved by reducing the weight of the control rod and the absorptive nuclei chained neutron abosrbers are used, mechanical nuclear life of the control rod can be increased. Thus, it is possible to prevent the outward deformation of the sheath, as well as prevent collision between the neutron absorber rod and the structural material on the side of inserting the control rod generated upon reactor scram by a simple structure. (Kamimura, M.)

[Adenovirus-mediated canine interferon-gamma expression and its antiviral activity against canine parvovirus].

Science.gov (United States)

Zhang, Kao; Jin, Huijun; Zhong, Fei; Li, Xiujin; Neng, Changai; Chen, Huihui; Li, Wenyan; Wen, Jiexia

2012-11-04

To construct recombinant adenovirus containing canine interferon-gamma (cIFN-gamma) gene and to investigate its antiviral activity against canine parvovirus in Madin-Darby canine kidney cells (MDCK). [Methods] The cIFN-gamma gene was inserted into adenovirus shuttle plasmid to construct pShuttle3-cIFN-gamma expression vector, from which the cIFN-gamma expression cassette was transferred into the adenovirus genomic plasmid pAdeno-X by specific restriction sites to generate recombinant adenovirus genomic plasmid pAd-cIFN-gamma. The pAd-cIFN-gamma plasmid was linearized by digestion and transfected into human embryonic kidney (HEK) 293T cells to generate the replication-defective cIFN-gamma recombinant adenovirus (Ad-cIFN-gamma). To analyze its anti-canine parvovirus activity, the MDCK cells were pre-infected by Ad-cIFN-gamma recombinant adenovirus, and then infected by canine parvovirus. The antiviral activity of the Ad-cIFN-gamma recombinant adenovirus against parvovirus was analyzed. The recombinant adenovirus containing cIFN-gamma gene was constructed by the ligation method. The recombinant adenovirus could mediates recombinant cIFN-gamma secretory expression in MDCK cells. The Ad-cIFN-gamma recombinant adenovirus could significantly inhibit canine parvovirus replication in MDCK cells pre-infected with the recombinant adenovirus. These results indicate that the Ad-cIFN-gamma recombinant adenovirus has the potent antiviral activity against canine parvovirus. The Ad-cIFN-gamma recombinant adenovirus was successfully constructed by the ligation method and possessed a powerful antiviral activity against canine parvovirus.

Two human cDNA molecules coding for the Duchenne muscular dystrophy (DMD) locus are highly homologous

Energy Technology Data Exchange (ETDEWEB)

Rosenthal, A.; Speer, A.; Billwitz, H. (Zentralinstitut fuer Molekularbiologie, Berlin-Buch (Germany Democratic Republic)); Cross, G.S.; Forrest, S.M.; Davies, K.E. (Univ. of Oxford (England))

1989-07-11

Recently the complete sequence of the human fetal cDNA coding for the Duchenne muscular dystrophy (DMD) locus was reported and a 3,685 amino acid long, rod-shaped cytoskeletal protein (dystrophin) was predicted as the protein product. Independently, the authors have isolated and sequenced different DMD cDNA molecules from human adult and fetal muscle. The complete 12.5 kb long sequence of all their cDNA clones has now been determined and they report here the nucleotide (nt) and amino acid (aa) differences between the sequences of both groups. The cDNA sequence comprises the whole coding region but lacks the first 110 nt from the 5{prime}-untranslated region and the last 1,417 nt of the 3{prime}-untranslated region. They have found 11 nt differences (approximately 99.9% homology) from which 7 occurred at the aa level.

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.

Quotient normed cones

Indian Academy of Sciences (India)

general setting of the space CL(X, Y ) of all continuous linear mappings from a normed cone (X, p) to a normed cone (Y, q), extending several well-known results related to open continuous linear mappings between normed linear spaces. Keywords. Normed cone; extended quasi-metric; continuous linear mapping; bicom-.

Control rod drives

International Nuclear Information System (INIS)

Futatsugi, Masao.

1980-01-01

Purpose: To secure the reactor operation safety by the provision of a fluid pressure detecting section for control rod driving fluid and a control rod interlock at the midway of the flow pass for supplying driving fluid to the control rod drives. Constitution: Between a driving line and a direction control valve are provided a pressure detecting portion, an alarm generating device, and a control rod inhibition interlock. The driving fluid from a driving fluid source is discharged by way of a pump and a manual valve into the reactor in which the control rods and reactor fuels are contained. In addition, when the direction control valve is switched and the control rods are inserted and extracted by the control rod drives, the pressure in the driving line is always detected by the pressure detection section, whereby if abnormal pressure is resulted, the alarm generating device is actuated to warn the abnormality and the control rod inhibition interlock is actuated to lock the direction control valve thereby secure the safety operation of the reactor. (Seki, T.)

Control rod drives

International Nuclear Information System (INIS)

Oonuki, Koji.

1981-01-01

Purpose: To increase the driving speed of control rods at rapid insertion with an elongate control rod and an extension pipe while ensuring sufficient buffering performance in a short buffering distance, by providing a plurality of buffers to an extension pipe between a control rod drive source and a control rod in LMFBR type reactor. Constitution: First, second and third buffers are respectively provided to an acceleration piston, an extension pipe and a control rod respectively and the insertion positions for each of the buffers are displaced orderly from above to below. Upon disconnection of energizing current for an electromagnet, the acceleration piston, the extension pipe and the control rod are rapidly inserted in one body. The first, second and third buffers are respectively actuated at each of their falling strokes upon rapid insertion respectively, and the acceleration piston, the extension pipe and the control rod receive the deceleration effect in the order correspondingly. Although the compression force is applied to the control rod only near the stroke end, it does not cause deformation. (Kawakami, Y.)

Neurocognitive Profiles in Duchenne Muscular Dystrophy and Gene Mutation Site

Science.gov (United States)

D’Angelo, Maria Grazia; Lorusso, Maria Luisa; Civati, Federica; Comi, Giacomo Pietro; Magri, Francesca; Del Bo, Roberto; Guglieri, Michela; Molteni, Massimo; Turconi, Anna Carla; Bresolin, Nereo

2011-01-01

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing. PMID:22000308

Intraocular pressure, corneal thickness, and corneal hysteresis in Steinert's myotonic dystrophy

Directory of Open Access Journals (Sweden)

Carlos Alexandre de A. Garcia Filho

2011-06-01

Full Text Available PURPOSE: Low intraocular pressure (IOP measured by Goldmann applanation tonometry (GAT is one of the ocular manifestations of Steinert's myotonic dystrophy. The goal of this study was to evaluate the corneal-compensated IOP as well as corneal properties (central corneal thickness and corneal hysteresis in patients with myotonic dystrophy. METHODS: A total of 12 eyes of 6 patients with Steinert's myotonic dystrophy (dystrophy group and 12 eyes of 6 age-, race-, and gender-matched healthy volunteers (control group were included in the study. GAT, Dynamic Contour Tonometry (DCT-Pascal and Ocular Response Analyzer (ORA were used to assess the IOP. Central corneal thickness was obtained by ultrasound pachymetry, and corneal hysteresis was analyzed using the ORA device. In light of the multiplicity of tests performed, the significance level was set at 0.01 rather than 0.05. RESULTS: The mean (standard deviation [SD] GAT, DCT, and corneal-compensated ORA IOP in the dystrophy group were 5.4 (1.4 mmHg, 9.7 (1.5 mmHg, and 10.1 (2.6 mmHg, respectively. The mean (SD GAT, DCT, and corneal-compensated ORA IOP in the control group was 12.6 (2.9 mmHg, 15.5 (2.7 mmHg, and 15.8 (3.4 mmHg, respectively. There were significant differences in IOP values between dystrophy and control groups obtained by GAT (mean, -7.2 mmHg; 99% confidence interval [CI], -10.5 to -3.9 mmHg; P<0.001, DCT (mean, -5.9 mmHg; 99% CI, -8.9 to -2.8 mmHg; P<0.001, and corneal-compensated ORA measurements (mean, -5.7 mmHg; 99% CI, -10.4 to -1.0 mmHg; P=0.003. The mean (SD central corneal thickness was similar in the dystrophy (542 [31] µm and control (537 [11] µm groups (P=0.65. The mean (SD corneal hysteresis in the dystrophy and control groups were 11.2 (1.5 mmHg and 9.7 (1.2 mmHg, respectively (P=0.04. CONCLUSIONS: Patients with Steinert's myotonic dystrophy showed lower Goldmann and corneal-compensated IOP in comparison with healthy individuals. Since central corneal thickness and

MR imaging of fukuyama congenital muscular dystrophy; a case report

International Nuclear Information System (INIS)

Yoo, Jeong Hyun; Kim, Yoo Kyung; Koo, Hae Soo; Park, Ki Deuk

2000-01-01

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

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

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......: The purpose of the study was to validate a new automated canine-specific immunoturbidimetric CRP method (Gentian cCRP). METHODS: Studies of imprecision, accuracy, prozone effect, interference, limit of quantification, and stability under different storage conditions were performed. The new method was compared...... 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

Control rod cluster with removable rods for nuclear fuel assembly

International Nuclear Information System (INIS)

Denizou, J.P.

1989-01-01

For each removable control rod, the open end section of the sleeve has a certain length of reduced diameter with openings in its wall. The top end of the rod is joined to an extension tube that surrounds the shaft over part of its lenght. This extension tube fits over the reduced part of the sleeve when the shaft is screwed into the bore of the sleeve. Rotation of the rod in the sleeve is prevented by deforming the extension tube locally in the openings of the end part of the sleeve. The rod is dismantled by exerting a torque on it using a gripping area near the end of the rod [fr

[Congenital myotonic dystrophy in a Neonatal Intensive Care Unit: case series].

Science.gov (United States)

Domingues, Sara; Alves Pereira, Clara; Machado, Angela; Pereira, Sandra; Machado, Leonilde; Fraga, Carla; Oliveira, Abílio; Vale, Isabel; Quelhas, Ilídio

2014-02-01

Steinert myotonic dystrophy is a multisystemic disease, autosomal dominant, with a wide spectrum of severity and clinical manifestations. The most severe form is one that manifests in the neonatal period, called congenital myotonic dystrophy. This condition is distinguished by overall hypotonia at birth and respiratory function compromise. Complications are frequent, mainly psychomotor development delay, growth failure, food difficulties and constipation. It is associated with a poor prognosis, with an overall mortality of up to 50% of severely affected children. We present five patients with congenital myotonic dystrophy in order to describe clinical manifestations, diagnosis, treatment and prognosis. Existing data in the literature on psychomotor development, complications and prognosis of survivors with congenital myotonic dystrophy are scarce. In our case studies, we have found significant chronic psychomotor limitations.

Control rod drive mechanism

International Nuclear Information System (INIS)

Nakamura, Akira.

1981-01-01

Purpose: To ensure the scram operation of a control rod by the reliable detection for the position of control rods. Constitution: A permanent magnet is provided to the lower portion of a connecting rod in engagement with a control rod and a tube having a plurality of lead switches arranged axially therein in a predetermined pitch is disposed outside of the control rod drives. When the control rod moves upwardly in the scram operation, the lead switches are closed successively upon passage of the permanent magnet to operate the electrical circuit provided by way of each of the lead switches. Thus, the position for the control rod during the scram can reliably be determined and the scram characteristic of the control rod can be recognized. (Furukawa, Y.)

Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged retinoic acid exposure

Directory of Open Access Journals (Sweden)

Cameron David A

2011-08-01

Full Text Available Abstract Background Retinoic acid (RA is important for vertebrate eye morphogenesis and is a regulator of photoreceptor development in the retina. In the zebrafish, RA treatment of postmitotic photoreceptor precursors has been shown to promote the differentiation of rods and red-sensitive cones while inhibiting the differentiation of blue- and UV-sensitive cones. The roles played by RA and its receptors in modifying photoreceptor fate remain to be determined. Results Treatment of zebrafish embryos with RA, beginning at the time of retinal progenitor cell proliferation and prior to photoreceptor terminal mitosis, resulted in a significant alteration of rod and cone mosaic patterns, suggesting an increase in the production of rods at the expense of red cones. Quantitative pattern analyses documented increased density of rod photoreceptors and reduced local spacing between rod cells, suggesting rods were appearing in locations normally occupied by cone photoreceptors. Cone densities were correspondingly reduced and cone photoreceptor mosaics displayed expanded and less regular spacing. These results were consistent with replacement of approximately 25% of positions normally occupied by red-sensitive cones, with additional rods. Analysis of embryos from a RA-signaling reporter line determined that multiple retinal cell types, including mitotic cells and differentiating rods and cones, are capable of directly responding to RA. The RA receptors RXRγ and RARαb are expressed in patterns consistent with mediating the effects of RA on photoreceptors. Selective knockdown of RARαb expression resulted in a reduction in endogenous RA signaling in the retina. Knockdown of RARαb also caused a reduced production of rods that was not restored by simultaneous treatments with RA. Conclusions These data suggest that developing retinal cells have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may influence the rod vs. cone cell fate

Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

Science.gov (United States)

Mazade, Reece E.

2013-01-01

Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light. PMID:23926034

Development of Non-Hormonal Steroids for the Treatment of Duchenne Muscular Dystrophy

Science.gov (United States)

2013-02-01

constructs envisioned in gene therapy, are also expressed in Becker muscular dystrophy (alleles of dystrophinopathy leading to milder disease). In other words...the Treatment of Duchenne Muscular Dystrophy PRINCIPAL INVESTIGATOR: Terence Partridge, PhD CONTRACTING ORGANIZATION: Children’s...Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0754 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Terence Partridge

Method of inserting fuel rod

International Nuclear Information System (INIS)

Kamimoto, Shuji; Imoo, Makoto; Tsuchida, Kenji.

1991-01-01

The present invention concerns a method of inserting a fuel rod upon automatic assembling, automatic dismantling and reassembling of a fuel assembly in a light water moderated reactor, as well as a device and components used therefor. That is, a fuel rod is inserted reliably to an aimed point of insertion by surrounding the periphery of the fuel rod to be inserted with guide rods, and thereby suppressing the movement of the fuel rod during insertion. Alternatively, a fuel rod is inserted reliably to a point of insertion by inserting guide rods at the periphery of the point of insertion for the fuel rod to be inserted thereby surrounding the point of insertion with the guide rods or fuel rods. By utilizing fuel rods already present in the fuel assembly as the guide rods described above, the fuel rod can be inserted reliably to the point of insertion with no additional devices. Dummy fuel rods are previously inserted in a fuel assembly which are then utilized as the above-mentioned guide rods to accurately insert the fuel rod to the point of insertion. (I.S.)

Three-year serologic immunity against canine parvovirus type 2 and canine adenovirus type 2 in dogs vaccinated with a canine combination vaccine.

Science.gov (United States)

Larson, L J; Schultz, R D

2007-01-01

A group of client-owned dogs and a group of dogs at a commercial kennel were evaluated for duration of antibody responses against canine parvovirus type 2 (CPV-2) and canine adenovirus type 1 (CAV-1) after receiving a combination vaccine containing recombinant canarypox-vectored canine distemper virus (CDV) and modified-live CPV-2, CAV-2, and canine parainfluenza virus, with (C6) or without (C4) two serovars of Leptospira (Recombitek C4 or C6, Merial). Duration of antibody, which correlates with protective immunity, was found to be at least 36 months in both groups. Recombitek combination vaccines can confidently be given every 3 years with assurance of protection in immunocompetent dogs against CPV-2 and CAV-1 as well as CDV. This allows this combination vaccine, like other, similar modified- live virus combination products containing CDV, CAV-2, and CPV-2, to be administered in accordance with the recommendations of the American Animal Hospital Association Canine Vaccine Task Force.

Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials.

Science.gov (United States)

Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S; Verschuuren, Jan J; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E; Muntoni, Francesco

2011-12-01

Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both

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. © The Author 2015. Published by Oxford University Press.

Aberrant Myokine Signaling in Congenital Myotonic Dystrophy

Directory of Open Access Journals (Sweden)

Masayuki Nakamori

2017-10-01

Full Text Available Summary: Myotonic dystrophy types 1 (DM1 and 2 (DM2 are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM, a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6 myokine signaling pathway in CDM muscles. We also found a correlation between muscle immaturity and not only IL-6 expression but also expanded CTG repeat length and CpG methylation status upstream of the repeats. Aberrant CpG methylation was associated with transcriptional dysregulation at the repeat locus, increasing the toxic RNA burden that upregulates IL-6. Because the IL-6 pathway is involved in myocyte maturation and muscle atrophy, our results indicate that enhanced RNA toxicity contributes to severe CDM phenotypes through aberrant IL-6 signaling. : Congenital myotonic dystrophy (CDM manifests characteristic genetic (very large CTG repeat expansions, epigenetic (CpG hypermethylation upstream of the repeat, and phenotypic (muscle immaturity features not seen in adult DM. Nakamori et al. find phenotype-genotype and epigenotype correlation in CDM muscle and reveal involvement of the IL-6 myokine signaling pathway in the disease process. Keywords: CTCF, ER stress, IL-6, muscular dystrophy, NF-κB, trinucleotide, cytokine, splicing

Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe

Directory of Open Access Journals (Sweden)

Anna McRee

2014-09-01

Full Text Available Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV and canine distemper virus (CDV, which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV. These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34% had detectable antibodies to CDV, whilst 191 (84% had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13% dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission.

Serological detection of infection with canine distemper virus, canine parvovirus and canine adenovirus in communal dogs from Zimbabwe.

Science.gov (United States)

McRee, Anna; Wilkes, Rebecca P; Dawson, Jessica; Parry, Roger; Foggin, Chris; Adams, Hayley; Odoi, Agricola; Kennedy, Melissa A

2014-09-05

Domestic dogs are common amongst communities in sub-Saharan Africa and may serve as important reservoirs for infectious agents that may cause diseases in wildlife. Two agents of concern are canine parvovirus (CPV) and canine distemper virus (CDV), which may infect and cause disease in large carnivore species such as African wild dogs and African lions, respectively. The impact of domestic dogs and their diseases on wildlife conservation is increasing in Zimbabwe, necessitating thorough assessment and implementation of control measures. In this study, domestic dogs in north-western Zimbabwe were evaluated for antibodies to CDV, CPV, and canine adenovirus (CAV). These dogs were communal and had no vaccination history. Two hundred and twenty-five blood samples were collected and tested using a commercial enzyme-linked immunosorbent assay (ELISA) for antibodies to CPV, CDV, and CAV. Of these dogs, 75 (34%) had detectable antibodies to CDV, whilst 191 (84%) had antibodies to CPV. Antibodies to canine adenovirus were present in 28 (13%) dogs. Canine parvovirus had high prevalence in all six geographic areas tested. These results indicate that CPV is circulating widely amongst domestic dogs in the region. In addition, CDV is present at high levels. Both pathogens can infect wildlife species. Efforts for conservation of large carnivores in Zimbabwe must address the role of domestic dogs in disease transmission.

Control rod drives

International Nuclear Information System (INIS)

Hayakawa, Hiroyasu.

1979-01-01

Purpose: To enable rapid control in a simple circuit by providing a motor control device having an electric capacity capable of simultaneously driving all of the control rods rapidly only in the inserting direction as well as a motor controlling device capable of fine control for the insertion and extraction at usual operation. Constitution: The control rod drives comprise a first motor control device capable of finely controlling the control rods both in inserting and extracting directions, a second motor control device capable of rapidly driving the control rods only in the inserting direction, and a first motor switching circuit and a second motor switching circuit switched by switches. Upon issue of a rapid insertion instruction for the control rods, the second motor switching circuit is closed by the switch and the second motor control circuit and driving motors are connected. Thus, each of the control rod driving motors is driven at a high speed in the inserting direction to rapidly insert all of the control rods. (Yoshino, Y.)

Prevalence of cardiomyopathy in duchenne and becker's muscular dystrophy

International Nuclear Information System (INIS)

Sultan, A.; Fayaz, M.

2008-01-01

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)

Berkeley Lighting Cone

Energy Technology Data Exchange (ETDEWEB)

Lask, Kathleen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gadgil, Ashok [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2016-10-24

A lighting cone is a simple metal cone placed on the fuel bed of a stove during ignition to act as a chimney, increasing the draft through the fuel bed. Many stoves tend to be difficult to light due to poor draft through the fuel bed, so lighting cones are used in various parts of the world as an inexpensive accessory to help with ignition.

Muscular Dystrophy: Hope Through Research

Science.gov (United States)

... of muscular dystrophy appeared in 1830, when Sir Charles Bell wrote an essay about an illness that ... linked disorder to their sons but their daughters will be carriers of that disorder. Carrier females occasionally ...

Acute Zonal Cone Photoreceptor Outer Segment Loss.

Science.gov (United States)

Aleman, Tomas S; Sandhu, Harpal S; Serrano, Leona W; Traband, Anastasia; Lau, Marisa K; Adamus, Grazyna; Avery, Robert A

2017-05-01

The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if

Canine gastritis.

Science.gov (United States)

Webb, Craig; Twedt, David C

2003-09-01

Gastritis--inflammation of the stomach--is a frequently cited differential yet rarely characterized diagnosis in cases of canine anorexia and vomiting. Although the list of rule-outs for acute or chronic gastritis is extensive, a review of the veterinary literature reveals fewer than 15 articles that have focused on clinical cases of canine gastritis over the last 25 years. The dog frequently appears in the human literature as an experimentally manipulated model for the study of endoscopic techniques or the effect of medications on gastric mucosa. In the veterinary patient, cases of acute gastritis are rarely pursued with the complete diagnostic armamentarium, and cases of chronic gastritis are rarely found to occur as an entity isolated from the rest of the gastrointestinal tract. This article focuses on those findings most clinically relevant to cases of canine gastritis in veterinary medicine.

Varied clinico-radiological presentations of transmigrated canines

Directory of Open Access Journals (Sweden)

Ishita Gupta

2015-01-01

Full Text Available Canine is one of the most commonly impacted teeth in the dental arch. An unerupted permanent canine crossing the midline is called transmigration and is an unusual event. We report nine cases of impacted canine transmigration. Maxillary canine transmigration, bilateral transmigration, and transmigration associated with odontoma are rare presentations. This article discusses the varied clinico-radiologic presentations, etiology, and treatment options of transmigration. It also emphasizes the importance of panoramic radiographs for evaluation of over-retained deciduous canines or missing permanent canines.

How Physicians Support Mothers of Children with Duchenne Muscular Dystrophy.

Science.gov (United States)

Fujino, Haruo; Saito, Toshio; Matsumura, Tsuyoshi; Shibata, Saki; Iwata, Yuko; Fujimura, Harutoshi; Shinno, Susumu; Imura, Osamu

2015-09-01

Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child's concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness. © The Author(s) 2015.

Muscle-Eye-Brain Disease; a Rare Form of Syndromic Congenital Muscular Dystrophy

Directory of Open Access Journals (Sweden)

Gosal Gurinder S

2011-03-01

Full Text Available Congenital muscular dystrophy (CMD is a heterogeneous group of disorders characterized by muscular hypotonia since birth and the histologic features of muscular dystrophy. Syndromic congenital muscular dystrophies are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We present a case of a rare form of syndromic congenital muscular dystrophy in an eight year old girl, born of first- degree consanguinity. She had: global developmental delay; a seizure disorder; hypotonia; progressive muscle contractures including bilateral symmetrical flexion contractures of hips, knees, equinus contracture and thoracolumbar scoliosis; diminished deep tendon reflexes: bilateral premature cataract; pseudophakia; and nystagmus. The patient was also highly myopic. Based on clinical features, muscle biopsy and MRI of the brain, a diagnosis of muscle- eye- brain disease was made. Identification of these patients may help to prevent this crippling disorder in the future siblings of probands by utilizing genetic counselling and mutation analysis.

Fission reactor control rod

International Nuclear Information System (INIS)

Irie, Tomoo.

1991-01-01

The present invention concerns a control rod in a PWR type reactor. A control rod has an inner cladding tube and an outer cladding tube disposed coaxially, and a water draining hole is formed at the inside of the inner cladding tube. Neutron absorbers are filled in an annular gap between the outer cladding tube and the inner cladding tube. The water draining hole opens at the lower end thereof to the top end of the control rod and at the upper end thereof to the side of the upper end plug of the control rod. If the control rod is dropped to a control rod guide thimble for reactor scram, coolants from the control rod guide thimble are flown from the lower end of the water draining hole and discharged from the upper end passing through the water draining hole. In this way, water from the control rod guide thimble is removed easily when the control rod is dropped. Further, the discharging amount of water itself is reduced by the provision of the water draining hole. Accordingly, sufficient control rod dropping speed can be attained. (I.N.)

Fuel rod simulator effects in flooding experiments single rod tests

International Nuclear Information System (INIS)

Nishida, M.

1984-09-01

The influence of a gas filled gap between cladding and pellet on the quenching behavior of a PWR fuel rod during the reflood phase of a LOCA has been investigated. Flooding experiments were conducted with a short length electrically heated single fuel rod simulator surrounded by glass housing. The gap of 0.05 mm width between the Zircaloy cladding and the internal Al 2 O 3 pellets of the rod was filled either wit helium or with argon to vary the radial heat resistance across the gap. This report presents some typical data and an evaluation of the reflood behavior of the fuel rod simulator used. The results show that the quench front propagates faster for increasing heat resistance in the gap between cladding and heat source of the rod. (orig.) [de

Bilateral nanophthalmos and pigmentary retinal dystrophy--an unusual syndrome.

Science.gov (United States)

Proença, Helena; Castanheira-Dinis, A; Monteiro-Grillo, M

2006-09-01

To report the clinical picture of the rare association of nanophthalmos and pigmentary retinal dystrophy and its cataract surgery outcome. We report a case of a 60-year-old female who presented with bilateral slowly progressive visual loss. The patient presented with bilateral light perception visual acuity, exotropia, brunescent cataract hindering fundus examination and hypodontia. Ultrasonography revealed bilateral nanophthalmos. A visual-evoked potential was also performed preoperatively. Cataract surgery with +40D IOL implantation was uneventful. Postoperative fundus examination revealed pigmentary retinal dystrophy, confirmed by electrophysiologic tests. Glycosaminoglycan urinary excretion was normal. Congenital bilateral nanophthalmos may rarely be associated with pigmentary retinal dystrophy. We suggest thorough preoperative evaluation in nanophthalmic eyes for the exclusion of significant features concerning visual prognosis.

Meaning of Muscular Dystrophy

Science.gov (United States)

... is very similar to Duchenne, except kids with Becker MD may not have problems until much later, when they're teenagers or adults. It takes a long time for their muscles to become weak. How Does a Kid Get Muscular Dystrophy? MD is not contagious (say: con-TAY-juss), ...

NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP).

Science.gov (United States)

Schorderet, Daniel F; Escher, Pascal

2009-11-01

NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients is night blindness, rudimental or absent rod function, and hyperfunction of the "blue" S-cones. A single p.G56R mutation is inherited in a dominant manner and causes retinitis pigmentosa (RP). We have established a new locus-specific database for NR2E3 (www.LOVD.nl/eye), containing all reported mutations, polymorphisms, and unclassified sequence variants, including novel ones. A high proportion of mutations are located in the evolutionarily-conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) of NR2E3. Based on homology modeling of these NR2E3 domains, we propose a structural localization of mutated residues. The high variability of clinical phenotypes observed in patients affected by NR2E3-linked retinal degenerations may be caused by different disease mechanisms, including absence of DNA-binding, altered interactions with transcriptional coregulators, and differential activity of modifier genes.

Maximum/minimum asymmetric rod detection

International Nuclear Information System (INIS)

Huston, J.T.

1990-01-01

This patent describes a system for determining the relative position of each control rod within a control rod group in a nuclear reactor. The control rod group having at least three control rods therein. It comprises: means for producing a signal representative of a position of each control rod within the control rod group in the nuclear reactor; means for establishing a signal representative of the highest position of a control rod in the control rod group in the nuclear reactor; means for establishing a signal representative of the lowest position of a control rod in the control rod group in the nuclear reactor; means for determining a difference between the signal representative of the position of the highest control rod and the signal representative of the position of the lowest control rod; means for establishing a predetermined limit for the difference between the signal representative of the position of the highest control rod and the signal representative of the position of the lowest control rod; and means for comparing the difference between the signals with the predetermined limit. The comparing means producing an output signal when the difference between the signals exceeds the predetermined limit

Urological manifestations of Duchenne muscular dystrophy.

Science.gov (United States)

Askeland, Eric J; Arlen, Angela M; Erickson, Bradley A; Mathews, Katherine D; Cooper, Christopher S

2013-10-01

Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Progress in light cone physics

International Nuclear Information System (INIS)

Preparata, G.

1973-01-01

A very brief review is given of the progress made in the physics of the light cone in the past year. Included are the light cone expansion, gauge invariance and the consequences of precocious scaling near threshold, the light cone description of the muon pair experiment, light cone expansions, and the assessment and exploitation of analyticity properties in both mass and energy of light cone amplitudes. (U.S.)

Disparities in the diagnostic process of Duchenne and Becker muscular dystrophy.

Science.gov (United States)

Holtzer, Caleb; Meaney, F John; Andrews, Jennifer; Ciafaloni, Emma; Fox, Deborah J; James, Katherine A; Lu, Zhenqiang; Miller, Lisa; Pandya, Shree; Ouyang, Lijing; Cunniff, Christopher

2011-11-01

To determine whether sociodemographic factors are associated with delays at specific steps in the diagnostic process of Duchenne and Becker muscular dystrophy. We examined abstracted medical records for 540 males from population-based surveillance sites in Arizona, Colorado, Georgia, Iowa, and western New York. We used linear regressions to model the association of three sociodemographic characteristics with age at initial medical evaluation, first creatine kinase measurement, and earliest DNA analysis while controlling for changes in the diagnostic process over time. The analytical dataset included 375 males with information on family history of Duchenne and Becker muscular dystrophy, neighborhood poverty levels, and race/ethnicity. Black and Hispanic race/ethnicity predicted older ages at initial evaluation, creatine kinase measurement, and DNA testing (P Becker muscular dystrophy predicted younger ages at initial evaluation, creatine kinase measurement and DNA testing (P Becker muscular dystrophy are evident even after adjustment for family history of Duchenne and Becker muscular dystrophy and changes in the diagnostic process over time. Black and Hispanic children are initially evaluated at older ages than white children, and the gap widens at later steps in the diagnostic process.

Ejecta evolution during cone impact

KAUST Repository

Marston, Jeremy

2014-07-07

We present findings from an experimental investigation into the impact of solid cone-shaped bodies onto liquid pools. Using a variety of cone angles and liquid physical properties, we show that the ejecta formed during the impact exhibits self-similarity for all impact speeds for very low surface tension liquids, whilst for high-surface tension liquids similarity is only achieved at high impact speeds. We find that the ejecta tip can detach from the cone and that this phenomenon can be attributed to the air entrainment phenomenon. We analyse of a range of cone angles, including some ogive cones, and impact speeds in terms of the spatiotemporal evolution of the ejecta tip. Using superhydrophobic cones, we also examine the entry of cones which entrain an air layer.

Genetics and emerging treatments for Duchenne and Becker muscular dystrophy.

Science.gov (United States)

Wein, Nicolas; Alfano, Lindsay; Flanigan, Kevin M

2015-06-01

Mutations in the DMD gene result in Duchenne or Becker muscular dystrophy due to absent or altered expression of the dystrophin protein. The more severe Duchenne muscular dystrophy typically presents around ages 2 to 5 with gait disturbance, and historically has led to the loss of ambulation by age 12. It is important for the practicing pediatrician, however, to be aware of other presenting signs, such as delayed motor or cognitive milestones, or elevated serum transaminases. Becker muscular dystrophy is milder, often presenting after age 5, with ambulation frequently preserved past 20 years and sometimes into late decades. Copyright © 2015 Elsevier Inc. All rights reserved.

Percussion drilling cone penetrometer with wireless operating in-tip gaschromatograph

Energy Technology Data Exchange (ETDEWEB)

Bracht, C.; Matz, G. [Technische Univ. Hamburg-Harburg, Hamburg (Germany)

2003-07-01

Percussion drilling cone penetrometric analysis is the fast alternative to soil sampling and laboratory analyses. Online detection enables the characterization of a large variety of contaminants in soil. This becomes very important in the reactivation of contaminated sites. Therefore a new system has been constructed, which avoids tedious harness handling through the penetrometer drill rods and minimizes the time for an analysis down to 30 minutes per drill hole. This system enables the in-situ analysis of soil gases up to a depth of 10 to 15 meters. This system consists of a remote controlled in-tip mounted gaschromatograph, a special gas inlet module and a data transfer unit including a rechargeable battery pack. The modules are shock proved to be suitable for percussion drilling techniques and can be removed easily for maintenance. A PDA (Pocket PC) controls the subsoil gaschromatograph unit, calculates and displays the concentration of the detected compounds and stores the acquired data. The gaschromatograph until is optimized to analyze VOCs e.g. BTEX within 10 seconds per analysis. It consists of a loop inlet, a capillary column and a Photo Ionization Detector. It is microcontroller operated and battery powered. The inlet module is optimized soil gases. It includes a sensor and solenoid valve system for water protection and humidity acquisition while drilling. A completely charged battery pack provides up to three hours of analyses. It could be exchanged fast and easy to enable continuous analyses. Digital data transfer between subsoil unit and surface is provided wireless by IR light through the rods. On surface data is transferred wireless by BLUETOOTH radio link to the PDA. The depth of the penetrometer, global position and local time are acquired on-line onto the surface and are transferred on request by BLUETOOTH radio link to the PDA. The wireless data transfer and battery powered modules avoid time consuming cable handling and enable this cone

Control rod drives

International Nuclear Information System (INIS)

Hayakawa, Hiroyasu; Kawamura, Atsuo.

1979-01-01

Purpose: To reduce pellet-clad mechanical interactions, as well as improve the fuel safety. Constitution: In the rod drive of a bwr type reactor, an electric motor operated upon intermittent input such as of pulse signals is connected to a control rod. A resolver for converting the rotational angle of the motor to electric signals is connected to the rotational shaft of the motor and the phase difference between the output signal from the resolver and a reference signal is adapted to detect by a comparator. Based on the detection result, the controller is actuated to control a motor for control rod drive so that fine control for the movement of the control rod is made possible. This can reduce the moving distance of the control rod, decrease the thermal stress applied to the control rod and decrease the pellet clad mechanical interaction failures due to thermal expansion between the cladding tube and the pellets caused by abrupt changes in the generated power. (Furukawa, Y.)

Limb girdle muscular dystrophy due to mutations in POMT2

DEFF Research Database (Denmark)

Østergaard, Sofie Thurø; Johnson, Katherine; Stojkovic, Tanya

2018-01-01

BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four...

Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge

Directory of Open Access Journals (Sweden)

Parish M

2018-02-01

Full Text Available Masoud Parish, Haleh Farzin Anesthesiology Department, Tabriz University of Medical Sciences, Shohada Teaching Hospital, Tabriz, Iran Abstract: Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications. Keywords: Becker dystrophy, orthopedic surgery, adult, intravenous anesthesia

[Human myopathy and animal muscular dystrophy].

Science.gov (United States)

Schapira, G; Dreyfus, J C; Schapira, F

1977-08-01

Two hereditary muscular dystrophies similar to human progressive muscular dystrophy (P.M.D. Duchenne type) have been isolated in animals, one in mouse, the other in chicken. The decrease in the activity of glycogenolytic enzymes is similar to that observed in denervated muscle. Isozymic fetal types for several muscular enzymes have been observed as well in chicken as in man, but this fetal type may also be found in neurogenic atrophy. The release in circulation of muscle enzymes seems more specific. But the origin of the genetic lesion is still unknown. We describe here the three different theories about this problem: i.e. neurogenic, vascular, or myogenic. This last theory implies a trouble of membrane permeability.

Development of the canine tooth in the beagle

International Nuclear Information System (INIS)

Amimoto, A.; Iwamoto, S.; Hachimura, H.; Miyamoto, T.; Murata, T.; Taura, Y.; Nakama, S.; Hayashi, K.

1993-01-01

The growth of the crown and root in the canine tooth of beagle dogs were observed macroscopically and radiographically, and changes of occlusion with age were investigated. Completion of growth in the crown of the canine tooth was observed in both mandible and maxilla, and its eruption was accompanied by development of the dental root. The permanent canine erupted on the lingual side of deciduous canine in the mandible, and on the mesial side of the deciduous canine in the maxilla. Movement of the permanent canine to normal occlusal position(buccal direction in mandibular canine, and distal direction in maxillary canine)was followed by the loss of the deciduous canine. Coexistence of the permanent and deciduous canines occurred for about 2.4 weeks in the maxilla and about 1.4 weeks in the mandible, on average. Macroscopically, the growth of the permanent canine was completed by 33 weeks of age in the mandible and about 34 weeks of age in the maxilla. The mature root of the permanent canine was recognized radiographically at about 43 weeks of age in the mandible and 47 weeks of age in the maxilla

KPG Index versus OPG Measurements: A Comparison between 3D and 2D Methods in Predicting Treatment Duration and Difficulty Level for Patients with Impacted Maxillary Canines

Directory of Open Access Journals (Sweden)

Domenico Dalessandri

2014-01-01

Full Text Available Aim. The aim of this study was to test the agreement between orthopantomography (OPG based 2D measurements and the KPG index, a new index based on 3D Cone Beam Computed Tomography (CBCT images, in predicting orthodontic treatment duration and difficulty level of impacted maxillary canines. Materials and Methods. OPG and CBCT images of 105 impacted canines were independently scored by three orthodontists at t0 and after 1 month (t1, using the KPG index and the following 2D methods: distance from cusp tip and occlusal plane, cusp tip position in relation to the lateral incisor, and canine inclination. Pearson’s coefficients were used to evaluate the degree of agreement and the χ2 with Yates correction test was used to assess the independence between them. Results. Inter- and intrarater reliability were higher with KPG compared to 2D methods. Pearson’s coefficients showed a statistically significant association between all the indexes, while the χ2 with Yates correction test resulted in a statistically significant rejection of independency only for one 2D index. Conclusions. 2D indexes for predicting impacted maxillary canines treatment duration and difficulty sometimes are discordant; a 3D index like the KPG index could be useful in solving these conflicts.

Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy

NARCIS (Netherlands)

van der Kooi, A. J.; Bonne, G.; Eymard, B.; Duboc, D.; Talim, B.; van der Valk, M.; Reiss, P.; Richard, P.; Demay, L.; Merlini, L.; Schwartz, K.; Busch, H. F. M.; de Visser, M.

2002-01-01

Mutations in the lamin A/C gene are found in Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy with cardiac conduction disturbances, dilated cardiomyopathy with conduction system disease, and familial partial lipodystrophy. Cases with lamin A/C mutations presenting with lipodystrophy

Ontogeny of canine dimorphism in extant hominoids.

Science.gov (United States)

Schwartz, G T; Dean, C

2001-07-01

Many behavioral and ecological factors influence the degree of expression of canine dimorphism for different reasons. Regardless of its socioecological importance, we know virtually nothing about the processes responsible for the development of canine dimorphism. Our aim here is to describe the developmental process(es) regulating canine dimorphism in extant hominoids, using histological markers of tooth growth. Teeth preserve a permanent record of their ontogeny in the form of short- and long-period incremental markings in both enamel and dentine. We selected 52 histological sections of sexed hominoid canine teeth from a total sample of 115, from which we calculated the time and rate of cuspal enamel formation and the rate at which ameloblasts differentiate along the future enamel-dentine junction (EDJ) to the end of crown formation. Thus, we were able to reconstruct longitudinal growth curves for height attainment in male and female hominoid canines. Male hominoids consistently take longer to form canine crowns than do females (although not significantly so for our sample of Homo). Male orangutans and gorillas occasionally take up to twice as long as females to complete enamel formation. The mean ranges of female canine crown formation times are similar in Pan, Gorilla, and Pongo. Interspecific differences between female Pan canine crown heights and those of Gorilla and Pongo, which are taller, result from differences in rates of growth. Differences in canine crown heights between male Pan and the taller, more dimorphic male Gorilla and Pongo canines result both from differences in total time taken to form enamel and from faster rates of growth in Gorilla and Pongo. Although modern human canines do not emerge as significantly dimorphic in this study, it is well-known that sexual dimorphism in canine crown height exists. Larger samples of sexed modern human canines are therefore needed to identify clearly what underlies this. Copyright 2001 Wiley-Liss, Inc.

Correlation Between Cone Penetration Rate And Measured Cone Penetration Parameters In Silty Soils

DEFF Research Database (Denmark)

Poulsen, Rikke; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

2013-01-01

This paper shows, how a change in cone penetration rate affects the cone penetration measurements, hence the cone resistance, pore pressure, and sleeve friction in silty soil. The standard rate of penetration is 20 mm/s, and it is generally accepted that undrained penetration occurs in clay while...... drained penetration occurs in sand. When lowering the penetration rate, the soil pore water starts to dissipate and a change in the drainage condition is seen. In intermediate soils such as silty soils, the standard cone penetration rate may result in a drainage condition that could be undrained......, partially or fully drained. However, lowering the penetration rate in silty soils has a great significance because of the soil permeability, and only a small change in penetration rate will result in changed cone penetration measurements. In this paper, analyses will be done on data from 15 field cone...

Status of rod consolidation

International Nuclear Information System (INIS)

Bailey, W.J.

1985-04-01

Two of the factors that need to be taken into account with rod consolidation are (1) the effects on rods from their removal from the fuel assembly and (2) the effects on rods as a result of the consolidation process. Potential components of both factors are described in the report. Discussed under (1) are scratches on the fuel rod surfaces, rod breakage, crud, extended burnup, and possible cladding embrittlement due to hydrogen injection at BWRs. Discussed under (2) are the increased water temperature (less than 10 0 C) because of closer packing of the rods, formation of crevices between rods in the close-packed mode, contact with dissimilar metals, and the potential for rapid heating of fuel rods following the loss of water from a spent fuel storage pool. Another factor that plays an important role in rod consolidation is the cost of disposal of the nonfuel-bearing components of the fuel assembly. Also, the dose rate from the components - especially Inconel spacer grids - can affect the handling procedures. Several licensing issues that exist are described. A list of recommendations is provided. 98 refs., 5 figs., 5 tabs

Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1.

Science.gov (United States)

Zhang, Chun-Li; Zou, Yuhua; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2006-05-15

During mammalian embryogenesis, precise coordination of progenitor cell proliferation and differentiation is essential for proper organ size and function. The involvement of TLX (NR2E1), an orphan nuclear receptor, has been implicated in ocular development, as Tlx-/- mice exhibit visual impairment. Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1. Additionally, TLX finely tunes the progenitor differentiation program by modulating the phospholipase C and mitogen-activated protein kinase (MAPK) pathways and the expression of an array of cell type-specific transcriptional regulators. Consequently, Tlx-/- mice have a dramatic reduction in retina thickness and enhanced generation of S-cones, and develop severe early onset retinal dystrophy. Furthermore, TLX interacts with atrophin1 (Atn1), a corepressor that is involved in human neurodegenerative dentatorubral-pallidoluysian atrophy (DRPLA) and that is essential for development of multiple tissues. Together, these results reveal a molecular strategy by which an orphan nuclear receptor can precisely orchestrate tissue-specific proliferation and differentiation programs to prevent retinal malformation and degeneration.

Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus.

Science.gov (United States)

Gore, Thomas C; Lakshmanan, Nallakannu; Duncan, Karen L; Coyne, Michael J; Lum, Melissa A; Sterner, Frank J

2005-01-01

A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.

Booster effect of canine distemper, canine parvovirus infection and infectious canine hepatitis combination vaccine in domesticated adult dogs.

Science.gov (United States)

Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Tsuchiya, Ryo; Sahara, Hiroeki

2012-08-01

Domesticated adult dogs with antibody titer classified as below 'high' to one or more of canine distemper virus (CDV), canine parvovirus type-2 (CPV-2) and canine adenovirus type-1 (CAdV-1) were then given an additional inoculation, and the effectiveness of this booster evaluated 2 months later. Consequently, CDV and CAdV-1 antibody titer experienced a significant increase, but the same effect was not observed in the antibody titer of CPV-2. These findings suggest that with additional inoculation, a booster effect may be expected in increasing antibody titers for CDV and CAdV-1, but it is unlikely to give an increase in CPV-2 antibody titer. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

The retinal phenotype of Usher syndrome: pathophysiological insights from animal models.

Science.gov (United States)

El-Amraoui, Aziz; Petit, Christine

2014-03-01

The Usher syndrome (USH) is the most prevalent cause of inherited deaf-blindness. Three clinical subtypes, USH1-3, have been defined, and ten USH genes identified. The hearing impairment due to USH gene defects has been shown to result from improper organisation of the hair bundle, the sound receptive structure of sensory hair cells. In contrast, the cellular basis of the visual defect is less well understood as this phenotype is absent in almost all the USH mouse models that faithfully mimic the human hearing impairment. Structural and molecular interspecies discrepancies regarding photoreceptor calyceal processes and the association with the distribution of USH1 proteins have recently been unravelled, and have led to the conclusion that a defect in the USH1 protein complex-mediated connection between the photoreceptor outer segment and the surrounding calyceal processes (in both rods and cones), and the inner segment (in rods only), probably causes the USH1 retinal dystrophy in humans. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice

Science.gov (United States)

Sahly, Iman; Dufour, Eric; Schietroma, Cataldo; Michel, Vincent; Bahloul, Amel; Perfettini, Isabelle; Pepermans, Elise; Estivalet, Amrit; Carette, Diane; Aghaie, Asadollah; Ebermann, Inga; Lelli, Andrea; Iribarne, Maria; Hardelin, Jean-Pierre; Weil, Dominique; Sahel, José-Alain

2012-01-01

The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins—myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans—do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner–outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients. PMID:23045546

Bilateral supernumerary primary maxillary canines

Directory of Open Access Journals (Sweden)

Santanu Mukhopadhyay

2018-01-01

Full Text Available Supernumerary teeth are more common in the permanent than in primary dentition. In the primary dentition, the anomaly is most frequently observed in the maxillary lateral incisor region, followed by the maxillary midline where they are termed as mesiodens. Supernumerary teeth in the primary canine region are rare. This paper describes a rare case of nonsyndromic supernumerary primary maxillary canine distributed bilaterally in a 4-year-old boy. Both the supernumeraries resembled size and shape of normal primary canine. The right supplemental canine is high labially placed, whereas the left one is seen normally aligned in the dental arch distal to lateral incisor. One of the most significant sequelae of primary supernumerary teeth is their duplication in the permanent series. Radiographic examination of supernumerary primary canine did not indicate any such anomaly in the permanent dentition. The patient was kept under observation.

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.

Dysphagia is present but mild in myotonic dystrophy type 2

NARCIS (Netherlands)

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

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

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 the...

Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy.

Science.gov (United States)

Tatulli, F; Caraglia, A; Delcuratolo, A; Cassano, S; Chetta, G S

2017-01-01

Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful. A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine. Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy.

Serum creatinine level: a supplemental index to distinguish Duchenne muscular dystrophy from Becker muscular dystrophy.

Science.gov (United States)

Zhang, Huili; Zhu, Yuling; Sun, Yiming; Liang, Yingyin; Li, Yaqin; Zhang, Yu; Deng, Langhui; Wen, Xingxuan; Zhang, Cheng

2015-01-01

To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. 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 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). Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

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

International Nuclear Information System (INIS)

Perloff, J.K.; Stevenson, W.G.; Roberts, N.K.; Cabeen, W.; Weiss, J.

1984-01-01

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

Control rod drive

International Nuclear Information System (INIS)

Okutani, Tetsuro.

1988-01-01

Purpose: To provide a simple and economical control rod drive using a control circuit requiring no pulse circuit. Constitution: Control rods in a BWR type reactor are driven by hydraulic pressure and inserted or withdrawn in the direction of applying the hydraulic pressure. The direction of the hydraulic pressure is controlled by a direction control valve. Since the driving for the control rod is extremely important in view of the operation, a self diagnosis function is disposed for rapid inspection of possible abnormality. In the present invention, two driving contacts are disposed each by one between the both ends of a solenoid valve of the direction control valve for driving the control rod and the driving power source, and diagnosis is conducted by alternately operating them. Therefore, since it is only necessary that the control circuit issues a driving instruction only to one of the two driving contacts, the pulse circuit is no more required. Further, since the control rod driving is conducted upon alignment of the two driving instructions, the reliability of the control rod drive can be improved. (Horiuchi, T.)

[Central aleolar choroidal dystrophy in sibilings coexisting with alopecia].

Science.gov (United States)

Brydak-Godowska, Joanna; Dróbecka-Brydak, Ewa; Paćkowska, Maria; Kecik, Dariusz

2007-01-01

Central areolar choroidal dystrophy is localized in macular region and is characterized by atrophy of pigment epithelium, photoreceptors and choriocapillaris. This paper presents the history of two sibilings at the age of 23 and 30, with central aleolar choroidal dystrophy coexisting with alopecia. The results of erg, eog and fluorescein angiography are presented. The results of therapy for glaucoma associated with the Sturge-Weber syndrome are often disappointing.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Science.gov (United States)

Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

2017-08-15

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Concurrence of myotonic dystrophy and epilepsy: a case report

OpenAIRE

Worku, Dawit Kibru

2014-01-01

Introduction Myotonic dystrophy is a clinically and genetically heterogeneous multisystem disorder with a prevalence of 1 in 8000 in the general population. Case presentation A 25-year-old Ethiopian man presented with symptoms of myotonia, muscle wasting, gait problems, frontal baldness, and family history characterizing the hereditary disorder myotonic dystrophy. He had been on treatment for idiopathic generalized epilepsy for over 15 years. A needle electromyography showed insertional class...

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 ...

Characterization of the canine urinary proteome.

Science.gov (United States)

Brandt, Laura E; Ehrhart, E J; Scherman, Hataichanok; Olver, Christine S; Bohn, Andrea A; Prenni, Jessica E

2014-06-01

Urine is an attractive biofluid for biomarker discovery as it is easy and minimally invasive to obtain. While numerous studies have focused on the characterization of human urine, much less research has focused on canine urine. The objectives of this study were to characterize the universal canine urinary proteome (both soluble and exosomal), to determine the overlap between the canine proteome and a representative human urinary proteome study, to generate a resource for future canine studies, and to determine the suitability of the dog as a large animal model for human diseases. The soluble and exosomal fractions of normal canine urine were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS). Biological Networks Gene Ontology (BiNGO) software was utilized to assign the canine urinary proteome to respective Gene Ontology categories, such as Cellular Component, Molecular Function, and Biological Process. Over 500 proteins were confidently identified in normal canine urine. Gene Ontology analysis revealed that exosomal proteins were largely derived from an intracellular location, while soluble proteins included both extracellular and membrane proteins. Exosome proteins were assigned to metabolic processes and localization, while soluble proteins were primarily annotated to specific localization processes. Several proteins identified in normal canine urine have previously been identified in human urine where these proteins are related to various extrarenal and renal diseases. The results of this study illustrate the potential of the dog as an animal model for human disease states and provide the framework for future studies of canine renal diseases. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

Three-dimensional prediction of the human eyeball and canthi for craniofacial reconstruction using cone-beam computed tomography.

Science.gov (United States)

Kim, Sang-Rok; Lee, Kyung-Min; Cho, Jin-Hyoung; Hwang, Hyeon-Shik

2016-04-01

An anatomical relationship between the hard and soft tissues of the face is mandatory for facial reconstruction. The purpose of this study was to investigate the positions of the eyeball and canthi three-dimensionally from the relationships between the facial hard and soft tissues using cone-beam computed tomography (CBCT). CBCT scan data of 100 living subjects were used to obtain the measurements of facial hard and soft tissues. Stepwise multiple regression analyses were carried out using the hard tissue measurements in the orbit, nasal bone, nasal cavity and maxillary canine to predict the most probable positions of the eyeball and canthi within the orbit. Orbital width, orbital height, and orbital depth were strong predictors of the eyeball and canthi position. Intercanine width was also a predictor of the mediolateral position of the eyeball. Statistically significant regression models for the positions of the eyeball and canthi could be derived from the measurements of orbit and maxillary canine. These results suggest that CBCT data can be useful in predicting the positions of the eyeball and canthi three-dimensionally. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Control rod withdrawal monitoring device

International Nuclear Information System (INIS)

Ebisuya, Mitsuo.

1984-01-01

Purpose: To prevent the power ramp even if a plurality of control rods are subjected to withdrawal operation at a time, by reducing the reactivity applied to the reactor. Constitution: The control rod withdrawal monitoring device is adapted to monitor and control the withdrawal of the control rods depending on the reactor power and the monitoring region thereof is divided into a control rod group monitoring region a transition region and a control group monitoring not interfere region. In a case if the distance between a plurality of control rods for which the withdrawal positions are selected is less than a limiting value, the coordinate for the control rods, distance between the control rods and that the control rod distance is shorter are displayed on a display panel, and the withdrawal for the control rods are blocked. Accordingly, even if a plurality of control rods are subjected successively to the withdrawal operation contrary to the control rod withdrawal sequence upon high power operation of the reactor, the power ramp can be prevented. (Kawakami, Y.)

Trends with corticosteroid use in males with Duchenne muscular dystrophy born 1982-2001.

Science.gov (United States)

Fox, Deborah J; Kumar, Anil; West, Nancy A; DiRienzo, A Gregory; James, Katherine A; Oleszek, Joyce

2015-01-01

This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy. © The Author(s) 2014.

[Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy].

Science.gov (United States)

Silva, Helga Cristina Almeida da; Hiray, Marcia; Vainzof, Mariz; Schmidt, Beny; Oliveira, Acary Souza Bulle; Amaral, José Luiz Gomes do

2017-05-31

Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040IU.L -1 (normal 174IU.L -1 ). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

Science.gov (United States)

Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

2014-05-01

Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

Inherited myopathies and muscular dystrophies

NARCIS (Netherlands)

Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

Thermal behavior simulation of a nuclear fuel rod through an eletrically heated rod

International Nuclear Information System (INIS)

Lima, R. de C.F. de.

1984-01-01

In thermalhydraulic loops the nuclear industry often uses electrically heated rods to simulate power transients, which occur in nuclear fuel rods. The development and design of a electrically heated rod, by supplying the dimensions and materials which should be used in order to yeld the same temperature and heat flux at the surfaces of the nuclear rod and the electrically heated rod are presented. To a given nuclear transient this equality was obtained by fitting the linear power through the lumped parameters technique. (Author) [pt

Miyoshi-type distal muscular dystrophy. Clinical spectrum in 24 Dutch patients

NARCIS (Netherlands)

Linssen, W. H.; Notermans, N. C.; van der Graaf, Y.; Wokke, J. H.; van Doorn, P. A.; Höweler, C. J.; Busch, H. F.; de Jager, A. E.; de Visser, M.

1997-01-01

Miyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history, muscle CT-scans and muscle biopsy findings.

Miyoshi-type distal muscular dystrophy. Clinical spectrum in 24 Dutch patients

NARCIS (Netherlands)

W.H.J.P. Linssen (Wim); N.C. Notermans (Nicolette); Y. van der Graaf (Yolanda); J.H.J. Wokke (John); P.A. van Doorn (Pieter); C.J. Höweler (Chris); H.F.M. Busch (Herman); A.E.J. de Jager (Aeiko); M. de Visser (Marianne)

1997-01-01

textabstractMiyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history muscle CT-scans and muscle biopsy

Miyoshi-type distal muscular dystrophy - Clinical spectrum in 24 Dutch patients

NARCIS (Netherlands)

Linssen, WHJP; Notermans, NC; VanderGraaf, Y; Wokke, JHJ; VanDoorn, PA; Howeler, CJ; Busch, HFM; DeJager, AEJ; DeVisser, M

1997-01-01

Miyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history, muscle CT-scans and muscle biopsy findings.

KMeyeDB: a graphical database of mutations in genes that cause eye diseases.

Science.gov (United States)

Kawamura, Takashi; Ohtsubo, Masafumi; Mitsuyama, Susumu; Ohno-Nakamura, Saho; Shimizu, Nobuyoshi; Minoshima, Shinsei

2010-06-01

KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user-interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene.

Duration of serological response to canine parvovirus-type 2, canine distemper virus, canine adenovirus type 1 and canine parainfluenza virus in client-owned dogs in Australia.

Science.gov (United States)

Mitchell, S A; Zwijnenberg, R J; Huang, J; Hodge, A; Day, M J

2012-12-01

To determine whether client-owned dogs in Australia, last vaccinated with Canvac(®) vaccines containing canine parvovirus-type 2 (CPV-2), canine distemper virus (CDV), canine adenovirus type 2 (CAV-2) ± canine parainfluenza virus (CPiV) at least 18 months ago, were seropositive or responded serologically to revaccination. A total of 235 dogs were recruited from 23 veterinary clinics, representing a variety of breeds, ages and time since last vaccination (TSLV: range 1.5-9 years, mean 2.8 years). Dogs had a blood sample taken and were revaccinated on day 0. A second blood sample was taken 7-14 days later. Blood samples were assessed for antibody titres to CPV-2 (by haemagglutination inhibition) and CDV, CAV type 1 (CAV-1) and CPiV (by virus neutralisation). Dogs with a day 0 titre >10 or a four-fold increase in titre following revaccination were considered to be serological responders. The overall percentage of dogs classified as serological responders was 98.7% for CPV-2, 96.6% for CDV, 99.6% for CAV-1 and 90.3% for CPiV. These results suggest that the duration of serological response induced by modified-live vaccines against CPV-2, CDV, CAV-1 and CPiV, including Canvac(®) vaccines, is beyond 18 months and may extend up to 9 years. Accordingly, these vaccines may be considered for use in extended revaccination interval protocols as recommended by current canine vaccine guidelines. © 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.

Benefit of spatial filtering for visual perception with a subretinal implant.

Science.gov (United States)

Rieger, Viola; Aryan, Naser Pour; Brendler, Christian; Rothermel, Albrecht

2014-01-01

Subretinal implants have proven to be capable of restoring vision to patients suffering from hereditary retinal degeneration diseases like retinitis pigmentosa and cone-rod dystrophy. Although they already provide basic visual perception, there is still much room for improvement in this field. Effects like electric field interference limit the visual acuity and may be the cause of the perceived vision to be blurred. This influence could be reduced by means of highpass spatial filtering. In this paper, based on the available reports about the visual perception parameters from the patients using the alpha-IMS subretinal implant, a model for the blurring effect of the patients retina is proposed. On this basis, highpass filters are suggested which will compensate the obscuring effect of the stimulator device plus retina system to some extent.

Nuclear fuel rod loading apparatus

International Nuclear Information System (INIS)

King, H.B.; Macivergan, R.; Mckenzie, G.W.

1980-01-01

An apparatus incorporating a microprocessor control is provided for automatically loading nuclear fuel pellets into fuel rods commonly used in nuclear reactor cores. The apparatus comprises a split ''v'' trough for assembling segments of fuel pellets in rows and a shuttle to receive the fuel pellets from the split ''v'' trough when the two sides of the split ''v'' trough are opened. The pellets are weighed while in the shuttle, and the shuttle then moves the pellets into alignment with a fuel rod. A guide bushing is provided to assist the transfer of the pellets into the fuel rod. A rod carousel which holds a plurality of fuel rods presents the proper rod to the guide bushing at the appropriate stage in the loading sequence. The bushing advances to engage the fuel rod, and the shuttle advances to engage the guide bushing. The pellets are then loaded into the fuel rod by a motor operated push rod. The guide bushing includes a photocell utilized in conjunction with the push rod to measure the length of the row of fuel pellets inserted in the fuel rod

Control rod shutdown system

International Nuclear Information System (INIS)

Miyamoto, Yoshiyuki; Higashigawa, Yuichi.

1996-01-01

The present invention provides a control rod terminating system in a BWR type nuclear power plant, which stops an induction electric motor as rapidly as possible to terminate the control rods. Namely, the control rod stopping system controls reactor power by inserting/withdrawing control rods into a reactor by driving them by the induction electric motor. The system is provided with a control device for controlling the control rods and a control device for controlling the braking device. The control device outputs a braking operation signal for actuating the braking device during operation of the control rods to stop the operation of the control rods. Further, the braking device has at least two kinds of breaks, namely, a first and a second brakes. The two kinds of brakes are actuated by receiving the brake operation signals at different timings. The brake device is used also for keeping the control rods after the stopping. Even if a stopping torque of each of the breaks is small, different two kinds of brakes are operated at different timings thereby capable of obtaining a large stopping torque as a total. (I.S.)

Antibody titers for canine parvovirus type-2, canine distemper virus, and canine adenovirus type-1 in adult household dogs.

Science.gov (United States)

Taguchi, Masayuki; Namikawa, Kazuhiko; Maruo, Takuya; Orito, Kensuke; Lynch, Jonathan; Sahara, Hiroeki

2011-09-01

Serum antibody titers for canine parvovirus type-2 (CPV-2), canine distemper virus (CDV) and canine adenovirus type-1 (CAV-1) were investigated in 1031 healthy adult household dogs (2 to 18 years old) given an annual inoculation in the previous 11 to 13 months. The number of dogs retaining significant titers of antibodies against CPV-2, CDV, and CAV-1 were 888 (86%), 744 (72%), and 732 (71%), respectively. There were no differences between males and females in antibody titers against the 3 viruses. Antibody titer for CPV-2 was significantly higher in younger dogs than in older dogs, CDV antibody was significantly higher in older dogs than in younger dogs, and CAV titer was not associated with age.

Effects of systemic multiexon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy.

Science.gov (United States)

Echigoya, Yusuke; Nakamura, Akinori; Nagata, Tetsuya; Urasawa, Nobuyuki; Lim, Kenji Rowel Q; Trieu, Nhu; Panesar, Dharminder; Kuraoka, Mutsuki; Moulton, Hong M; Saito, Takashi; Aoki, Yoshitsugu; Iversen, Patrick; Sazani, Peter; Kole, Ryszard; Maruyama, Rika; Partridge, Terry; Takeda, Shin'ichi; Yokota, Toshifumi

2017-04-18

Duchenne muscular dystrophy (DMD) is a lethal genetic disorder caused by an absence of the dystrophin protein in bodywide muscles, including the heart. Cardiomyopathy is a leading cause of death in DMD. Exon skipping via synthetic phosphorodiamidate morpholino oligomers (PMOs) represents one of the most promising therapeutic options, yet PMOs have shown very little efficacy in cardiac muscle. To increase therapeutic potency in cardiac muscle, we tested a next-generation morpholino: arginine-rich, cell-penetrating peptide-conjugated PMOs (PPMOs) in the canine X-linked muscular dystrophy in Japan (CXMD J ) dog model of DMD. A PPMO cocktail designed to skip dystrophin exons 6 and 8 was injected intramuscularly, intracoronarily, or intravenously into CXMD J dogs. Intravenous injections with PPMOs restored dystrophin expression in the myocardium and cardiac Purkinje fibers, as well as skeletal muscles. Vacuole degeneration of cardiac Purkinje fibers, as seen in DMD patients, was ameliorated in PPMO-treated dogs. Although symptoms and functions in skeletal muscle were not ameliorated by i.v. treatment, electrocardiogram abnormalities (increased Q-amplitude and Q/R ratio) were improved in CXMD J dogs after intracoronary or i.v. administration. No obvious evidence of toxicity was found in blood tests throughout the monitoring period of one or four systemic treatments with the PPMO cocktail (12 mg/kg/injection). The present study reports the rescue of dystrophin expression and recovery of the conduction system in the heart of dystrophic dogs by PPMO-mediated multiexon skipping. We demonstrate that rescued dystrophin expression in the Purkinje fibers leads to the improvement/prevention of cardiac conduction abnormalities in the dystrophic heart.

Fuel rod leak detector

International Nuclear Information System (INIS)

Womack, R.E.

1978-01-01

A typical embodiment of the invention detects leaking fuel rods by means of a radiation detector that measures the concentration of xenon-133 ( 133 Xe) within each individual rod. A collimated detector that provides signals related to the energy of incident radiation is aligned with one of the ends of a fuel rod. A statistically significant sample of the gamma radiation (γ-rays) that characterize 133 Xe is accumulated through the detector. The data so accumulated indicates the presence of a concentration of 133 Xe appropriate to a sound fuel rod, or a significantly different concentration that reflects a leaking fuel rod

Autonomic Dysfunction in Muscular Dystrophy: A Theoretical Framework for Muscle Reflex Involvement

Directory of Open Access Journals (Sweden)

Scott Alan Smith

2014-02-01

Full Text Available Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

Chloride currents in cones modify feedback from horizontal cells to cones in goldfish retina

Science.gov (United States)

Endeman, Duco; Fahrenfort, Iris; Sjoerdsma, Trijntje; Steijaert, Marvin; ten Eikelder, Huub; Kamermans, Maarten

2012-01-01

In neuronal systems, excitation and inhibition must be well balanced to ensure reliable information transfer. The cone/horizontal cell (HC) interaction in the retina is an example of this. Because natural scenes encompass an enormous intensity range both in temporal and spatial domains, the balance between excitation and inhibition in the outer retina needs to be adaptable. How this is achieved is unknown. Using electrophysiological techniques in the isolated retina of the goldfish, it was found that opening Ca2+-dependent Cl− channels in recorded cones reduced the size of feedback responses measured in both cones and HCs. Furthermore, we show that cones express Cl− channels that are gated by GABA released from HCs. Similar to activation of ICl(Ca), opening of these GABA-gated Cl− channels reduced the size of light-induced feedback responses both in cones and HCs. Conversely, application of picrotoxin, a blocker of GABAA and GABAC receptors, had the opposite effect. In addition, reducing GABA release from HCs by blocking GABA transporters also led to an increase in the size of feedback. Because the independent manipulation of Ca2+-dependent Cl− currents in individual cones yielded results comparable to bath-applied GABA, it was concluded that activation of either Cl− current by itself is sufficient to reduce the size of HC feedback. However, additional effects of GABA on outer retinal processing cannot be excluded. These results can be accounted for by an ephaptic feedback model in which a cone Cl− current shunts the current flow in the synaptic cleft. The Ca2+-dependent Cl− current might be essential to set the initial balance between the feedforward and the feedback signals active in the cone HC synapse. It prevents that strong feedback from HCs to cones flood the cone with Ca2+. Modulation of the feedback strength by GABA might play a role during light/dark adaptation, adjusting the amount of negative feedback to the signal to noise ratio of the

Dysphagia in facioscapulohumeral muscular dystrophy.

NARCIS (Netherlands)

Wohlgemuth, M.; Swart, B.J.M. de; Kalf, J.G.; Joosten, F.B.M.; Vliet, A.M. van der; Padberg, G.W.A.M.

2006-01-01

Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy (FSHD). In this study, the authors found that dysphagia does occur in patients with advanced FSHD showing mild involvement of the jaw and lingual muscles. Dysphagia is seldom life threatening in these patients. The

AMPUTATION AND REFLEX SYMPATHETIC DYSTROPHY

NARCIS (Netherlands)

GEERTZEN, JHB; EISMA, WH

Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic

Fuel rods

International Nuclear Information System (INIS)

Hattori, Shinji; Kajiwara, Koichi.

1980-01-01

Purpose: To ensure the safety for the fuel rod failures by adapting plenum springs to function when small forces such as during transportation of fuel rods is exerted and not to function the resilient force when a relatively great force is exerted. Constitution: Between an upper end plug and a plenum spring in a fuel rod, is disposed an insertion member to the lower portion of which is mounted a pin. This pin is kept upright and causes the plenum spring to function resiliently to the pellets against the loads due to accelerations and mechanical vibrations exerted during transportation of the fuel rods. While on the other hand, if a compression force of a relatively high level is exerted to the plenum spring during reactor operation, the pin of the insertion member is buckled and the insertion member is inserted to the inside of the plenum spring, whereby the pellets are allowed to expand freely and the failures in the fuel elements can be prevented. (Moriyama, K.)

Critical condition for the transformation from Taylor cone to cone-jet

International Nuclear Information System (INIS)

Wei Cheng; Zhao Yang; Gang Tie-Qiang; Chen Li-Jie

2014-01-01

An energy method is proposed to investigate the critical transformation condition from a Taylor cone to a cone-jet. Based on the kinetic theorem, the system power allocation and the electrohydrodynamics stability are discussed. The numerical results indicate that the energy of the liquid cone tip experiences a maximum value during the transformation. With the proposed jetting energy, we give the critical transformation condition under which the derivative of jetting energy with respect to the surface area is greater than or equal to the energy required to form a unit of new liquid surface

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...

Multiple fuel rod gripper

International Nuclear Information System (INIS)

Shields, E.P.

1987-01-01

An apparatus is described for gripping an array of rods comprising: (a) gripping members grippingly engageable with the rods, each of which has a hollow portion terminating in an open end for receiving the end of one of the rods; (b) a closing means for causing the hollow portion of each of the gripping members to apply substantially the same gripping force onto the end of its respective rod, including (i) a locking plate having a plurality of tapered holes registrable with the array of rods, wherein the exterior of each of the gripping members is tapered and nested within one of the tapered holes, (ii) a withdrawing means having a hydraulic plunger operatively connected to each of the gripping members for applying a substantially identical withdrawing force on each of the gripping members, whereby the hollow portion of each of the gripping members applies substantially the same gripping force on its respective rod, and (c) means for detecting whether each of the gripping members has grippingly engaged its respective rod

Review on resonance cone fields

International Nuclear Information System (INIS)

Ohnuma, Toshiro.

1980-02-01

Resonance cone fields and lower hybrid heating are reviewed in this report. The resonance cone fields were reported by Fisher and Gould, and they proposed the use of the measurement of resonance cones and structure as a diagnostic tool to determine the plasma density and electron temperature in magnetoplasma. After the resonance cone, a wave-like disturbance persists. Ohnuma et al. have measured bending, reflection and ducting of resonance cones in detail. The thermal modes in inhomogeneous magnetoplasma were seen. The reflection of thermal mode near an electron plasma frequency layer and an insulating plate has been observed. The non-linear effects of resonance cones is reported. Monochromatic electron beam produces the noise of broad band whistler mode. Lower hybrid waves have been the subject of propagation from the edge of plasma to the lower hybrid layer. Linear lower hybrid waves were studied. The lower hybrid and ion acoustic waves radiated from a point source were observed. The parametric decay of finite-extent, cold electron plasma waves was studied. The lower hybrid cone radiated from a point source going along magnetic field lines was observed. Several experimental data on the lower hybrid heating in tokamak devices have been reported. The theories on resonance cones and lower hybrid waves are introduced in this report. (Kato, T.)

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.

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…

High-yield production of hydrophobins RodA and RodB from Aspergillus fumigatus in Pichia pastoris

DEFF Research Database (Denmark)

Pedersen, Mona Højgaard; Borodina, Irina; Moresco, Jacob Lange

2011-01-01

A as well as rRodB were able to convert a glass surface from hydrophilic to hydrophobic similar to native RodA, but only rRodB was able to decrease the hydrophobicity of a Teflon-like surface to the same extent as native RodA, while rRodA showed this ability to a lesser extent. Recombinant RodA and native...

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

Science.gov (United States)

Dörken, Veit Martin; Rudall, Paula J

2018-01-01

Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Epiretinal membrane: a treatable cause of visual disability in myotonic dystrophy type 1.

Science.gov (United States)

Kersten, Hannah M; Roxburgh, Richard H; Child, Nicholas; Polkinghorne, Philip J; Frampton, Chris; Danesh-Meyer, Helen V

2014-01-01

A wide range of ocular abnormalities have been documented to occur in patients with myotonic dystrophy type 1. The objectives of this study were to investigate the macular and optic nerve morphology using optical coherence tomography in patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1 patients and 28 controls were recruited for participation. All participants underwent a thorough ophthalmologic examination, including spectral-domain optical coherence tomography of the macula and retinal nerve fibre layer. Images were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of the participants. Average macular thickness was significantly greater in the myotonic dystrophy group compared to controls [327.3 μm vs. 308.5 μm (p Visual acuity was reduced due to the presence of epiretinal membrane in six patient eyes and none of the control eyes. The presence of an epiretinal membrane was significantly correlated with increasing age in the patient group. We report an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1 group. This may be a previously under-recognised form of visual impairment in this group. Epiretinal membranes can be treated surgically. We suggest that, in addition to a comprehensive clinical examination, optical coherence tomography examination is implemented as part of an ophthalmological assessment for the myotonic dystrophy type 1 patient with reduced visual acuity.

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.

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.

Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

Science.gov (United States)

Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

2015-01-01

Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

Zebrafish models flex their muscles to shed light on muscular dystrophies.

Science.gov (United States)

Berger, Joachim; Currie, Peter D

2012-11-01

Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.

SIRT1: A Novel Target for the Treatment of Muscular Dystrophies

Directory of Open Access Journals (Sweden)

Atsushi Kuno

2016-01-01

Full Text Available 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+-dependent histone/protein deacetylase that plays roles in diverse cellular processes, including stress resistance and cell survival. Studies have shown that SIRT1 activation provides beneficial effects in the dystrophin-deficient mdx mouse, a model of DMD. SIRT1 activation leads to the attenuation of oxidative stress and inflammation, a shift from the fast to slow myofiber phenotype, and the suppression of tissue fibrosis. Although further research is needed to clarify the molecular mechanisms underlying the protective role of SIRT1 in mdx mice, we propose SIRT1 as a novel therapeutic target for patients with muscular dystrophies.

New and emerging pathogens in canine infectious respiratory disease.

Science.gov (United States)

Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

2014-03-01

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Cones for dental radiography

Energy Technology Data Exchange (ETDEWEB)

Butler, M J [National Radiological Protection Board, Harwell (UK)

1977-04-01

Dental radiographic techniques are summarized. The advantages and disadvantages of the use of both the conventional plastic pointer cone and the open-ended cylinders or divergent cones favoured both by the ICRP (Protection against Ionizing Radiation from External Sources, Oxford, Pergamon Press, 1973, ICRP Publication 15), and in the Code of Practice for the Protection of Persons against Ionizing Radiation arising from Medical and Dental Use (1972, 3rd edition, London, HMSO) are discussed. The use of the word 'should' in these recommendations to signify a desirable requirement, not an essential one, is noted. This wording is currently of interest both nationally and internationally in relation to regulations, standards and notes for guidance. The National Radiological Protection Board (NRPB) has been reviewing the position, and has concluded that open-ended cones have disadvantages which may sometimes outweigh their advantages. Although open-ended cones are preferable under some circumstances, the recommendation that they should be used ought not to be followed without an understanding of the issues involved. The hazards associated with the use of interchangeable cones are considered. The NRPB now proposes that the requirement for the replacement of pointer cones (for both new and existing equipment) should be withdrawn.

Control rod drive for vertical movement

International Nuclear Information System (INIS)

Suskov, I.I.; Gorjunov, V.S.; Zajcev, B.I.; Derevjankin, N.E.; Petrov, V.A.; Istomin, S.D.; Kovalencik, D.I.; Archipov, E.A.; Serebrjakov, V.I.; Kacalin, V.S.

1982-01-01

The control of the rod repositioning gear unit and the control unit of the profile grab of the control rod drive for the alkali metal-cooled fast breeder reactor is achieved by an electromotor being arranged outside the hermetic drive casing. The guide tube is directly repositioned by the rod repositioning gear unit. Coupling control of the drive with the control rod is done in the lower operative position of the control rod and that because of the interaction of the tie rod arranged on the spring-mounted control rod with the induction transmitter for the lower position of the control rod. In the transfer position the rod is fixed within the guide tube. (orig.)

Delayed healing of corneal epithelium after phototherapeutic keratectomy for lattice dystrophy.

Science.gov (United States)

Das, Sujata; Langenbucher, Achim; Seitz, Berthold

2005-04-01

To evaluate the time period necessary for complete epithelial healing after phototherapeutic keratectomy (o-PTK) carried out for various superficial corneal opacities. A total of 197 eyes were divided into 9 groups: group 1, Cogan dystrophy including recurrences (n = 15); group 2, Reis Bucklers dystrophy including recurrences (n = 12); group 3, granular dystrophy including recurrences (n = 63); group 4, lattice dystrophy including recurrences (n = 19); group 5, macular dystrophy including recurrences (n = 10); group 6, herpetic scars (n = 5); group 7, corneal scars of nonherpetic origin (including scrofulous, traumatic, central keratoconus, post-pterygium surgery) (n = 31); group 8, Salzmann nodular degeneration (n = 22); and group 9, miscellaneous (such as bullous keratopathy, acute chemical burn, corneal degeneration) (n = 20). After o-PTK, patients were examined daily at the slit lamp using fluorescein and blue light. The time period necessary for complete healing of the epithelial defect was compared among these groups. Delayed healing was considered where the epithelium was not closed after 7 days. One hundred sixty-one eyes (95%) healed within 7 days. Overall, 63%, 80%, and 85% of epithelial defects were closed within 3, 4, and 5 days, respectively. Out of 9 eyes that had delayed healing, 6 eyes (67%) belonged to lattice dystrophy category. Mean time taken for healing in group 4 (8.6 +/- 8.4 days) was significantly longer than those in group 1 (3.0 +/- 1.5 days, P = 0.009), group 2 (3.7 +/- 3.1 days, P = 0.03), group 3 (3.1 +/- 1.5 days, P = 0.001), group 5 (2.7 +/- 0.8 days, P = 0.01), group 7 (3.6 +/- 2.4 days, P = 0.007), group 8 (3.3 +/- 1.3 days, P = 0.009), and group 9 (3.0 +/- 1.9 days, P = 0.011). Eyes with lattice corneal dystrophy suffered from delayed epithelial healing after o-PTK. In addition to adequate counseling, these patients should be followed up closely until complete closure of the epithelium to avoid ulceration, scarring, or even

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis

Directory of Open Access Journals (Sweden)

Veit Martin Dörken

2018-06-01

Full Text Available Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales. The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Safety rod driving device

International Nuclear Information System (INIS)

Murakami, Kiyonobu; Kurosaki, Akira.

1988-01-01

Purpose: To rapidly insert safety rods for a criticality experiment device into a reactor core container to stop the criticality reaction thereby prevent reactivity accidents. Constitution: A cylinder device having a safety rod as a cylinder rod attached with a piston at one end is constituted. The piston is elevated by pressurized air and attracted and fixed by an electromagnet which is a stationary device disposed at the upper portion of the cylinder. If the current supply to the electromagnet is disconnected, the safety rod constituting the cylinder rod is fallen together with the piston to the lower portion of the cylinder. Since the cylinder rod driving device has neither electrical motor nor driving screw as in the conventional device, necessary space can be reduced and the weight is decreased. In addition, since the inside of the nuclear reactor can easily be shielded completely from the external atmosphere, leakage of radioactive materials can be prevented. (Horiuchi, T.)

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....

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

International Nuclear Information System (INIS)

Gor'kova, N.B.; Starykh, L.M.; Karpova, L.E.

1991-01-01

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

Genetics of Human and Canine Dilated Cardiomyopathy.

Science.gov (United States)

Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F N; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

2015-01-01

Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

Light-cone quantization of quantum chromodynamics

International Nuclear Information System (INIS)

Brodsky, S.J.; Pauli, H.C.

1991-06-01

We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, ''discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism

Light-cone quantization of quantum chromodynamics

Energy Technology Data Exchange (ETDEWEB)

Brodsky, S.J. (Stanford Linear Accelerator Center, Menlo Park, CA (USA)); Pauli, H.C. (Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany, F.R.))

1991-06-01

We discuss the light-cone quantization of gauge theories from two perspectives: as a calculational tool for representing hadrons as QCD bound-states of relativistic quarks and gluons, and also as a novel method for simulating quantum field theory on a computer. The light-cone Fock state expansion of wavefunctions at fixed light cone time provides a precise definition of the parton model and a general calculus for hadronic matrix elements. We present several new applications of light-cone Fock methods, including calculations of exclusive weak decays of heavy hadrons, and intrinsic heavy-quark contributions to structure functions. A general nonperturbative method for numerically solving quantum field theories, discretized light-cone quantization,'' is outlined and applied to several gauge theories, including QCD in one space and one time dimension, and quantum electrodynamics in physical space-time at large coupling strength. The DLCQ method is invariant under the large class of light-cone Lorentz transformations, and it can be formulated such at ultraviolet regularization is independent of the momentum space discretization. Both the bound-state spectrum and the corresponding relativistic light-cone wavefunctions can be obtained by matrix diagonalization and related techniques. We also discuss the construction of the light-cone Fock basis, the structure of the light-cone vacuum, and outline the renormalization techniques required for solving gauge theories within the light-cone Hamiltonian formalism.

9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

Science.gov (United States)

2010-01-01

... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine...

Direct interaction of the inhibitory gamma-subunit of Rod cGMP phosphodiesterase (PDE6) with the PDE6 GAFa domains.

Science.gov (United States)

Muradov, Khakim G; Granovsky, Alexey E; Schey, Kevin L; Artemyev, Nikolai O

2002-03-26

Retinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vertebrate visual transduction cascade. The activity of PDE6 catalytic subunits is controlled by the Pgamma-subunits. In addition to the inhibition of cGMP hydrolysis at the catalytic sites, Pgamma is known to stimulate a noncatalytic binding of cGMP to the regulatory GAFa-GAFb domains of PDE6. The latter role of Pgamma has been attributed to its polycationic region. To elucidate the structural basis for the regulation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to the polycationic region of Pgamma, Pgamma-21-45, was specifically cross-linked to rod PDE6alphabeta. The site of Pgamma-21-45 cross-linking was localized to Met138Gly139 within the PDE6alpha GAFa domain using mass spectrometric analysis. Chimeras between PDE5 and cone PDE6alpha', containing GAFa and/or GAFb domains of PDE6alpha' have been generated to probe a potential role of the GAFb domains in binding to Pgamma. Analysis of the inhibition of the PDE5/PDE6alpha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with Pgamma. Our results suggest that a direct binding of the polycationic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGMP-binding sites.

Surgical Orthodontic Treatment of a Patient Affected by Type 1 Myotonic Dystrophy (Steinert Syndrome)

OpenAIRE

Cacucci, Laura; Ricci, Beatrice; Moretti, Maria; Gasparini, Giulio; Pelo, Sandro; Grippaudo, Cristina

2017-01-01

Myotonic dystrophy, or Steinert’s disease, is the most common form of muscular dystrophy that occurs in adults. This multisystemic form involves the skeletal muscles but affects also the eye, the endocrine system, the central nervous system, and the cardiac system. The weakness of the facial muscles causes a characteristic facial appearance frequently associated with malocclusions. Young people with myotonic dystrophy, who also have severe malocclusions, have bad oral functions such as chewin...

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.

Testing device for control rod drives

International Nuclear Information System (INIS)

Hayakawa, Toshifumi.

1992-01-01

A testing device for control rod drives comprises a logic measuring means for measuring an output signal from a control rod drive logic generation circuit, a control means for judging the operation state of a control rod and a man machine interface means for outputting the result of the judgement. A driving instruction outputted from the control rod operation device is always monitored by the control means, and if the operation instruction is stopped, a testing signal is outputted to the control rod control device to simulate a control rod operation. In this case, the output signal of the control rod drive logic generation circuit is held in a control rod drive memory means and intaken into a logic analysis means for measurement and an abnormality is judged by the control means. The stopping of the control rod drive instruction is monitored and the operation abnormality of the control rod is judged, to mitigate the burden of an operator. Further, the operation of the control rod drive logic generation circuit can be confirmed even during a nuclear plant operation by holding the control rod drive instruction thereby enabling to improve maintenance efficiency. (N.H.)

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.

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

Science.gov (United States)

van Heerden, J; Bingham, J; van Vuuren, M; Burroughs, R E J; Stylianides, E

2002-03-01

Wild dogs Lycaon pictuis (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.

Factitious lymphoedema as a psychiatric condition mimicking reflex sympathetic dystrophy: a case report

Directory of Open Access Journals (Sweden)

Nwaejike Nnamdi

2008-06-01

Full Text Available Abstract Introduction Reflex sympathetic dystrophy can result in severe disability with only one in five patients able to fully resume prior activities. Therefore, it is important to diagnose this condition early and begin appropriate treatment. Factitious lymphoedema can mimic reflex sympathetic dystrophy and is caused by self-inflicted tourniquets, blows to the arm or repeated skin irritation. Patients with factitious lymphoedema have an underlying psychiatric disorder but usually present to emergency or orthopaedics departments. Factitious lymphoedema can then be misdiagnosed as reflex sympathetic dystrophy. The treatment for factitious lymphoedema is dealing with the underlying psychiatric condition. Case presentation We share our experience of treating a 33-year-old man, who presented with factitious lymphoedema, initially diagnosed as reflex sympathetic dystrophy. Conclusion Awareness of this very similar differential diagnosis allows early appropriate treatment to be administered.

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... from each dog shall be individually tested for neutralizing antibody against canine parvovirus to...

Hereditary muscular dystrophies and the heart

NARCIS (Netherlands)

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

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

Application of xenogeneic anti-canine distemper virus antibodies in treatment of canine distemper puppies.

Science.gov (United States)

Liu, P C; Chen, C A; Chen, C M; Yen, C H; Lee, M H; Chuang, C K; Tu, C F; Su, B L

2016-11-01

The clinical feasibility of passive immunotherapy has not been demonstrated in dogs naturally infected with canine distemper. In this study, porcine anti-canine distemper virus IgG and F(ab') 2 antibody fragments were used to treat infected puppies. A total of 41 naturally infected puppies (age Äsix months) exhibiting severe respiratory signs, but lacking neurological signs, were enrolled in the study. Twenty-five puppies were treated with a combination of IgG or F(ab') 2 antibody fragments (Group 1) and supportive therapy and 16 puppies received routine supportive care only (Group 2). The survival rate of dogs in Group 1 (19/25; 76%) was significantly higher than that in Group 2 (5/16; 31·3%) (Pdistemper virus antibodies improved survival in puppies affected with canine distemper with minimal adverse effects. Therefore, this therapy could be considered for treatment of endangered animal species infected with canine distemper virus. © 2016 British Small Animal Veterinary Association.

Genetics of Human and Canine Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Siobhan Simpson

2015-01-01

Full Text Available Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge.

Science.gov (United States)

Parish, Masoud; Farzin, Haleh

2018-01-01

Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications.

A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

Science.gov (United States)

2018-04-17

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

Duchenne and Becker muscular dystrophy in adolescents: current perspectives

Directory of Open Access Journals (Sweden)

Andrews JG

2018-03-01

Full Text Available Jennifer G Andrews, Richard A Wahl Department of Pediatrics, University of Arizona, Tucson, AZ, USA Abstract: Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are life-limiting and progressive neuromuscular conditions with significant comorbidities, many of which manifest during adolescence. BMD is a milder presentation of the condition and much less prevalent than DMD, making it less represented in the literature, or more severely affected individuals with BMD may be subsumed into the DMD population using clinical cutoffs. Numerous consensus documents have been published on the clinical management of DMD, the most recent of which was released in 2010. The advent of these clinical management consensus papers, particularly respiratory care, has significantly increased the life span for these individuals, and the adolescent years are now a point of transition into adult lives, rather than a period of end of life. This review outlines the literature on DMD and BMD during adolescence, focusing on clinical presentation during adolescence, impact of living with a chronic illness on adolescents, and the effect that adolescents have on their chronic illness. In addition, we describe the role that palliative-care specialists could have in improving outcomes for these individuals. The increasing proportion of individuals with DMD and BMD living into adulthood underscores the need for more research into interventions and intracacies of adolescence that can improve the social aspects of their lives. Keywords: adolescent health, review, Duchenne muscular dystrophy, Becker muscular dystrophy, dystrophinopathy, palliative care

Failed fuel rod detector

Energy Technology Data Exchange (ETDEWEB)

Uchida, Katsuya; Matsuda, Yasuhiko

1984-05-02

The purpose of the project is to enable failed fuel rod detection simply with no requirement for dismantling the fuel assembly. A gamma-ray detection section is arranged so as to attend on the optional fuel rods in the fuel assembly. The fuel assembly is adapted such that a gamma-ray shielding plate is detachably inserted into optional gaps of the fuel rods or, alternatively, the fuel assembly can detachably be inserted to the gamma-ray shielding plate. In this way, amount of gaseous fission products accumulated in all of the plenum portions in the fuel rods as the object of the measurement can be determined without dismantling the fuel assembly. Accordingly, by comparing the amounts of the gaseous fission products, the failed fuel rod can be detected.

Dystrophin Immunity in Duchenne’s Muscular Dystrophy

Science.gov (United States)

Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

2010-01-01

SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

Kinetics of canine dental calculus crystallization: an in vitro study on the influence of inorganic components of canine saliva.

Science.gov (United States)

Borah, Ballav M; Halter, Timothy J; Xie, Baoquan; Henneman, Zachary J; Siudzinski, Thomas R; Harris, Stephen; Elliott, Matthew; Nancollas, George H

2014-07-01

This work identifies carbonated hydroxyapatite (CAP) as the primary component of canine dental calculus, and corrects the long held belief that canine dental calculus is primarily CaCO3 (calcite). CAP is known to be the principal crystalline component of human dental calculus, suggesting that there are previously unknown similarities in the calcification that occurs in these two unique oral environments. In vitro kinetic experiments mimicking the inorganic components of canine saliva have examined the mechanisms of dental calculus formation. The solutions were prepared so as to mimic the inorganic components of canine saliva; phosphate, carbonate, and magnesium ion concentrations were varied individually to investigate the roll of these ions in controlling the nature of the phases that is nucleated. To date, the inorganic components of the canine oral systems have not been investigated at concentrations that mimic those in vivo. The mineral composition of the synthetic calculi grown under these conditions closely resembled samples excised from canines. This finding adds new information about calculus formation in humans and canines, and their sensitivity to chemicals used to treat these conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

RodPilotR - The Innovative and Cost-Effective Digital Control Rod Drive Control System for PWRs

International Nuclear Information System (INIS)

Baron, Clemens

2008-01-01

With RodPilot, AREVA NP offers an innovative and cost-effective system for controlling control rods in Pressurized Water Reactors. RodPilot controls the three operating coils of the control rod drive mechanism (lift, moveable gripper and stationary gripper coil). The rods are inserted into or withdrawn from the core as required by the Reactor Control System. The system combines modern components, state-of-the-art logic and a proven electronic control rod drive control principle to provide enhanced reliability and lower maintenance costs. (author)

Integrated control rod monitoring device

International Nuclear Information System (INIS)

Saito, Katsuhiro

1997-01-01

The present invention provides a device in which an entire control rod driving time measuring device and a control rod position support device in a reactor building and a central control chamber are integrated systematically to save hardwares such as a signal input/output device and signal cables between boards. Namely, (1) functions of the entire control rod driving time measuring device for monitoring control rods which control the reactor power and a control rod position indication device are integrated into one identical system. Then, the entire devices can be made compact by the integration of the functions. (2) The functions of the entire control rod driving time measuring device and the control rod position indication device are integrated in a central operation board and a board in the site. Then, the place for the installation of them can be used in common in any of the cases. (3) The functions of the entire control rod driving time measuring device and the control rod position indication device are integrated to one identical system to save hardware to be used. Then, signal input/output devices and drift branching panel boards in the site and the central operation board can be saved, and cables for connecting both of the boards is no more necessary. (I.S.)

Rod drive and latching mechanism

International Nuclear Information System (INIS)

Veronesi, L.; Sherwood, D.G.

1982-01-01

Hydraulic drive and latching mechanisms for driving reactivity control mechanisms in nuclear reactors are described. Preferably, the pressurized reactor coolant is utilized to raise the drive rod into contact with and to pivot the latching mechanism so as to allow the drive rod to pass the latching mechanism. The pressure in the housing may then be equalized which allows the drive rod to move downwardly into contact with the latching mechanism but to hold the shaft in a raised position with respect to the reactor core. Once again, the reactor coolant pressure may be utilized to raise the drive rod and thus pivot the latching mechanism so that the drive rod passes above the latching mechanism. Again, the mechanism pressure can be equalized which allows the drive rod to fall and pass by the latching mechanism so that the drive rod approaches the reactor core. (author)

Role of canine circovirus in dogs with acute haemorrhagic diarrhoea.

Science.gov (United States)

Anderson, A; Hartmann, K; Leutenegger, C M; Proksch, A L; Mueller, R S; Unterer, S

2017-06-03

Canine circovirus (CanineCV) has been detected in some dogs with severe haemorrhagic diarrhoea, but its pathogenic role is unclear. This study evaluated a suspected association between the presence of CanineCV and acute haemorrhagic diarrhoea syndrome (AHDS) in dogs. The prevalence of CanineCV in dogs with AHDS was compared with that in healthy dogs and those infected with canine parvovirus (CPV). Additionally, time to recovery and mortality rate were compared between CanineCV-positive and CanineCV-negative dogs. Faecal samples of dogs with AHDS (n=55), healthy dogs (n=66) and dogs infected with CPV (n=54) were examined by two real-time TaqMan PCR assays targeting the replicase and capsid genes of CanineCV. CanineCV was detected in faecal samples of two dogs with AHDS, three healthy controls and seven dogs infected with CPV. Among the three groups, there was no significant difference in prevalence of CanineCV. CPV-infected animals that were coinfected with CanineCV had a significantly higher mortality rate compared with those negative for CanineCV. CanineCV does not appear to be the primary causative agent of AHDS in dogs, but might play a role as a negative co-factor in disease outcome in dogs with CPV infection. British Veterinary Association.

Control rods

International Nuclear Information System (INIS)

Koga, Isao; Masuoka, Ryuzo.

1979-01-01

Purpose: To prevent fuel element failures during power conditioning by removing liquid absorbents in poison tubes of control rods in a fast power up step and extracting control rods to slightly increase power in a medium power up step. Constitution: A plurality of poison tubes are disposed in a coaxial or plate-like arrangement and divided into a region capable of compensating the reactivity from the initial state at low temperature to 40% power operation and a region capable of compensating the reactivity in the power up above 40% power operation. Soluble poisons are used as absorbers in the poison tubes corresponding to above 40% power operation and they are adapted to be removed independently from the driving of control rods. The poison tubes filled with the soluble absorbers are responsible for the changes in the reactivity from the initial state at low temperature to the medium power region and the reactivity control is conducted by the elimination of liquid absorbers from the poison tubes. In the succeeding slight power up region above the medium power, power up is proceeding by extracting the control rods having remaining poison tubes filled with solid or liquid absorbers. (Seki, T.)

Simulation of nuclear fuel rods by using process computer-controlled power for indirect electrically heated rods

International Nuclear Information System (INIS)

Malang, S.

1975-11-01

An investigation was carried out to determine how the simulation of nuclear fuel rods with indirect electrically heated rods could be improved by use of a computer to control the electrical power during a loss-of-coolant accident (LOCA). To aid in the experiment, a new version of the HETRAP code was developed which simulates a LOCA with heater rod power controlled by a computer that adjusts rod power during a blowdown to minimize the difference in heat flux of the fuel and heater rods. Results show that without computer control of heater rod power, only the part of a blowdown up to the time when the heat transfer mode changes from nucleate boiling to transition or film boiling can be simulated well and then only for short times. With computer control, the surface heat flux and temperature of an electrically heated rod can be made nearly identical to that of a reactor fuel rod with the same cooling conditions during much of the LOCA. A small process control computer can be used to achieve close simulation of a nuclear fuel rod with an indirect electrically heated rod

Vibration therapy tolerated in children with Duchenne muscular dystrophy: a pilot study.

Science.gov (United States)

Myers, Kenneth A; Ramage, Barbara; Khan, Aneal; Mah, Jean K

2014-07-01

Duchenne muscular dystrophy is an X-linked recessive muscular dystrophy. Clinical management primarily involves rehabilitation strategies aimed at preserving functional mobility as long as possible. Side-alternating vibration therapy is a rehabilitation intervention that has shown promise in a number of different neuromuscular disorders, and has the potential to preserve strength, functional mobility, and bone mass. There has been little research regarding the tolerance to side-alternating vibration therapy in muscle diseases such as Duchenne muscular dystrophy. Four patients were recruited for a pilot study assessing the safety and tolerance of side-alternating vibration therapy in individuals with Duchenne muscular dystrophy. All patients participated in a 4-week training period involving side-alternating vibration therapy sessions three times per week. Serum creatine kinase was measured, and adverse effects reviewed at each session with functional mobility assessed before and after the training period. All patients tolerated the training protocol well, and there were no major changes in functional mobility. One patient had a transient increase in creatine kinase during the study; however, levels of this enzyme were stable overall when comparing the pretraining and posttraining values. Some patients reported subjective improvement during the training period. Side-alternating vibration therapy is well tolerated in children with Duchenne muscular dystrophy and may have potential to improve or maintain functional mobility and strength in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Reliability of mandibular canines as indicators for sexual dichotomy.

Science.gov (United States)

Hosmani, Jagadish V; Nayak, Ramakant S; Kotrashetti, Vijayalakshmi S; S, Pradeep; Babji, Deepa

2013-02-01

Amongst the various calcified structures in the human body, teeth have gained lot of popularity in estimating the sex of an individual as they are highly resistant to destruction and decomposition. Using permanent mandibular canines many researchers have predicted a high level of accuracy in identifying the sex correctly. The purpose of our study was to gauge the effectiveness of mandibular canines in discerning sex. Fifty dental casts each of males and females were utilized for the study. Mesio-distal dimension and inter-canine distance of mandibular right and left canine was recorded using digital vernier caliper and mandibular canine index was calculated. The mean value of mesio-distal dimensions of right and left mandibular canine was slightly greater in males compared to females. The mandibular canine index was equal in both sexes. Inter-canine distance was marginally higher in males compared to females. Despite of higher values in males none of the parameters were statistically significant. The results herein bolster contemporary studies that mesio-distal dimensions of mandibular canines and mandibular canine index do not reflect sexual dimorphism and that its application should be discontinued in sex prediction among Indian populations. How to cite this article: Hosmani J V, Nayak R S, Kotrashetti V S, Pradeep S, Babji D. Reliability of Mandibular Canines as Indicators for Sexual Dichotomy. J Int Oral Health 2013; 5(1):1-7.

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.

Approaches to canine health surveillance.

Science.gov (United States)

O'Neill, Dan G; Church, David B; McGreevy, Paul D; Thomson, Peter C; Brodbelt, Dave C

2014-01-01

Effective canine health surveillance systems can be used to monitor disease in the general population, prioritise disorders for strategic control and focus clinical research, and to evaluate the success of these measures. The key attributes for optimal data collection systems that support canine disease surveillance are representativeness of the general population, validity of disorder data and sustainability. Limitations in these areas present as selection bias, misclassification bias and discontinuation of the system respectively. Canine health data sources are reviewed to identify their strengths and weaknesses for supporting effective canine health surveillance. Insurance data benefit from large and well-defined denominator populations but are limited by selection bias relating to the clinical events claimed and animals covered. Veterinary referral clinical data offer good reliability for diagnoses but are limited by referral bias for the disorders and animals included. Primary-care practice data have the advantage of excellent representation of the general dog population and recording at the point of care by veterinary professionals but may encounter misclassification problems and technical difficulties related to management and analysis of large datasets. Questionnaire surveys offer speed and low cost but may suffer from low response rates, poor data validation, recall bias and ill-defined denominator population information. Canine health scheme data benefit from well-characterised disorder and animal data but reflect selection bias during the voluntary submissions process. Formal UK passive surveillance systems are limited by chronic under-reporting and selection bias. It is concluded that active collection systems using secondary health data provide the optimal resource for canine health surveillance.

Fuel rod technology

International Nuclear Information System (INIS)

Bezold, H.; Romeiser, H.J.

1979-07-01

By extensive mechanization and automation of the fuel rod production, also at increasing production numbers, an efficient production shall be secured, simultaneously corresponding to the high quality standard of the fuel rods. The works done up to now concentrated on the lay out of a rough concept for a mechanized production course. Detail-studies were made for the problems of fuel rod humidity, filling and resistance welding. Further promotion of this project and thus further report will be stopped, since the main point of these works is the production technique. (orig.) [de

Prevalence and correlates of apathy in myotonic dystrophy type 1

OpenAIRE

Gallais, Benjamin; Montreuil, Mich?le; Gargiulo, Marcela; Eymard, Bruno; Gagnon, Cynthia; Laberge, Luc

2015-01-01

Background Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. Methods Levels of apathy in 38 DM1 patients with adul...

The Effect of Using a Modified Dentoalveolar Distractor on Canine Angulation following Rapid Canine Retraction: A Split-mouth Design Randomized Controlled Trial.

Science.gov (United States)

Al-Ainawi, Khaled I; Al-Mdalal, Yaser; Hajeer, Mohammad Y

2016-01-01

New studies have been published and aimed to retract canines by means of distraction osteogenesis to reduce treatment time. Although a great care has been given to achieve a bodily movement of the canines, a significant amount of tipping of the canines has been observed. This trial aimed to assess the effect of applying a modified distractor on canine angulation. The sample of the study consisted of 14 canines in seven patients (16-25 years). After the osteotomy procedure, two distractors were applied (one distractor on each side). After 5 days of a latency period, the two distractors were activated at a rate of 1 mm/day. There was a significant difference between the two distractors regarding the time required to retract the canines (p = 0.008) and the observed change in canine angulation following retraction (p = 0.028). The change in the overjet and the mandibular plane angle was statistically insignificant. Eight out of 14 distracted canines reacted positively to the pulp vitality tester after 3 months of completion of distraction. There was no clinical sign of discoloration or pulpal pain in any canine. Within the limits of this study, the modified distractor caused a bodily movement of the canine with a minimal tipping. Further research is required on a long-term basis on a larger group of patients to gain more insight on the observed changes.

Management of myocardial damage in muscular dystrophy

International Nuclear Information System (INIS)

Tamura, Takuhisa

2011-01-01

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)

Digital control rod blocking monitor

International Nuclear Information System (INIS)

Funayama, Yoshio.

1996-01-01

The present invention system is used for monitoring of a power region of a reactor, and used for monitoring of simultaneous withdrawal of a plurality of control rods without increasing the size or complicating the system. Namely, the system processes signals from a neutron flux detectors at the periphery of control rods controlled for withdrawal. As a result of the processing, the digital monitoring system generates an alarm when the reactor power at the periphery of the control rods fluctuates exceeding an allowable range. In the system, a control rod information forming means prepares frame data comprising front data, positions of the control rods to be withdrawn, frame numbers and completion data. A serial data transmitting means transmits the frame data successively as repeating frame data rows. A control rod information receiving means takes up the frame data of each of control rods to be withdrawn from the transmitted frame data rows. Since the system of the present invention can monitor the withdrawal of a plurality of control rods simultaneously without increasing the size or complicating the system, cost can be saved and the maintenance can be improved. (I.S.)

Congenital muscular dystrophies--problems of classification.

Science.gov (United States)

Lenard, H G

1991-04-01

The classification of congenital muscular dystrophies (CMD), based on perceived clinical and morphological similarities or differences, is controversial. CMD without cerebral involvement has sometimes been divided into a mild and a severe form. This distinction is, however, arbitrary and not uncontested. Whether Ullrich's disease, formerly called atonic-sclerotic dystrophy, is a disease entity and if so, whether it is a primary muscle disorder, is uncertain. CMD without cerebral involvement is inherited in an autosomal recessive fashion in the great majority of cases. CMDs with cerebral involvement are usually classified into at least three forms: the Fukuyama type of CMD, occurring almost exclusively in Japanese patients; CMD with hypomyelination, sometimes also called the occidental type of cerebromuscular dystrophy; and Walker-Warburg syndrome. Muscle-eye-brain disease, described in a number of Finnish patients, may or may not belong in this last category. In CMD with cerebral involvement inheritance is also autosomal recessive. It is possible that single sporadic cases are phenocopies due to infectious or other exogenous causes. Reports of clinical and morphological findings from an increasing number of patients show a high degree of variability within and, on the other hand, certain similarities between the forms of CMD with cerebral involvement. In addition, neuroradiological changes are also found with increasing frequency in CMD patients without clinical neuropsychological abnormalities. It is not unreasonable to speculate that molecular genetic techniques will reveal in the near future a variable defect in one gene locus or defects in a few gene loci as the cause of the various clinical forms of CMDs.

Complementary and alternative medicine for Duchenne and Becker muscular dystrophies: characteristics of users and caregivers.

Science.gov (United States)

Zhu, Yong; Romitti, Paul A; Conway, Kristin M; Andrews, Jennifer; Liu, Ke; Meaney, F John; Street, Natalie; Puzhankara, Soman; Druschel, Charlotte M; Matthews, Dennis J

2014-07-01

Complementary and alternative medicine is frequently used in the management of chronic pediatric diseases, but little is known about its use by those with Duchenne or Becker muscular dystrophy. Complementary and alternative medicine use by male patients with Duchenne or Becker muscular dystrophy and associations with characteristics of male patients and their caregivers were examined through interviews with 362 primary caregivers identified from the Muscular Dystrophy Surveillance, Tracking, and Research Network. Overall, 272 of the 362 (75.1%) primary caregivers reported that they had used any complementary and alternative medicine for the oldest Muscular Dystrophy Surveillance, Tracking, and Research Network male in their family. The most commonly reported therapies were from the mind-body medicine domain (61.0%) followed by those from the biologically based practice (39.2%), manipulative and body-based practice (29.3%), and whole medical system (6.9%) domains. Aquatherapy, prayer and/or blessing, special diet, and massage were the most frequently used therapies. Compared with nonusers, male patients who used any therapy were more likely to have an early onset of symptoms and use a wheel chair; their caregivers were more likely to be non-Hispanic white. Among domains, associations were observed with caregiver education and family income (mind-body medicines [excluding prayer and/or blessing only] and whole medical systems) and Muscular Dystrophy Surveillance, Tracking, and Research Network site (biologically based practices and mind-body medicines [excluding prayer and/or blessing only]). Complementary and alternative medicine use was common in the management of Duchenne and Becker muscular dystrophies among Muscular Dystrophy Surveillance, Tracking, and Research Network males. This widespread use suggests further study to evaluate the efficacy of integrating complementary and alternative medicine into treatment regimens for Duchenne and Becker muscular

Cone photoreceptor structure in patients with x-linked cone dysfunction and red-green color vision deficiency

DEFF Research Database (Denmark)

Patterson, Emily J.; Wilk, Melissa; Langlo, Christopher S.

2016-01-01

encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS. Our findings provide a direct link between disruption of the cone mosaic and L/ M opsin variants......PURPOSE. Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/ M opsin gene mutations...... to clarify the link between color vision deficiency and cone dysfunction.  METHODS. We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone...

The NLO jet vertex in the small-cone approximation for kt and cone algorithms

International Nuclear Information System (INIS)

Colferai, D.; Niccoli, A.

2015-01-01

We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

The NLO jet vertex in the small-cone approximation for kt and cone algorithms

Energy Technology Data Exchange (ETDEWEB)

Colferai, D.; Niccoli, A. [Dipartimento di Fisica e Astronomia, Università di Firenze and INFN, Sezione di Firenze, 50019 Sesto Fiorentino (Italy)

2015-04-15

We determine the jet vertex for Mueller-Navelet jets and forward jets in the small-cone approximation for two particular choices of jet algoritms: the kt algorithm and the cone algorithm. These choices are motivated by the extensive use of such algorithms in the phenomenology of jets. The differences with the original calculations of the small-cone jet vertex by Ivanov and Papa, which is found to be equivalent to a formerly algorithm proposed by Furman, are shown at both analytic and numerical level, and turn out to be sizeable. A detailed numerical study of the error introduced by the small-cone approximation is also presented, for various observables of phenomenological interest. For values of the jet “radius” R=0.5, the use of the small-cone approximation amounts to an error of about 5% at the level of cross section, while it reduces to less than 2% for ratios of distributions such as those involved in the measure of the azimuthal decorrelation of dijets.

QCD on the light cone

International Nuclear Information System (INIS)

Brodsky, S.J.

1992-09-01

The quantization of gauge theory at fixed light-cone time τ = t - z/c provides new perspectives for solving non-perturbative problems in quantum chromodynamics. The light-cone Fock state expansion provides both a precise definition of the relativistic wavefunctions of hadrons as bound-states of quarks and gluons and a general calculus for predicting QCD processes at the amplitude level. Applications to exclusive processes and weak decay amplitudes are discussed. The problem of computing the hadronic spectrum and the corresponding light-cone wavefunctions of QCD in one space and one time dimension has been successfully reduced to the diagonalization of a discrete representation of the light-cone Hamiltonian. The problems confronting the solution of gauge theories in 3 + 1 dimensions in the light-cone quantization formalism,, including zero modes and non-perturbative renormalization, are reviewed

Thresholds and noise limitations of colour vision in dim light.

Science.gov (United States)

Kelber, Almut; Yovanovich, Carola; Olsson, Peter

2017-04-05

Colour discrimination is based on opponent photoreceptor interactions, and limited by receptor noise. In dim light, photon shot noise impairs colour vision, and in vertebrates, the absolute threshold of colour vision is set by dark noise in cones. Nocturnal insects (e.g. moths and nocturnal bees) and vertebrates lacking rods (geckos) have adaptations to reduce receptor noise and use chromatic vision even in very dim light. In contrast, vertebrates with duplex retinae use colour-blind rod vision when noisy cone signals become unreliable, and their transition from cone- to rod-based vision is marked by the Purkinje shift. Rod-cone interactions have not been shown to improve colour vision in dim light, but may contribute to colour vision in mesopic light intensities. Frogs and toads that have two types of rods use opponent signals from these rods to control phototaxis even at their visual threshold. However, for tasks such as prey or mate choice, their colour discrimination abilities fail at brighter light intensities, similar to other vertebrates, probably limited by the dark noise in cones.This article is part of the themed issue 'Vision in dim light'. © 2017 The Author(s).

The BWR Hybrid 4 control rod

International Nuclear Information System (INIS)

Gross, H.; Fuchs, H.P.; Lippert, H.J.; Dambietz, W.

1988-01-01

The service life of BWR control rods designed in the past has been unsatisfactory. The main reason was irradiation assisted stress corrosion cracking of B 4 C rods caused by external swelling of the B 4 C powder. By this reason KWU developed an improved BWR control rod (Hybrid 4 control rod) with extended service life and increased control rod worth. It also allows the procedure for replacing and rearranging fuel assemblies to be considerably simplified. A complete set of Hydbrid 4 control rods is expected to last throughout the service life of a plant (assumption: ca. 40 years) if an appropriate control rod reshuffling management program is used. (orig.)

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.

Platelets Inhibit Migration of Canine Osteosarcoma Cells.

Science.gov (United States)

Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

2017-01-01

The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

Skeletal muscle CT of lower extremities in myotonic dystrophy

International Nuclear Information System (INIS)

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

1988-01-01

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. (author)

Prevalence and Diagnostic Spectrum of Generalized Retinal Dystrophy in Danish Children

DEFF Research Database (Denmark)

Bertelsen, Mette; Jensen, Hanne; Larsen, Michael

2013-01-01

Abstract Purpose: The aim of the present population-based cross-sectional study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in Danish children. Methods: The Danish Registry for the Blind and Partially Sighted Children comprises all visually impaired......: Of the 1,204,235 Danish children aged 0-17 years on 1 October 2011, 2017 children were registered as visually impaired. Of these, 153 cases were attributed to generalized retinal dystrophy, corresponding to a prevalence of 13 per 100,000 children. The age-specific prevalence increased prominently...... children residing in Denmark aged 0-17 years. Among registered children, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Age-specific data for live children in Denmark were retrieved from Statistics Denmark. Results...

Burnable poison rod

International Nuclear Information System (INIS)

Natsume, Tomohiro.

1988-01-01

Purpose: To decrease the effect of water elimination and the effect of burn-up residue boron, thereby reduce the effect of burnable poison rods as the neutron poisons at the final stage of reactor core lifetime. Constitution: In a burnable poison rod according to the present invention, a hollow burnable poison material is filled in an external fuel can, an inner fuel can mounted with a carbon rod is inserted to the hollow portion of the burnable poison material and helium gases are charged in the outer fuel can. In such a burnable poison rod, the reactivity worths after the burning are reduced to one-half as compared with the conventional case. Accordingly, since the effect of the burnable poison as the neutron poisons is reduced at the final stage of the reactor core of lifetime, the excess reactivity of the reactor core is increased. (Horiuchi, T.)

How Do People Cope with Muscular Dystrophy?

Science.gov (United States)

... topic are answered in this section. How do people cope with muscular dystrophy (MD)? Although MD presents ... improve health and quality of life. Almost all people with any form of MD experience a worsening ...

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... REQUIREMENTS Killed Virus Vaccines § 113.201 Canine Distemper Vaccine, Killed Virus. Canine Distemper Vaccine... canine distemper susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood...

Biomechanics of lumbar cortical screw-rod fixation versus pedicle screw-rod fixation with and without interbody support.

Science.gov (United States)

Perez-Orribo, Luis; Kalb, Samuel; Reyes, Phillip M; Chang, Steve W; Crawford, Neil R

2013-04-15

Seven different combinations of posterior screw fixation, with or without interbody support, were compared in vitro using nondestructive flexibility tests. To study the biomechanical behavior of a new cortical screw (CS) fixation construct relative to the traditional pedicle screw (PS) construct. The CS is an alternative to the PS for posterior fixation of the lumbar spine. The CS trajectory is more sagittally and cranially oriented than the PS, being anchored in the pars interarticularis. Like PS fixation, CS fixation uses interconnecting rods fastened with top-locking connectors. Stability after bilateral CS fixation was compared with stability after bilateral PS fixation in the setting of intact disc and with direct lateral interbody fixation (DLIF) or transforaminal lateral interbody fixation (TLIF) support. Standard nondestructive flexibility tests were performed in cadaveric lumbar specimens, allowing non-paired comparisons of specific conditions from 28 specimens (4 groups of 7) within a larger experiment of multiple hardware configurations. Condition tested and group from which results originated were as follows: (1) intact (all groups); (2) with L3-L4 bilateral PS-rods (group 1); (3) with bilateral CS-rods (group 2); (4) with DLIF (group 3); (5) with DLIF + CS-rods (group 4); (6) with DLIF + PS-rods (group 3); (7) with TLIF + CS-rods (group 2), and (8) with TLIF + PS-rods (group 2). To assess spinal stability, the mean range of motion, lax zone, and stiff zone at L3-L4 were compared during flexion-extension, lateral bending, and axial rotation. With intact disc, stability was equivalent after PS-rod and CS-rod fixation, except that PS-rod fixation was stiffer during axial rotation. With DLIF support, there was no significant difference in stability between PS-rod and CS-rod fixation. With TLIF support, PS-rod fixation was stiffer than CS-rod fixation during lateral bending. Bilateral CS-rod fixation provided about the same stability in cadaveric specimens

Recombinant canine distemper virus serves as bivalent live vaccine against rabies and canine distemper.

Science.gov (United States)

Wang, Xijun; Feng, Na; Ge, Jinying; Shuai, Lei; Peng, Liyan; Gao, Yuwei; Yang, Songtao; Xia, Xianzhu; Bu, Zhigao

2012-07-20

Effective, safe, and affordable rabies vaccines are still being sought. Attenuated live vaccine has been widely used to protect carnivores from canine distemper. In this study, we generated a recombinant canine distemper virus (CDV) vaccine strain, rCDV-RVG, expressing the rabies virus glycoprotein (RVG) by using reverse genetics. The recombinant virus rCDV-RVG retained growth properties similar to those of vector CDV in Vero cell culture. Animal studies demonstrated that rCDV-RVG was safe in mice and dogs. Mice inoculated intracerebrally or intramuscularly with rCDV-RVG showed no apparent signs of disease and developed a strong rabies virus (RABV) neutralizing antibody response, which completely protected mice from challenge with a lethal dose of street virus. Canine studies showed that vaccination with rCDV-RVG induced strong and long-lasting virus neutralizing antibody responses to RABV and CDV. This is the first study demonstrating that recombinant CDV has the potential to serve as bivalent live vaccine against rabies and canine distemper in animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Military Working Dogs and Canine Ehrlichiosis (Tropical Canine Pancytopenia) in the Vietnam War

Science.gov (United States)

1981-06-05

anemia, dermatitis, edema of the limbs and scrotum, and petechial hemorrhages on the penis (116). Hematologic findings included a leucopenia with...idiopathic hemorrhagic disease, and canine hemorrhagic fever (116). Attempts to identity the cause of tropical canine pancytopenia continued in 1969...Following inoculation with infective blood, signs of acute disease appear within 7-10 days and consfst of fever , serous nasal and ocular discharges

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.

Mapping of the human cone transducin {alpha} subunit (GNAT2) gene to 1p13 and mutation analysis in patients with Stargardt`s disease

Energy Technology Data Exchange (ETDEWEB)

Magovcevic, I.; Weremowicz, S.; Morton, C.C. [Harvard Medical School, Boston, MA (United States)] [and others

1994-09-01

Transducin {alpha} subunits are members of a large family of G-proteins and play an important role in phototransduction in rod and cone photoreceptors. We report the localization of the human cone {alpha} transducin (GNAT2) gene using fluorescence in situ hybridization (FISH) on chromosome 1 in band p13. The recent assignment of a gene for Stargardt`s disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. Stargardt`s disease is characterized by degeneration in late childhood or early adulthood of the macula of the retina, a region rich in cones. We screened patients with Stargardt`s disease, with or without peripheral cone involvement as monitored by the full-field ERG, for mutations in this gene. We investigated 66 unrelated patients including 22 with peripheral cone dysfunction for mutations in the coding region of the GNAT2 gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. One patient (034-16) was heterozygous for a silent change in exon VI, Asp238Asp (GAT to GAC). Two patients, one (035-005) with peripheral cone involvement and one (071-001) without peripheral cone involvement, were heterozygous for the missense change Val124Met (GTG to ATG) in exon IV. A subsequent screen of 96 unrelated, unaffected controls revealed one individual (N10) who was also heterozygous for the Val124Met alteration. We concluded that Asp238Asp and Val124Met are rare variants not causing Stargardt`s disease. Hence, no disease-specific mutations were found indicating that GNAT2 is probably not involved in the pathogenesis of most cases of Stargardt`s disease.

Concomitant canine distemper, infectious canine hepatitis, canine parvoviral enteritis, canine infectious tracheobronchitis, and toxoplasmosis in a puppy.

Science.gov (United States)

Headley, Selwyn Arlington; Alfieri, Amauri Alcindo; Fritzen, Juliana Torres Tomazi; Garcia, João Luis; Weissenböck, Herbert; da Silva, Ana Paula; Bodnar, Livia; Okano, Werner; Alfieri, Alice Fernandes

2013-01-01

The concomitant infections of Canine distemper virus (CDV), Canine adenovirus A types 1 (CAdV-1) and 2 (CAdV-2), Canine parvovirus type 2 (CPV-2), and Toxoplasma gondii are described in a 43-day-old mixed-breed puppy. Clinically, there were convulsions and blindness with spontaneous death; 14 siblings of this puppy, born to a 10-month-old dam, which was seropositive (titer: 1,024) for T. gondii, also died. Necropsy revealed unilateral corneal edema (blue eye), depletion of intestinal lymphoid tissue, non-collapsible lungs, congestion of meningeal vessels, and a pale area in the myocardium. Histopathology demonstrated necrotizing myocarditis associated with intralesional apicomplexan protozoa; necrotizing and chronic hepatitis associated with rare intranuclear inclusion bodies within hepatocytes; necrotizing bronchitis and bronchiolitis; interstitial pneumonia associated with eosinophilic intracytoplasmic inclusion bodies within epithelial cells; atrophy and fusion of intestinal villi with cryptal necrosis; and white matter demyelination of the cerebrum and cerebellum associated with intranuclear inclusion bodies within astrocytes. Polymerase chain reaction (PCR) amplified the partial fragments (bp) of the CDV N gene (290 bp), CPV-2c VP2 capsid protein gene (583 bp), and CAdV-1 (508 bp) and CAdV-2 (1,030 bp) E gene from urine and tissue samples. The PCR assays demonstrated that the apicomplexan protozoa observed within several organs contained DNA specific for T. gondii; genotyping revealed T. gondii type III. The findings support the characterization of concomitant infections of CDV, CAdV-1, CAdV-2, CPV-2, and T. gondii in this puppy. Further, seroreactivity to T. gondii of the dam in association with the systemic disease observed in the puppy described herein is suggestive of congenital toxoplasmosis.

Ontogenic retinal changes in three ecologically distinct elopomorph fishes (Elopomorpha:Teleostei) correlate with light environment and behavior.

Science.gov (United States)

Taylor, Scott M; Loew, Ellis R; Grace, Michael S

2015-01-01

Unlike the mammalian retina, the teleost fish retina undergoes persistent neurogenesis from intrinsic stem cells. In marine teleosts, most cone photoreceptor genesis occurs early in the embryonic and larval stages, and rods are added primarily during and after metamorphosis. This study demonstrates a developmental paradigm in elopomorph fishes in which retinas are rod-dominated in larvae, but undergo periods of later cone genesis. Retinal characteristics were compared at different developmental stages among three ecologically distinct elopomorph fishes-ladyfish (Elops saurus), bonefish (Albula vulpes), and speckled worm eel (Myrophis punctatus). The objectives were to improve our understanding of (1) the developmental strategy in the elopomorph retina, (2) the functional architecture of the retina as it relates to ecology, and (3) how the light environment influences photoreceptor genesis. Photoreceptor morphologies, distributions, and spectral absorption were studied at larval, juvenile, and adult stages. Premetamorphic retinas in all three species are rod-dominated, but the retinas of these species undergo dramatic change over the course of development, resulting in juvenile and adult retinal characteristics that correlate closely with ecology. Adult E. saurus has high rod densities, grouped photoreceptors, a reflective tapetum, and longer-wavelength photopigments, supporting vision in turbid, low-light conditions. Adult A. vulpes has high cone densities, low rod densities, and shorter-wavelength photopigments, supporting diurnal vision in shallow, clear water. M. punctatus loses cones during metamorphosis, develops new cones after settlement, and maintains high rod but low cone densities, supporting primarily nocturnal vision. M. punctatus secondary cone genesis occurs rapidly throughout the retina, suggesting a novel mechanism of vertebrate photoreceptor genesis. Finally, in postsettlement M. punctatus, the continuous presence or absence of visible light

The Intriguing Regulators of Muscle Mass in Sarcopenia and Muscular Dystrophy

OpenAIRE

Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko