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1

Targeting Inflammatory Demyelinating Lesions to Sites of Wallerian Degeneration  

PubMed Central

In Theiler’s murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits inflammatory cells to sites of Wallerian degeneration, leading to demyelination. Three weeks after TMEV infection, axonal degeneration was induced in the posterior funiculus of mice by injecting the toxic lectin Ricinus communis agglutinin (RCA) I into the sciatic nerve. Neuropathology was examined 1 week after lectin injection. Control mice, infected with TMEV but receiving no RCA I, had inflammatory demyelinating lesions in the anterior/lateral funiculi. Other control mice that received RCA I alone did not develop inflammatory lesions. In contrast, RCA I injection into TMEV-infected mice induced lesions in the posterior funiculus in addition to the anterior/lateral funiculi. We found no differences in lymphoproliferative responses or antibody titers against TMEV among the groups. This suggests that axonal degeneration contributes to the recruitment of inflammatory cells into the central nervous system by altering the local microenvironment. In this scenario, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model). PMID:17823280

Tsunoda, Ikuo; Tanaka, Tomoko; Saijoh, Yukio; Fujinami, Robert S.

2007-01-01

2

Evidence for complex selection on four-fold degenerate sites in Drosophila melanogaster.  

PubMed

We considered genome-wide four-fold degenerate sites from an African Drosophila melanogaster population and compared them to short introns. To include divergence and to polarize the data, we used its close relatives Drosophila simulans, Drosophila sechellia, Drosophila erecta and Drosophila yakuba as outgroups. In D. melanogaster, the GC content at four-fold degenerate sites is higher than in short introns; compared to its relatives, more AT than GC is fixed. The former has been explained by codon usage bias (CUB) favouring GC; the latter by decreased intensity of directional selection or by increased mutation bias towards AT. With a biallelic equilibrium model, evidence for directional selection comes mostly from the GC-rich ancestral base composition. Together with a slight mutation bias, it leads to an asymmetry of the unpolarized allele frequency spectrum, from which directional selection is inferred. Using a quasi-equilibrium model and polarized spectra, however, only purifying and no directional selection is detected. Furthermore, polarized spectra are proportional to those of the presumably unselected short introns. As we have no evidence for a decrease in effective population size, relaxed CUB must be due to a reduction in the selection coefficient. Going beyond the biallelic model and considering all four bases, signs of directional selection are stronger. In contrast to short introns, complementary bases show strand specificity and allele frequency spectra depend on mutation directions. Hence, the traditional biallelic model to describe the evolution of four-fold degenerate sites should be replaced by more complex models assuming only quasi-equilibrium and accounting for all four bases. PMID:23020078

Clemente, F; Vogl, C

2012-12-01

3

Characteristics of a 4-fold segmented clover detectore  

Microsoft Academic Search

Four high-purity germanium 4-fold segmented Clover detectors have been applied in the experiment of neutron-rich nucleus 21N. The performance of those four Clovers have been tested with radioactive sources and in-beam experiments, and the main results including energy resolution, peak-to-total ratios, the variation of the hit pattern distribution in different crystals of one Clover detector with the energy of gamma

Jian-Ling Lou; Zhi-Huan Li; Yan-Lin Ye; Dong-Xing Jiang; Hui Hua; Xiang-Qing Li; Shuang-Quan Zhang; Tao Zheng; Yu-Cheng Ge; Zan Kong; Lin-Hui Lu; Chen Li; Fei Lu; Feng-Ying Fan; Zhong-Yu Li; Zhong-Xin Cao; Li-Ying Ma; J. Faisal Q; Hu-Shan Xu; Zheng-Guo Hu; Meng Wang; Xiang-Guo Lei; Li-Min Duan; Zhi-Gang Xiao; Wen-Long Zhan; Guo-Qing Xiao; Tian-Heng Huang; Fen Fu; Xue-Heng Zhang; Chuan Zheng; Yu-Hong Yu; Xiao-Lin Tu; Ya-Peng Zhang; Yan-Yun Yang; Hong-Bin Zhang; Bin Tang; Yu-Lin Tian; Zhen Ouyang; Mei-Rong Huang; Zhi-Guo Xu; Ke Yue; Qi Gao

2009-01-01

4

American Macular Degeneration Foundation  

MedlinePLUS

... A + A Search Search Welcome Welcome to the American Macular Degeneration Foundation web site where you can ... the United States, affecting more than ten million Americans. This time-lapse animation illustrates the central vision ...

5

Cerebellar Degeneration  

MedlinePLUS

... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

6

Is the subcallosal medial prefrontal cortex a common site of atrophy in Alzheimer's disease and frontotemporal lobar degeneration?  

PubMed

Regions affected late in neurodegenerative disease are thought to be anatomically connected to regions affected earlier. The subcallosal medial prefrontal cortex (SMPC) has connections with the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and hippocampus (HC), which are regions that may become atrophic in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). We hypothesized that the SMPC is a common site of frontal atrophy in the FTLD subtypes and in AD. The volume of the SMPC, DLPFC, OFC, HC, and entorhinal cortex (EC) were manually delineated for 12 subjects with frontotemporal dementia (FTD), 13 with semantic dementia (SD), 9 with progressive nonfluent aphasia (PNFA), 10 AD cases, and 13 controls. Results revealed significant volume loss in the left SMPC in FTD, SD, and PNFA, while the right SMPC was also atrophied in SD and FTD. In AD a non significant tendency of volume loss in the left SMPC was found (p = 0.08), with no volume loss on the right side. Results indicated that volume loss reflected the degree of brain connectivity. In SD and AD temporal regions displayed most atrophy. Among the frontal regions, the SMPC (which receives the strongest temporal projections) demonstrated most volume loss, the OFC (which receives less temporal projections) less volume loss, while the DLPFC (which is at multisynaptic distance from the temporal regions) demonstrated no volume loss. In PNFA, the left SMPC was atrophic, possibly reflecting progression from the left anterior insula, while FTD patients may have had SMPC atrophy at the initial stages of the disease. Atrophy of the SMPC may thus be affected by either initial temporal or initial frontal atrophy, making it a common site of frontal atrophy in the dementia subtypes investigated. PMID:23189052

Lindberg, Olof; Westman, Eric; Karlsson, Sari; Ostberg, Per; Svensson, Leif A; Simmons, Andrew; Wahlund, Lars-Olof

2012-01-01

7

The Existence of a Smooth Divisor on Fano 4-FOLDS of INDEX 2  

NASA Astrophysics Data System (ADS)

Let X be a smooth Fano 4-fold of index 2, and H a fundamental divisor on X, that is, an ample divisor such that K_X=2H. It is proved that there is a smooth irreducible element in the linear system \\vert H\\vert.Bibliography: 23 titles.

Prokhorov, Yu G.

1995-02-01

8

Precision half-life measurement of the 4-fold forbidden electron capture of V-50  

E-print Network

A sensitive search of the 4-fold forbidden non-unique beta decay of V-50 has been performed. A total exposure of 185.8 kg x d has been accumulated. A reliable half-life value with the highest precision so far of $(2.29 \\pm 0.25) \\cdot 10^{17}$ years of the electron capture decay of V-50 into the first excited state of Ti-50 could be obtained. A photon emission line following the 4-fold forbidden beta decay into the first excited state of Cr-50 could not be observed, resulting in a lower limit on the half-life of the beta decay branch of $1.7 \\cdot 10^{18}$ years. This is barely in agreement with a claimed observation of this decay branch.

H. Dombrowski; S. Neumaier; K. Zuber

2011-03-30

9

Precision half-life measurement of the 4-fold forbidden {beta} decay of {sup 50}V  

SciTech Connect

A sensitive search of the 4-fold forbidden nonunique decay of {sup 50}V has been performed. A total mass measuring time product of 186 kg d has been accumulated. A reliable half-life value with the highest precision so far of (2.29{+-}0.25)x10{sup 17} years of the electron capture decay of {sup 50}V into the first excited state of {sup 50}Ti could be obtained. A photon emission line following the {beta} decay into the first excited state of {sup 50}Cr could not be observed, resulting in a lower limit on the half-life of the {beta}-decay branch of 1.7x10{sup 18} years. This is not in good agreement with a claimed observation of this decay branch published in 1989.

Dombrowski, H.; Neumaier, S. [Physikalisch-Technische Bundesanstalt (PTB), D-38116 Braunschweig (Germany); Zuber, K. [Institut fuer Kern- und Teilchenphysik, Technische Universitaet Dresden, D-01069 Dresden (Germany)

2011-05-15

10

Degenerate mitochondria  

PubMed Central

Mitochondria are the main sites of biological energy generation in eukaryotes. These organelles are remnants of a bacterial endosymbiont that took up residence inside a host cell over 1,500 million years ago. Comparative genomics studies suggest that the mitochondrion is monophyletic in origin. Thus, the original mitochondrial endosymbiont has evolved independently in anaerobic and aerobic environments that are inhabited by diverse eukaryotic lineages. This process has resulted in a collection of morphologically, genetically and functionally heterogeneous organelle variants that include anaerobic and aerobic mitochondria, hydrogenosomes and mitosomes. Current studies aim to determine whether a central common function drives the retention of mitochondrial organelles in different eukaryotic organisms. PMID:15940286

van der Giezen, Mark; Tovar, Jorge

2005-01-01

11

4-fold enhancement in the critical current density of YBa2Cu3O7 films by practical ion irradiation  

NASA Astrophysics Data System (ADS)

We report an up-to-4-fold enhancement in the in-magnetic-field critical current density at 77 K of epitaxial YBa2Cu3O7 films on CeO2-buffered SrTiO3 substrates by 3-MeV Au2+ irradiation. This indicates that irradiation using an industrially practical ion beam, which generally has kinetic energy less than 5 MeV, can provide a substantial increase in the in-field current performance of high-temperature superconductor films. Transmission electron microscopy results show that point-like defects smaller than 6 nm in diameter were created in the films by the irradiation.

Matsui, H.; Ogiso, H.; Yamasaki, H.; Kumagai, T.; Sohma, M.; Yamaguchi, I.; Manabe, T.

2012-12-01

12

Biomechanics of disc degeneration.  

PubMed

Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the "gold standard" in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

Palepu, V; Kodigudla, M; Goel, V K

2012-01-01

13

Biomechanics of Disc Degeneration  

PubMed Central

Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

Palepu, V.; Kodigudla, M.; Goel, V. K.

2012-01-01

14

Quantitative T2* (T2 Star) Relaxation Times Predict Site Specific Proteoglycan Content and Residual Mechanics of the Intervertebral Disc Throughout Degeneration  

PubMed Central

Degeneration alters the biochemical composition of the disc, affecting the mechanical integrity leading to spinal instability. Quantitative T2* MRI probes water mobility within the macromolecular network, a potentially more sensitive assessment of disc health. We determined the relationship between T2* relaxation time and proteoglycan content, collagen content, and compressive mechanics throughout the degenerative spectrum. Eighteen human cadaveric lumbar (L4–L5) discs were imaged using T2* MRI. The T2* relaxation time at five locations (nucleous pulposus or NP, anterior annulus fibrosis or AF, posterior AF, inner AF, and outer AF) was correlated with sulfated-glycosaminoglycan (s-GAG) content, hydroxyproline content, and residual stress and strain at each location. T2* relaxation times were significantly correlated with s-GAG contents in all test locations and were particularly strong in the NP (r = 0.944; p < 0.001) and inner AF (r = 0.782; p < 0.001). T2* relaxation times were also significantly correlated with both residual stresses and excised strains in the NP (r = 0.857; p < 0.001: r = 0.816; p < 0.001), inner AF (r = 0.535; p = 0.022: r = 0.516; p = 0.028), and outer AF (r = 0.668; p = 0.002: r = 0.458; p = 0.041). These strong correlations highlight T2* MRI’s ability to predict the biochemical and mechanical health of the disc. T2* MRI assessment of disc health is a clinically viable tool showing promise as a biomarker for distinguishing degenerative changes. PMID:24788830

Ellingson, Arin M.; Nagel, Tina M.; Polly, David W.; Ellermann, Jutta; Nuckley, David J.

2014-01-01

15

Kraepelin and degeneration theory.  

PubMed

Emil Kraepelin's contribution to the clinical and scientific field of psychiatry is recognized world-wide. In recent years, however, there have been a number of critical remarks on his acceptance of degeneration theory in particular and on his political opinion in general, which was said to have carried "overtones of proto-fascism" by Michael Shepherd [28]. The present paper discusses the theoretical cornerstones of Kraepelinian psychiatry with regard to their relevance for Kraepelin's attitude towards degeneration theory. This theory had gained wide influence not only in scientific, but also in philosophical and political circles in the last decades of the nineteenth century. There is no doubt that Kraepelin, on the one hand, accepted and implemented degeneration theory into the debate on etiology and pathogenesis of mental disorders. On the other hand, it is not appropriate to draw a simple and direct line from early versions of degeneration theory to the crimes of psychiatrists and politicians during the rule of national socialism. What we need, is a differentiated view, since this will be the only scientific one. Much research needs to be done here in the future, and such research will surely have a significant impact not only on the historical field, but also on the continuous debate about psychiatry, neuroscience and neurophilosophy. PMID:18516511

Hoff, Paul

2008-06-01

16

Signaling mechanisms regulating Wallerian degeneration.  

PubMed

Wallerian degeneration (WD) occurs after an axon is cut or crushed and entails the disintegration and clearance of the severed axon distal to the injury site. WD was initially thought to result from the passive wasting away of the distal axonal fragment, presumably because it lacked a nutrient supply from the cell body. The discovery of the slow Wallerian degeneration (Wld(s)) mutant mouse, in which distal severed axons survive intact for weeks rather than only one to two days, radically changed our thoughts on the autonomy of axon survival. Wld(s) taught us that under some conditions the axonal compartment can survive for weeks after axotomy without a cell body. The phenotypic and molecular characterization of Wld(S) and current models for Wld(S) molecular function are reviewed herein-the mechanism(s) by which Wld(S) spares severed axons remains unresolved. However, recent studies inspired by Wld(s) have led to the identification of the first 'axon death' signaling molecules whose endogenous activities promote axon destruction during WD. PMID:24907513

Freeman, Marc R

2014-08-01

17

Frontotemporal Lobar Degeneration  

PubMed Central

Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathologic heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD genetics and molecular pathology make the prospect of biologically driven, disease-specific therapies for FTLD seem closer than ever. PMID:20369906

Rabinovici, Gil D.; Miller, Bruce L.

2010-01-01

18

Canine intervertebral disc degeneration  

Microsoft Academic Search

Introduction: Due to advancements in veterinary care and veterinary\\u000adiets in the last four decades, dogs that are kept as companion animals\\u000ahave reached a life expectancy of 10 to 15 years. Together with\\u000aintensive breeding of chondrodystrophic and non-chondrodystrophic\\u000adogs canine intervertebral disc degeneration (IVDD) has become an\\u000aincreasingly important veterinary disorder.\\u000aMethods: IVDD occurs as a clinical entity

B. P. Meij; L. A. Smolders; N. Bergknut

2010-01-01

19

Local reactivity descriptors from degenerate frontier molecular orbitals  

NASA Astrophysics Data System (ADS)

Conceptual Density Functional Theory (DFT) has proposed a set of local descriptors to measure the reactivity on specific sites of a molecule, as an example dual descriptor has been successfully used in analyzing interesting systems to understand their local reactivity, however under the frozen orbital approximation (FOA), it is defined from non-degenerate frontier molecular orbitals (FMOs). In this work, the degeneration is taken into account to propose approximated expressions to obtain the dual descriptor, nucleophilic and electrophilic Fukui functions in closed-shell systems. The proposed expressions have been tested on molecules presenting degenerate FMOs.

Martínez, Jorge

2009-08-01

20

Alternative splicing and retinal degeneration.  

PubMed

Alternative splicing is highly regulated in tissue-specific and development-specific patterns, and it has been estimated that 15% of disease-causing point mutations affect pre-mRNA splicing. In this review, we consider the cis-acting splice site and trans-acting splicing factor mutations that affect pre-mRNA splicing and contribute to retinal degeneration. Numerous splice site mutations have been identified in retinitis pigmentosa (RP) and various cone-rod dystrophies. Mutations in alternatively spliced retina-specific exons of the widely expressed RPGR and COL2A1 genes lead primarily to X-linked RP and ocular variants of Stickler syndrome, respectively. Furthermore, mutations in general pre-mRNA splicing factors, such as PRPF31, PRPF8, and PRPF3, predominantly cause autosomal dominant RP. These findings suggest an important role for pre-mRNA splicing in retinal homeostasis and the pathogenesis of retinal degenerative diseases. The development of novel therapeutic strategies to modulate aberrant splicing, including small molecule-based therapies, has the potential to lead to new treatments for retinal degenerative diseases. PMID:23647439

Liu, M M; Zack, D J

2013-08-01

21

Neural remodeling in retinal degeneration  

Microsoft Academic Search

Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three

Robert E Marc; Bryan W Jones; Carl B Watt; Enrica Strettoi

2003-01-01

22

Neural remodeling in retinal degeneration  

Microsoft Academic Search

Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three

Robert E. Marc; Bryan W. Jones; Carl B. Watt; Enrica Strettoi

23

Disc degeneration in Scheuermann disease.  

PubMed

Comparison of the radiographic signs of Scheuermann disease and the corresponding disc degeneration on thoracolumbar magnetic resonance (MR) images was made in 21 young patients. Marginal sclerosis, Schmorl nodes and narrowed disc spaces, but not irregular or wedge-shaped end-plates, were significantly associated with disc degeneration. Fifty-five percent of the discs in the patients with Scheuermann disease were abnormal on MRI, compared with 10% in asymptomatic controls. Our study confirms that thoracolumbar disc degeneration is enhanced in 20-year-old patients with low back pain who have radiological evidence of Scheuermann disease. PMID:2588031

Paajanen, H; Alanen, A; Erkintalo, M; Salminen, J J; Katevuo, K

1989-01-01

24

MRI in subacute combined degeneration  

Microsoft Academic Search

We describe a patient with clear lesions in the spinal cord on MRI due to subacute combined degeneration. T2-weighted images clearly showed abnormal high signals in the posterior columns, which disappeared on recovery from the disease.

S. Murata; H. Naritomi; T. Sawada

1994-01-01

25

Axon degeneration in Parkinson's disease.  

PubMed

Parkinson's disease (PD) is the most common neurodegenerative disease of the basal ganglia. Like other adult-onset neurodegenerative disorders, it is without a treatment that forestalls its chronic progression. Efforts to develop disease-modifying therapies to date have largely focused on the prevention of degeneration of the neuron soma, with the tacit assumption that such approaches will forestall axon degeneration as well. We herein propose that future efforts to develop neuroprotection for PD may benefit from a shift in focus to the distinct mechanisms that underlie axon degeneration. We review evidence from human post-mortem studies, functional neuroimaging, genetic causes of the disease and neurotoxin models that axon degeneration may be the earliest feature of the disease, and it may therefore be the most appropriate target for early intervention. In addition, we present evidence that the molecular mechanisms of degeneration of axons are separate and distinct from those of neuron soma. Progress is being made in understanding these mechanisms, and they provide possible new targets for therapeutic intervention. We also suggest that the potential for axon re-growth in the adult central nervous system has perhaps been underestimated, and it offers new avenues for neurorestoration. In conclusion, we propose that a new focus on the neurobiology of axons, their molecular pathways of degeneration and growth, will offer novel opportunities for neuroprotection and restoration in the treatment of PD and other neurodegenerative diseases. PMID:22285449

Burke, Robert E; O'Malley, Karen

2013-08-01

26

Frontotemporal lobar degeneration: current perspectives  

PubMed Central

The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer’s disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. PMID:24600223

Riedl, Lina; Mackenzie, Ian R; Forstl, Hans; Kurz, Alexander; Diehl-Schmid, Janine

2014-01-01

27

Fluoroquinolone-induced retinal degeneration in cats.  

PubMed

Although the exact mechanism of fluoroquinolone-induced retinal degeneration in cats remains to be elucidated, it appears from the literature that a similar retinal degeneration can be reproduced from either direct intravitreal injection of high concentrations of drug or exposure to UVA light and drug in laboratory animals. (19,25) The fluoroquinolone molecular structure is also similar structurally to other drugs that are known to directly induce retinal degeneration, including the cinchona alkaloids and halogenated hydroquinolones. Experimental evidence suggests that both the parent compound and its breakdown products via metabolism and photodegradation are active inducers of retinal degeneration. (18,25) Development of toxicoses also appears to be dependent on the maximum concentration of active drug, metabolite, or both reaching the retina over time. (18) Evaluation of the literature suggests that risk factors predisposing cats to fluoroquinolone-induced retinal degeneration may include the following: 1) large doses or plasma concentrations of drug, 2) rapid IV infusion of the antibiotic, 3) prolonged courses of treatment, and 4) age. Theoretically, other risk factors may also be involved including the following: 1) prolonged exposure to UVA light while the antibiotic is being administered, 2) drug interactions, and 3) drug or metabolite accumulation from altered metabolism or reduced elimination. To date, there are no published reports suggesting that the dose of fluoroquinolones should be reduced in geriatric cats or those with renal or hepatic failure. However, accumulation of fluoroquinolone metabolites in dogs and of the parent compound in humans with decreased renal function has been reported. (8-10) In humans with decreased renal function has been reported. (8-10) humans, fluoroquinolone doses are typically decreased in response to the degree of renal impairment. (28) In general, all fluoroquinolone antibiotics should be reserved for severe or recurrent infections, and whenever possible their use should be based on results whenever possible their use should be based on results of culture and susceptibility tests. When indicated, the fluoroquinolones, including enrofloxacin, can be used with limited risk of developing retinal degeneration in cats, provided the manufacturer's guidelines are adhered to and dose reduction is considered in geriatric cats or those with renal impairment. Dosing on renal impairment. Dosing on exact body weight using split dosing (2.5 mg/kg, PO, q 12 h) and avoidance of rapid IV infusions, and drug interactions may help to reduce the risk of retinal degeneration in some cases. Furthermore, monitoring cats for mydriasis and avoidance of UVA light while undergoing treatment may also be of benefit. Further evaluation of the pharmacokinetics of enrofloxacin and the other fluoroquinolones is required in geriatric cats or those with mild to moderate renal or liver impairment to determine whether drug accumulation, elevated peak concentrations of drug, or both may be occurring in this subset of cats. Therapeutic monitoring of drug concentrations may not always be feasible because of time and cost, but renal panels with dose or frequency reduction in response to the degree of renal impairment and the site and severity of infection may help to reduce retinal toxicosis. PMID:12479325

Wiebe, Valerie; Hamilton, Patti

2002-12-01

28

The Degeneration of Tropical Geography  

Microsoft Academic Search

How did colonial and tropical geography as practiced in the aftermath of World War II become development geography by the 1970s? We excavate the genealogy of development geography, relating it to geopolitical, economic, and social traumas of decolonization. We examine how revolutionary pressures and insurgencies, coupled with the eclipse of formal colonialism, led to the degeneration and displacement of a

Marcus Power; James D. Sidaway

2004-01-01

29

Retinal remodeling triggered by photoreceptor degenerations  

Microsoft Academic Search

Many photoreceptor degenerations initially affect rods, secondarily leading to cone death. It has long been assumed that the surviving neural retina is largely resistant to this sensory deafferentation. New evidence from fast retinal degenerations reveals that subtle plasticities in neuronal form and connectivity emerge early in disease. By screening mature natural, trans- genic, and knockout retinal degeneration models with computational

BRYAN W. JONES; Carl B. Watt; Jeanne M. Frederick; Wolfgang Baehr; Ching-Kang Chen; Edward M. Levine; Ann H. Milam; Matthew M. Lavail; Robert E. Marc

2003-01-01

30

Retinal degeneration mutants in the mouse.  

PubMed

The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to look for genetically determined eye variations and disorders. Through ophthalmoscopy, electroretinography and histology, we have discovered disorders affecting all aspects of the eye including the lid, cornea, iris, lens and retina, resulting in corneal disorders, cataracts, glaucoma and retinal degenerations. Mouse models of retinal degeneration have been investigated for many years in the hope of understanding the causes of photoreceptor cell death. Sixteen naturally occurring mouse mutants that manifest degeneration of photoreceptors in the retina with preservation of all other retinal cell types have been found: retinal degeneration (formerly rd, identical with rodless retina, r, now Pde6b(rd1)); Purkinje cell degeneration (pcd); nervous (nr); retinal degeneration slow (rds, now Prph(Rd2)); retinal degeneration 3 (rd3); motor neuron degeneration (mnd); retinal degeneration 4 (Rd4); retinal degeneration 5 (rd5, now tub); vitiligo (vit, now Mitf(mi-vit)); retinal degeneration 6 (rd6); retinal degeneration 7 (rd7, now Nr2e3(rd7)); neuronal ceroid lipofuscinosis (nclf); retinal degeneration 8 (rd8); retinal degeneration 9 (Rd9); retinal degeneration 10 (rd10, now Pde6b(rd10)); and cone photoreceptor function loss (cpfl1). In this report, we first review the genotypes and phenotypes of these mutants and second, list the mouse strains that carry each mutation. We will also provide detailed information about the cpfl1 mutation. The phenotypic characteristics of cpfl1 mice are similar to those observed in patients with complete achromatopsia (ACHM2, OMIM 216900) and the cpfl1 mutation is the first naturally-arising mutation in mice to cause cone-specific photoreceptor function loss. cpfl1 mice may provide a model for congenital achromatopsia in humans. PMID:11853768

Chang, B; Hawes, N L; Hurd, R E; Davisson, M T; Nusinowitz, S; Heckenlively, J R

2002-02-01

31

Neuropsychiatric features of corticobasal degeneration  

Microsoft Academic Search

OBJECTIVETo characterise the neuropsychiatric symptoms of patients with corticobasal degeneration (CBD).METHODSThe neuropsychiatric inventory (NPI), a tool with established validity and reliability, was administered to 15 patients with CBD (mean (SEM), age 67.9 (2) years); 34 patients with progressive supranuclear palsy (PSP) (66.6 (1.2) years); and 25 controls (70 (0.8) years), matched for age and education. Both patient groups had similar

Irene Litvan; Jeffrey L Cummings; Michael Mega

1998-01-01

32

Synaptic Remodeling in Retinal Degeneration  

Microsoft Academic Search

Retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases with a complex molecular etiology. Hundreds\\u000a of RP-inducing mutations, involving dozens of genes, have been identified in patients (see references in other chapters in this book; a list of identified mutations that cause retinal degeneration is updated at www.sph.uth.\\u000a tmc.edu\\/RetNet). Despite this genetic heterogeneity, patients with RP tend to

You-Wei Peng; Fulton Wong

33

Molecular genetics of macular degeneration  

Microsoft Academic Search

Macular degeneration is a leading cause of blindness that affects the aged population. The complexity of the molecular basis of macular disease is now beginning to be elucidated with the identification of disease-causing genes. For example, mutations in the ABCR gene, (recently identified in cones as well) which codes for retinal rod-specific ABCR protein is responsible for Stargardt macular dystrophy\\/fundus

Maria A. Musarella

2001-01-01

34

Radial keratotomy associated endothelial degeneration  

PubMed Central

Purpose To describe the presentation and clinical course of eyes with a history of radial keratotomy (RK) and varying degrees of endothelial degeneration. Methods Retrospective case series were used. Results Thirteen eyes (seven patients) were identified with clinical findings of significant guttata and a prior history of RK. The mean age of presentation for cornea evaluation was 54.3 years (range: 38–72 years), averaging 18.7 years (range: 11–33 years) after RK. The presentation of guttata varied in degree from moderate to severe. Best corrected visual acuity (BCVA) ranged from 20/25 to 20/80. All patients had a history of bilateral RK, except one patient who did not develop any guttata in the eye without prior RK. No patients reported a family history of Fuch’s Dystrophy. One patient underwent a penetrating keratoplasty in one eye and a Descemet’s stripping automated endothelial keratoplasty (DSAEK) in the other eye. Conclusions RK may induce a spectrum of endothelial degeneration. In elderly patients, the findings of guttata may signify comorbid Fuch’s dystrophy in which RK incisions could potentially hasten endothelial decomposition. In these select patients with stable cornea topography and prior RK, DSAEK may successfully treat RK endothelial degeneration. PMID:22347792

Moshirfar, Majid; Ollerton, Andrew; Semnani, Rodmehr T; Hsu, Maylon

2012-01-01

35

Synthesis and RNA polymerase incorporation of the degenerate ribonucleotide analogue rPTP.  

PubMed Central

The synthesis and enzymatic incorporation into RNA of the hydrogen bond degenerate nucleoside analogue 6-(beta-d-ribofuranosyl)-3, 4-dihydro-8H-pyrimido[4,5-c]-[1,2]oxazin-7-one (P) is described. The 5'-triphosphate of this analogue is readily incorporated by T3, T7 and SP6 RNA polymerases into RNA transcripts, being best incorporated in place of UTP, but also in place of CTP. When all the uridine residues in an HIV-1 TAR RNA transcript are replaced by P the transcript has similar characteristics to the wild-type TAR RNA, as demonstrated by similar melting temperatures and CD spectra. The P-substituted TAR transcript binds to the Tat peptide ADP-1 with only 4-fold lowered efficiency compared with wild-type TAR. PMID:9547267

Moriyama, K; Negishi, K; Briggs, M S; Smith, C L; Hill, F; Churcher, M J; Brown, D M; Loakes, D

1998-01-01

36

Supranuclear ophthalmoplegia in olivopontocerebellar degeneration.  

PubMed

Autosomal dominant olivopontocerebellar degeneration was diagnosed in a family of Scottish ancestry by clinical examination and autopsy. In addition to having progressive cerebellar ataxia, head titubation, and severe dysarthria, the patients are unable to initiate saccadic eye movements. Slow pursuit movements are normal. Reflex movements of the eyes caused by passive rotation or caloric labyrinthine stimulation are not impaired but are not associated with nystagmus. The phenomenon can be classified as supranuclear pseudo-ophthalmoplegia. It differs from congenital ocular motor apraxia in age at onset and the absence of random eye movements. The anatomic lesion responsible for the defect of saccadic eye movements remains to be established. PMID:945871

Koeppen, A H; Hans, M B

1976-08-01

37

Programmed cell death in intervertebral disc degeneration  

Microsoft Academic Search

Intervertebral disc (IVD) degeneration is largely a process of destruction and failure of the extracellular matrix (ECM),\\u000a and symptomatic IVD degeneration is thought to be one of the leading causes of morbidity or life quality deterioration in\\u000a the elderly. To date, however, the mechanism of IVD degeneration is still not fully understood. Cellular loss from cell death\\u000a in the process

Chang-Qing Zhao; Lei-Sheng Jiang; Li-Yang Dai

2006-01-01

38

Lumbar Intervertebral Disk Degeneration in Athletes  

Microsoft Academic Search

Background: Several studies have reported that physical loading related to competitive sports activities is associated with lumbar intervertebral disk degeneration. However, the association between types of sports activities and disk degeneration has not been clarified.Hypothesis: The frequencies of disk degeneration may vary with the competitive sport because of the different postures and actions specific to each sport.Study Design: Cross-sectional study

Mika Hangai; Koji Kaneoka; Shiro Hinotsu; Ken Shimizu; Yu Okubo; Shumpei Miyakawa; Naoki Mukai; Masataka Sakane; Naoyuki Ochiai

2009-01-01

39

[Pathogenesis of age-related macular degeneration].  

PubMed

Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells. PMID:19341030

Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

2009-01-01

40

Macular degeneration: recent advances and therapeutic opportunities  

Microsoft Academic Search

The central retina mediates high acuity vision, and its progressive dysfunction due to macular degeneration is the leading cause of visual disability among adults in industrialized societies. Here, we summarize recent progress in understanding the pathophysiology of macular degeneration and the implications of this new knowledge for treatment and prevention. The past decade has witnessed remarkable advances in this field,

Amir Rattner; Jeremy Nathans

2006-01-01

41

Degeneration and Regeneration in Peripheral Nerve.  

National Technical Information Service (NTIS)

Neurorrhaphies with and without tubular cuffs of silicone rubber were performed in chimpanzees. The rate of degeneration in the zone of nerve severance and repair is much more rapid and of earlier onset than the Wallerian degeneration present in the dista...

G. J. Hayes, R. A. W. Lehman

1967-01-01

42

Sarcomatous degeneration in Paget's bone disease  

Microsoft Academic Search

The authors report 12 cases (8 men and 4 women) of sarcomatous degeneration in Paget's bone disease, with an average age of 72.3 years. Sarcomatous degeneration occurred often in polyostotic Paget's disease, and osteitis deformans was seen in 4 cases. Femur and pelvis were the most affected bones. Pain was a constant feature, whereas tumefaction and fracture were less common.

P. Seret; M. F. Basle; A. Rebel; J. C. Renier; J. P. Saint-Andre; G. Bertrans; M. Audran

1987-01-01

43

Genetics of Frontotemporal Lobar Degeneration  

PubMed Central

Frontotemporal lobar degeneration (FTLD), the most frequent neurodegenerative disorder with a presenile onset, presents with a spectrum of clinical manifestations, ranging from behavioral and executive impairment to language disorders and motor dysfunction. Familial aggregation is frequently reported, and about 10% of cases have an autosomal dominant transmission. Microtubule associated protein tau (MAPT) gene mutations have been the first ones identified and are associated with early onset behavioral variant frontotemporal dementia phenotype. More recently, progranulin gene (GRN) mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified. In this review, current knowledge about mutations at the basis of familial FTLD will be described, together with genetic risk factors influencing the susceptibility to FTLD. PMID:22536193

Galimberti, Daniela; Scarpini, Elio

2012-01-01

44

Hunting Quasi-Degenerate Higgsinos  

E-print Network

We present a new strategy to uncover light, quasi-degenerate Higgsinos, a likely ingredient in a natural supersymmetric model. Our strategy focuses on Higgsinos with inter-state splittings of O(5-50) GeV that are produced in association with a hard, initial state jet and decay via off-shell gauge bosons to two or more leptons and missing energy, $pp \\to j + \\text{MET}\\, + 2^+\\, \\ell$. The additional jet is used for triggering, allowing us to significantly loosen the lepton requirements and gain sensitivity to small inter-Higgsino splittings. Focusing on the two-lepton signal, we find the seemingly large backgrounds from diboson plus jet, $\\bar tt$ and $Z/\\gamma^* + j$ can be reduced with careful cuts, and that fake backgrounds appear minor. For Higgsino masses $m_{\\chi}$ just above the current LEP II bound ($\\mu \\simeq 110\\,$) GeV we find the significance can be as high as 3 sigma at the LHC using the existing 20 fb$^{-1}$ of 8 TeV data. Extrapolating to LHC at 14 TeV with 100 fb$^{-1}$ data, and as one example $M_1 = M_2 = 500$ GeV, we find 5 sigma evidence for $m_{\\chi} \\lesssim\\, 140\\,$ GeV and 2 sigma evidence for $m_{\\chi} \\lesssim\\, 200\\,$ GeV . We also present a reinterpretation of ATLAS/CMS monojet bounds in terms of degenerate Higgsino ($\\delta m_{\\chi} \\ll 5\\,$) GeV plus jet production. We find the current monojet bounds on $m_{\\chi}$ are no better than the chargino bounds from LEP II.

Zhenyu Han; Graham D. Kribs; Adam Martin; Arjun Menon

2014-01-06

45

Gelatinous degeneration presenting as a preleukaemic syndrome.  

PubMed Central

Gelatinous degeneration of marrow is a rare histological disorder associated with chronic debilitating diseases, such as anorexia nervosa, AIDS and postchemotherapy aplasia. Solid tumours have been associated with this condition but it has been reported in only two patients with leukaemia. In these cases leukaemia and gelatinous degeneration were diagnosed simultaneously. In the case reported here, a 48 year old man, gelatinous degeneration was the only histological finding observed more than two years before the diagnosis of acute myelogenous leukaemia with monosomy 7. The significance of hyaluronic acid deposition remains uncertain. Two hypotheses have been put forward: (1) that gelatinous degeneration occurs during tissue repair; and (2) that gelatinous degeneration inhibits haemopoiesis by altering the microenvironment of the bone marrow. In the case reported here, the presence of monosomy 7 suggests that myelodysplasia was the underlying disorder which finally evolved into acute leukaemia. Images PMID:8763271

Arranz, R; Gil-Fernandez, J J; Acevedo, A; Tomas, J F; Alegre, A; Fernandez-Ranada, J M

1996-01-01

46

Mouse models for cone degeneration.  

PubMed

Loss of cone vision has devastating effects on everyday life. Even though much effort has been made to understand cone physiology and pathophysiology, no successful therapies are available for patients suffering from cone disorders. As complex retinal interactions cannot be studied in vitro, utilization of different animal models is inevitable. Due to recent advances in transgenesis, mice became the most popular animal model to study human diseases, also in ophthalmology. While there are similarities in retinal anatomy and pathophysiology between mice and humans, there are also differences, most importantly the lack of a cone-rich macula in mice. Instead, cones in mice are rare and distributed over the whole retina, which makes the analysis of cone pathophysiology very difficult in these animals. This hindrance is one of the reasons why our understanding of rod pathophysiological processes is much more advanced. Recently, however, the sparseness of cones was overcome by the generation of the Nrl (- / -) mouse that expresses only cone photoreceptors in the retina. This paper will give a brief overview of some of the known mouse models to study cone degeneration and discuss the current knowledge gained from the analysis of these models. PMID:24664745

Samardzija, Marijana; Grimm, Christian

2014-01-01

47

Retinal Remodeling Triggered by Photoreceptor Degenerations  

E-print Network

Retinal Remodeling Triggered by Photoreceptor Degenerations BRYAN W. JONES,1* CARL B. WATT,1 JEANNE of the anti-hapten IgGs used in this research. *Correspondence to: Bryan W. Jones, John A. Moran Eye Center

Marc, Robert E.

48

A new degenerate Fermi gas apparatus  

E-print Network

In the summer of 2004, the BEC 2 lab of Wolfgang Ketterle's group at MIT started a new research direction of studying degenerate fermionic Lithium atoms in optical lattices. The major contributions to the new experimental ...

Setiawan, Widagdo

2007-01-01

49

Molecular genetic basis of tapetoretinal degeneration  

Microsoft Academic Search

The review considers tapetoretinal degeneration (TD), a severe incurable disease occurring at a frequency of 1 per 3500–5000\\u000a people. TD is most commonly caused by mutations of the genes for rhodopsin (RHO), peripherin (RDS), and retinol acetyltransferase (RPE65). Since pigmentary degeneration strongly correlates with mutations of these genes, it is possible to develop approaches to\\u000a DNA diagnosis of hereditary retinal

L. U. Dzhemileva; E. R. Grinberg; A. M. Tazetdinov; I. S. Zaidullin; M. M. Bikbov; V. V. Musina; E. K. Khusnutdinova

2008-01-01

50

Retinal Degenerations: Planning for the Future  

Microsoft Academic Search

Retinal degenerations are a leading cause of blindness in many parts of the world (Bunker et al., 1984; Grondahl, 1987; Berson,\\u000a 1993; Klein et al., 1995; Attebo et al., 1996; Klaver et al., 1998; Novak-Laus et al., 2002). In the United States an estimated\\u000a 6 million people have age-related macular degeneration with a decrease in central vision after age 60.

Eliot L. Berson

51

Potential outcome factors in subacute combined degeneration  

Microsoft Academic Search

BACKGROUND: Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement\\u000a in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown;\\u000a therefore, predicting complete recovery of neurologic deficits is challenging.\\u000a \\u000a \\u000a PURPOSE: To identify potential correlates of outcome and to generate hypotheses concerning predictors

Olavo M. Vasconcelos; Erika H. Poehm; Robert J. McCarter; William W. Campbell; Zenaide M. N. Quezado

2006-01-01

52

The Gravitational Demise of Cold Degenerate Stars  

E-print Network

We consider the long term fate and evolution of cold degenerate stars under the action of gravity alone. Although such stars cannot emit radiation through the Hawking mechanism, the wave function of the star will contain a small admixture of black hole states. These black hole states will emit radiation and hence the star can lose its mass energy in the long term. We discuss the allowed range of possible degenerate stellar evolution within this framework.

Fred C. Adams; Greg Laughlin; Manasse Mbonye; Malcolm J. Perry

1998-08-23

53

Secondary degeneration of the optic nerve following partial transection: the benefits of lomerizine.  

PubMed

Secondary degeneration is a form of 'bystander' damage that can affect neural tissue both nearby and remote from an initial injury. Partial optic nerve transection is an excellent model in which to unequivocally differentiate events occurring during secondary degeneration from those resulting from primary CNS injury. We analysed the primary injury site within the optic nerve (ON) and intact areas vulnerable to secondary degeneration. Areas affected by the primary injury showed morphological disruption, loss of beta-III tubulin axonal staining, reduced myelinated axon density, greater proteoglycan expression (phosphacan), increased microglia and macrophage numbers and increased oxidative stress. Similar, but less extreme, changes were seen in areas of the optic nerve undergoing secondary degeneration. The CNS-specific L- and T-type calcium channel blocker lomerizine alleviated some of the changes in areas vulnerable to secondary degeneration. Lomerizine reduced morphological disruption, oxidative stress and phosphacan expression, and limited early increases in macrophage numbers. However, lomerizine failed to prevent progressive de-myelination of ON axons. Within the retina, secondary retinal ganglion cell (RGC) death was significant in areas vulnerable to secondary degeneration. Lomerizine protected RGCs from secondary death at 4 weeks but did not fully restore behavioural function (optokinetic nystagmus). We conclude that blockade of calcium channels is neuroprotective and limits secondary degenerative changes following CNS injury. However such an approach may need to be combined with other treatments to ensure long-term maintenance of full visual function. PMID:19118550

Fitzgerald, Melinda; Bartlett, Carole A; Evill, Lauren; Rodger, Jenny; Harvey, Alan R; Dunlop, Sarah A

2009-03-01

54

Protection of Retina by ?B Crystallin in Sodium Iodate Induced Retinal Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD and ?B crystallin expression is increased in RPE and associated drusen in AMD. The purpose of this study was to investigate the role of ?B crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a model of AMD in which the primary site of pathology is the RPE. Dose dependent effects of intravenous NaIO3 (20-70 mg/kg) on development of retinal degeneration (fundus photography) and RPE and retinal neuronal loss (histology) were determined in wild type and ?B crystallin knockout mice. Absence of ?B crystallin augmented retinal degeneration in low dose (20 mg/kg) NaIO3-treated mice and increased retinal cell apoptosis which was mainly localized to the RPE layer. Generation of reactive oxygen species (ROS) was observed with NaIO3 in mouse and human RPE which increased further after ?B crystallin knockout or siRNA knockdown, respectively. NaIO3 upregulated AKT phosphorylation and peroxisome proliferator–activator receptor–? (PPAR?) which was suppressed after ?B crystallin siRNA knockdown. Further, PPAR? ligand inhibited NaIO3-induced ROS generation. Our data suggest that ?B crystallin plays a critical role in protection of NaIO3-induced oxidative stress and retinal degeneration in part through upregulation of AKT phosphorylation and PPAR? expression. PMID:24874187

Zhou, Peng; Kannan, Ram; Spee, Christine; Sreekumar, Parameswaran G.; Dou, Guorui; Hinton, David R.

2014-01-01

55

The periodic table of n-categories for low dimensions I: degenerate categories and degenerate bicategories  

E-print Network

The periodic table of n-categories for low dimensions I: degenerate categories and degenerate bicategories Eugenia Cheng and Nick Gurski Abstract. We examine the periodic table of weak n the first few entries in the "Periodic Table" of n- categories. This table was first described by Baez

Cheng, Eugenia

56

Prospectives for Gene Therapy of Retinal Degenerations  

PubMed Central

Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell growth factors (VEGF), have been used to prevent the neovascularization that accompanies AMD and DR resulting in the amelioration of vision in a significant number of patients. In animal models it has been shown that transfection of RPE cells with the gene for PEDF and other growth factors can prevent or slow degeneration. A limited number of studies in humans have also shown that transfection of RPE cells in vivo with the gene for PEDF is effective in preventing degeneration and restore vision. Most of these studies have used virally mediated gene delivery with all its accompanying side effects and have not been widely used. New techniques using non-viral protocols that allow efficient delivery and permanent integration of the transgene into the host cell genome offer novel opportunities for effective treatment of retinal degenerations. PMID:23372421

Thumann, Gabriele

2012-01-01

57

Antioxidative nanofullerol prevents intervertebral disk degeneration  

PubMed Central

Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or an inflammatory cytokine interleukin (IL)-1? was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were significantly diminished by fullerol. IL-1?-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H2O2 or IL-1?. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration. PMID:24876775

Yang, Xinlin; Jin, Li; Yao, Lu; Shen, Francis H; Shimer, Adam L; Li, Xudong

2014-01-01

58

Degenerate quasicrystal of hard triangular bipyramids.  

PubMed

We report a degenerate quasicrystal in Monte Carlo simulations of hard triangular bipyramids each composed of two regular tetrahedra sharing a single face. The dodecagonal quasicrystal is similar to that recently reported for hard tetrahedra [Haji-Akbari et al., Nature (London) 462, 773 (2009)] but degenerate in the pairing of tetrahedra, and self-assembles at packing fractions above 54%. This notion of degeneracy differs from the degeneracy of a quasiperiodic random tiling arising through phason flips. Free energy calculations show that a triclinic crystal is preferred at high packing fractions. PMID:22181897

Haji-Akbari, Amir; Engel, Michael; Glotzer, Sharon C

2011-11-18

59

Superfluid regimes in degenerate atomic Fermi gases  

SciTech Connect

We give a brief overview of recent studies of quantum degenerate regimes in ultracold Fermi gases. The attention is focused on the regime of Bose-Einstein condensation of weakly bound molecules of fermionic atoms, formed at a large positive scattering length for the interspecies atom-atom interaction. We analyze remarkable collisional stability of these molecules and draw prospects for future studies.

Shlyapnikov, G.V. [Laboratoire Physique Theorique et Modeles Statistique, Universite Paris Sud, Bat. 100, 91405 Orsay (France); Van der Waals-Zeeman Institute, University of Amsterdam, Valckenierstraat 65/67, 1018 XEAmsterdam (Netherlands)

2005-05-05

60

Depression in Age-Related Macular Degeneration  

ERIC Educational Resources Information Center

Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

Casten, Robin; Rovner, Barry

2008-01-01

61

Driving and Age-Related Macular Degeneration  

PubMed Central

This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research. PMID:20046818

Owsley, Cynthia; McGwin, Gerald

2009-01-01

62

The many faces of corticobasal degeneration  

Microsoft Academic Search

Corticobasal degeneration (CBD) has characteristic neuropathological features, but is a clinically heterogeneous disorder. It can present with various clinical syndromes. The corticobasal syndrome (CBS) is the best recognized and over the course of the illness may be the most common manifestation. Dementia, progressive non-fluent aphasia, speech apraxia, progressive supranuclear palsy (PSP)-like syndrome and posterior cortical atrophy syndrome are other presentations

Pettarusp M. Wadia; Anthony E. Lang

2007-01-01

63

The Psychosocial Impact of Macular Degeneration  

Microsoft Academic Search

Background: Age-related macular degeneration (AMD), the leading cause of irreversible blindness and low vi- sion among the elderly, has not been well studied with regard to its impact on daily life. This study was de- signed to demonstrate the impact of AMD on quality of life, emotional distress, and functional level. Participants: The study sample consisted of 86 elderly adults

Rebecca A. Williams; Barbara L. Brody; Ronald G. Thomas; Robert M. Kaplan; Stuart I. Brown

1998-01-01

64

Neuronal degeneration Xp44+/+ APP695/swe  

E-print Network

Neuronal degeneration Xp44+/+ APP695/swe p44+/+;APP695/swe Accelerated aging Alzheimer's Disease-like pathology Increased dosage of p44 causes memory loss, neurodegeneration and premature death Pehar M.1, O been recently shown to regulate longevity and aging independently of its tumor suppressor activity

Wisconsin at Madison, University of

65

Genetic susceptibility to age related macular degeneration  

Microsoft Academic Search

Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and a major cause of blindness in the developed world. The disease can take two forms, geographic atrophy and choroidal neovascularisation. The pathogenesis of AMD is poorly understood. There are undoubtedly environmental and other risk factors involved and the adverse effect of smoking is well

John R W Yates; Anthony T Moore

2000-01-01

66

Genetics of Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Age-related Macular Degeneration (AMD) is a multifactorial disease involving genetic and environmental influences. Complement\\u000a Factor H (CFH) and HTRA1\\/LOC387715 are the two main loci associated with AMD. A genetic understanding of AMD may allow for\\u000a early diagnosis and treatment.

Daniel T. Kasuga; Yuhong Chen; Kang Zhang

67

Potential Outcome Factors in Subacute Combined Degeneration  

Microsoft Academic Search

DATA EXTRACTION, SYNTHESIS: We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a di- agnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS: Eight patients (14%) achieved clinical resolution and 49 (86%) improved with

Olavo M. Vasconcelos; Erika H. Poehm; Robert J. McCarter; William W. Campbell; Zenaide M. N. Quezado

68

Late-onset retinal macular degeneration: clinical insights into an inherited retinal degeneration  

Microsoft Academic Search

Aim:This study describes, in detail, the phenotype of late-onset retinal macular degeneration (L-ORMD) an inherited condition affecting both the retina and anterior segment. A staging based on clinical characteristics is proposed, and the relevance of this condition to current understanding of age-related macular degeneration is discussed.Methods:A systematic review of the literature regarding this condition supports a detailed description of the

S Borooah; C Collins; A Wright; B Dhillon

2009-01-01

69

Degenerate Primer Design using Computational Tools Computational Molecular Biology  

E-print Network

1 Degenerate Primer Design using Computational Tools Computational Molecular Biology Veronica and sensitive primers to yield good results. Primers can target a specific, known sequence, but what is often more interesting is the use of degenerate primers to target unknown sequences. Degenerate primers

70

Degenerate Primer Design via Clustering School of Computer Science,  

E-print Network

Degenerate Primer Design via Clustering Xintao Wei School of Computer Science, Florida. giri@cs.fiu.edu Abstract This paper describes a new strategy for designing degenerate primers for a given multiple alignment of amino acid sequences. Degenerate primers are useful for amplifying

Narasimhan, Giri

71

Retrograde pyramidal tract degeneration in a patient with cervical haematomyelia  

Microsoft Academic Search

Retrograde pyramidal tract degeneration has been described only very rarely in the human central nervous system. In most of these cases the thoracic or cervical corticospinal tracts were shown to have degenerated following long-standing, lower spinal cord lesions. In a 67 year old man, who lived 2 years following the rupture of a mid-cervical cavernous angioma, we observed such degeneration

T Yamamoto; M Yamasaki; T Imai

1989-01-01

72

Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: A model for macular degeneration  

Microsoft Academic Search

Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a

G. Karan; C. Lillo; Z. Yang; D. J. Cameron; K. G. Locke; Y. Zhao; S. Thirumalaichary; C. Li; D. G. Birch; H. R. Vollmer-Snarr; D. S. Williams; K. Zhang

2005-01-01

73

[New aspects in age related macular degeneration].  

PubMed

Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina. PMID:22888685

Turlea, C

2012-01-01

74

Spheroidal degeneration of cornea and conjunctiva.  

PubMed Central

A study of almost 1000 outpatients at a London eye hospital showed the presence of asymptomatic yellowish, spheroidal deposits in the peripheral cornea or conjunctiva, or both, in about 6 per cent, with a preponderance of males and older subjects among those affected. This prevalence is less than is observed in people in countries exposed to higher levels of sunlight. Histological study of the deposits showed some tinctorial similarities with pseudoelastic fibres of pingueculae, with which they were sometimes associated, but also significant differences suggesting that the spheroidal deposits might be a composite of degenerate collagen and a second non-collagenous protein. Until a more precise terminology is feasible we suggest that a purely descriptive name such as spheroidal degeneration or droplet keratopathy should be used to describe this entity. Images PMID:952819

Garner, A; Fraunfelder, F T; Barras, T C; Hinzpeter, E N

1976-01-01

75

Prevention of age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective\\u000a treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment\\u000a for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review\\u000a looks at current evidence on preventive

Ian Yat Hin Wong; Simon Chi Yan Koo; Clement Wai Nang Chan

2011-01-01

76

Unitary Holonomies by Direct Degenerate Projections  

E-print Network

An incomplete quantum measurement can induce non-trivial dynamics between degenerate subspaces, a closed sequence of such projections produces a non-abelian holonomy. We show how to induce unitary evolution on an initial subspace from such finite discrete sequences and also construct a near deterministic repeat-until-success protocol. We also prove necessary and sufficient criteria on the auxiliary Hilbert space dimension required for inducing isometries between between subspaces.

Daniel Kuan Li Oi

2014-02-05

77

Discovery of supersymmetry with degenerated mass spectrum  

E-print Network

Discovery of supersymmetric (SUSY) particles at the Large Hadron Collider(LHC) has been studied for the models where squarks and gluino are much heavier than the lightest supersymetric particle (LSP). In this paper, we investigate the SUSY discovery in the models with degenerated mass spectrum up to m_LSP~0.7 m_sq. Such mass spectrum is predicted in certain parameter region of the mixed modulas anomaly mediation (MMAM) model. We find that the effective transverse mass of the signal for the degenerated parameters shows the distribution similar to that of the background. Experimental sensitivity of the SUSY particles at the LHC therefore depends on the uncertainty of the background in this class of model. We also find that SUSY signal shows an interesting correlation between M_eff and ETmiss which may be used to determine the signal region properly to enhance the S/N ratio even if the sparticle masses are rather degenerated. The structure is universal for the models with new heavy colored particles decaying into visible particles and a stable neutral particle, dark matter.

Kiyotomo Kawagoe; Mihoko M. Nojiri

2006-06-09

78

Tensor Operations on Degenerate Inner Product Spaces  

E-print Network

Well-known operations defined on a non-degenerate inner product vector space are extended to the case of a degenerate inner product. The main obstructions to the extension of these operations to the degenerate case are (1) the index lowering operation is not invertible, and (2) we cannot associate to the inner product in a canonical way a reciprocal inner product on the dual of the vector space. This article shows how these obstructions can be avoided naturally, allowing a canonical definition of covariant contraction for some important special cases. The primary motivation of this article is to lay down the algebraic foundation for the construction of invariants in Singular Semi-Riemannian Geometry, especially those related to the curvature. It turns out that the operations discussed here are enough for this purpose (arXiv:1105.0201, arXiv:1105.3404, arXiv:1111.0646). Such invariants can be applied to the study of singularities in the theory of General Relativity (arXiv:1111.4837, arXiv:1111.4332, arXiv:1111.7082, arXiv:1108.5099, arXiv:1112.4508).

Ovidiu Cristinel Stoica

2011-12-26

79

Patterns of striatal degeneration in frontotemporal dementia  

PubMed Central

Behavioral variant frontotemporal dementia and semantic dementia have been associated with striatal degeneration, but few studies have delineated striatal subregion volumes in vivo or related them to clinical phenotype. We traced caudate, putamen, and nucleus accumbens on MR images to quantify volumes of these structures in behavioral variant frontotemporal dementia, semantic dementia, Alzheimer’s disease, and healthy controls (n = 12 per group). We further related these striatal volumes to clinical deficits and neuropathological findings in a subset of patients. Behavioral variant frontotemporal dementia and semantic dementia showed significant overall striatal atrophy compared with controls. Moreover, behavioral variant frontotemporal dementia showed panstriatal degeneration whereas semantic dementia featured a more focal pattern involving putamen and accumbens. Right-sided striatal atrophy, especially in the putamen, correlated with overall behavioral symptom severity and with specific behavioral domains. At autopsy, patients with behavioral variant frontotemporal dementia and semantic dementia showed striking and severe tau or TAR DNA-binding protein of 43 kDa pathology, especially in ventral parts of the striatum. These results demonstrate that ventral striatum degeneration is a prominent shared feature in behavioral variant frontotemporal dementia and semantic dementia and may contribute to social-emotional deficits common to both disorders. PMID:22367382

Halabi, Cathra; Halabi, Anasheh; Dean, David L.; Wang, Pei-Ning; Boxer, Adam L.; Trojanowski, John Q.; DeArmond, Stephen J.; Miller, Bruce L.; Kramer, Joel H.; Seeley, William W.

2012-01-01

80

Quantum degenerate Fermi gas entanglement in optomechanics  

NASA Astrophysics Data System (ADS)

We explain the steady-state entanglement of a quantum degenerate Fermi gas with a light field inside a Fabry-Perot cavity. The logarithmic negativity, from the covariance matrix formalism in a unified framework, shows that the bi-stability parameter and the effective detuning depend explicitly on the behavior of the entanglement. Numerical experiments reveal the sensitivity of the entanglement to experimentally controlled parameters such as, the mass of the atoms, the pump rate of the cavity, the effective detuning, and the bi-stability parameters.

Asjad, Muhammad; Shahzad, Muhammad Adnan; Saif, Farhan

2013-09-01

81

Landau Diamagnetism of Degenerate Collisional Plasma  

E-print Network

For the first time the kinetic description of Landau diamagnetism for degenerate collisional plasma is given. The correct expression for transverse electric conductivity of the quantum plasma, found by authors (see arXiv:1002.1017 [math-ph] 4 Feb 2010) is used. In work S. Dattagupta, A.M. Jayannavar and N. Kumar [Current science, V. 80, No. 7, 10 April, 2001] was discussed the important problem of dissipation (collisions) influence on Landau diamagnetism. The analysis of this problem is given with the use of exact expression for transverse conductivity of quantum plasma.

A. V. Latyshev; A. A. Yushkanov

2010-07-05

82

Degenerate Fermi Gas of {sup 87}Sr  

SciTech Connect

We report quantum degeneracy in a gas of ultracold fermionic {sup 87}Sr atoms. By evaporatively cooling a mixture of spin states in an optical dipole trap for 10.5 s, we obtain samples well into the degenerate regime with T/T{sub F}=0.26{sub -0.06}{sup +0.05}. The main signature of degeneracy is a change in the momentum distribution as measured by time-of-flight imaging, and we also observe a decrease in evaporation efficiency below T/T{sub F{approx}}0.5.

DeSalvo, B. J.; Yan, M.; Mickelson, P. G.; Martinez de Escobar, Y. N.; Killian, T. C. [Department of Physics and Astronomy, Rice University, Houston, Texas, 77251 (United States)

2010-07-16

83

Relativistic Bernstein waves in a degenerate plasma  

SciTech Connect

Bernstein mode for a relativistic degenerate electron plasma is investigated. Using relativistic Vlasov-Maxwell equations, a general expression for the conductivity tensor is derived and then employing Fermi-Dirac distribution function a generalized dispersion relation for the Bernstein mode is obtained. Two limiting cases, i.e., non-relativistic and ultra-relativistic are discussed. The dispersion relations obtained are also graphically presented for some specific values of the parameters depicting how the propagation characteristics of Bernstein waves as well as the Upper Hybrid oscillations are modified with the increase in plasma number density.

Ali, Muddasir; Hussain, Azhar [Department of Physics, G.C. University, Lahore 54000 (Pakistan); Salam Chair in Physics, G.C. University, Lahore 54000 (Pakistan); Murtaza, G. [Salam Chair in Physics, G.C. University, Lahore 54000 (Pakistan)

2011-09-15

84

Bladder dysfunction in subacute combined degeneration  

Microsoft Academic Search

Objective\\u000a   In view of the paucity of studies on micturition disturbance in subacute combined degeneration (SACD), this prospective study\\u000a reports micturition disturbance in SACD and correlations with urodynamic and MRI findings.\\u000a \\u000a \\u000a \\u000a \\u000a Methods\\u000a   SACD was diagnosed by clinical features and low serum B12 level (< 211 pg\\/ml) and\\/or megaloblastic bone marrow. Micturition\\u000a disturbances were categorized into voiding and storage symptoms and

U. K. Misra; J. Kalita; G. Kumar; R. Kapoor

2008-01-01

85

Mechanism of Calcium Entry during Axon Injury and Degeneration  

Microsoft Academic Search

Axon degeneration is a hallmark consequence of chemical neurotoxicant exposure (e.g., acrylamide), mechanical trauma (e.g., nerve transection, spinal cord contusion), deficient perfusion (e.g., ischemia, hypoxia), and inherited neuropathies (e.g., infantile neuroaxonal dystrophy). Regardless of the initiating event, degeneration in the PNS and CNS progresses according to a characteristic sequence of morphological changes. These shared neuropathologic features suggest that subsequent degeneration,

Richard M. LoPachin; Ellen J. Lehning

1997-01-01

86

Genetics and molecular pathology of Stargardt-like macular degeneration  

Microsoft Academic Search

Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third

Vidyullatha Vasireddy; Paul Wong; Radha Ayyagari

2010-01-01

87

Stanniocalcin-1 Rescued Photoreceptor Degeneration in Two Rat Models of Inherited Retinal Degeneration  

PubMed Central

Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors. We first tested STC-1 in the rhodopsin transgenic rat characterized by rapid photoreceptor loss. Intravitreal STC-1 decreased the loss of photoreceptor nuclei and transcripts and resulted in measurable retinal function when none is otherwise present in this rapid degeneration. We then tested STC-1 in the Royal College of Surgeons (RCS) rat characterized by a slower photoreceptor degeneration. Intravitreal STC-1 reduced the number of pyknotic nuclei in photoreceptors, delayed the loss of photoreceptor transcripts, and improved function of rod photoreceptors. Additionally, STC-1 upregulated UCP-2 and decreased levels of two protein adducts generated by reactive oxygen species (ROS). Microarrays from the two models demonstrated that STC-1 upregulated expression of a similar profile of genes for retinal development and function. The results suggested that intravitreal STC-1 is a promising therapy for various forms of RD including retinitis pigmentosa and atrophic age-related macular degeneration (AMD). PMID:22294148

Roddy, Gavin W; Rosa Jr, Robert H; Youn Oh, Joo; Ylostalo, Joni H; Bartosh, Thomas J; Choi, Hosoon; Lee, Ryang Hwa; Yasumura, Douglas; Ahern, Kelly; Nielsen, Gregory; Matthes, Michael T; LaVail, Matthew M; Prockop, Darwin J

2012-01-01

88

Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration  

Microsoft Academic Search

A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse “knock-in” model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse

Xinhua Shu; Ulrich F. O. Luhmann; Tomas S. Aleman; Susan E. Barker; Alan Lennon; Brian Tulloch; Mei Chen; Heping Xu; Samuel G. Jacobson; Robin Ali; Alan F. Wright

2011-01-01

89

Congenital Head Nodding and Nystagmus with Cerebrocerebellar Degeneration  

ERIC Educational Resources Information Center

Reported are three case histories of children with congenital head nodding and nystagmus (rhytmic oscillation of the eyeballs) associated with brain degeneration and motor and mental retardation. (DB)

Kalyanaraman, K.; And Others

1973-01-01

90

Metabolic anatomy of paraneoplastic cerebellar degeneration  

SciTech Connect

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

1988-06-01

91

Variational functions in degenerate open quantum systems  

SciTech Connect

We have derived a Lyapunov functional for a degenerate open atomic system. This functional develops monotonically towards its stationary state. The open system is described by a Lindblad-type master equation. For the construction of the variational functional it is necessary that the Lindblad operator can be diagonalized. Since the generator of motion is non-Hermitian, diagonalization is, in general, only possible if the eigenvalues are nondegenerate. In this paper, we propose that in a physical system the biorthogonal eigenbasis of the Lindblad operator remains complete even when degeneracy is present. Thus diagonalization of the Lindblad operator, and consequently the construction of the variational functional, is still possible. We discuss the reasons and illustrate the theory of the variational functional for a driven {lambda}-type three-level atom with degenerate ground state. The degeneracy has interesting effects on the variational functional in the steady state with respect to its interpretation as an entropic quantity. In case of the driven three-level atom, the dark state turns out to be an isentropic state.

Jakob, Matthias; Stenholm, Stig [Laser Physics and Quantum Optics, Royal Institute of Technology (KTH), Alba Nova, Roslagstullsbacken 21, SE-10691 Stockholm (Sweden)

2004-04-01

92

Variational functions in degenerate open quantum systems  

NASA Astrophysics Data System (ADS)

We have derived a Lyapunov functional for a degenerate open atomic system. This functional develops monotonically towards its stationary state. The open system is described by a Lindblad-type master equation. For the construction of the variational functional it is necessary that the Lindblad operator can be diagonalized. Since the generator of motion is non-Hermitian, diagonalization is, in general, only possible if the eigenvalues are nondegenerate. In this paper, we propose that in a physical system the biorthogonal eigenbasis of the Lindblad operator remains complete even when degeneracy is present. Thus diagonalization of the Lindblad operator, and consequently the construction of the variational functional, is still possible. We discuss the reasons and illustrate the theory of the variational functional for a driven ? -type three-level atom with degenerate ground state. The degeneracy has interesting effects on the variational functional in the steady state with respect to its interpretation as an entropic quantity. In case of the driven three-level atom, the dark state turns out to be an isentropic state.

Jakob, Matthias; Stenholm, Stig

2004-04-01

93

Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait  

Microsoft Academic Search

The retina provides exquisitely sensitive vision that relies on the integrity of a uniquely vulnerable cell, the photoreceptor (PR). The genetic and mechanistic causes of retinal degeneration due to PR cell death — which occurs in conditions such as retinitis pigmentosa and age-related macular degeneration — are being successfully dissected. Over one hundred loci, some containing common variants but most

Christina F. Chakarova; Mai M. Abd El-Aziz; Alan F. Wright; Shomi S. Bhattacharya

2010-01-01

94

Differential role of Jak-STAT signaling in retinal degenerations  

Microsoft Academic Search

Retinal degeneration is a major cause of severe visual impairment or blindness. Understanding the underlying molecular mechanisms is a prerequisite to develop therapeutic approaches for human patients. We show in three mouse models that induced and inherited retinal degeneration induces LIF and CLC as members of the interleukin (IL)-6 family of proteins, activates proteins of the Jak-STAT signaling pathway, and

Marijana Samardzija; Andreas Wenzel; Svenja Aufenberg; Markus Thiersch; Charlotte Reme; Christian Grimm

2006-01-01

95

Age-Related Macular Degeneration: Etiology, Pathogenesis, and Therapeutic Strategies  

Microsoft Academic Search

Age-related macular degeneration is the principal cause of registered legal blindness among those aged over 65 in the United States, western Europe, Australia, and Japan. Despite intensive research, the precise etiology of molecular events that underlie age-related macular degeneration is poorly understood. However, investigations on parallel fronts are addressing this prevalent public health problem. Sophisticated biochemical and biophysical techniques have

Jayakrishna Ambati; Balamurali K Ambati; Sonia H Yoo; Sean Ianchulev; Anthony P Adamis

2003-01-01

96

Accumulation of Rhodopsin in Late Endosomes Triggers Photoreceptor Cell Degeneration  

Microsoft Academic Search

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In

Yashodhan Chinchore; Amitavo Mitra; Patrick J. Dolph

2009-01-01

97

ANNULAR TEARS AND DISC DEGENERATION IN THE LUMBAR SPINE  

Microsoft Academic Search

Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogemc pain. The degenerating human intervertebral disc shows dehydration and fraying of the

L. OSTI; B. VERNON-ROBERTS; R. MOORE; R. D. FRASER

98

Teaching NeuroImages: hemorrhagic cavernoma with secondary development of hypertrophic olivary degeneration.  

PubMed

Hypertrophic olivary degeneration (HOD) is secondary degeneration of the inferior olivary nucleus (ION) due to a primary lesion in the dento-rubro-olivary pathway. This pathway is known as the Guillain and Mollert triangle, containing the dentate nucleus and the contralateral red and inferior olivary nuclei (figure e-1 on the Neurology® Web site at www.neurology.org). The commonest presenting symptom is palatal myoclonus occurring 8-12 months after the primary insult. MRI of the ION initially has normal results (figure 1). Three phases of HOD exist on MRI: hyperintense signal change without hypertrophy, hyperintense signal change with hypertrophy (figure 2), and regression of hypertrophy with persistent hyperintense signal.(1.) PMID:23650241

Crosbie, Ian; McNally, Stephen; Brennan, Paul; Looby, Seamus

2013-05-01

99

Muller's Ratchet and the Degeneration of the Drosophila miranda Neo-Y Chromosome  

PubMed Central

Since its formation about 1.75 million years ago, the Drosophila miranda neo-Y chromosome has undergone a rapid process of degeneration, having lost approximately half of the genes that it originally contained. Using estimates of mutation rates and selection coefficients for loss-of-function mutations, we show that the high rate of accumulation of these mutations can largely be explained by Muller's ratchet, the process of stochastic loss of the least-loaded mutational class from a finite, nonrecombining population. We show that selection at nonsynonymous coding sites can accelerate the process of gene loss and that this effect varies with the number of genes still present on the degenerating neo-Y chromosome. PMID:20215466

Kaiser, Vera B.; Charlesworth, Brian

2010-01-01

100

Degenerate R-S perturbation theory  

NASA Technical Reports Server (NTRS)

A concise, systematic procedure is given for determining the Rayleigh-Schrodinger energies and wave functions of degenerate states to arbitrarily high orders even when the degeneracies of the various states are resolved in arbitrary orders. The procedure is expressed in terms of an iterative cycle in which the energy through the (2n+1)st order is expressed in terms of the partially determined wave function through the n-th order. Both a direct and an operator derivation are given. The two approaches are equivalent and can be transcribed into each other. The direct approach deals with the wave functions (without the use of formal operators) and has the advantage that it resembles the usual treatment of nondegenerate perturbations and maintains close contact with the basic physics. In the operator approach, the wave functions are expressed in terms of infinite order operators which are determined by the successive resolution of the space of the zeroth order functions.

Hirschfelder, J. O.; Certain, P. R.

1973-01-01

101

Frontotemporal lobar degeneration: diversity of FTLD lesions.  

PubMed

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group including both sporadic and familial diseases, characterized by a macroscopic alteration. It may correspond to various cognitive syndromes: behavioral variant of frontotemporal dementia (bvFTD), progressive nonfluent aphasia, and semantic dementia. The neuropathologic classification is now based on identification of the protein that accumulates in neurons and glia: Tau, TAR DNA Binding Protein 43 (TDP-43), and FUsed in Sarcoma (FUS). The disorders in which the corresponding proteins accumulate have been named FTLD-Tau, FTLD-TDP, and FTLD-FUS. FTLD-Tau includes sporadic cases (e.g. Pick's disease) and Tau mutations. FTLD-TDP are subdivided within four types (A, B, C, D) according to the shape and distribution of TDP-43 positive lesions within the associative frontal cortex. The FTLD-FUS group includes atypical FTLD with ubiquitinated lesions (FTLD-U), Neuronal Intermediate Filament Inclusion Disease (NIFID) and Basophilic Inclusion Body Disease (BIBD). PMID:24035575

Seilhean, D; Bielle, F; Plu, I; Duyckaerts, C

2013-10-01

102

Prevention of age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

2011-02-01

103

Prevention of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

Koo, Simon Chi Yan; Chan, Clement Wai Nang

2010-01-01

104

Anterior insula degeneration in frontotemporal dementia  

PubMed Central

The human anterior insula is anatomically and functionally heterogeneous, containing key nodes within distributed speech–language and viscero-autonomic/social–emotional networks. The frontotemporal dementias selectively target these large-scale systems, leading to at least three distinct clinical syndromes. Examining these disorders, researchers have begun to dissect functions which rely on specific insular nodes and networks. In the behavioral variant of frontotemporal dementia, early-stage frontoinsular degeneration begets progressive “Salience Network” breakdown that leaves patients unable to model the emotional impact of their own actions or inactions. Ongoing studies seek to clarify local microcircuit- and cellular-level factors that confer selective frontoinsular vulnerability. The search for frontotemporal dementia treatments will depend on a rich understanding of insular biology and could help clarify specialized human language, social, and emotional functions. PMID:20512369

2010-01-01

105

Output radiation from a degenerate parametric oscillator  

E-print Network

We study the squeezing as well as the statistical properties of the output radiation from a degenerate parametric oscillator coupled to a squeezed vacuum reservoir employing the stochastic differential equations associated with the normal ordering. It is found that the degree of squeezing of the output radiation is less than the corresponding cavity radiation. However, for output radiation the correlation of the quadrature operators evaluated at different times also exhibits squeezing, which is the reason for quenching of the overall noise in one of the quadrature components of the squeezing spectrum even when the oscillator is coupled to a vacuum reservoir. Moreover, coupling the oscillator to the squeezed vacuum reservoir enhances the squeezing exponentially and it also increases the mean photon number.

Sintayehu Tesfa

2007-02-12

106

Odor identification in frontotemporal lobar degeneration subtypes.  

PubMed

Odor identification impairment is a feature of several neurodegenerative disorders. Although neurodegenerative changes in the frontotemporal lobar degeneration (FTLD) subtypes involve areas important for olfactory processing, data on olfactory function in these patients are limited. An 18-item, multiple-choice odor identification test developed at our memory clinic, the Motol Hospital smell test, was administered to 9 patients with behavioral variant frontotemporal dementia, 13 patients with the language variants, primary nonfluent aphasia (n = 7) and semantic dementia (n = 6), and 8 patients with progressive supranuclear palsy. Compared to the control group (n = 15), all FTLD subgroups showed significant impairment of odor identification (P < .05). The differences between the FTLD subgroups were not significant. No correlation between odor identification and neuropsychological tests results was found. Our data suggest that odor identification impairment is a symptom common to FTLD syndromes, and it seems to be based on olfactory structure damage rather than cognitive decline. PMID:24939002

Magerova, Hana; Vyhnalek, Martin; Laczo, Jan; Andel, Ross; Rektorova, Irena; Kadlecova, Alexandra; Bojar, Martin; Hort, Jakub

2014-12-01

107

Subacute combined degeneration without nutritional anemia.  

PubMed

Subacute combined degeneration (SCD) is a rare neurological complication of cobalamin deficiency, characterized by demyelination of the dorsal and lateral spinal cord. The diagnosis and treatment of SCD can be delayed if a patient does not present with clear clinical and laboratory signs of nutritional anemia, which has a marked effect on neurological recovery. We report a 62-year-old man with SCD with a history of gastric cancer and chronic alcoholism who presented with ataxia, gait disturbance, urinary incontinence, and limb weakness, but without other clinical or laboratory signs of cobalamin deficiency. The SCD diagnosis was confirmed by 3-Tesla MRI, which showed intramedullary signal alteration in the posterior columns of the entire spinal cord. PMID:23022212

Miscusi, M; Testaverde, L; Rago, A; Raco, A; Colonnese, C

2012-12-01

108

Ouabain-induced cochlear degeneration in rat  

PubMed Central

Ouabain, an potent inhibitor of the Na+/K+-ATPase pump, selectively destroys spiral ganglion neurons (SGNs) in gerbils and mice whereas in guinea pigs it preferentially damages cochlear hair cells. To elucidate the effects of ouabain on the rat inner ear, a species widely used in research, 5 µl of 1 mM or 10 mM ouabain was applied to the round window membrane. Distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) were used identify functional deficits in hair cells and neurons respectively and histological techniques were used to characterize cochlear pathologies. High-frequency ABR thresholds were elevated after treatment with 1 mM ouabain whereas DPOAEs remained normal. In contrast, 10 mM ouabain increased ABR thresholds and reduced DPOAE amplitudes. Consistent with the physiological changes, 1 mM ouabain only damaged the SGNs and auditory nerve fibers in the basal turn of the cochlea whereas 10 mM ouabain destroyed both SGNs and cochlear hair cells; damage was greatest near the base and decreased toward the apex. The nuclei of degenerating SGNs and hair cells were condensed and fragmented and many cells were TUNEL-positive, morphological features of apoptotic cell death. Thus, ouabain-induced cochlear degeneration in rats is apoptotic and concentration dependent; low concentrations preferentially damage SGNs in the base of the cochlea, producing an animal model of partial auditory neuropathy, whereas high concentrations damage both hair cells and SGNs with damage decreasing from the base towards the apex. PMID:22476946

Fu, Yong; Ding, Dalian; Jiang, Haiyan; Salvi, Richard

2012-01-01

109

Anomalous skin effects in a weakly magnetized degenerate electron plasma  

NASA Astrophysics Data System (ADS)

Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

Abbas, G.; Sarfraz, M.; Shah, H. A.

2014-09-01

110

Age-related macular degeneration: what do patients find on the internet?  

PubMed Central

Objective To assess the quality of information and readability of the top internet sites for age-related macular degeneration (AMD). Design An examination of the technical information provision, quality and readability of websites found during an internet search for ‘age-related macular degeneration’. Setting Six internet search engines were used to find 26 unique sites on AMD. Main outcome measures Technical information and quality were assessed using a simple grading system. Readability was assessed using a Simple Measure Of Gobbledygook (SMOG) rating. Results Twelve organizational, seven academic and seven commercial sites were identified. The average technical scores were 82.3%, 67.9% and 65.2% for each type of site, respectively (P=0.097, one way ANOVA). The average quality scores were 62.2%, 62.6%, and 49.5% for each type of site, respectively (P=0.356, one-way ANOVA). The average SMOG ratings were 16.3, 16.1, and 16.2 for each type of site, respectively (P=0.983, one-way ANOVA). Fifteen of the sites provided details of new and emerging treatments, with seven providing a detailed discussion. Conclusions Many websites are now meeting the challenge of providing comprehensive information about AMD and its new treatments. Quality scores were disappointing, with sites needing to provide more evidence of authorship and attribution of information. The majority of sites had SMOG scores above 10, making them difficult for the average person to understand. As physicians we need to help design and direct patients to sites that provide high quality, current information. PMID:17911131

Rennie, Christina A; Hannan, Shabeeba; Maycock, Nick; Kang, Chee

2007-01-01

111

Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration.  

PubMed

This work presents a combined light and electron microscopical approach to investigate the initial breakdown of the retinal pigment epithelium (RPE) and choriocapillaris (CC) in age-related macular degeneration (AMD). Perimacular sections of 12 dry and wet AMD eyes (82 ± 15 years) and 7 age-matched controls (75 ± 10 years) without retinal pathology were investigated. Disease progression was classified into 5 stages of retinal degeneration to investigate the concurrent CC breakdown. Special emphasis was laid on transitions where intact CC-RPE-retina complexes went over into highly atrophied areas. AMD sections showed elevated loss of photoreceptors, RPE and CC (p < 0.01), and thickened Bruch's membrane with increased basal laminar and linear deposits compared with controls. Up to 27% of the CC was lost in controls although RPE and retina were still intact. This primary loss of CC further increased with AMD (up to 100%). The data implicate that CC breakdown already occurs during normal aging and precedes degeneration of the RPE and retina with AMD, defining AMD as a vascular disease. Particular attention should be given to the investigation of early AMD stages and transitional stages to the late stage that reveal a possible sequence of degenerative steps with aging and AMD. PMID:24925811

Biesemeier, Antje; Taubitz, Tatjana; Julien, Sylvie; Yoeruek, Efdal; Schraermeyer, Ulrich

2014-11-01

112

Intrinsic axonal degeneration pathways are critical for glaucomatous damage.  

PubMed

Glaucoma is a neurodegenerative disease affecting 70million people worldwide. For some time, analysis of human glaucoma and animal models suggested that RGC axonal injury in the optic nerve head (where RGC axons exit the eye) is an important early event in glaucomatous neurodegeneration. During the last decade advances in molecular biology and genome manipulation have allowed this hypothesis to be tested more critically, at least in animal models. Data indicate that RGC axon degeneration precedes soma death. Preventing soma death using mouse models that are mutant for BAX, a proapoptotic gene, is not sufficient to prevent the degeneration of RGC axons. This indicates that different degeneration processes occur in different compartments of the RGC during glaucoma. Furthermore, the Wallerian degeneration slow allele (Wld(s)) slows or prevents RGC axon degeneration in rodent models of glaucoma. These experiments and many others, now strongly support the hypothesis that axon degeneration is a critical pathological event in glaucomatous neurodegeneration. However, the events that lead from a glaucomatous insult (e.g. elevated intraocular pressure) to axon damage in glaucoma are not well defined. For developing new therapies, it will be necessary to clearly define and order the molecular events that lead from glaucomatous insults to axon degeneration. PMID:22285251

Howell, Gareth R; Soto, Ileana; Libby, Richard T; John, Simon W M

2013-08-01

113

Potential regenerative treatment strategies for intervertebral disc degeneration in dogs  

PubMed Central

Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies. PMID:24387033

2014-01-01

114

Keratan sulfate expression is associated with activation of a subpopulation of microglia/macrophages in Wallerian degeneration.  

PubMed

Wallerian degeneration is a fundamental process of axonal degeneration distal to the injury site. Although axonal degeneration itself is accomplished in a few days, the subsequent process of removing debris, including myelin debris, in the central nervous system takes more time. Since this debris is a potent inhibitor of axonal regeneration, the removal process is critical for functional recovery after neuronal injuries. Although it is known that microglia/macrophages are involved in this process, the underlying mechanisms are not fully understood. Here, we found that keratan sulfate (KS) expression was induced far from the injury site after spinal cord injury. A hemilateral section of the spinal cord at the third cervical level induced KS expression in a restricted area of the ipsilateral column at the first lumbar level 1 week after injury. This localized KS expression lasted for at least 1 month after injury. The KS signal was merged with a portion of Iba1-positive cells, suggesting that a subpopulation of microglia/macrophages expressed KS. KS-positive cells expressed CD68 and CD86, but not CD206 or arginase 1, suggesting that these microglia/macrophages were in an activated state probably polarized to M1. Our study has explored for the first time the relation between KS expression and activation of microglia/macrophages in Wallerian degeneration. PMID:25046157

Shinjo, Ryuichi; Imagama, Shiro; Ito, Zenya; Ando, Kei; Nishida, Yoshihiro; Ishiguro, Naoki; Kadomatsu, Kenji

2014-09-01

115

WldS prevents axon degeneration through increased mitochondrial flux and enhanced mitochondrial Ca2+ buffering  

PubMed Central

Summary WldS (slow Wallerian degeneration) is a remarkable protein that can suppress Wallerian degeneration of axons and synapses [1] but how it exerts this effect remains unclear [2]. Here, using Drosophila and mouse models, we identify mitochondria as a key site of action for WldS neuroprotective function. Targeting the NAD+ biosynthetic enzyme Nmnat to mitochondria was sufficient to fully phenocopy WldS, and WldS was specifically localized to mitochondria in synaptic preparations from mouse brain. Axotomy of live wild type axons induced a dramatic spike in axoplasmic Ca2+ and termination of mitochondrial movement—WldS potently suppressed both of these events. Surprisingly, WldS also promoted increased basal mitochondrial motility in axons before injury, and genetically suppressing mitochondrial motility in vivo dramatically reduced the protective effect of WldS. Intriguingly, purified mitochondria from WldS mice exhibited enhanced Ca2+ buffering capacity. We propose that the enhanced Ca2+ buffering capacity of WldS+ mitochondria leads to increased mitochondrial motility, suppression of axotomy-induced Ca2+ elevation in axons, and thereby suppression of Wallerian degeneration. PMID:22425157

Avery, Michelle A.; Rooney, Timothy M.; Pandya, Jignesh D.; Wishart, Thomas M.; Gillingwater, Thomas H.; Geddes, James W.; Sullivan, Patrick; Freeman, Marc R.

2014-01-01

116

Mechanism of a musical systolic murmur caused by a degenerated porcine bioprosthetic valve.  

PubMed

The cause of a musical (cooing) murmur produced by a degenerated bioprosthetic valve in the mitral position was investigated. Spectral analysis of the murmur recorded at the chest wall at the site of the maximum palpable impulse showed virtually all sound in a narrow frequency band around the dominant frequency of 158 hertz. The same valve, surgically removed and mounted in the mitral position in a pulse duplicating system, produced an audible musical murmur detected by a phonocatheter in the atrial chamber. Nearly all of the sound-pressure occurred in a narrow band of frequency around 145 hertz. High speed motion pictures (500 frames/s) showed systolic flutter of a flail leaflet. The frequency of this leaflet flutter was 142 hertz. Hot film anemometry showed minimal turbulence, all located near the margin of the regurgitant leaflet. The intensity of the murmur was unrelated to the intensity of turbulence. A second degenerated bioprosthetic valve that produced in vivo a typical blowing holosystolic mitral regurgitant murmur produced in vitro a murmur with a broad range of frequencies (20 to 500 hertz). With this valve, the intensity of the murmur was related to the intensity of the turbulence. Motion pictures showed no leaflet flutter. Flutter of an insufficient valve leaflet causing uniform and periodic high frequency fluctuating pressures therefore appeared to be the cause of the musical quality of the systolic murmur in a degenerated bioprosthetic valve. PMID:7081071

Stein, P D; Sabbah, H N; Magilligan, D J; Lakier, J B

1982-06-01

117

Mechanisms of axonal spheroid formation in central nervous system Wallerian degeneration.  

PubMed

Wallerian degeneration of the CNS is accompanied by axonal dystrophy or swelling. To understand the mechanisms by which swellings arise, we studied their spatiotemporal dynamics, ultrastructure, composition, and the conditions that affect their formation in vivo and ex vivo. In contrast to peripheral nerve axons, lesioned optic nerve (ON) axons in vivo developed focal swellings asynchronously within 6 hours, long before there is any axon fragmentation. Axons in ON, spinal cord dorsal column, and corpus callosum all showed marked gradients with more swellings in proximal regions of their distal stumps early after lesion. Time-lapse imaging of a validated ex vivo system showed that multiple focal swellings arise after around 1 hour close to the injury site, followed by anterograde wave-like progression on continuous ON axon stumps. Swellings were largely stable but occasionally seemed to fuse with neighboring swellings. Their ultrastructural appearances resembled disease-associated spheroids. Although accumulation of axonal markers suggested transport deficits, large accumulations of mitochondria were not observed. Early swelling formation was decreased in Wld gene-expressing rodents and by removing extracellular calcium. Several pharmacologic agents that inhibit axon loss in vitro and/or in vivo also prevented early formation of axonal spheroids in acute ON explants. Because axonal swellings are hallmarks of many neurodegenerative conditions, these data suggest that they are a manifestation of Wallerian-like degeneration in some cases. Thus, Wallerian-like degeneration may be a more common component mechanism in CNS diseases than previously thought. PMID:20418780

Beirowski, Bogdan; Nógrádi, Antal; Babetto, Elisabetta; Garcia-Alias, Guillermo; Coleman, Michael P

2010-05-01

118

Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration.  

PubMed

After an incomplete spinal cord injury (SCI), partial recovery of locomotion is accomplished with time. Previous studies have established a functional link between extension of axon collaterals from spared spinal tracts and locomotor recovery after SCI, but the tissular signals triggering collateral sprouting have not been identified. Here, we investigated whether axonal degeneration after SCI contributes to the sprouting of collaterals from axons spared after injury. To this end, we evaluated collateral sprouting from BDA-labeled uninjured corticospinal axons after spinal cord hemisection (SCI(H)) in wild type (WT) mouse and Wld(S) mouse strains, which shows a significant delay in Wallerian degeneration after injury. After SCI(H), spared fibers of WT mice extend collateral sprouts to both intact and denervated sides of the spinal cord distant from the injury site. On the contrary, in the Wld(S) mice collateral sprouting from spared fibers was greatly reduced after SCI(H). Consistent with a role for collateral sprouting in functional recovery after SCI, locomotor recovery after SCI(H) was impaired in Wld(S) mice compared to WT animals. In conclusion, our results identify axonal degeneration as one of the triggers for collateral sprouting from the contralesional uninjured fibers after an SCI(H). These results open the path for identifying molecular signals associated with tissular changes after SCI that promotes collateral sprouting and functional recovery. PMID:25079366

Collyer, E; Catenaccio, A; Lemaitre, D; Diaz, P; Valenzuela, V; Bronfman, F; Court, F A

2014-11-01

119

CERKL Knockdown Causes Retinal Degeneration in Zebrafish  

PubMed Central

The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration. PMID:23671706

Riera, Marina; Burguera, Demian; Garcia-Fernandez, Jordi; Gonzalez-Duarte, Roser

2013-01-01

120

Degenerate crystals from colloidal dimers under confinement.  

PubMed

Colloidal aperiodic phases (i.e., entropy stabilized degenerate crystals, DCs) are realized via self-assembly of hollow fluorescent silica dimers under wedge-cell confinement. The dimer building blocks approximate two tangent spheres and their arrangements are studied via laser scanning confocal microscopy. In the DCs, the individual lobes tile a lattice and five distinct DC arrangements with square, triangular or rectangular layer symmetry are determined as a function of confinement height. Moreover, Monte Carlo simulations are used to construct the phase diagram for DCs up to two layer confinements and to analyze structural order in detail. Just as for spheres, the DC structural transitions under confinement are attributed to the ability or frustration to accommodate an integral number of particle layers between hard walls. Unlike spheres, dimers can also experience transitions involving changes in orientation. DCs are among the unconventional structures (e.g., semi-regular tilings, quasicrystals, plastic crystals) expected to enhance the properties of photonic solids. PMID:25366128

Muangnapoh, Kullachate; Avendaño, Carlos; Escobedo, Fernando A; Liddell Watson, Chekesha M

2014-11-19

121

Dynesys fixation for lumbar spine degeneration.  

PubMed

The dynamic fixation system Dynesys is utilized in the last 10 years for treatment of degenerative segmental disease of the lumbar spine. Dynesys is a semi-rigid fixation system that allows minimal lengthening and shortening between two segmental pedicle screws as opposed to a rigid metal bar. Thus, the system is regarded to maintain stability and near physiological motion patterns of the lumbar spine. The theoretical advantage of this system is to stabilize the treated segment and to prevent adjacent segment degeneration. The goal of this prospective trial was to evaluate clinical, radiographic, and computed tomography (CT) scan outcomes in 54 consecutive cases. Postoperative complications are discussed in detail. Forty cases were recruited with a mean follow-up of 16 months (range, 12 to 37). Postoperative pain scores (Hannover Activities of Daily Living Questionnaire and VAS for back and leg pain) improved in 29 cases (73%) and was best when dynamic fusion was combined with nerve root decompression. Outcome data were not superior to conventional rigid fusion systems and had a considerable number of complications requiring revision surgery in 27.5% of cases. PMID:17906883

Bothmann, Matthias; Kast, Erich; Boldt, Gerald Jens; Oberle, Joachim

2008-04-01

122

Cortical degeneration in frontotemporal lobar degeneration with TDP-43 proteinopathy caused by progranulin gene mutation.  

PubMed

Familial frontotemporal lobar degeneration with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP) is most commonly caused by progranulin (GRN) gene mutation. To characterize cortical degeneration in these cases, changes in density of the pathology across the cortical laminae of the frontal and temporal lobe were studied in seven cases of FTLD-TDP with GRN mutation using quantitative analysis and polynomial curve fitting. In 50% of gyri studied, neuronal cytoplasmic inclusions (NCI) exhibited a peak of density in the upper cortical laminae. Most frequently, neuronal intranuclear inclusions (NII) and dystrophic neurites (DN) exhibited a density peak in lower and upper laminae, respectively, glial inclusions (GI) being distributed in low densities across all laminae. Abnormally enlarged neurons (EN) were distributed either in the lower laminae or were more uniformly distributed across the cortex. The distribution of all neurons present varied between cases and regions, but most commonly exhibited a bimodal distribution, density peaks occurring in upper and lower laminae. Vacuolation primarily affected the superficial laminae and density of glial cell nuclei increased with distance across the cortex from pia mater to white matter. The densities of the NCI, GI, NII, and DN were not spatially correlated. The laminar distribution of the pathology in GRN mutation cases was similar to previously reported sporadic cases of FTLD-TDP. Hence, pathological changes initiated by GRN mutation, and by other causes in sporadic cases, appear to follow a parallel course resulting in very similar patterns of cortical degeneration in FTLD-TDP. PMID:24494724

Armstrong, Richard A

2014-12-01

123

Many-Body Green Function of Degenerate Systems  

SciTech Connect

A rigorous nonperturbative adiabatic approximation of the evolution operator in the many-body physics of degenerate systems is derived. This approximation is used to solve the long-standing problem of the choice of the initial states of H{sub 0} leading to eigenstates of H{sub 0}+V for degenerate systems. These initial states are eigenstates of P{sub 0}VP{sub 0}, where P{sub 0} is the projection onto a degenerate eigenspace of H{sub 0}. This result is used to give the proper definition of the Green function, the statistical Green function and the nonequilibrium Green function of degenerate systems. The convergence of these Green functions is established.

Brouder, Christian [Institut de Mineralogie et de Physique des Milieux Condenses, CNRS UMR 7590, Universites Paris 6 et 7, IPGP, 140 rue de Lourmel, 75015 Paris (France); Panati, Gianluca [Dipartimento di Matematica, Universita di Roma La Sapienza, Roma (Italy); Stoltz, Gabriel [Universite Paris Est, CERMICS, Projet MICMAC ENPC-INRIA, 6 and 8 Avenue Pascal, 77455 Marne-la-Vallee Cedex 2 (France)

2009-12-04

124

[Progress on the degeneration mechanism of cave fishes' eyes].  

PubMed

Attempts to understand the degeneration of the eyes in cave fish has largely been explained by either various extents of gradual degeneration, ranging from partial to total loss, observed in various species or by acceleration of loss caused by dark environments. However, neither the theory of biological evolution developed by Charles Darwin nor the neutral theory of molecular evolution formulated by Kimura Motoo adequately explains these phenomena. Recent trends in utilizing multidisciplinary research, however, have yielded better results, helping reveal a more complex picture of the mechanisms of degeneration. Here, we summarize the current progress of the research via morphology and anatomy, development biology, animal behavior science and molecular genetics, and offer some perspectives on the ongoing research into the development and degeneration of eyes in cave fish. PMID:22855449

Gu, Xian; Ning, Tiao; Xiao, Heng

2012-08-01

125

A FINITE DIFFERENCE APPROACH TO DEGENERATE BERNOULLI AND STIRLING POLYNOMIALS  

E-print Network

A FINITE DIFFERENCE APPROACH TO DEGENERATE BERNOULLI AND STIRLING POLYNOMIALS Arnold Adelberg, 1992 1 #12; RUNNING HEAD: Degen Bernoulli/Stirling Pols Professor Arnold Adelberg Department parameters), which includes Bernoulli and Stirling polynomials and various generalizations, is developed

Adelberg, Arnold

126

Emotion Regulation Deficits in Frontotemporal Lobar Degeneration and Alzheimer's Disease  

E-print Network

Emotion Regulation Deficits in Frontotemporal Lobar Degeneration and Alzheimer's Disease Madeleine), which presents with profound emotional and personality changes; patients with Alzheimer's disease (AD, N in the emotional realm. Keywords: emotion, emotion regulation, frontotemporal dementia, Alzheimer's disease

Levenson, Robert W.

127

Spheroid degeneration, keratopathy, pinguecula, and pterygium in Japan (Kyoto).  

PubMed

The prevalences of various possibly sunlight-induced degenerations of the exposed section of the eye have been studied in a series of 189 Japanese (Mongols) in Kyoto (subtropical climate, 35 degrees N. lat.). The results were compared with those of the author's examinations, using the same method and apparatus, in Jordan near the Red Sea (Arabs, N = 127) in Greenland (Eskimos, N = 659), and in Denmark (Caucasians, N = 810). In the Japanese series conjunctival spheroid degeneration was noticed in 31% and pinguecula in 60%, i.e. less frequently than in the sunny Jordan, but more frequently than in Greenland and Denmark. Climatokeratopathy was more rarely observed than in Greenland. This goes to show that the risk of corneal complications is lower in Japan despite the high prevalence of solar conjunctival degenerations. Pterygium was seen in a surprisingly small number of cases (1%), indicating that pterygium bears no relation to the conjunctival degenerations. PMID:6720277

Norn, M

1984-02-01

128

Intervertebral disc degeneration: evidence for two distinct phenotypes  

PubMed Central

We review the evidence that there are two types of disc degeneration. ‘Endplate-driven’ disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. ‘Annulus-driven’ disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

Adams, Michael A; Dolan, Patricia

2012-01-01

129

Degenerate four-wave mixing in triply resonant Kerr cavities  

E-print Network

We demonstrate theoretical conditions for highly efficient degenerate four-wave mixing in triply resonant nonlinear (Kerr) cavities. We employ a general and accurate temporal coupled-mode analysis in which the interaction ...

Ramirez, David M.

130

Rhodopsin homeostasis and retinal degeneration: lessons from the fly  

PubMed Central

Rhodopsins (Rh) are G-protein-coupled receptors that function as light sensors in photoreceptors. In humans, mutations in Rhodopsins cause retinitis pigmentosa, a degenerative disease that ultimately results in blindness. Studies in Drosophila have provided many insights into basic Rhodopsin biology and identified pathways that lead to retinal degeneration. It has been shown that because Rhodopsin is very abundant in photoreceptors, its accumulation in numerous organelles induces severe stress and results in degeneration of these cells. Moreover, genetic lesions that affect proper activation of membrane-bound Rh lead to disruption in Ca2+ homeostasis which also causes photoreceptor degeneration. Here, we review the molecular signals involved in Rhodopsin homeostasis and the mechanisms underlying retinal degeneration in flies, and discuss possible links to human diseases. PMID:24012059

Xiong, Bo; Bellen, Hugo J.

2013-01-01

131

EARLY REMODELING IN AN INDUCIBLE ANIMAL MODEL OF RETINAL DEGENERATION  

E-print Network

of deafferentation independent of the cause of degeneration. We addressed this by inducing selective photoreceptor de been suggested that these secondary changes are similar to those observed after deafferentation

Dhingra, Narender K.

132

ORIGINAL ARTICLE Effects of medial temporal lobe degeneration on brain  

E-print Network

of AD type: deafferentation and functional compensation? Eric Guedj & Emmanuel J. Barbeau & Mira Didic perfusion may reflect the deafferentation of a temporocingulate network due to mediotemporal degeneration MCI . AD . Deafferentation . Functional compensation . Brain SPECT. SPM Introduction Over recent years

Barbeau, Emmanuel J.

133

Cell transplantation in lumbar spine disc degeneration disease  

Microsoft Academic Search

Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given\\u000a that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process,\\u000a seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain.\\u000a The most apparent

C. Hohaus; T. M. Ganey; Y. Minkus; H. J. Meisel

2008-01-01

134

Molecular Inflammatory Mediators in Peripheral Nerve Degeneration and Regeneration  

Microsoft Academic Search

Wallerian degeneration, the self-destructive set of cellular and molecular processes by which degenerating axons and myelin are cleared after injury, is initiated by macrophages and Schwann cells. Molecular inflammatory mediators such as cytokines (IL-1, IL-6, IL-10, and TNF-?, among others), transcription factors (NF-?B, c-Jun), the complement system and arachidonic acid metabolites have been shown to modulate these processes in various

Carlos Rodrigo Cámara-Lemarroy; Francisco Javier Guzmán-de la Garza; Nancy Esthela Fernández-Garza

2010-01-01

135

Jahn–Teller effects in the doubly degenerate Hubbard model  

Microsoft Academic Search

We investigate the Jahn–Teller (JT) effects in the doubly degenerate Hubbard model by using the exact diagonalization (Lanczo¨s algorithm) technique. This is in connection with the newly discovered “colossal magnetoresistance” perovskite-based La1?xAxMnO3 compounds. We first obtain the parameter region where the ground state of the doubly degenerate Hubbard model is ferromagnetically ordered analytically for a dimer, and numerically for larger

H. Q. Lin

1997-01-01

136

Jahn-Teller effects in the doubly degenerate Hubbard model  

Microsoft Academic Search

We investigate the JahnâTeller (JT) effects in the doubly degenerate Hubbard model by using the exact diagonalization (Lancz{umlt o}s algorithm) technique. This is in connection with the newly discovered {open_quotes}colossal magnetoresistance{close_quotes} perovskite-based La{sub 1-x}AâMnOâ compounds. We first obtain the parameter region where the ground state of the doubly degenerate Hubbard model is ferromagnetically ordered analytically for a dimer, and numerically

H. Q. Lin

1997-01-01

137

Cartilage intermediate layer protein promotes lumbar disc degeneration.  

PubMed

Lumbar disc disease (LDD) is one of the most common musculoskeletal disorders, and accompanies intervertebral disc degeneration. CILP encodes cartilage intermediate layer protein, which is highly associated with LDD. Moreover, CILP inhibits transcriptional activation of cartilage matrix genes in nucleus pulposus (NP) cells in vitro by binding to TGF-?1 and inhibiting the phosphorylation of Smads. However, the aetiology and mechanism of pathogenesis of LDD in vivo are unknown. To demonstrate the role of CILP in LDD in vivo, we generated transgenic mice that express CILP specifically in the intervertebral disc tissues and assessed whether CILP exacerbates disc degeneration. Degeneration of the intervertebral discs was assessed using magnetic resonance imaging (MRI) and histology. The level of phosphorylation of Smad2/3 in intervertebral discs was measured to determine whether overexpressed CILP suppressed TGF-beta signalling. Although the macroscopic skeletal phenotype of transgenic mice appeared normal, histological findings revealed significant degeneration of lumbar discs. MRI analysis of the lumbar intervertebral discs indicated a significantly lower signal intensity of the nucleus pulposus where CILP was overexpressed. Intervertebral disc degeneration was also observed. The number of phosphorylation of Smad2/3 immuno-positive cells in the NP significantly was decreased in CILP transgenic mice compared with normal mice. In summary, overexpression of CILP in the NP promotes disc degeneration, indicating that CILP plays a direct role in the pathogenesis of LDD. PMID:24631904

Seki, Shoji; Tsumaki, Noriyuki; Motomura, Hiraku; Nogami, Makiko; Kawaguchi, Yoshiharu; Hori, Takeshi; Suzuki, Kayo; Yahara, Yasuhito; Higashimoto, Mami; Oya, Takeshi; Ikegawa, Shiro; Kimura, Tomoatsu

2014-04-18

138

The advantages of frontotemporal degeneration drug development (part 2 of frontotemporal degeneration: the next therapeutic frontier).  

PubMed

Frontotemporal degeneration (FTD) encompasses a spectrum of related neurodegenerative disorders with behavioral, language, and motor phenotypes for which there are currently no effective therapies. This is the second of two articles that summarize the presentations and discussions that occurred at two symposia in 2011 sponsored by the Frontotemporal Degeneration Treatment Study Group, a collaborative group of academic and industry researchers that is devoted to developing treatments for FTD. This article discusses the current status of FTD clinical research that is relevant to the conduct of clinical trials, and why FTD research may be an attractive pathway for developing therapies for neurodegenerative disorders. The clinical and molecular features of FTD, including rapid disease progression and relatively pure molecular pathology, suggest that there are advantages to developing drugs for FTD as compared with other dementias. FTD qualifies as orphan indication, providing additional advantages for drug development. Two recent sets of consensus diagnostic criteria will facilitate the identification of patients with FTD, and a variety of neuropsychological, functional, and behavioral scales have been shown to be sensitive to disease progression. Moreover, quantitative neuroimaging measurements demonstrate progressive brain atrophy in FTD at rates that may surpass Alzheimer's disease. Finally, the similarities between FTD and other neurodegenerative diseases with drug development efforts already underway suggest that FTD researchers will be able to draw on this experience to create a road map for FTD drug development. We conclude that FTD research has reached sufficient maturity to pursue clinical development of specific FTD therapies. PMID:23062850

Boxer, Adam L; Gold, Michael; Huey, Edward; Hu, William T; Rosen, Howard; Kramer, Joel; Gao, Fen-Biao; Burton, Edward A; Chow, Tiffany; Kao, Aimee; Leavitt, Blair R; Lamb, Bruce; Grether, Megan; Knopman, David; Cairns, Nigel J; Mackenzie, Ian R; Mitic, Laura; Roberson, Erik D; Van Kammen, Daniel; Cantillon, Marc; Zahs, Kathleen; Jackson, George; Salloway, Stephen; Morris, John; Tong, Gary; Feldman, Howard; Fillit, Howard; Dickinson, Susan; Khachaturian, Zaven S; Sutherland, Margaret; Abushakra, Susan; Lewcock, Joseph; Farese, Robert; Kenet, Robert O; Laferla, Frank; Perrin, Steve; Whitaker, Steve; Honig, Lawrence; Mesulam, Marsel M; Boeve, Brad; Grossman, Murray; Miller, Bruce L; Cummings, Jeffrey L

2013-03-01

139

Differential charge-transfer cross sections for systems with energetically degenerate or near-degenerate channels  

NASA Astrophysics Data System (ADS)

Resolution plays a vital role in spectroscopic studies. In the usual recoil-ion momentum spectroscopy (RIMS), Q-value resolution is relied upon to distinguish between different collision channels: The better the Q-value resolution, the better one is able to resolve energetically similar channels. Although traditional COLTRIMS greatly improves Q-value resolution by cooling the target and thus greatly reducing the initial target momentum spread, the resolution of the technique is still limited by target temperature. However, with the recent development in RIMS, namely, magneto-optical trap recoil ion momentum spectroscopy (MOTRIMS) superior recoil ion momentum resolution as well as charge transfer measurements with laser excited targets have become possible. Through MOTRIMS, methods for the measurements of target excited state fraction and kinematically complete relative charge transfer cross sections have been developed, even for some systems having energetically degenerate or nearly degenerate channels. In the present work, the systems of interest having energy degeneracies or near degeneracies are Rb+ , K+ , and Li+ colliding with trapped Rb(5l) , where l=s and p .

Nguyen, H.; Brédy, R.; Camp, H. A.; Awata, T.; Depaola, B. D.

2004-09-01

140

Differential charge-transfer cross sections for systems with energetically degenerate or near-degenerate channels  

SciTech Connect

Resolution plays a vital role in spectroscopic studies. In the usual recoil-ion momentum spectroscopy (RIMS), Q-value resolution is relied upon to distinguish between different collision channels: The better the Q-value resolution, the better one is able to resolve energetically similar channels. Although traditional COLTRIMS greatly improves Q-value resolution by cooling the target and thus greatly reducing the initial target momentum spread, the resolution of the technique is still limited by target temperature. However, with the recent development in RIMS, namely, magneto-optical trap recoil ion momentum spectroscopy (MOTRIMS) superior recoil ion momentum resolution as well as charge transfer measurements with laser excited targets have become possible. Through MOTRIMS, methods for the measurements of target excited state fraction and kinematically complete relative charge transfer cross sections have been developed, even for some systems having energetically degenerate or nearly degenerate channels. In the present work, the systems of interest having energy degeneracies or near degeneracies are Rb{sup +}, K{sup +}, and Li{sup +} colliding with trapped Rb(5l), where l=s and p.

Nguyen, H.; Bredy, R.; Camp, H.A.; DePaola, B.D. [J.R. Macdonald Laboratory, Department of Physics, Kansas State University, Manhattan, Kansas 66506-2601 (United States); Awata, T. [Department of Physics, Naruto University of Education, Naruto, Tokushima 772-8502 (Japan)

2004-09-01

141

Evidence for degenerate tetraploidy in bdelloid rotifers  

PubMed Central

Rotifers of class Bdelloidea have evolved for millions of years apparently without sexual reproduction. We have sequenced 45- to 70-kb regions surrounding the four copies of the hsp82 gene of the bdelloid rotifer Philodina roseola, each of which is on a separate chromosome. The four regions comprise two colinear gene-rich pairs with gene content, order, and orientation conserved within each pair. Only a minority of genes are common to both pairs, also in the same orientation and order, but separated by gene-rich segments present in only one or the other pair. The pattern is consistent with degenerate tetraploidy with numerous segmental deletions, some in one pair of colinear chromosomes and some in the other. Divergence in 1,000-bp windows varies along an alignment of a colinear pair, from zero to as much as 20% in a pattern consistent with gene conversion associated with recombinational repair of DNA double-strand breaks. Although pairs of colinear chromosomes are a characteristic of sexually reproducing diploids and polyploids, a quite different explanation for their presence in bdelloids is suggested by the recent finding that bdelloid rotifers can recover and resume reproduction after suffering hundreds of radiation-induced DNA double-strand breaks per oocyte nucleus. Because bdelloid primary oocytes are in G1 and therefore lack sister chromatids, we propose that bdelloid colinear chromosome pairs are maintained as templates for the repair of DNA double-strand breaks caused by the frequent desiccation and rehydration characteristic of bdelloid habitats. PMID:18362354

Mark Welch, David B.; Mark Welch, Jessica L.; Meselson, Matthew

2008-01-01

142

Evidence for degenerate tetraploidy in bdelloid rotifers.  

PubMed

Rotifers of class Bdelloidea have evolved for millions of years apparently without sexual reproduction. We have sequenced 45- to 70-kb regions surrounding the four copies of the hsp82 gene of the bdelloid rotifer Philodina roseola, each of which is on a separate chromosome. The four regions comprise two colinear gene-rich pairs with gene content, order, and orientation conserved within each pair. Only a minority of genes are common to both pairs, also in the same orientation and order, but separated by gene-rich segments present in only one or the other pair. The pattern is consistent with degenerate tetraploidy with numerous segmental deletions, some in one pair of colinear chromosomes and some in the other. Divergence in 1,000-bp windows varies along an alignment of a colinear pair, from zero to as much as 20% in a pattern consistent with gene conversion associated with recombinational repair of DNA double-strand breaks. Although pairs of colinear chromosomes are a characteristic of sexually reproducing diploids and polyploids, a quite different explanation for their presence in bdelloids is suggested by the recent finding that bdelloid rotifers can recover and resume reproduction after suffering hundreds of radiation-induced DNA double-strand breaks per oocyte nucleus. Because bdelloid primary oocytes are in G(1) and therefore lack sister chromatids, we propose that bdelloid colinear chromosome pairs are maintained as templates for the repair of DNA double-strand breaks caused by the frequent desiccation and rehydration characteristic of bdelloid habitats. PMID:18362354

Mark Welch, David B; Mark Welch, Jessica L; Meselson, Matthew

2008-04-01

143

Criteria for the diagnosis of corticobasal degeneration  

PubMed Central

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ?50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed. PMID:23359374

Armstrong, Melissa J.; Lang, Anthony E.; Bak, Thomas H.; Bhatia, Kailash P.; Borroni, Barbara; Boxer, Adam L.; Dickson, Dennis W.; Grossman, Murray; Hallett, Mark; Josephs, Keith A.; Kertesz, Andrew; Lee, Suzee E.; Miller, Bruce L.; Reich, Stephen G.; Riley, David E.; Tolosa, Eduardo; Troster, Alexander I.; Vidailhet, Marie; Weiner, William J.

2013-01-01

144

Perceptual learning in patients with macular degeneration  

PubMed Central

Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex. PMID:25368597

Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Ruhle, Sabine; Greenlee, Mark W.

2014-01-01

145

Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration  

Microsoft Academic Search

The aim of this study was to improve the neuropathologic recognition and provide criteria for the pathological diagnosis in\\u000a the neurodegenerative diseases grouped as frontotemporal lobar degeneration (FTLD); revised criteria are proposed. Recent\\u000a advances in molecular genetics, biochemistry, and neuropathology of FTLD prompted the Midwest Consortium for Frontotemporal\\u000a Lobar Degeneration and experts at other centers to review and revise the

Nigel J. Cairns; Eileen H. Bigio; Ian R. A. Mackenzie; Manuela Neumann; Virginia M.-Y. Lee; Kimmo J. Hatanpaa; Charles L. White; Julie A. Schneider; Lea Tenenholz Grinberg; Glenda Halliday; Charles Duyckaerts; James S. Lowe; Ida E. Holm; Markus Tolnay; Koichi Okamoto; Hideaki Yokoo; Shigeo Murayama; John Woulfe; David G. Munoz; Dennis W. Dickson; Paul G. Ince; John Q. Trojanowski; David M. A. Mann

2007-01-01

146

NAD+ and axon degeneration revisited: Nmnat1 cannot substitute for WldS to delay Wallerian degeneration  

Microsoft Academic Search

The slow Wallerian degeneration protein (WldS), a fusion protein incorporating full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays axon degeneration caused by injury, toxins and genetic mutation. Nmnat1 overexpression is reported to protect axons in vitro, but its effect in vivo and its potency remain unclear. We generated Nmnat1-overexpressing transgenic mice whose Nmnat activities closely match that of WldS mice. Nmnat1

L Conforti; G Fang; B Beirowski; M S Wang; L Sorci; S Asress; R Adalbert; A Silva; K Bridge; X P Huang; G Magni; J D Glass; M P Coleman

2007-01-01

147

Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration  

Microsoft Academic Search

· Background: Macular rotation to treat exudative age-related macular degeneration (AMD) involves translocation of the fovea\\u000a to a site with intact retinal pigment epithelium. To avoid the inevitable postoperative cyclotropia we combined this procedure\\u000a with torsional muscle surgery.?· Patients and methods: In 30 eyes the macula was rotated upward by 30–50° following complete\\u000a artificial retinal detachment and a 360° retinotomy.

Claus Eckardt; Ute Eckardt; Hans-Georg Conrad

1999-01-01

148

Trilayer graphene nanoribbon carrier statistics in degenerate and non degenerate limits  

NASA Astrophysics Data System (ADS)

We present trilayer graphene nanoribbon carrier statistics in the degenerate and the nondegenerate limits. Within zero to 3kBT from the conduction or valence band edgers high concentrations of carriers sensitively depend on a normalized Fermi energy which is independent of temperature. The effect of different stacking orders of graphene multilayers on the electric field induced band gap is studied. The gap for trilayer graphene with the ABC stacking is much larger than the corresponding gap for the ABA trilayer. The gap for the different types of stacking is much larger as compared to the case of Bernal stacking. A non-monotonic dependence of the true energy gap in trilayer graphene on the charge density is investigated along with the electronic low-energy band structure of ABC stacked multilayer graphene. The band structure of trilayer graphene systems in the presence of a perpendicular electric field is obtained using a tight-binding approach.

Rahmani, M.; Ahmadi, M. T.; Webb, J. F.; Shayesteh, N.; Mousavi, S. M.; Sadeghi, H.; Ismail, R.

2012-11-01

149

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration  

PubMed Central

Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Protein-based therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration. PMID:25171110

Vasiliadis, Elias S; Pneumaticos, Spyros G; Evangelopoulos, Demitrios S; Papavassiliou, Athanasios G

2014-01-01

150

Electrostatic Solitary Structures in a Relativistic Degenerate Multispecies Plasma  

NASA Astrophysics Data System (ADS)

The nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multispecies plasma has been investigated theoretically. This plasma system is assumed to contain both relativistic degenerate electron and positron fluids, nonrelativistic degenerate positive and negative ions, and positively charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of positive and negative ions. The positively charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The nonplanar K-dV and mK-dV equations are derived by using reductive perturbation technique and numerically analyzed to identify the basic features (speed, amplitude, width, etc.) of mIA solitary structures. The basic characteristics of mIA solitary waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge states of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., nonrotating white dwarfs, neutron stars, etc.) are briefly mentioned.

Hossen, M. R.; Mamun, A. A.

2014-08-01

151

Wallerian degeneration: an emerging axon death pathway linking injury and disease.  

PubMed

Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay Wallerian degeneration has provided insight into mechanisms underlying axon degeneration in disease. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1 and PHR1. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is essential for axon growth and survival. Its loss from injured axons may activate Wallerian degeneration, whereas NMNAT overexpression rescues axons from degeneration. Here, we discuss the roles of these and other proposed regulators of Wallerian degeneration, new opportunities for understanding disease mechanisms and intriguing links between Wallerian degeneration, innate immunity, synaptic growth and cell death. PMID:24840802

Conforti, Laura; Gilley, Jonathan; Coleman, Michael P

2014-06-01

152

Accumulation of Rhodopsin in Late Endosomes Triggers Photoreceptor Cell Degeneration  

PubMed Central

Progressive retinal degeneration is the underlying feature of many human retinal dystrophies. Previous work using Drosophila as a model system and analysis of specific mutations in human rhodopsin have uncovered a connection between rhodopsin endocytosis and retinal degeneration. In these mutants, rhodopsin and its regulatory protein arrestin form stable complexes, and endocytosis of these complexes causes photoreceptor cell death. In this study we show that the internalized rhodopsin is not degraded in the lysosome but instead accumulates in the late endosomes. Using mutants that are defective in late endosome to lysosome trafficking, we were able to show that rhodopsin accumulates in endosomal compartments in these mutants and leads to light-dependent retinal degeneration. Moreover, we also show that in dying photoreceptors the internalized rhodopsin is not degraded but instead shows characteristics of insoluble proteins. Together these data implicate buildup of rhodopsin in the late endosomal system as a novel trigger of death of photoreceptor neurons. PMID:19214218

Chinchore, Yashodhan; Mitra, Amitavo; Dolph, Patrick J.

2009-01-01

153

Degenerate tetraploidy was established before bdelloid rotifer families diverged.  

PubMed

Rotifers of Class Bdelloidea are abundant freshwater invertebrates known for their remarkable ability to survive desiccation and their lack of males and meiosis. Sequencing and annotation of approximately 50-kb regions containing the four hsp82 heat shock genes of the bdelloid Philodina roseola, each located on a separate chromosome, have suggested that its genome is that of a degenerate tetraploid. In order to determine whether a similar structure exists in a bdelloid distantly related to P. roseola and if degenerate tetraploidy was established before the two species separated, we sequenced regions containing the hsp82 genes of a bdelloid belonging to a different family, Adineta vaga, and the histone gene clusters of P. roseola and A. vaga. Our findings are entirely consistent with degenerate tetraploidy and show that it was established before the two bdelloid families diverged and therefore probably before the bdelloid radiation. PMID:18996928

Hur, Jae H; Van Doninck, Karine; Mandigo, Morgan L; Meselson, Matthew

2009-02-01

154

Stem cell regeneration of degenerated intervertebral discs: current status (update).  

PubMed

Low back pain, strongly associated with intervertebral disc (IVD) degeneration, affects a large proportion of the population and has major social and economic costs. Current treatments remain inadequate, targeting the symptoms without addressing the underlying cause. As such, efforts are being directed towards development of therapies aimed at alleviating pain through the restoration of IVD function. The potential of cell-based therapies for the treatment of IVD degeneration are being actively explored, with an emphasis on cell/biomaterial tissue engineering. Adult mesenchymal stem cells, capable of differentiating down the discogenic lineage, have shown promise as a suitable cell source for IVD tissue engineering. However, a number of factors, (discussed in this review), remain to be addressed, including development of a differentiation protocol to produce the correct cell phenotype, identification of suitable biomaterials for cell delivery/implantation, and ensuring cell survival and correct function upon implantation into the degenerate IVD. PMID:24234817

Gilbert, Hamish T J; Hoyland, Judith A; Richardson, Stephen M

2013-12-01

155

N=2 gauge theories and degenerate fields of Toda theory  

SciTech Connect

We discuss the correspondence between degenerate fields of the W{sub N} algebra and punctures of Gaiotto's description of the Seiberg-Witten curve of N=2 superconformal gauge theories. Namely, we find that the type of degenerate fields of the W{sub N} algebra, with null states at level one, is classified by Young diagrams with N boxes, and that the singular behavior of the Seiberg-Witten curve near the puncture agrees with that of W{sub N} generators. We also find how to translate mass parameters of the gauge theory to the momenta of the Toda theory.

Kanno, Shoichi; Matsuo, Yutaka; Shiba, Shotaro [Department of Physics, Faculty of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Tachikawa, Yuji [School of Natural Sciences, Institute for Advanced Study, Princeton, New Jersey 08540 (United States)

2010-02-15

156

Approximate controllability for nonlinear degenerate parabolic problems with bilinear control  

NASA Astrophysics Data System (ADS)

In this paper, we study the global approximate multiplicative controllability for nonlinear degenerate parabolic Cauchy-Neumann problems. First, we obtain embedding results for weighted Sobolev spaces, that have proved decisive in reaching well-posedness for nonlinear degenerate problems. Then, we show that the above systems can be steered in L2 from any nonzero, nonnegative initial state into any neighborhood of any desirable nonnegative target-state by bilinear piecewise static controls. Moreover, we extend the above result relaxing the sign constraint on the initial data.

Floridia, Giuseppe

2014-11-01

157

Two-stream instabilities in degenerate quantum plasmas  

NASA Astrophysics Data System (ADS)

The quantum effects on the plasma two-stream instability are studied by the dielectric function approach. The analysis suggests that the instability condition in a degenerate dense plasma deviates from the classical theory when the electron drift velocity is comparable to the Fermi velocity. Specifically, for a high wave vector comparable to the Fermi wave vector, a degenerate quantum plasma has larger regime of instability than predicted by the classical theory. A regime is identified, where there are unstable plasma waves with frequency 1.5 times of a normal Langmuir wave.

Son, Seunghyeon

2014-07-01

158

Polarization degenerate micropillars fabricated by designing elliptical oxide apertures  

E-print Network

A method for fabrication of polarization degenerate oxide apertured micropillar cavities is demon- strated. Micropillars are etched such that the size and shape of the oxide front is controlled. The polarization splitting in the circular micropillar cavities due to the native and strain induced bire- fringence can be compensated by elongating the oxide front in the [110] direction, thereby reducing stress in this direction. By using this technique we fabricate a polarization degenerate cavity with a quality factor of 1.7*?10^4 and a mode volume of 2.7 u?m3, enabling a calculated maximum Purcell factor of 11.

Bakker, Morten P; Zhan, Alan; Coldren, Larry A; van Exter, Martin P; Bouwmeester, Dirk

2014-01-01

159

Polarization degenerate micropillars fabricated by designing elliptical oxide apertures  

E-print Network

A method for fabrication of polarization degenerate oxide apertured micropillar cavities is demon- strated. Micropillars are etched such that the size and shape of the oxide front is controlled. The polarization splitting in the circular micropillar cavities due to the native and strain induced bire- fringence can be compensated by elongating the oxide front in the [110] direction, thereby reducing stress in this direction. By using this technique we fabricate a polarization degenerate cavity with a quality factor of 1.7*?10^4 and a mode volume of 2.7 u?m3, enabling a calculated maximum Purcell factor of 11.

Morten P. Bakker; Ajit V. Barve; Alan Zhan; Larry A. Coldren; Martin P. van Exter; Dirk Bouwmeester

2014-04-17

160

Mitochondrial degeneration after organic phosphate poisoning in prosimian primates.  

PubMed

The degenerative reaction of mitochondria to tricresylphosphate (TCP) poisoning in spinal ganglion cells of Slow Loris (Nycticebus coucang coucang) were studied with the electron microscope. In neurones of animals treated with TCP, mitochondria display various stages of alterations which confirm mitochondrial involvement in TCP poisoning. The role of degenerated mitochondria in the formation of neuronal lipofuscin is discussed. It is suggested that the lipofuscin granule is a metabolic product inherently related to mitochondrial degeneration, irrespective of the primary cause: ageing or intoxication. PMID:401474

Ahmed, M M; Glees, P

1977-01-01

161

Bilayer Graphene Nanoribbon Carrier Statistics in the Degenerate Regime  

NASA Astrophysics Data System (ADS)

In this paper we discuss the energy band structure of bilayer graphene nanoribbons (BGNRs) near the Fermi level between zero and 3kBT away from the conduction and valence bands. BGNRs can be used as the channel in field effect transistors (FETs). A FET can be created using graphene bilayers with the gate voltage perpendicular to the layers. We focus on carrier statistics in the degenerate regime and the density of states, and consider them to be fundamental properties of BGNRs. The model presented indicates that the normalized Fermi energy in the degenerate regime strongly depends on carrier concentration and is independent of temperature.

Mousavi, S. M.; Ahmadi, M. T.; Webb, J. F.; Sadeghi, H.; Nilghaz, A.; Amin, A.; Johari, Z.; Ismail, R.

2011-06-01

162

Extended Hellmann-Feynman theorem for degenerate eigenstates  

NASA Astrophysics Data System (ADS)

In a previous paper, we reported a failure of the traditional Hellmann-Feynman theorem (HFT) for degenerate eigenstates. This has generated enormous interest among different groups. In four independent papers by Fernandez, by Balawender, Hola, and March, by Vatsya, and by Alon and Cederbaum, an elegant method to solve the problem was devised. The main idea is that one has to construct and diagonalize the force matrix for the degenerate case, and only the eigenforces are well defined. We believe this is an important extension to HFT. Using our previous example for an energy level of fivefold degeneracy, we find that those eigenforces correctly reflect the symmetry of the molecule.

Zhang, G. P.; George, Thomas F.

2004-04-01

163

Oxidative damage to mitochondria at the nodes of Ranvier precedes axon degeneration in ex vivo transected axons.  

PubMed

Oxidative stress and mitochondrial dysfunction appear to contribute to axon degeneration in numerous neurological disorders. However, how these two processes interact to cause axonal damage-and how this damage is initiated-remains unclear. In this study we used transected motor axons from murine peripheral roots to investigate whether oxidative stress alters mitochondrial dynamics in myelinated axons. We show that the nodes of Ranvier are the initial sites of mitochondrial damage induced by oxidative stress. There, mitochondria became depolarized, followed by alterations of the external morphology and disruption of the cristae, along with reduced mitochondrial transport. These mitochondrial changes expanded from the nodes of Ranvier bidirectionally towards both internodes and eventually affected the entire mitochondrial population in the axon. Supplementing axonal bioenergetics by applying nicotinamide adenine dinucleotide and methyl pyruvate, rendered the mitochondria at the nodes of Ranvier resistant to these oxidative stress-induced changes. Importantly, this inhibition of mitochondrial damage protected the axons from degeneration. In conclusion, we present a novel ex vivo approach for monitoring mitochondrial dynamics within axons, which proved suitable for detecting mitochondrial changes upon exogenous application of oxidative stress. Our results indicate that the nodes of Ranvier are the site of initial mitochondrial damage in peripheral axons, and suggest that dysregulation of axonal bioenergetics plays a critical role in oxidative stress-triggered mitochondrial alterations and subsequent axonal injury. These novel insights into the mechanisms underlying axon degeneration may have implications for neurological disorders with a degenerative component. PMID:24973623

Bros, Helena; Millward, Jason M; Paul, Friedemann; Niesner, Raluca; Infante-Duarte, Carmen

2014-11-01

164

Nerve fiber layer (NFL) degeneration associated with acute q-switched laser exposure in the nonhuman primate  

NASA Astrophysics Data System (ADS)

We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.

Zwick, Harry; Zuclich, Joseph A.; Stuck, Bruce E.; Gagliano, Donald A.; Lund, David J.; Glickman, Randolph D.

1995-01-01

165

Three Ca2+ channel inhibitors in combination limit chronic secondary degeneration following neurotrauma.  

PubMed

Following neurotrauma, cells beyond the initial trauma site undergo secondary degeneration, with excess Ca2+ a likely trigger for loss of neurons, compact myelin and function. Treatment using inhibitors of specific Ca2+ channels has shown promise in preclinical studies, but clinical trials have been disappointing and combinatorial approaches are needed. We assessed efficacy of multiple combinations of three Ca2+ channel inhibitors at reducing secondary degeneration following partial optic nerve transection in rat. We used lomerizine to inhibit voltage gated Ca2+ channels; oxidised adenosine-triphosphate (oxATP) to inhibit purinergic P2X7 receptors and/or 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-1,2,3,4-tetrahydro quinoxalin-1-yl]acetic acid (INQ) to inhibit Ca2+ permeable ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Only the three Ca2+ channel inhibitors delivered in combination significantly preserved visual function, as assessed using the optokinetic nystagmus visual reflex, at 3 months after injury. Preservation of retinal ganglion cells was partial and is unlikely to have accounted for differential effects on function. A range of the Ca2+ channel inhibitor combinations prevented swelling of optic nerve vulnerable to secondary degeneration. Each of the treatments involving lomerizine significantly increased the proportion of axons with normal compact myelin. Nevertheless, limiting decompaction of myelin was not sufficient for preservation of function in our model. Multiple combinations of Ca2+ channel inhibitors reduced formation of atypical node/paranode complexes; outcomes were not associated with preservation of visual function. However, prevention of lengthening of the paranodal gap that was only achieved by treatment with the three Ca2+ channel inhibitors in combination was an important additional effect that likely contributed to the associated preservation of the optokinetic reflex using this combinatorial treatment strategy. PMID:23958451

Savigni, Donna L; O'Hare Doig, Ryan L; Szymanski, Charis R; Bartlett, Carole A; Lozi?, Ivan; Smith, Nicole M; Fitzgerald, Melinda

2013-12-01

166

On root systems in spaces with degenerate metric  

E-print Network

A root systems in Carroll spaces with degenerate metric are defined. It is shown that their Cartan matrices and reflection groups are affine. With the help of the geometric consideration the root system structure of affine algebras is determined by a sufficiently simple algorithm.

I. V. Kostyakov; N. A. Gromov; V. V. Kuratov

2001-02-09

167

A dyadic decomposition approach to a finitely degenerate hyperbolic problem  

Microsoft Academic Search

We use the Littlewood-Paley decomposition technique to obtain a C?-well-posedness result for a weakly hyperbolic equation with a finite order of degeneration.\\u000a \\u000a Keywords: Littlewood-Paley decomposition, Hyperbolic equations, C?-well-posedness, Approximate energy method

Massimo Cicognani; Daniele Del Santo; Michael Reissig

2006-01-01

168

Energy estimate and fundamental solution for degenerate hyperbolic Cauchy problems  

Microsoft Academic Search

The aim of this paper is to give an uniform approach to different kinds of degenerate hyperbolic Cauchy problems. We prove that a weakly hyperbolic equation, satisfying an intermediate condition between effective hyperbolicity and the C? Levi condition, and a strictly hyperbolic equation with non-regular coefficients with respect to the time variable can be reduced to first-order systems of the

Alessia Ascanelli; Massimo Cicognani

2005-01-01

169

Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration  

PubMed Central

In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca2+-dependent proteases calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 hours after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 hours post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration. PMID:23542511

Ma, Marek; Ferguson, Toby A.; Schoch, Kathleen M.; Li, Jian; Qian, Yaping; Shofer, Frances S.; Saatman, Kathryn E.; Neumar, Robert W.

2013-01-01

170

Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain  

PubMed Central

Although degeneration of the intervertebral disk has historically been described as a misbalance between anabolic and catabolic factors, the role of inflammatory mediators has long been neglected. However, past research clearly indicates that inflammatory mediators such as interleukin (IL)-1?, IL-6, IL-8 and tumor necrosis factor-? are expressed at higher levels in “diseased” intervertebral disks. Both disk cells as well as invading macrophages can be the source of the detected cytokines. Importantly, occurrence of inflammatory mediators in the disk can worsen the progress of degeneration by inducing the expression of matrix degrading enzymes as well as by inhibiting extracellular matrix synthesis. In addition, inflammatory mediators play a crucial role in pain development during intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e., discogenic pain). This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain. PMID:24436868

Wuertz, Karin; Haglund, Lisbet

2013-01-01

171

Quantum interference effects in degenerate systems. Spontaneous and stimulated radiation  

Microsoft Academic Search

We study the effect of quantum interference on the structure and properties of spontaneous and stimulated transitions in a degenerate V-type three-level atom with an arbitrary total momentum of each state. Explicit expressions for the factors in the terms of the relaxation operator and stimulated transition operator with account of quantum interference effects are obtained. It has been demonstrated that

A. A. Panteleev; Vl. K. Roerich

2004-01-01

172

The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration  

ERIC Educational Resources Information Center

Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

Stoodley, Catherine J.; Schmahmann, Jeremy D.

2009-01-01

173

The Mechanobiology of Articular Cartilage Development and Degeneration  

E-print Network

The Mechanobiology of Articular Cartilage Development and Degeneration Dennis R. Carter, PhD; Gary, PhD The development, maintenance, and destruction of cartilage are regulated by mechanical factors throughout life. Me- chanical cues in the cartilage fetal endoskeleton influence the expression of genes

Stanford University

174

Why study rod cell death in retinal degenerations and how?  

Microsoft Academic Search

Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease.

C. E. Remé; C. Grimm; F. Hafezi; H.-P. Iseli; A. Wenzel

2003-01-01

175

Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration  

ERIC Educational Resources Information Center

Paraneoplastic cerebellar degeneration (PCD) is an autoimmune disease that can be associated with cancer of the breast, lung, and ovary. The clinical presentation of PCD commonly includes ataxia, visual disturbances, and dysarthria. The speech disturbances associated with PCD have not been well characterized, despite general acceptance that…

Paslawski, Teresa; Duffy, Joseph R.; Vernino, Steven

2005-01-01

176

Neuroanatomy of Apathy and Disinhibition in Frontotemporal Lobar Degeneration  

Microsoft Academic Search

Objective: To investigate the neural basis for the behavioral symptoms of frontotemporal lobar degeneration (FTLD) that cause the greatest caregiver distress. Background: FTLD is a progressive neurodegenerative disease associated with behavioral disturbances. Group studies have related these behaviors to volume loss on MRI. Methods: Forty caregivers of patients with the clinical diagnosis of FTLD completed the Neuropsychiatric Inventory. Twelve neuropsychiatric

Lauren Massimo; Chivon Powers; Peachie Moore; Luisa Vesely; Brian Avants; James Gee; David J. Libon; Murray Grossman

2009-01-01

177

Rothe's method for parabolic problems with nonlinear degenerating coefficient  

E-print Network

Rothe's method for parabolic problems with nonlinear degenerating coefficient Volker Pluschke on the solution u. We approximate the problem by semidiscretization in time (Rothe's method) and prove uniform in time (Rothe's method). Here G ae R N , N â?? 2, denotes a simply connected, bounded domain with boundary

178

Conditional Gene Targeting: Dissecting the Cellular Mechanisms of Retinal Degenerations  

PubMed Central

Retinal neuron degeneration and survival are often regulated by the same trophic factors that are required for embryonic development and are usually expressed in multiple cell-types. Therefore, the conditional gene targeting approach is necessary to investigate the cell-specific function of widely expressed and developmentally regulated genes in retinal degeneration. The discussion in this review will be focused on the use of Cre/lox-based conditional gene targeting approach in mechanistic studies for retinal degeneration. In addition to the basic experimental designs, this article addresses various factors influencing the outcomes of conditional gene targeting studies, limitations of current technologies, availability of Cre-drive lines for various retinal cells, and issues related to the generation of Cre-expressing mice. Finally, this review will update the current status on the use of Cre/lox-based gene targeting approach in mechanistic studies for retinal degeneration, which includes rod photoreceptor survival under photo-oxidative stress and protein trafficking in photoreceptors. PMID:21253511

Le, Yun-Zheng

2011-01-01

179

Adaptive Evolution of Eye Degeneration in the Mexican Blind Cavefish  

Microsoft Academic Search

The evolutionary mechanisms responsible for eye degeneration in cave-adapted animals have not been resolved. Opposing hypotheses invoking neural mutation or natural selection, each with certain genetic and developmental expectations, have been advanced to explain eye regression, although little or no experimental evidence has been presented to support or reject either theory. Here we review recent developmental and molecular studies in

W. R. Jeffery

2005-01-01

180

Complement factor d in age-related macular degeneration  

Microsoft Academic Search

Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was

C. M. Stanton; J. R. W. Yates; A. I. den Hollander; J. M. Seddon; A. Swaroop; D. Stambolian; S. Fauser; C. B. Hoyng; Y. Yu; K. Atsuhiro; K. Branham; M. Othman; W. Chen; E. Kortvely; K. Chalmers; C. Hayward; A. T. Moore; B. Dhillon; M. Ueffing; A. F. Wright

2011-01-01

181

Complete population transfer in degenerate n-state atoms  

E-print Network

We find a set of conditions to achieve complete population transfer, via coherent population trapping, from an initial state to a designated final state at a designated time in a degenerate n-state atom, where the transitions are caused by an external interaction.

J. H. McGuire; Kh. Kh. Shakov; Kh. Yu. Rakhimov

2003-06-03

182

Genetic Background Predicts Poor Prognosis in Frontotemporal Lobar Degeneration  

Microsoft Academic Search

Background: Ruling out predictors of survival in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Little is known about determinants of survival in FTLD. Objective: The aim of the present study was to identify whether genetic determinants are key, not only as risk factors but as predictors of survival in FTLD. Methods:

B. Borroni; M. Grassi; S. Archetti; A. Papetti; R. Del Bo; C. Bonvicini; G. P. Comi; M. Gennarelli; G. Bellelli; M. Di Luca; A. Padovani

2011-01-01

183

Inflammation in Dry Age-Related Macular Degeneration  

Microsoft Academic Search

Purpose: To summarize the current information regarding the role of immune and inflammatory response in the pathogenesis of dry age-related macular degeneration (ARMD). Methods: A Pubmed search was conducted of the period January 1999 to 2005. Relevant information in the literature on the role of inflammation in early dry ARMD was reviewed. Results: Some important evidence for inflammation in early

Eduardo B. Rodrigues

2007-01-01

184

Retinal Remodeling: Circuitry Revisions Triggered by Photoreceptor Degeneration  

Microsoft Academic Search

Structural, molecular and physiological responses of the neural retina to ablation of the sensory retina triggered by inherited or induced photoreceptor degeneration reveal a surprising degree of dynamic capacity in mature neurons. All classes of mature retinal neurons (bipolar, horizontal, amacrine and ganglion cells) show the capacity for five dynamic processes characteristic of developing neurons and stressed neurons displaying negative

Robert E. Marc; Bryan W. Jones; Carl B. Watt

185

Retinal Degeneration and RPE Transplantation in Rpe65\\/ Mice  

Microsoft Academic Search

mice. The other eye received a subretinal injection of saline or was not touched. Corneal electroretinograms (ERGs) from both eyes were monitored before and after surgery to follow progression of the degeneration. The width of the outer nu- clear layer was measured in the area of transplantation and compared with a similar area in control retinas. RESULTS. Transplantation of RPE

Peter Gouras; Jian Kong; Stephen H. Tsang

2002-01-01

186

Cesare Lombroso: an anthropologist between evolution and degeneration  

PubMed Central

Summary Cesare Lombroso (1835–1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration , a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the “born delinquent” whose development had stopped at an early stage, making them the most “atavistic” types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of “biological compensation” for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso’s anthropological ideas fuelled a heated debate on the biological determinism of human behaviour. PMID:21729591

Mazzarello, Paolo

187

Optical Camera Tracking in Virtual Studios: Degenerate Cases  

Microsoft Academic Search

Over the past few years, virtual studios applications have significantly attracted the attention of the entertainment industry. Optical tracking systems for virtual sets production have become particularly popular tending to substitute electro-mechanical ones. In this work, an existing optical tracking system is revisited, in order to tackle with inherent degenerate cases; namely, reduction of the perspective projection model to the

Athanasios I. Drosopoulos; Yiannis Xirouhakis; Anastasios Delopoulos

2000-01-01

188

Gestural Imitation and Limb Apraxia in Corticobasal Degeneration  

ERIC Educational Resources Information Center

Limb apraxia is a common symptom of corticobasal degeneration (CBD). While previous research has shown that individuals with CBD have difficulty imitating transitive (tool-use actions) and intransitive non-representational gestures (nonsense actions), intransitive representational gestures (actions without a tool) have not been examined. In the…

Salter, Jennifer E.; Roy, Eric A.; Black, Sandra E.; Joshi, Anish; Almeida, Quincy

2004-01-01

189

DEGENERATE ELLIPTIC EQUATION INVOLVING A SUBCRITICAL SOBOLEV EXPONENT  

Microsoft Academic Search

Abstract: We prove the existence of a solution of degenerate elliptic equation (1) involving a subcritical Sobolev exponent. To solve (1) we establish the existence of a solution of the constrained minimization problem (3). A relative compactness of a minimizing sequence is obtained by examining a possible loss of a mass at inflnity of a minimizing sequence.

Portugaliae Mathematica; J. Chabrowski

190

Nonlinear isothermal waves in a degenerate electron plasma  

SciTech Connect

A nonlinear differential equation describing oscillations of the chemical potential in a one-dimensional steady-state wave propagating in a degenerate electron gas against an immobile neutralizing ion background is derived, investigated, and solved exactly. It is found that the wave phase velocity is bounded below by a critical velocity, whose exact value is obtained.

Dubinov, A. E. [Sarov State Physical and Technical Institute (Russian Federation); Dubinova, A. A. [Lobachevsky Nizhni Novgorod State University, Advanced School of General and Applied Physics (Russian Federation)

2008-05-15

191

Age-related macular degeneration among the Inuit in Greenland  

Microsoft Academic Search

Objectives. To investigate the clinical appearance and prevalence of Age-related Macular Degeneration (AMD) among the Inuit in Greenland, to investigate risk factors and to initiate the search for possible genetic markers. Study design. A cross-sectional population study including all individuals older than 60 years of age, born in Greenland and living in the communities of Nuuk and Sisimiut, was performed

Nis Andersen

2003-01-01

192

Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation  

Microsoft Academic Search

We have investigated the pathological correlates of dementia in the brains from a consecutive series of 70 patients dying with a clinical diagnosis of frontotemporal lobar degeneration (FTLD). Clinical misdiagnosis rate was low with only 3 patients (4%) failing to show pathological changes consistent with this diagnosis; 1 patient had Alzheimer’s disease and 2 had cerebrovascular disease (CVD). In the

Jing Shi; Catherine L. Shaw; Daniel Du Plessis; Anna M. T. Richardson; Kathryn L. Bailey; Camille Julien; Cheryl Stopford; Jennifer Thompson; Anoop Varma; David Craufurd; Jinzhou Tian; Stuart Pickering-Brown; David Neary; Julie S. Snowden; David M. A. Mann

2005-01-01

193

Is the Z degenerate with an exotic quarkonium?  

Microsoft Academic Search

We propose an explanation for the recently discovered CERN events containing a hard photon, interpreting them as Z --> llgammagamma decays (l = e, mu, nu) where one photon is soft and not seen. We suggest that Z mixes with a degenerate bound state of an exotic color fermion and its antiparticle, which decays via ``onium'' cascade. Predictions include a

Stephen F. King; Stephen R. Sharpe

1984-01-01

194

Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings  

Microsoft Academic Search

OBJECTIVEVitamin B12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients.METHODSClinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients

B Hemmer; F X Glocker; M Schumacher; G Deuschl; C H Lücking

1998-01-01

195

Lhermitte's sign in subacute combined degeneration of the cord  

Microsoft Academic Search

Lhermitte's sign is a common early symptom of subacute combined degeneration of the cord occurring in 11 out of 44 patients admitted to the National Hospitals for Nervous Diseases during the decade 1962-71 with this diagnosis. Two patients, in both of whom it was the presenting complaint, are described in detail. It is concluded that, in these cases, Lhermitte's sign

P. C. Gautier-Smith

1973-01-01

196

Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation of  

E-print Network

Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation producing oxyradical stress, autophagy, and neurite degeneration. Key words: methamphetamine; VMAT2; oxidative stress; neurodegeneration; dopamine; ventral midbrain; autophagy Methamphetamine (METH), a widely

Sulzer, David

197

Mechanism of calcium entry during axon injury and degeneration.  

PubMed

Axon degeneration is a hallmark consequence of chemical neurotoxicant exposure (e.g., acrylamide), mechanical trauma (e.g., nerve transection, spinal cord contusion), deficient perfusion (e.g., ischemia, hypoxia), and inherited neuropathies (e.g., infantile neuroaxonal dystrophy). Regardless of the initiating event, degeneration in the PNS and CNS progresses according to a characteristic sequence of morphological changes. These shared neuropathologic features suggest that subsequent degeneration, although induced by different injury modalities, might evolve via a common mechanism. Studies conducted over the past two decades indicate that Ca2+ accumulation in injured axons has significant neuropathic implications and is a potentially unifying mechanistic event. However, the route of Ca2+ entry and the involvement of other relevant ions (Na+, K+) have not been adequately defined. In this overview, we discuss evidence for reverse operation of the Na+-Ca2+ exchanger as a primary route of Ca2+ entry during axon injury. We propose that diverse injury processes (e.g., axotomy, ischemia, trauma) which culminate in axon degeneration cause an increase in intraaxonal Na+ in conjunction with a loss of K+ and axolemmal depolarization. These conditions favor reverse Na+-Ca2+ exchange operation which promotes damaging extraaxonal Ca2+ entry and subsequent Ca2+-mediated axon degeneration. Deciphering the route of axonal Ca2+ entry is a fundamental step in understanding the pathophysiologic processes induced by chemical neurotoxicants and other types of nerve damage. Moreover, the molecular mechanism of Ca2+ entry can be used as a target for the development of efficacious pharmacotherapies that might be useful in preventing or limiting irreversible axon injury. PMID:9144441

LoPachin, R M; Lehning, E J

1997-04-01

198

A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies.  

PubMed

Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect. PMID:19430481

Khanna, Hemant; Davis, Erica E; Murga-Zamalloa, Carlos A; Estrada-Cuzcano, Alejandro; Lopez, Irma; den Hollander, Anneke I; Zonneveld, Marijke N; Othman, Mohammad I; Waseem, Naushin; Chakarova, Christina F; Maubaret, Cecilia; Diaz-Font, Anna; MacDonald, Ian; Muzny, Donna M; Wheeler, David A; Morgan, Margaret; Lewis, Lora R; Logan, Clare V; Tan, Perciliz L; Beer, Michael A; Inglehearn, Chris F; Lewis, Richard A; Jacobson, Samuel G; Bergmann, Carsten; Beales, Philip L; Attié-Bitach, Tania; Johnson, Colin A; Otto, Edgar A; Bhattacharya, Shomi S; Hildebrandt, Friedhelm; Gibbs, Richard A; Koenekoop, Robert K; Swaroop, Anand; Katsanis, Nicholas

2009-06-01

199

Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration  

Microsoft Academic Search

Purpose: Our objective was to comprehensively assess the nature and chronology of neural remodeling in retinal degenerations triggered by light-induced retinal damage (LIRD) in adult albino rodents. Our primary hypothesis is that all complete photoreceptor degenerations devolve to extensive remodeling. An hypothesis emergent from data analysis is that the LIRD model closely mimics late-stage atrophic age relared macular degeneration (AMD).

Robert E. Marc; B. W. Jones; C. B. Watt; F. Vazquez-Chona; D. K. Vaughan; D. T. Organisciak

2008-01-01

200

Control of muscle degeneration following autotomy of a hindleg in the grasshopper, Barytettix humphreysii  

Microsoft Academic Search

When the grasshopper, Barrytettix humphreysii, sheds a hindlimb during autotomy, certain thoracic muscles degenerate although they are neither directly damaged nor denervated. Muscle degeneration is induced when a leg nerve (N5) that does not innervate the thoracic muscles is severed. Together these results suggest that transneuronal mechanisms influence muscle survival. To further characterize this autotomy-induced process, we studied the degeneration

K. E. Personius; R. F. Chapman

2002-01-01

201

Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia  

PubMed Central

Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types A–D). Of these four subtypes, motor neuron disease is more commonly associated with type B pathology, but has also been reported with type A pathology. We have noted, however, the unusual occurrence of cases of type C pathology having corticospinal tract degeneration. We aimed to assess the severity of corticospinal tract degeneration in a large cohort of cases with type C (n = 31). Pathological analysis included semi-quantitation of myelin loss of fibres of the corticospinal tract and associated macrophage burden, as well as axonal loss, at the level of the medullary pyramids. We also assessed for motor cortex degeneration and fibre loss of the medial lemniscus/olivocerebellar tract. All cases were subdivided into three groups based on the degree of corticospinal tract degeneration: (i) no corticospinal tract degeneration; (ii) equivocal corticospinal tract degeneration; and (iii) moderate to very severe corticospinal tract degeneration. Clinical, genetic, pathological and imaging comparisons were performed across groups. Eight cases had no corticospinal tract degeneration, and 14 cases had equivocal to mild corticospinal tract degeneration. Nine cases, however, had moderate to very severe corticospinal tract degeneration with myelin and axonal loss. In these nine cases, there was degeneration of the motor cortex without lower motor neuron degeneration or involvement of other brainstem tracts. These cases most commonly presented as semantic dementia, and they had longer disease duration (mean: 15.3 years) compared with the other two groups (10.8 and 9.9 years; P = 0.03). After adjusting for disease duration, severity of corticospinal tract degeneration remained significantly different across groups. Only one case, without corticospinal tract degeneration, was found to have a hexanucleotide repeat expansion in the C9ORF72 gene. All three groups were associated with anterior temporal lobe atrophy on MRI; however, the cases with moderate to severe corticospinal tract degeneration showed right-sided temporal lobe asymmetry and greater involvement of the right temporal lobe and superior motor cortices than the other groups. In contrast, the cases with no or equivocal corticospinal tract degeneration were more likely to show left-sided temporal lobe asymmetry. For comparison, the corticospinal tract was assessed in 86 type A and B cases, and only two cases showed evidence of corticospinal tract degeneration without lower motor neuron degeneration. These findings confirm that there exists a unique association between frontotemporal lobar degeneration with type C pathology and corticospinal tract degeneration, with this entity showing a predilection to involve the right temporal lobe. PMID:23358603

Whitwell, Jennifer L.; Murray, Melissa E.; Parisi, Joseph E.; Graff-Radford, Neill R.; Knopman, David S.; Boeve, Bradley F.; Senjem, Matthew L.; Rademakers, Rosa; Jack, Clifford R.; Petersen, Ronald C.; Dickson, Dennis W.

2013-01-01

202

Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia.  

PubMed

Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types A-D). Of these four subtypes, motor neuron disease is more commonly associated with type B pathology, but has also been reported with type A pathology. We have noted, however, the unusual occurrence of cases of type C pathology having corticospinal tract degeneration. We aimed to assess the severity of corticospinal tract degeneration in a large cohort of cases with type C (n = 31). Pathological analysis included semi-quantitation of myelin loss of fibres of the corticospinal tract and associated macrophage burden, as well as axonal loss, at the level of the medullary pyramids. We also assessed for motor cortex degeneration and fibre loss of the medial lemniscus/olivocerebellar tract. All cases were subdivided into three groups based on the degree of corticospinal tract degeneration: (i) no corticospinal tract degeneration; (ii) equivocal corticospinal tract degeneration; and (iii) moderate to very severe corticospinal tract degeneration. Clinical, genetic, pathological and imaging comparisons were performed across groups. Eight cases had no corticospinal tract degeneration, and 14 cases had equivocal to mild corticospinal tract degeneration. Nine cases, however, had moderate to very severe corticospinal tract degeneration with myelin and axonal loss. In these nine cases, there was degeneration of the motor cortex without lower motor neuron degeneration or involvement of other brainstem tracts. These cases most commonly presented as semantic dementia, and they had longer disease duration (mean: 15.3 years) compared with the other two groups (10.8 and 9.9 years; P = 0.03). After adjusting for disease duration, severity of corticospinal tract degeneration remained significantly different across groups. Only one case, without corticospinal tract degeneration, was found to have a hexanucleotide repeat expansion in the C9ORF72 gene. All three groups were associated with anterior temporal lobe atrophy on MRI; however, the cases with moderate to severe corticospinal tract degeneration showed right-sided temporal lobe asymmetry and greater involvement of the right temporal lobe and superior motor cortices than the other groups. In contrast, the cases with no or equivocal corticospinal tract degeneration were more likely to show left-sided temporal lobe asymmetry. For comparison, the corticospinal tract was assessed in 86 type A and B cases, and only two cases showed evidence of corticospinal tract degeneration without lower motor neuron degeneration. These findings confirm that there exists a unique association between frontotemporal lobar degeneration with type C pathology and corticospinal tract degeneration, with this entity showing a predilection to involve the right temporal lobe. PMID:23358603

Josephs, Keith A; Whitwell, Jennifer L; Murray, Melissa E; Parisi, Joseph E; Graff-Radford, Neill R; Knopman, David S; Boeve, Bradley F; Senjem, Matthew L; Rademakers, Rosa; Jack, Clifford R; Petersen, Ronald C; Dickson, Dennis W

2013-02-01

203

Differences in peripheral nerve degeneration/regeneration between wild-type and neuronal nitric oxide synthase knockout mice.  

PubMed

Nitric oxide (NO), a unique biological messenger molecule, is synthesized by three isoforms of the enzyme NO synthase (NOS) and diffuses from the site of production across cellular membranes. A postulated role for NO in degeneration and regeneration of peripheral nerves has been explored in a sciatic nerve model comparing wild-type mice and mice lacking neuronal NOS after transection and microsurgical repair. In NOS knockout mice, regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). In the regenerated nerve, pruning of uncontrolled sprouts was disturbed, leading to an enhanced number of axons, whereas remyelination seemed to be less affected. Delayed regeneration was associated with a delayed recovery of sensor and motor function. In such a context, possible NO targets are neurofilaments and myelin sheaths of the interrupted axon, filopodia of the growth cone, newly formed neuromuscular endplates, and Schwann cells in the distal nerve stump. The results presented suggest that 1) local release of NO following peripheral nerve injury is a crucial factor in degeneration/regeneration, 2) success of fiber regeneration in the peripheral nervous system depends on a regular WD, and 3) manipulation of NO supply may offer interesting therapeutic options for treatment of peripheral nerve lesions. PMID:11992469

Keilhoff, Gerburg; Fansa, Hisham; Wolf, Gerald

2002-05-15

204

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration  

PubMed Central

The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD. PMID:17909628

Combadiere, Christophe; Feumi, Charles; Raoul, William; Keller, Nicole; Rodero, Mathieu; Pezard, Adeline; Lavalette, Sophie; Houssier, Marianne; Jonet, Laurent; Picard, Emilie; Debre, Patrice; Sirinyan, Mirna; Deterre, Philippe; Ferroukhi, Tania; Cohen, Salomon-Yves; Chauvaud, Dominique; Jeanny, Jean-Claude; Chemtob, Sylvain; Behar-Cohen, Francine; Sennlaub, Florian

2007-01-01

205

Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor.  

PubMed

Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling the consequences of haploinsufficiency of the human CAMTA1 locus. Gene-expression analysis identified a large collection of neuronal genes that were dysregulated in the brains of CAMTA1-mutant mice, and elucidation of a consensus sequence for binding of CAMTA proteins to DNA revealed the association of CAMTA-binding sites with many of these genes. We conclude that CAMTA1 plays an essential role in the control of Purkinje cell function and survival. CAMTA1-mutant mice provide a model to study the molecular mechanisms of neurodegenerative diseases and for screening potential therapeutic interventions for such disorders. PMID:25049392

Long, Chengzu; Grueter, Chad E; Song, Kunhua; Qin, Song; Qi, Xiaoxia; Kong, Y Megan; Shelton, John M; Richardson, James A; Zhang, Chun-Li; Bassel-Duby, Rhonda; Olson, Eric N

2014-08-01

206

Resistive collimation of electron beams in relativistic and degenerate plasma  

NASA Astrophysics Data System (ADS)

The purpose of this research is the study of the effects of plasma state and fiber on collimating relativistic electron beam in fast ignition. In this paper, for collimating relativistic electrons produced at the laser plasma interaction, a thin fiber of aluminum, lithium or CH either in the classical, degenerate or relativistic plasma states is considered. The fast electron beam could be collimated down to radii of 10 ?m, in that case, the best results are achieved when there is a sharp transition in resistance. This ensures that the correct magnetic growth rate is used for hot electrons at different energy levels. Calculations show that the resistivity of the material surrounding the CH fiber in the degenerate plasma is smaller than that for classical and relativistic plasma.

Mahdavi, M.; Khodadadi Azadboni, F.

2014-09-01

207

Molecular pathology of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

2009-01-01

208

Clinical diagnostic criteria and classification controversies in frontotemporal lobar degeneration  

PubMed Central

Frontotemporal lobar degeneration (FTLD) can manifest as a spectrum of clinical syndromes, ranging from behavioural impairment to language or motor dysfunction. Recently, revised diagnostic criteria have been proposed for the behavioural and progressive aphasia syndromes associated with frontotemporal degeneration. The present review will summarize these diagnostic guidelines and highlight some lingering controversies in the classification of FTLD clinical syndromes. We will discuss common tools and methods used to identify the insidious changes of behavioural variant frontotemporal dementia (bvFTD), the value of new, patient-based tasks of orbitofrontal function, and the issue of a benign or ‘phenocopy’ variant of bvFTD. With regard to primary progressive aphasia (PPA), we will discuss the scope of the semantic disorder in semantic-variant PPA, the nature of the speech disorder in non-fluent, agrammatic PPA, and the preliminary utility of a logopenic PPA classification. PMID:23611345

RASCOVSKY, KATYA; GROSSMAN, MURRAY

2014-01-01

209

Paraneoplastic cerebellar degeneration associated with serous adenocarcinoma of the ovary.  

PubMed

We report a case of a 68-year-old woman who presented with symptoms of cerebellar degeneration which initiated a suspicion of underlying malignancy. The patient presented with progressive ataxia and dysarthria and after excluding primary cerebellar pathology, paraneoplastic syndrome was suspected and she was investigated for a malignancy. CT scan of the pelvis showed a left-sided ovarian mass later diagnosed as serous adenocarcinoma of the ovary. She underwent surgery and histology of the mass showed poorly-differentiated serous adenocarcinoma. Paraneoplastic neurological syndrome encompasses several neurological disorders including paraneoplastic cerebellar degeneration (PCD) caused by an immune-mediated mechanism in patients with an underlying malignancy. PCD is a rare condition that occurs in less than 1% of patients with cancer and is associated with specific groups of cancer. It is important to identify PCD due to its association with certain cancers and also to limit the disabilities associated with the syndrome. PMID:25432905

Saeed, Duaa B; Gupta, Limci

2014-01-01

210

Experimental analysis of degenerate vector phase-sensitive amplification.  

PubMed

We comprehensively investigate a degenerate vector phase-sensitive amplifier (PSA). We determine the gain dependence on the relative phase and polarization angle between the pumps and the degenerate signal wave. The vector PSA is experimentally shown to be sensitive to the pump states of polarization (SOP) due to polarization mode dispersion in the fiber. However, the scheme performance agrees well with theory under specific pump SOPs and we achieve an on-off gain over 10 dB with a small deviation from the theoretically expected results. In comparison to the scalar scheme, the proposed vector scheme has larger tolerance for pump depletion due to four-wave mixing between pumps and generation of higher-order idlers. PMID:25321564

Lorences-Riesgo, Abel; Chiarello, Fabrizio; Lundström, Carl; Karlsson, Magnus; Andrekson, Peter A

2014-09-01

211

[A case of mediastinal seminoma undergoing extremely cystic degeneration].  

PubMed

A-25-year-old male had an abnormal shadow on chest X-ray. CT and MRI films revealed a cystic lesion, with irregular nodules in the right anterior mediastinum. A cystic teratoma was suggested. Antero-axillary thoracotomy revealed a cystic lesion originating from the right lobe of the thymus. The lesion was extirpated, along with the right lobe of the thymus. The cystic part of the lesion, filled with brown fluid, was occupied by several masses originating from the wall of the tumor. Pathologically, the lesion was diagnosed as a seminoma undergoing cystic degeneration. The patient was given post-operative irradiation of 20Gy. No apparent recurrence has been detected 33 months after surgery. Mediastinal seminomas generally occur as a solid tumor consisting of stroma and tumor cells. However, this case report suggests that mediastinal seminomas may undergo extremely cystic degeneration. PMID:9465624

Kataoka, K; Seno, N

1997-10-01

212

A commutative algebra on degenerate CP^1 and Macdonald polynomials  

E-print Network

We introduce a unital associative algebra A over degenerate CP^1. We show that A is a commutative algebra and whose Poincar'e series is given by the number of partitions. Thereby we can regard A as a smooth degeneration limit of the elliptic algebra introduced by one of the authors and Odesskii. Then we study the commutative family of the Macdonald difference operators acting on the space of symmetric functions. A canonical basis is proposed for this family by using A and the Heisenberg representation of the commutative family studied by one of the authors. It is found that the Ding-Iohara algebra provides us with an algebraic framework for the free filed construction. An elliptic deformation of our construction is discussed, showing connections with the Drinfeld quasi-Hopf twisting a la Babelon Bernard Billey, the Ruijsenaars difference operator and the operator M(q,t_1,t_2) of Okounkov-Pandharipande.

Feigin, B; Hoshino, A; Shiraishi, J; Yanagida, S

2009-01-01

213

An alternative to source degeneration of CMOS differential pair  

Microsoft Academic Search

This paper presents a method to extend linear range of conventional CMOS source-coupled pair with transistor polarised on\\u000a saturation of strong inversion. The used principle is similar to the principle of source degeneration, but the additional\\u000a device is horizontally added, in parallel with the input transistors, which overcame the constraints on common mode range\\u000a and supply voltage and allow low

Aimad El Mourabit; Mohamed-halim Sbaa; Guo-Neng Lu; Patrick Pittet

2010-01-01

214

Degenerate dispersive equations arising in the study of magma dynamics  

Microsoft Academic Search

An outstanding problem in Earth science is understanding the method of transport of magma in the Earth's mantle. Two proposed methods for this transport are percolation through porous rock and flow up conduits. Under reasonable assumptions and simplifications, both means of transport can be described by a class of degenerate nonlinear dispersive partial differential equations of the form: \\\\[ \\\\begin{equation*}\\\\phi_{t}+(\\\\phi^{n})_{z}-(\\\\phi^{n}(\\\\phi^{-m}\\\\phi_{t})_{z})_{z}=0,\\\\end{equation*}

Gideon Simpson; Marc Spiegelman; Michael I. Weinstein

2007-01-01

215

Magnetic susceptibility and Landau diamagnetism of quantum collisional degenerate plasmas  

E-print Network

With the use of correct expression of the electric conductivity of quantum collisional degenerate plasmas (A. V. Latyshev and A. A. Yushkanov, Transverse electrical conductivity of a quantum collisional plasma in the Mermin approach, - Theor. and Math. Phys., {\\bf 175}(1): 559-569 (2013)) the kinetic description of a magnetic susceptibility is obtained and the formula for calculation of Landau diamagnetism is deduced.

Latyshev, A V

2013-01-01

216

Magnetic susceptibility and Landau diamagnetism of quantum collisional degenerate plasmas  

E-print Network

With the use of correct expression of the electric conductivity of quantum collisional degenerate plasmas (A. V. Latyshev and A. A. Yushkanov, Transverse electrical conductivity of a quantum collisional plasma in the Mermin approach, - Theor. and Math. Phys., {\\bf 175}(1): 559-569 (2013)) the kinetic description of a magnetic susceptibility is obtained and the formula for calculation of Landau diamagnetism is deduced.

A. V. Latyshev; A. A. Yushkanov

2013-05-21

217

Analytic integrability for some degenerate planar vector fields  

NASA Astrophysics Data System (ADS)

In this paper we study the analytic integrability of degenerate vector fields of the form (y3+2ax3y+⋯,-x5-3ax2y2+⋯) around the origin. For these vector fields it is proved that integrability does not imply formal orbital equivalence to the Hamiltonian leading part. Moreover, it is shown the existence of a system in this class which has a center but is neither analytically integrable nor formal orbital reversible.

Algaba, Antonio; García, Cristóbal; Giné, Jaume

2014-07-01

218

Fundus Imaging of Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Digital fundus cameras and confocal scanning laser ophthalmoscopes have increased the efficiency and resolution of fundus\\u000a photography. Autofluorescent images yield information about the functional status of the outer retina and retinal pigment\\u000a epithelium (RPE). Fluorescein angiography remains invaluable for studying retinal vascular anatomy and physiology in eyes\\u000a with neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) permits visualization of

Allen Chiang; Andre J. Witkin; Carl D. Regillo; Allen C. Ho

219

Parkin deficiency increases vulnerability to inflammation-related nigral degeneration  

PubMed Central

The loss of nigral dopaminergic (DA) neurons in idiopathic Parkinson's disease (PD) is believed to result from interactions between genetic susceptibility and environmental factors. Evidence that inflammatory processes modulate PD risk comes from prospective studies which suggest that higher plasma concentrations of a number of pro-inflammatory cytokines correlate with an increased risk of developing PD and chronic nonsteroidal anti-inflammatory drug (NSAID) regimens reduce the incidence of PD. Although loss-of-function mutations in the parkin gene cause early onset familial PD, Parkin-deficient (parkin-/-) mice do not display nigrostriatal pathway degeneration, suggesting that a genetic factor is not sufficient and an environmental trigger may be needed to cause nigral DA neuron loss. To test the hypothesis that parkin -/- mice require an inflammatory stimulus to develop nigral DA neuron loss, low-dose lipopolysaccaride (LPS) was administered intraperitoneally for prolonged periods. Quantitative real-time PCR and immunofluorescence labeling of inflammatory markers indicated that this systemic LPS treatment regimen triggered persistent neuroinflammation in wild-type and parkin-/- mice. Although inflammatory and oxidative stress responses to the inflammation regimen did not differ significantly between the two genotypes, only parkin-/- mice displayed subtle fine-motor deficits and selective loss of DA neurons in substantia nigra. Therefore, our studies suggest that loss of Parkin function increases the vulnerability of nigral DA neurons to inflammation-related degeneration. This new model of nigral DA neuron loss may enable identification of early biomarkers of degeneration and aid in pre-clinical screening efforts to identify compounds that can halt or delay the progressive degeneration of the nigrostriatal pathway. PMID:18945890

Frank-Cannon, Tamy C.; Tran, Thi; Ruhn, Kelly A.; Martinez, Terina N.; Hong, John; Marvin, Marian; Hartley, Meagan; Trevino, Isaac; O'Brien, Daniel E.; Casey, Bradford; Goldberg, Matthew S.; Tansey, Malu G.

2008-01-01

220

Autophagy Protects the Retina from Light-induced Degeneration*  

PubMed Central

Autophagy is a conserved feature of lysosome-mediated intracellular degradation. Dysregulated autophagy is implicated as a contributor in neurodegenerative diseases; however, the role of autophagy in retinal degeneration remains largely unknown. Here, we report that the photo-activated visual chromophore, all-trans-retinal, modulated autophagosome formation in ARPE19 retinal cells. Increased formation of autophagosomes in these cells was observed when incubated with 2.5 ?m all-trans-retinal, a condition that did not cause cell death after 24 h in culture. However, autophagosome formation was decreased at concentrations, which caused cell death. Increased expression of activating transcription factor 4 (Atf4), which indicates the activation of oxidative stress, was recorded in response to light illumination in retinas of Abca4?/?Rdh8?/? mice, which showed delayed clearance of all-trans-retinal after light exposure. Expression of autophagosome marker LC3B-II and mitochondria-specific autophagy, mitophagy, regulator Park2, were significantly increased in the retinas of Abca4?/?Rdh8?/? mice after light exposure, suggesting involvement of autophagy and mitophagy in the pathogenesis of light-induced retinal degeneration. Deletion of essential genes required for autophagy, including Beclin1 systemically or Atg7 in only rod photoreceptors resulted in increased susceptibility to light-induced retinal damage. Increased photoreceptor cell death was observed when retinas lacking the rod photoreceptor-specific Atg7 gene were coincubated with 20 ?m all-trans-retinal. Park2?/? mice also displayed light-induced retinal degeneration. Ultra-structural analyses showed mitochondrial and endoplasmic reticulum impairment in retinas of these model animals after light exposure. Taken together, these observations provide novel evidence implicating an important role of autophagy and mitophagy in protecting the retina from all-trans-retinal- and light-induced degeneration. PMID:23341467

Chen, Yu; Sawada, Osamu; Kohno, Hideo; Le, Yun-Zheng; Subauste, Carlos; Maeda, Tadao; Maeda, Akiko

2013-01-01

221

Suppression of Density Fluctuations in a Quantum Degenerate Fermi Gas  

NASA Astrophysics Data System (ADS)

We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations (atom shot noise) for cold clouds deep in the quantum degenerate regime. Strong suppression is observed for probe volumes containing more than 10 000 atoms. Measuring the level of suppression provides sensitive thermometry at low temperatures. After this method of sensitive noise measurements has been validated with an ideal Fermi gas, it can now be applied to characterize phase transitions in strongly correlated many-body systems.

Sanner, Christian; Su, Edward J.; Keshet, Aviv; Gommers, Ralf; Shin, Yong-Il; Huang, Wujie; Ketterle, Wolfgang

2010-07-01

222

Differential neuroglycan C expression during retinal degeneration in Rpe65  

Microsoft Academic Search

Purpose: An increased mRNA expression of the genes coding for the extracellular matrix proteins neuroglycan C (NGC), interphotoreceptor matrix proteoglycan 2 (IMPG2), and CD44 antigen (CD44) has been observed during retinal degeneration in mice with a targeted disruption of the Rpe65 gene (Rpe65?\\/? mouse). To validate these data, we analyzed this differential expression in more detail by characterizing retinal NGC

Pascal Escher; Sandra Cottet; Saichiko Aono; Atsuhiko Oohira; Daniel F. Schorderet

2008-01-01

223

Immunopathological aspects of age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological\\u000a aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic\\u000a processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and\\u000a beneath the retinal pigment epithelium, recruitment of macrophages for

Mrinali Patel; Chi-Chao Chan

2008-01-01

224

Age-related macular degeneration: a perspective on genetic studies  

Microsoft Academic Search

AimAge-related macular degeneration (AMD) is a common macular disease in the developed world and recent studies have shown that specific genes may be associated with it and may contribute to a higher risk of developing AMD.ObjectiveOur objective was to review systematically recent publications related to the genetics of AMD and provide relevant information that would help both scientists and clinicians

N Patel; T Adewoyin; N V Chong; Victor Chong

2008-01-01

225

Massive jejunal diverticulosis and subacute combined degeneration of the cord  

Microsoft Academic Search

Summary  A case of massive jejunal diverticulosis is described. The condition was complicated by small intestinal bacterial overgrowth\\u000a which lead to steatorrhoea, vitamin B12 deficiency and subacute combined degeneration of the cord. Conventional treatment\\u000a may not completely eliminate the abnormal microflora. In severe jejunal diverticulosis with neurological complications long\\u000a term replacement with vitamin B12 is recommended.

K. Ward; A. Robinson; M. McMurray; D. G. Weir

1983-01-01

226

Subacute Combined Degeneration of the Cord: Putnam-Dana Syndrome  

Microsoft Academic Search

The association of anaemia and gastro-intestinal abnormalities with disorders of the brain, spinal cord, and peripheral nerves has been recognized since the mid 19th century. In early reports interpretable as subacute combined degeneration, anaemia was overlooked, and conversely in Addison’s and other early reports of pernicious anaemia, cord and nerve changes were not recorded. This paper shows that Lichtheim first

J. M. S. Pearce

2008-01-01

227

A case of subacute combined degeneration: MRI findings  

Microsoft Academic Search

The specific spinal cord lesion caused by vitamin B12 deficiency is known as subacute combined degeneration (SCD). Neuropathological\\u000a studies of SCD show lesions mainly in the posterior and lateral columns, involving the cortico-spinal and spino-cerebellar\\u000a tracts. We report a case of SCD in a 19-year-old man who presented with 4 weeks history of gradually progressing tingling\\u000a in both hands. MRI

K. Yamada; D. A. Shrier; H. Tanaka; Y. Numaguchi

1998-01-01

228

Ignition Regime for Fusion in a Degenerate Plasma  

SciTech Connect

We identify relevant parameter regimes in which aneutronic fuels can undergo fusion ignition in hot-ion degenerate plasma. Because of relativistic effects and partial degeneracy, the self-sustained burning regime is considerably larger than previously calculated. Inverse bremsstrahlung plays a major role in containing the reactor energy. We solve the radiation transfer equation and obtain the contribution to the heat conductivity from inverse bremsstrahlung.

Son, S.; Fisch, N.J.

2005-12-01

229

Blood flow Magnetic Resonance Imaging of Retinal Degeneration  

Microsoft Academic Search

PURPOSE. This study aims to investigate quantitative basal blood flow as well as hypercapnia- and hyperoxia-induced blood flow changes in the retinas of the Royal College of Surgeons (RCS) rats with spontaneous retinal degeneration, and to compare with those of normal rat retinas. METHODS. Experiments were performed on male RCS rats at post-natal days P90 (n 4) and P220 (n

Yingxia Li; Haiying Cheng; Qiang Shen; Moon Kim; Peter M. Thule; Darin E. Olson; Machelle T. Pardue; Timothy Q. Duong

2009-01-01

230

Blood Flow Magnetic Resonance Imaging of Retinal Degeneration  

E-print Network

Blood Flow Magnetic Resonance Imaging of Retinal Degeneration Yingxia Li,1 Haiying Cheng,1 Qiang Shen,1,2,3,4,5,6 Moon Kim,7 Peter M. Thule,7,8 Darin E. Olson,7,8 Machelle T. Pardue,7,9 and Timothy Q. Duong1,2,3,4,5,6,7 PURPOSE. This study aims to investigate quantitative basal blood flow as well

Duong, Timothy Q.

231

Measurement of smoke concentration using degenerate four-wave mixing  

Microsoft Academic Search

Degenerate four-wave mixing (DFWM) was successfully used to monitor a wide range of smoke concentrations (0.1-10 mg m?3) in sample cells. To the authors' knowledge, this is the first measurement of smoke by DFWM. The DFWM method is very sensitive, measuring down to ?0.1 ppb soot volume fraction. To verify the visible laser DFWM system, NO2 concentrations from 2 to

T C Cole; W A Cole; R W Pitz

2002-01-01

232

Degeneration of the Y chromosome in evolutionary aging models  

NASA Astrophysics Data System (ADS)

The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

Lobo, M. P.; Onody, R. N.

2005-06-01

233

Non-functional adrenocortical adenoma with extensive degeneration.  

PubMed

We report a case of non-functional adrenocortical adenoma of 5.5 x 5.5 x 3.2 cm in size that had an unusual histopathological appearance in two respects. First, the tumor contained small adipose foci with osteogenesis and was suspected of being a myelolipoma based on its appearance on computerized tomography (CT) and magnetic resonance imaging. However, pathologically, the fat element was seen focally and was not accompanied by hematopoietic cells, and the diagnosis of myelolipoma was abandoned. Second, the tumor was suspected of being an adrenal carcinoma based on its appearance on CT scans and showed extensive degeneration: fibrosis, hemorrhage, loss of parenchyma and moderate atypism of the tumor cells. However, as the architecture of the tumor cells was non-diffuse and there were no necrotic foci or mitoses, and vascular or capsular invasion were not present, the tumor was concluded to be an adrenocortical adenoma rather than a carcinoma. We diagnosed the tumor as a non-functional adrenocortical adenoma with extensive degeneration as the extensive areas of fibrosis were particularly remarkable. Furthermore, the extensive areas of degeneration might have been caused not only by an ischemic effect but also by low hormone levels. PMID:12675769

Masugi, Youhei; Kameyama, Kaori; Aiba, Motohiko; Mukai, Makio; Hara, Satoshi; Ohigashi, Takashi; Murai, Masaru

2003-04-01

234

Exact nonlinear excitations in double-degenerate plasmas  

SciTech Connect

In this work, we use the conventional hydrodynamics formalism and incorporate the Chew-Goldberger-Low double-adiabatic theory to evaluate the nonlinear electrostatic ion excitations in double-degenerate (electron spin-orbit degenerate) magnetized quantum plasmas. Based on the Sagdeev pseudopotential method, an exact general pseudopotential is calculated which leads to the allowed Mach-number range criteria for such localized density structures in an anisotropic magnetized plasma. We employ the criteria on the Mach-number range for diverse magnetized quantum plasma with different equations of state. It is remarked that various plasma fractional parameters such as the system dimensionality, ion-temperature, relativistic-degeneracy, Zeeman-energy, and plasma composition are involved in the stability of an obliquely propagating nonlinear ion-acoustic wave in a double-degenerate quantum plasma. Current study is most appropriate for nonlinear wave analysis in dense astrophysical magnetized plasma environments such as white-dwarfs and neutron-star crusts where the strong magnetic fields can be present.

Akbari-Moghanjoughi, M. [Department of Physics, Faculty of Sciences, Azarbaijan University of Tarbiat Moallem, 51745-406 Tabriz (Iran, Islamic Republic of)

2012-06-15

235

Accretion of gas and comets onto a nearby degenerate star  

NASA Astrophysics Data System (ADS)

Conditions under which accretion onto a nearby degenerate star, i.e., a white dwarf (WD) or neutron star (NS), could produce a sufficient flux of high-energy radiation to threaten the Earth's protective ozone layer are investigated. Both the case of a field star making a brief encounter with the Solar System and that of a degenerate solar companion ("Nemesis") are considered. For steady accretion from the interstellar medium (ISM), no significant flux is expected from a WD or a low-mass NS. A 1 M_sun; NS could deplete the ozone layer but only if either its closest approach is on the order of 1000 AU or the local ISM density is somewhat higher than average. A field star has a probability of about 2% of making such a close encounter over the lifetime of the Solar System. In the Nemesis case, an ellipticity of 0.99 is implied for a canonical period of 26 myr. In both cases, accretion of comets from the Oort cloud could result in ?-ray bursts, whose fluence could reach a significant level if the star came near the inner edge of the comet cloud. A degenerate Nemesis, if now at the aphelion of its proposed orbit, could be potentially observable as an X-ray or ?-ray source.

Pineault, S.

1987-04-01

236

Electrostatic rogue-waves in relativistically degenerate plasmas  

NASA Astrophysics Data System (ADS)

In this paper, we investigate the modulational instability and the possibility of electrostatic rogue-wave propagations in a completely degenerate plasma with arbitrary degree of degeneracy, i.e., relativistically degenerate plasma, ranging from solid density to the astrophysical compact stars. The hydrodynamic approach along with the perturbation method is used to reduce the governing equations to the nonlinear Schrödinger equation from which the modulational instability, the growth rate of envelope excitations and the occurrence of rogue as well as super-rogue waves in the plasma, is evaluated. It is observed that the modulational instability in a fully degenerate plasma can be quite sensitive to the plasma number-density and the wavenumber of envelop excitations. It is further revealed that the relativistically degeneracy plasmas (R0 > 1) are almost always modulationally unstable. It is found, however, that the highly energetic sharply localized electrostatic rogue as well as super-rogue waves can exist in the astrophysical compact objects like white dwarfs and neutron star crusts. The later may provide a link to understand many physical processes in such stars and it may lead us to the origin of the random-localized intense short gamma-ray bursts, which "appear from nowhere and disappear without a trace" quite similar to oceanic rogue structures.

Akbari-Moghanjoughi, M.

2014-10-01

237

Membrane-shaping disorders: a common pathway in axon degeneration.  

PubMed

Neurons with long projections are particularly liable to damage, which is reflected by a large group of hereditary neurodegenerative disorders that primarily affect these neurons. In the group of hereditary spastic paraplegias motor axons of the central nervous system degenerate, while distal pure motor neuropathies, Charcot-Marie-Tooth disorders and the group of hereditary sensory and autonomic neuropathies are characterized by degeneration of peripheral nerve fibres. Because the underlying pathologies share many parallels, the disorders are also referred to as axonopathies. A large number of genes has been associated with axonopathies and one of the emerging subgroups encodes membrane-shaping proteins with a central reticulon homology domain. Association of these proteins with lipid bilayers induces positive membrane curvature and influences the architecture of cellular organelles. Membrane-shaping proteins closely cooperate and directly interact with each other, but their structural features and localization to distinct subdomains of organelles suggests mutually exclusive roles. In some individuals a mutation in a shaping protein can result in upper motor neuron dysfunction, whereas in other patients it can lead to a degeneration of peripheral neurons. This suggests that membrane-shaping disorders might be considered as a continuous disease-spectrum of the axon. PMID:25281866

Hübner, Christian A; Kurth, Ingo

2014-12-01

238

Neuroproteomics Approaches to Decipher Neuronal Regeneration and Degeneration*  

PubMed Central

Given the complexity of brain and nerve tissues, systematic approaches are essential to understand normal physiological conditions and functional alterations in neurological diseases. Mass spectrometry-based proteomics is increasingly used in neurosciences to determine both basic and clinical differential protein expression, protein-protein interactions, and post-translational modifications. Proteomics approaches are especially useful to understand the mechanisms of nerve regeneration and degeneration because changes in axons following injury or in disease states often occur without the contribution of transcriptional events in the cell body. Indeed, the current understanding of axonal function in health and disease emphasizes the role of proteolysis, local axonal protein synthesis, and a broad range of post-translational modifications. Deciphering how axons regenerate and degenerate has thus become a postgenomics problem, which depends in part on proteomics approaches. This review focuses on recent proteomics approaches designed to uncover the mechanisms and molecules involved in neuronal regeneration and degeneration. It emerges that the principal degenerative mechanisms converge to oxidative stress, dysfunctions of axonal transport, mitochondria, chaperones, and the ubiquitin-proteasome systems. The mechanisms regulating nerve regeneration also impinge on axonal transport, cytoskeleton, and chaperones in addition to changes in signaling pathways. We also discuss the major challenges to proteomics work in the nervous system given the complex organization of the brain and nerve tissue at the anatomical, cellular, and subcellular levels. PMID:20019051

Sun, Faneng; Cavalli, Valeria

2010-01-01

239

Pattern of Sertoli cell degeneration in cryptorchid prepubertal testes.  

PubMed

Seventy-three testicular biopsies from 54 children (aged 2 months-14 years) with undescended testes were examined by light and electron microscopy. The biopsies included abdominal, inguinally fixed, inguinally moveable, and retractile testes. Alterations in Sertoli cell morphology were found in all biopsies. The alterations included dilated elements of rough endoplasmic reticulum, vacuolization of the cytoplasm, mitochondria with poorly preserved cristae, increase in electron density of the matrix, elongation of the nuclei, and irregularities of the nuclear membrane. According to the numerical appearance of these cells and to the extent of lesions in single Sertoli cells, seven phases in the continuous process of tubular alteration were distinguished. The most severe tubular damaged (phase VII) occurred when the seminiferous epithelium consisted exclusively of necrotic cells. All phases of tubular alterations were seen regularly in each of the biopsies investigated. Germ cells occurred only in phases I-IV and were never observed in tubules in phases V-VII. Significant differences became evident between inguinal and retractile testes by morphometric evaluation. It was demonstrated that the number of germ cells per cross-sectioned tubule (S/T value) correlated negatively with the percentage of tubules in phases V-VII. In contrast to inguinal testes, a complete absence of Sertoli cells and an S/T value less than 0.1 were never found in retractile testes and the percentage of tubules in phases V-VII was reduced significantly compared with inguinal testes. Our findings indicate that (i) maldescended testis in patients between 1 and 15 years-of-age is associated with a special pattern of Sertoli cell degeneration; (ii) Sertoli cell degeneration is a continuous process, which can lead eventually to complete dissolution of the seminiferous epithelium; (iii) total degeneration is not related to age but is dependent on testicular position; (iv) a defined phase of degeneration excludes germ cell development, and therefore enhanced Sertoli cell degeneration in cryptorchid testes must also account for the reduction in germ cell number. PMID:1347512

Rune, G M; Mayr, J; Neugebauer, H; Anders, C; Sauer, H

1992-02-01

240

Retinal degeneration increases susceptibility to myopia in mice  

PubMed Central

Purpose Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Methods Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6brd1/rd1 (rd1), or Pde6brd10/rd10 (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. Results The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (?6.14±0.62 and ?7.38±1.46 diopter, respectively) compared to the WT mice (?2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Conclusions Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge. PMID:24146540

Park, Hanna; Tan, Christopher C.; Faulkner, Amanda; Jabbar, Seema B.; Schmid, Gregor; Abey, Jane; Iuvone, P. Michael

2013-01-01

241

Surface Waves in Anisotropic Elastic Materials for Which the Matrix N(v) is Extraordinary Degenerate, Degenerate, or Semisimple  

Microsoft Academic Search

The 6 × 6 real matrix N(v) for anisotropic elastic materials under a two-dimensional steady-state motion with speed v is extraordinary degenerate when N(v) has three identical complex eigenvalues p but has only one associated eigenvector. It has been an open question if such an N(v) exists for surface waves. In this paper we first modify the solution for ordinary

T. C. T. Ting

1997-01-01

242

Combined effects of light and water availability on photosynthesis and growth of Arisaema heterophyllum in the forest understory and an open site  

Microsoft Academic Search

Photosynthetic characteristics, leaf longevity and biomass accumulation of a threatened herb species, Arisaema heterophyllum, were studied in the understory of a riparian forest and at a neighboring deforested open site for 3 years in order to understand\\u000a the combined effects of light and water availability. Light availability was 2- to 4-fold higher at the deforested than at\\u000a the forest site

H. Muraoka; Y. Tang; H. Koizumi; I. Washitani

1997-01-01

243

Multicystic cerebral degeneration in neonatal herpes simplex virus encephalitis.  

PubMed

Typical herpetic papulovesicular skin lesions developed in an apparently normal infant at 12 days of age and were followed within 48 hours by signs and symptoms of acute encephalitis. Herpes simplex virus type 2 was cultured from the intact skin vesicles, and a fourfold increase in complement fixation titer to herpes simplex virus type 2 was found over the ensuing 24 days. The infant survived her acute illness, but was left with severe neurologic sequelae manifested as microcephaly with multicystic cerebral degeneration. The short-term and convalescent course is documented by serial, clinical, and EEG examinations, and the nature of the cerebral damage is demonstrated by computerized transaxial tomography. PMID:193394

Smith, J B; Groover, R V; Klass, D W; Houser, O W

1977-05-01

244

Construction of Gaiotto states with fundamental multiplets through Degenerate DAHA  

E-print Network

We construct Gaiotto states with fundamental multiplets in $SU(N)$ gauge theories, in terms of the orthonormal basis of spherical degenerate double affine Hecke algebra (SH in short), the representations of which are equivalent to those of $W_n$ algebra with additional $U(1)$ current. The generalized Whittaker conditions are demonstrated under the action of SH, and further rewritten in terms of $W_n$ algebra. Our approach not only consists with the existing literature but also holds for general $SU(N)$ case.

Yutaka Matsuo; Chaiho Rim; Hong Zhang

2014-05-13

245

Construction of Gaiotto states with fundamental multiplets through Degenerate DAHA  

E-print Network

We construct Gaiotto states with fundamental multiplets in $SU(N)$ gauge theories, in terms of the orthonormal basis of spherical degenerate double affine Hecke algebra (SH in short), the representations of which are equivalent to those of $W_n$ algebra with additional $U(1)$ current. The generalized Whittaker conditions are demonstrated under the action of SH, and further rewritten in terms of $W_n$ algebra. Our approach not only consists with the existing literature but also holds for general $SU(N)$ case.

Matsuo, Yutaka; Zhang, Hong

2014-01-01

246

Genetic and Epigenetic Regulation in Age-related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the older population worldwide. While strong genetic risk factors have been associated with AMD etiology, environmental influences through epigenetic regulation are also likely to play a role. Recent advances in epigenetic studies have resulted in the development of numerous epigenetic drugs for the treatment of cancer and inflammation. Here, we review the current literature on the genetic and epigenetic mechanisms of AMD and suggest that understanding the cooperation of epigenetic and genetic mechanisms will greatly advance the clinical management of AMD. PMID:23997991

Wei, Lai; Chen, Ping; Lee, Joo Hyun; Nussenblatt, Robert B.

2013-01-01

247

Hydrodynamics in a Degenerate, Strongly Attractive Fermi Gas  

NASA Technical Reports Server (NTRS)

In summary, we use all-optical methods with evaporative cooling near a Feshbach resonance to produce a strongly interacting degenerate Fermi gas. We observe hydrodynamic behavior in the expansion dynamics. At low temperatures, collisions may not explain the expansion dynamics. We observe hydrodynamics in the trapped gas. Our observations include collisionally-damped excitation spectra at high temperature which were not discussed above. In addition, we observe weakly damped breathing modes at low temperature. The observed temperature dependence of the damping time and hydrodynamic frequency are not consistent with collisional dynamics nor with collisionless mean field interactions. These observations constitute the first evidence for superfluid hydrodynamics in a Fermi gas.

Thomas, John E.; Kinast, Joseph; Hemmer, Staci; Turlapov, Andrey; O'Hara, Ken; Gehm, Mike; Granade, Stephen

2004-01-01

248

Coupling and degenerating modes in longitudinal-torsional step horns.  

PubMed

Longitudinal-torsional vibration is used and proposed for a variety of ultrasonic applications including motors, welding, and rock-cutting. To obtain this behavior in an ultrasonic step horn one can either, (i) couple the longitudinal and torsional modes of the horn by incorporating a ring of diagonal slits in the thick base section or, (ii) place helical flutes in the thin stem section to degenerate the longitudinal mode into a modified behavior with a longitudinal-torsional motion. This paper compares the efficacy of these two design approaches using both numerical and experimental techniques. PMID:22770885

Harkness, Patrick; Lucas, Margaret; Cardoni, Andrea

2012-12-01

249

Peptide and steroid regulation of muscle degeneration in an insect.  

PubMed

Two types of cell death occur in the intersegmental muscles of the giant silkmoth Antheraea polyphemus. The first results from a slow atrophy of the fibers, and the second is a rapid, programmed dissolution of the muscle. Both types appear to be mediated by endocrine factors. The slow atrophy is brought about by the decline in the steroid molting hormone 20-hydroxyecdysone and can be prevented with exogenous steroid. The rapid degeneration is triggered by the peptide eclosion hormone, but the sensitivity of the muscle to the peptide depends on the history of exposure of the muscle to 20-hydroxyecdysone. PMID:6278594

Schwartz, L M; Truman, J W

1982-03-12

250

Complete population transfer in a degenerate 3-level atom  

E-print Network

We find conditions required to achieve complete population transfer, via coherent population trapping, from an initial state to a designated final state at a designated time in a degenerate 3-level atom, where transitions are caused by an external interaction. Complete population transfer from an initially occupied state 1 to a designated state 2 occurs under two conditions. First, there is a constraint on the ratios of the transition matrix elements of the external interaction. Second, there is a constraint on the action integral over the interaction, or "area", corresponding to the phase shift induced by the external interaction. Both conditions may be expressed in terms of simple odd integers.

Kh. Yu. Rakhimov; J. H. McGuire; Kh. Kh. Shakov

2003-06-23

251

Engineering mixed states in a degenerate four-state system.  

PubMed

A method is proposed for preparing any pure and wide class of mixed quantum states in the decoherence-free ground-state subspace of a degenerate multilevel lambda system. The scheme is a combination of optical pumping and a series of coherent excitation processes, and for a given pulse sequence the same final state is obtained regardless of the initial state of the system. The method is robust with respect to the fluctuation of the pulse areas, as in adiabatic methods; however, the field amplitude can be adjusted in a larger range. PMID:15600831

Karpati, A; Kis, Z; Adam, P

2004-11-01

252

Present and Possible Therapies for Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment options for this condition remain substantially limited. In this review, we outline the existing arsenal of therapies available for AMD and discuss the additional role of further novel therapies currently under investigation for this debilitating disease. PMID:25097787

Kamal, Ahmed

2014-01-01

253

Experimental position-time entanglement with degenerate single photons  

SciTech Connect

We report an experiment in which two-photon interference occurs between degenerate single photons that never meet. The two photons travel in opposite directions through our fiber-optic interferometer and interference occurs when the photons reach two different, spatially separated, two-by-two couplers at the same time. We show that this experiment is analogous to the conventional Franson-type entanglement experiment where the photons are entangled in position and time. We measure wave-function overlaps for the two photons as high as 94{+-}3%.

Bennett, A. J.; Gevaux, D. G.; Yuan, Z. L.; Shields, A. J.; Atkinson, P.; Ritchie, D. A. [Toshiba Research Europe Limited, Cambridge Research Laboratory, 208 Science Park, Milton Road, Cambridge, CB4 0GZ (United Kingdom); Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge, CB3 0HE (United Kingdom)

2008-02-15

254

Suppression of density fluctuations in a quantum degenerate Fermi gas.  

PubMed

We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations (atom shot noise) for cold clouds deep in the quantum degenerate regime. Strong suppression is observed for probe volumes containing more than 10?000 atoms. Measuring the level of suppression provides sensitive thermometry at low temperatures. After this method of sensitive noise measurements has been validated with an ideal Fermi gas, it can now be applied to characterize phase transitions in strongly correlated many-body systems. PMID:20867822

Sanner, Christian; Su, Edward J; Keshet, Aviv; Gommers, Ralf; Shin, Yong-Il; Huang, Wujie; Ketterle, Wolfgang

2010-07-23

255

Degenerate quantum codes and the quantum Hamming bound  

SciTech Connect

The parameters of a nondegenerate quantum code must obey the Hamming bound. An important open problem in quantum coding theory is whether the parameters of a degenerate quantum code can violate this bound for nondegenerate quantum codes. In this article we show that Calderbank-Shor-Steane (CSS) codes, over a prime power alphabet q{>=}5, cannot beat the quantum Hamming bound. We prove a quantum version of the Griesmer bound for the CSS codes, which allows us to strengthen the Rains' bound that an [[n,k,d

Sarvepalli, Pradeep [Department of Physics and Astronomy, University of British Columbia, Vancouver V6T 1Z1 (Canada); Klappenecker, Andreas [Department of Computer Science, Texas A and M University, College Station, Texas 77843 (United States)

2010-03-15

256

Aetiology of spheroidal degeneration of the cornea in Labrador.  

PubMed Central

To determine the aetiology of spheroidal degeneration of the cornea (Labrador keratopathy), total population surveys were conducted in 5 communities in coastal Labrador and northern Newfoundland. For 4 years records were also kept on all clinic patients aged 40 or more throughout the region. Both methods gave a peak prevalence at latitudes 55 degrees--56 degrees north. The greatest severity and earliest age of onset occurred around the same latitudes. Of the proposed environmental causative agents only ultraviolet radiation, reflected from ice and snow, explains the distribution of the disease. The high cumulative UV dosage is due to the unique geographical and climatic features of the region. Images PMID:7236572

Johnson, G J

1981-01-01

257

Chemically reacting mixtures in terms of degenerated parabolic setting  

NASA Astrophysics Data System (ADS)

The paper analyzes basic mathematical questions for a model of chemically reacting mixtures. We derive a model of several (finite) component compressible gas taking rigorously into account the thermodynamical regime. Mathematical description of the model leads to a degenerate parabolic equation with hyperbolic deviation. The thermodynamics implies that the diffusion terms are non-symmetric, not positively defined, and cross-diffusion effects must be strongly marked. The mathematical goal is to establish the existence of weak solutions globally in time for arbitrary number of reacting species. A key point is an entropy-like estimate showing possible renormalization of the system.

Mucha, P. B.; Pokorný, M.; Zatorska, E.

2013-07-01

258

Subacute combined degeneration mimicking traumatic spinal cord injury.  

PubMed

Subacute combined degeneration (SCD) of the spinal cord is the most common neurologic manifestation of vitamin B12 (cobalamin) deficiency and is usually secondary to autoimmune gastritis, but may also be seen in malnutrition syndromes such as chronic alcoholism, strict vegetarianism, gastrectomy, and also in nitrous oxide abuse. Although traumatic spinal cord injury is routinely encountered in the medical examiner's office, medical causes of spinal cord abnormalities such as SCD should be considered in the appropriate clinical setting. We report a case of alcohol-associated SCD mimicking traumatic spinal cord injury. PMID:19237854

Paul, Ian; Reichard, R Ross

2009-03-01

259

Quantum Simulation using Next Generation Degenerate Fermi Gas Apparatus  

NASA Astrophysics Data System (ADS)

Ultracold neutral atoms in optical lattices are a perfect toy model to simulate and study Hubbard model physics relevant to high temperature superconductivity and other exotic phases of matter. We present the design and construction of a novel apparatus to study these exciting condensed matter systems. We also investigate the viability of a various transport schemes to transport a quantum-degenerate Fermi gas of ultracold lithium atoms into a Science Chamber. The high optical access of the science chamber permits innovative probing and manipulation of BECs.

Wooley-Brown, Kate; Huber, Florian; Setiawan, Widagdo; Greiner, Markus

2010-03-01

260

Regulation of axon degeneration after injury and in development by the endogenous calpain inhibitor calpastatin.  

PubMed

Axon degeneration is widespread both in neurodegenerative disease and in normal neural development, but the molecular pathways regulating these degenerative processes and the extent to which they are distinct or overlapping remain incompletely understood. We report that calpastatin, an inhibitor of calcium-activated proteases of the calpain family, functions as a key endogenous regulator of axon degeneration. Calpastatin depletion was observed in degenerating axons after physical injury, and maintaining calpastatin inhibited degeneration of transected axons in vitro and in the optic nerve in vivo. Calpastatin depletion also occurred in a caspase-dependent manner in trophic factor-deprived sensory axons and was required for this in vitro model of developmental degeneration. In vivo, calpastatin regulated the normal pruning of retinal ganglion cell axons in their target field. These findings identify calpastatin as a key checkpoint for axonal survival after injury and during development, and demonstrate downstream convergence of these distinct pathways of axon degeneration. PMID:24210906

Yang, Jing; Weimer, Robby M; Kallop, Dara; Olsen, Olav; Wu, Zhuhao; Renier, Nicolas; Uryu, Kunihiro; Tessier-Lavigne, Marc

2013-12-01

261

On deformations of one-dimensional Poisson structures of hydrodynamic type with degenerate metric  

E-print Network

We provide a complete list of two- and three-component Poisson structures of hydrodynamic type with degenerate metric, and study their homogeneous deformations. In the non-degenerate case any such deformation is trivial, that is, can be obtained via infinitesimal Miura transformation. We demonstrate that in the degenerate case this class of deformations is non-trivial, and depends on a certain number of arbitrary functions. In particular, this shows that the second cohomology group does not vanish.

Andrea Savoldi

2014-10-13

262

Cost-effectiveness of smoking cessation to prevent age-related macular degeneration  

Microsoft Academic Search

BACKGROUND: Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk. METHODS: We fitted a function predicting the decline in risk of macular degeneration after quitting to data from 7 studies involving 1,488 patients. We assessed the cost-effectiveness of smoking cessation in terms of its impact on macular degeneration-related outcomes

Susan F Hurley; Jane P Matthews; Robyn H Guymer

2008-01-01

263

Bax-Induced Apoptosis in Leber's Congenital Amaurosis: A Dual Role in Rod and Cone Degeneration  

Microsoft Academic Search

Pathogenesis in the Rpe65?\\/? mouse model of Leber's congenital amaurosis (LCA) is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65?\\/? mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65), was previously reported to depend on continuous activation

Séverine Hamann; Daniel F. Schorderet; Sandra Cottet; Dong-Yan Jin

2009-01-01

264

Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration  

Microsoft Academic Search

Fluoro-Jade B, like its predecessor Fluoro-Jade, is an anionic fluorescein derivative useful for the histological staining of neurons undergoing degeneration. However, Fluoro-Jade B has an even greater specific affinity for degenerating neurons. This notion is supported by the conspicuous staining of degenerating neuronal elements with minimal background staining. This improved signal-to-noise ratio means that fine neuronal processes including distal dendrites,

Larry C Schmued; Keri J Hopkins

2000-01-01

265

Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration  

PubMed Central

Intervertebral disc (IVD) degeneration is frequent, appearing from the second decade of life and progressing with age. Conservative management often fails, and patients with IVD degeneration may need surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. Biological strategies aim to prevent and manage IVD degeneration, improving the function and anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells and inhibiting matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration. PMID:25098367

Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

266

Resveratrol delays Wallerian degeneration in a NAD(+) and DBC1 dependent manner.  

PubMed

Axonal degeneration is a central process in the pathogenesis of several neurodegenerative diseases. Understanding the molecular mechanisms that are involved in axonal degeneration is crucial to developing new therapies against diseases involving neuronal damage. Resveratrol is a putative SIRT1 activator that has been shown to delay neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Alzheimer, and Huntington's disease. However, the effect of resveratrol on axonal degeneration is still controversial. Using an in vitro model of Wallerian degeneration based on cultures of explants of the dorsal root ganglia (DRG), we showed that resveratrol produces a delay in axonal degeneration. Furthermore, the effect of resveratrol on Wallerian degeneration was lost when SIRT1 was pharmacologically inhibited. Interestingly, we found that knocking out Deleted in Breast Cancer-1 (DBC1), an endogenous SIRT1 inhibitor, restores the neuroprotective effect of resveratrol. However, resveratrol did not have an additive protective effect in DBC1 knockout-derived DRGs, suggesting that resveratrol and DBC1 are working through the same signaling pathway. We found biochemical evidence suggesting that resveratrol protects against Wallerian degeneration by promoting the dissociation of SIRT1 and DBC1 in cultured ganglia. Finally, we demonstrated that resveratrol can delay degeneration of crushed nerves in vivo. We propose that resveratrol protects against Wallerian degeneration by activating SIRT1 through dissociation from its inhibitor DBC1. PMID:24252177

Calliari, Aldo; Bobba, Natalia; Escande, Carlos; Chini, Eduardo N

2014-01-01

267

Coupled modes in magnetized dense plasma with relativistic-degenerate electrons  

SciTech Connect

Low frequency electrostatic and electromagnetic waves are investigated in ultra-dense quantum magnetoplasma with relativistic-degenerate electron and non-degenerate ion fluids. The dispersion relation is derived for mobile as well as immobile ions by employing hydrodynamic equations for such plasma under the influence of electromagnetic forces and pressure gradient of relativistic-degenerate Fermi gas of electrons. The result shows the coexistence of shear Alfven and ion modes with relativistically modified dispersive properties. The relevance of results to the dense degenerate plasmas of astrophysical origin (for instance, white dwarf stars) is pointed out with brief discussion on ultra-relativistic and non-relativistic limits.

Khan, S. A. [National Centre for Physics, Quaid-i-Azam University Campus, Islamabad 45320 (Pakistan)

2012-01-15

268

Retinal remodeling during retinal degeneration Bryan W. Jones, Robert E. Marc  

E-print Network

deafferentation of the neural retina eliminates the intrinsic glutamatergic drive of the sensory retina and central nervous system degenerations, deafferentation activates remodeling. Neuronal remodeling

Marc, Robert E.

269

Three dimensional electrostatic solitary waves in a dense magnetoplasma with relativistically degenerate electrons  

SciTech Connect

In this paper, small but finite amplitude electrostatic solitary waves in a relativistic degenerate magnetoplasma, consisting of relativistically degenerate electrons and non-degenerate cold ions, are investigated. The Zakharov-Kuznetsov equation is derived employing the reductive perturbation technique and its solitary wave solution is analyzed. It is shown that only compressive electrostatic solitary structures can propagate in such a degenerate plasma system. The effects of plasma number density, ion cyclotron frequency, and direction cosines on the profiles of ion acoustic solitary waves are investigated and discussed at length. The relevance of the present investigation vis-a-vis pulsating white dwarfs is also pointed out.

Ata-ur-Rahman,; Qamar, A. [Institute of Physics and Electronics, University of Peshawar, Peshawar 25000 (Pakistan) [Institute of Physics and Electronics, University of Peshawar, Peshawar 25000 (Pakistan); National Centre for Physics, QAU Campus, Shahdrah Valley Road, Islamabad 44000 (Pakistan); Masood, W. [National Centre for Physics, QAU Campus, Shahdrah Valley Road, Islamabad 44000 (Pakistan) [National Centre for Physics, QAU Campus, Shahdrah Valley Road, Islamabad 44000 (Pakistan); COMSATS, Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000 (Pakistan); Eliasson, B. [Physics Department, University of Strathclyde, Glasgow G4 0NG, Scotland (United Kingdom)] [Physics Department, University of Strathclyde, Glasgow G4 0NG, Scotland (United Kingdom)

2013-09-15

270

Emotional reactivity and emotion recognition in frontotemporal lobar degeneration  

PubMed Central

Background Frontotemporal lobar degeneration (FTLD) is associated with a profound decline in social and emotional behavior; however, current understanding regarding the specific aspects of emotional functioning that are preserved and disrupted is limited. Objective To assess preservation of function and deficits in two aspects of emotional processing (emotional reactivity and emotion recognition) in FTLD. Methods Twenty-eight FTLD patients were compared with 16 controls in emotional reactivity (self-reported emotional experience, emotional facial behavior, and autonomic nervous system response to film stimuli) and emotion recognition (ability to identify a target emotion of fear, happy, or sad experienced by film characters). Additionally, the neural correlates of emotional reactivity and emotion recognition were investigated. Results FTLD patients were comparable to controls in 1) emotional reactivity to the fear, happy, and sad film clips and 2) emotion recognition for the happy film clip. However, FTLD patients were significantly impaired compared with controls in emotion recognition for the fear and sad film clips. Volumetric analyses revealed that deficits in emotion recognition were associated with decreased lobar volumes in the frontal and temporal lobes. Conclusions The socioemotional decline typically seen in frontotemporal lobar degeneration patients may result more from an inability to process certain emotions in other people than from deficits in emotional reactivity. PMID:17620547

Werner, K.H.; Roberts, N.A.; Rosen, H.J.; Dean, D.L.; Kramer, J.H.; Weiner, M.W.; Miller, B.L.; Levenson, R.W.

2008-01-01

271

Symmetry of quantum phase space in a degenerate Hamiltonian system.  

PubMed

The structure of the global "quantum phase space" is analyzed for the harmonic oscillator perturbed by a monochromatic wave in the limit when the perturbation amplitude is small. Usually, the phenomenon of quantum resonance was studied in nondegenerate [G. M. Zaslavsky, Chaos in Dynamic Systems (Harwood Academic, Chur, 1985)] and degenerate [Demikhovskii, Kamenev, and Luna-Acosta, Phys. Rev. E 52, 3351 (1995)] classically chaotic systems only in the particular regions of the classical phase space, such as the center of the resonance or near the separatrix. The system under consideration is degenerate, and even an infinitely small perturbation generates in the classical phase space an infinite number of the resonant cells which are arranged in the pattern with the axial symmetry of the order 2&mgr; (where &mgr; is the resonance number). We show analytically that the Husimi functions of all Floquet states (the quantum phase space) have the same symmetry as the classical phase space. This correspondence is demonstrated numerically for the Husimi functions of the Floquet states corresponding to the motion near the elliptic stable points (centers of the classical resonance cells). The derived results are valid in the resonance approximation when the perturbation amplitude is small enough, and the stochastic layers in the classical phase space are exponentially thin. The developed approach can be used for studying a global symmetry of more complicated quantum systems with chaotic behavior. (c) 2000 American Institute of Physics. PMID:12779416

Berman, G. P.; Demikhovskii, V. Ya.; Kamenev, D. I.

2000-09-01

272

Neuropsychological Decline in Frontotemporal Lobar Degeneration: A Longitudinal Analysis  

PubMed Central

Few studies have assessed whether the patterns of neuropsychological impairment in patients with different frontotemporal lobar degeneration (FTLD) subtypes remain distinct over the duration of their illness or devolve into a common, undifferentiated neuropsychological state. A longitudinal neuropsychological analysis was obtained over 100 months assessing executive control, language/naming, and visuoconstruction in 441 patients diagnosed with Alzheimer’s disease (AD) and four FTLD subtypes, i.e., a social comportment/dysexecutive (SOC/EXEC) disorder; progressive non-fluent aphasia (PNFA); semantic dementia (SemD); and corticobasal degeneration (CBD). Initial group differences on each measure were maintained over the duration of illness, including several double dissociations. For example, AD patients exhibited a decline in ‘animal’ fluency; PNFA patients had difficulty on tests of executive control, SemD maintained their impairment on tests of naming, and CBD had presented with performance on visuoconstructional tests. None of the group by neuropsychological task interactions evaluating longitudinal decline was significant, suggesting that performance does not converge onto a common subtype over time. These data indicate that distinct patterns of neuropsychological impairment are maintained longitudinally, reflecting the unique anatomic distribution of relative disease burden in AD and FTLD. PMID:19413447

Libon, David J.; Xie, Sharon X.; Wang, Xingmei; Massimo, Lauren; Moore, Peachie; Vesely, Luisa; Khan, Alea; Chatterjee, Anjan; Coslett, H. Branch; Hurtig, Howard I.; Grossman, Murray; Liang, Tsao-Wei

2009-01-01

273

Perpendicular propagating modes for weakly magnetized relativistic degenerate plasma  

SciTech Connect

Using the Vlasov-Maxwell system of equations, the dispersion relations for the perpendicular propagating modes (i.e., X-mode, O-mode, and upper hybrid mode) are derived for a weakly magnetized relativistic degenerate electron plasma. By using the density (n{sub 0}=p{sub F}{sup 3}/3{pi}{sup 2} Planck-Constant-Over-Two-Pi {sup 3}) and the magnetic field values for different relativistic degenerate environments, the propagation characteristics (i.e., cutoff points, resonances, dispersions, and band widths in k-space) of these modes are examined. It is observed that the relativistic effects suppress the effect of ambient magnetic field and therefore the cutoff and resonance points shift towards the lower frequency regime resulting in enhancement of the propagation domain. The dispersion relations of these modes for the non-relativistic limit (p{sub F}{sup 2} Much-Less-Than m{sub 0}{sup 2}c{sup 2}) and the ultra-relativistic limit (p{sub F}{sup 2} Much-Greater-Than m{sub 0}{sup 2}c{sup 2}) are also presented.

Abbas, Gohar; Bashir, M. F. [Salam Chair in Physics, G. C. University Lahore, Punjab 54000 (Pakistan); Department of Physics, G. C. University Lahore, Punjab 54000 (Pakistan); Murtaza, G. [Salam Chair in Physics, G. C. University Lahore, Punjab 54000 (Pakistan)

2012-07-15

274

The brain basis of musicophilia: evidence from frontotemporal lobar degeneration  

PubMed Central

Musicophilia, or abnormal craving for music, is a poorly understood phenomenon that has been associated in particular with focal degeneration of the temporal lobes. Here we addressed the brain basis of musicophilia using voxel-based morphometry (VBM) on MR volumetric brain images in a retrospectively ascertained cohort of patients meeting clinical consensus criteria for frontotemporal lobar degeneration: of 37 cases ascertained, 12 had musicophilia, and 25 did not exhibit the phenomenon. The syndrome of semantic dementia was relatively over-represented among the musicophilic subgroup. A VBM analysis revealed significantly increased regional gray matter volume in left posterior hippocampus in the musicophilic subgroup relative to the non-musicophilic group (p < 0.05 corrected for regional comparisons); at a relaxed significance threshold (p < 0.001 uncorrected across the brain volume) musicophilia was associated with additional relative sparing of regional gray matter in other temporal lobe and prefrontal areas and atrophy of gray matter in posterior parietal and orbitofrontal areas. The present findings suggest a candidate brain substrate for musicophilia as a signature of distributed network damage that may reflect a shift of hedonic processing toward more abstract (non-social) stimuli, with some specificity for particular neurodegenerative pathologies. PMID:23801975

Fletcher, Phillip D.; Downey, Laura E.; Witoonpanich, Pirada; Warren, Jason D.

2013-01-01

275

Testing the single degenerate channel for supernova Ia  

NASA Astrophysics Data System (ADS)

The progenitors of supernova Ia are close binaries containing white dwarfs. Of crucial importance to the evolution of these systems is how much material the white dwarf can stably accrete and hence grow in mass. This occurs during a short-lived intense phase of mass transfer known as the super soft source (SSS) phase. The short duration of this phase and large extinction to soft X-rays means that only a handful are known in our Galaxy. Far more can be learned from the underlying SSS progenitor population of close white dwarf plus FGK type binaries. Unfortunately, these systems are hard to find since the main-sequence stars completely outshine the white dwarfs at optical wavelengths. Because of this, there are currently no known close white dwarf binaries with F, G or early K type companions, making it impossible to determine the contribution of the single degenerate channel towards supernova Ia. Using the GALEX and RAVE surveys we have now identified the first large sample of FGK stars with UV excesses, a fraction of which are these illusive, close systems. Following an intense ground based spectroscopic investigation of these systems, we have identified 5 definite close binaries, with periods of less than a few days. Here we apply for COS spectroscopic observations to measure the mass and temperature of the white dwarfs in order to determine the future evolution of these systems. This will provide a crucial test for the single degenerate channel towards supernova Ia.

Parsons, Steven

2014-10-01

276

Ablation of the X-Linked Retinitis Pigmentosa 2 (Rp2) Gene in Mice Results in Opsin Mislocalization and Photoreceptor Degeneration  

PubMed Central

Purpose. Mutations in the RP2 gene are associated with 10% to 15% of X-linked retinitis pigmentosa (XLRP), a debilitating disorder characterized by the degeneration of retinal rod and cone photoreceptors. The molecular mechanism of pathogenesis of photoreceptor degeneration in XLRP-RP2 has not been elucidated, and no treatment is currently available. This study was undertaken to investigate the pathogenesis of RP2-associated retinal degeneration. Methods. We introduced loxP sites that flank exon 2, a mutational hotspot in XLRP-RP2, in the mouse Rp2 gene. We then produced Rp2-null allele using transgenic mice that expressed Cre-recombinase under control of the ubiquitous CAG promoter. Electroretinography (ERG), histology, light microscopy, transmission electron microscopy, and immunofluorescence microscopy were performed to ascertain the effect of ablation of Rp2 on photoreceptor development, function, and protein trafficking. Results. Although no gross abnormalities were detected in the Rp2null mice, photopic (cone) and scotopic (rod) function as measured by ERG showed a gradual decline starting as early as 1 month of age. We also detected slow progressive degeneration of the photoreceptor membrane discs in the mutant retina. These defects were associated with mislocalization of cone opsins to the nuclear and synaptic layers and reduced rhodopsin content in the outer segment of mutant retina prior to the onset of photoreceptor degeneration. Conclusions. Our studies suggest that RP2 contributes to the maintenance of photoreceptor function and that cone opsin mislocalization represents an early step in XLRP caused by RP2 mutations. The Rp2null mice should serve as a useful preclinical model for testing gene- and cell-based therapies. PMID:23745007

Li, Linjing; Khan, Naheed; Hurd, Toby; Ghosh, Amiya Kumar; Cheng, Christiana; Molday, Robert; Heckenlively, John R.; Swaroop, Anand; Khanna, Hemant

2013-01-01

277

Growth of injured rabbit optic axons within their degenerating optic nerve  

SciTech Connect

Spontaneous growth of axons after injury is extremely limited in the mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can be induced to elongate when provided with a suitable environment. Thus injured CNS axons can elongate, but they do not do so unless their environment is altered. We now show apparent regenerative growth of injured optic axons. This growth is achieved in the adult rabbit optic nerve by the use of a combined treatment consisting of: (1) supplying soluble substances originating from growing axons to be injured rabbit optic nerves, and (2) application of low energy He-Ne laser irradiation, which appears to delay degenerative changes in the injured axons. Two to 8 weeks after this treatment, unmyelinated and thinly myelinated axons are found at the lesion site and distal to it. Morphological and immunocytochemical evidence indicate that these thinly myelinated and unmyelinated axons are growing in close association with glial cells. Only these axons are identified as being growing axons. These newly growing axons transverse the site of injury and extend into the distal stump of the nerve, which contains degenerating axons. Axons of this type could be detected distal to the lesion only in nerves subjected to the combined treatment. No unmyelinated or thinly myelinated axons in association with glial cells were seen at 6 or 8 weeks postoperatively in nerves that were not treated, or in nerves in which the two stumps were completely disconnected. Two millimeters distal to the site of injury, the growing axons are confined to a compartment comprising 5%-30% of the cross section of the nerve. A temporal analysis indicates that axons have grown as far as 6 mm distal to the site of injury, by 8 weeks postoperatively.

Lavie, V.; Murray, M.; Solomon, A.; Ben-Bassat, S.; Belkin, M.; Rumelt, S.; Schwartz, M. (Weizmann Institute of Science, Rehovot (Israel))

1990-08-15

278

The impact of germanium in strained Si/relaxed Si1-xGex on carrier performance in non-degenerate and degenerate regimes  

NASA Astrophysics Data System (ADS)

The impact of the fraction of germanium on the carrier performance of two-dimensional strained silicon, which embraces both the non-degenerate and degenerate regimes, is developed. In this model, the Fermi integral of order zero is employed. The impact of the fraction of germanium on the relaxed Si1-xGex substrate (x), carrier concentration and temperature is reported. It is revealed that the effect of x on the hole concentration is dominant for a normalized Fermi energy of more than three, or in other words the non-degenerate regime. On the contrary, the x gradient has less influence in the degenerate regime. Furthermore, by increasing x there is an increase in the intrinsic velocity, particularly with high carrier concentration and temperature.

Kang, EngSiew; Anwar, S.; Ahmadi, M. T.; Ismail, Razali

2013-06-01

279

Degenerate Primer Design: Theoretical Analysis and the HYDEN program1 Non-standard  

E-print Network

Chapter 1 Degenerate Primer Design: Theoretical Analysis and the HYDEN program1 Non-standard format chapter Chaim Linhart and Ron Shamir Abstract A PCR primer sequence is called degenerate if some of its positions have several possible bases. The degeneracy of the primer is the number of unique sequence

Shamir, Ron

280

A Nonlinear Master Equation for a Degenerate Diffusion Model of Biofilm Growth  

E-print Network

A Nonlinear Master Equation for a Degenerate Diffusion Model of Biofilm Growth Hassan Khassehkhan1@math.ualberta.ca Abstract. We present a continuous time/discrete space model of biofilm growth, starting from the semi models of biofilms. Grid refinement leads formally to a degenerate parabolic equation. We show that a set

Hillen, Thomas

281

Ultrastructure of degenerating cerebellothalamic terminals in the ventral medial nucleus of the cat  

Microsoft Academic Search

Terminal degeneration of cerebellar afferents in the ventral medial thalamic nucleus (VM) was studied in cats at the ultrastructural level after uni- or bilateral lesions in the brachium conjunctivum (BC). To achieve discrete lesions within the BC, a new very accurate stereotaxic technique was used. Numerous large terminals belonging to a population of so-called LR boutons were observed degenerating in

K. Kultas-Ilinsky; I. A. Ilinsky; P. A. Young; K. R. Smith

1980-01-01

282

Degenerate Correlation and Information Energy of Interval-Valued Fuzzy Numbers  

Microsoft Academic Search

This paper considers the degenerate cases of the correlation and information energy in the interval-valued fuzzy numbers, proposed by Wang and Li (8). Later, Hong (5) provided four counterexamples to the necessity parts of the theorems in Wang and Li (8) concerning the degenerate cases of correlation and information energy. In this paper, we generalize the counterexamples and present the

Chi-Chi Chen; Hui-Chin Tang

2008-01-01

283

Effect of intervertebral disk degeneration on spinal stenosis during magnetic resonance imaging with axial loading.  

PubMed

Magnetic resonance (MR) imaging with axial loading can simulate the physiological standing state and disclose spinal stenosis undetected or underestimated in the conventional position. Intervertebral disk degeneration may be an important factor in spinal stenosis. This study investigated whether intervertebral disk degeneration increases spinal stenosis during axial loading. MR imaging with and without axial loading was obtained in 51 patients with neurogenic intermittent claudication and/or sciatica and reviewed retrospectively. The grade of disk degeneration was rated in four disk spaces from L2-3 to L5-S1. The dural sac cross-sectional area (DCSA) was measured on MR images taken in both conventional and axial loading positions, and the change in the DCSA was calculated. The effect of disk degeneration on the DCSA was statistically analyzed. Significant decreases in the DCSA occurred with grade 4 disk degeneration (mean +/- standard deviation, 20.1 +/- 14.1 mm(2)), followed by grade 3 (18.3 +/- 15.1 mm(2)) and grade 2 (8.9 +/- 13.1 mm(2)). DCSA decreased considerably with increased severity of disk degeneration with axial loading, except for grade 5 disk degeneration. More accurate diagnosis of stenosis can be achieved using MR imaging with axial loading, especially if grade 2 to 4 disk degeneration is present. PMID:19556732

Ahn, Tae-Joon; Lee, Sang-Ho; Choi, Gun; Ahn, Yong; Liu, Wei Chiang; Kim, Ho-Jin; Lee, Ho-Yeon

2009-06-01

284

Dependency of disc degeneration on shear and tensile strains between annular fiber layers for complex loads  

Microsoft Academic Search

BackgroundOne of the first signs of disc degeneration is the formation of circumferential tears within the annulus fibrosus. It is assumed that high shear and tensile strains between the lamellae mainly cause the initiation of these failures. However, it is not known which load application and which degree of disc degeneration could lead to the highest strains and therefore, might

Hendrik Schmidt; Frank Heuer; Hans-Joachim Wilke

2009-01-01

285

Visual function after removal of subretinal neovascular membranes in patients with age-related macular degeneration  

Microsoft Academic Search

Background: Retinal pigment epithelial (RPE) cells have been transplanted to replace the RPE cells lost after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration. The purpose of this study was to analyze the visual function of eyes with altered RPE after surgical excision of choroidal neovascular membranes (CNV) associated with age-related macular degeneration, and to determine

Toshiaki Abe; Madoka Yoshida; Tetsuya Kano; Makoto Tamai

2001-01-01

286

Degenerate U-and V -statistics under ergodicity: Asymptotics, bootstrap and applications in statistics  

E-print Network

Degenerate U- and V -statistics under ergodicity: Asymptotics, bootstrap and applications in statistics Anne Leucht Universit¨at Hamburg Fachbereich Mathematik, SPST Bundesstra�e 55 D-20146 Hamburg.neumann@uni-jena.de Abstract We derive the asymptotic distributions of degenerate U- and V -statistics of stationary

287

White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis  

Microsoft Academic Search

In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in MS might lead to axonal degeneration. White-matter astrocytes in MS show a reduced metabolism of adenosine triphosphate-generating phosphocreatine, which

Melissa Cambron; Miguel D'Haeseleer; Guy Laureys; Ralph Clinckers; Jan Debruyne; Jacques De Keyser

2012-01-01

288

Identification of potyviruses using the polymerase chain reaction with degenerate primers  

Microsoft Academic Search

Local areas of conserved amino acid sequence in the replicase and coat proteins of potyviruses were used to select nucleotide sequences for use in the construction of sets of degenerate oligonucleotide primers for amplification of DNA fragments on potyvirus-specific templates in a combined assay of reverse transcription and the polymerase chain reaction (RT-PCR). Sequences selected for the construction of degenerate

Simon A. Langeveld; Jean-Michel Dore; Johan Memelink; Antonius F. L. M. Derks; Cornelia I. M. van der Vlugt; Cees J. Asjes; John F. Bol

1991-01-01

289

Changes in the basement membrane zone components during skeletal muscle fiber degeneration and regeneration  

Microsoft Academic Search

The basement membrane of skeletal muscle fibers is believed to persist unchanged during myofiber degeneration and act as a tubular structure within which the regeneration of new myofibers occurs. In the present study we describe macromolecular changes in the basement membrane zone during muscle degeneration and regeneration, as monitored by immunofluorescence using specific antibodies against types IV and V collagen,

A. K. Gulati; A. H. REDDI; A. A. ZALEWSKI

1983-01-01

290

Associations between Lutein, Zeaxanthin, and Age-Related Macular Degeneration: An Overview  

Microsoft Academic Search

Age-related macular degeneration, the leading cause of blindness in the elderly, is a degenerative condition of the macula characterized by death or dysfunction of the photoreceptors. With the aging population growing, the incidence of age-related macular degeneration is expected to increase. This raises concern about the future of visual dysfunction related falls and the resulting injuries in the elderly population.

Shannon Carpentier; Maria Knaus; Miyoung Suh

2009-01-01

291

Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD)  

Microsoft Academic Search

Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of macular degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease.

Hema L. Ramkumar; Jun Zhang; Chi-Chao Chan

2010-01-01

292

Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment  

Microsoft Academic Search

Subacute combined degeneration of the cord is a rare complication of folate deficiency. Disturbance of methylation reactions in nervous tissue probably underlie subacute combined degeneration of the cord arising from folate as well as vitamin B12 deficiency. Methyl tetrahydrofolate is the form in which folic acid is transported into the CNS. Therefore methyl tetrahydrofolate treatment of the neurological and psychiatric

E G Lever; R D Elwes; A Williams; E H Reynolds

1986-01-01

293

Subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia  

Microsoft Academic Search

Vitamin B12 deficiency causes haematological, gastrointestinal and neurological diseases. Subacute combined degeneration (SCD)\\u000a of the spinal cord is characterised by degeneration of the posterior and lateral columns. We report a case of SCD associated\\u000a with nitrous oxide anaesthesia.

Dimitri Renard; Anais Dutray; Anouck Remy; Giovanni Castelnovo; Pierre Labauge

2009-01-01

294

Subacute combined degeneration of the spinal cord caused by nitrous oxide anaesthesia.  

PubMed

Vitamin B12 deficiency causes haematological, gastrointestinal and neurological diseases. Subacute combined degeneration (SCD) of the spinal cord is characterised by degeneration of the posterior and lateral columns. We report a case of SCD associated with nitrous oxide anaesthesia. PMID:19169627

Renard, Dimitri; Dutray, Anais; Remy, Anouck; Castelnovo, Giovanni; Labauge, Pierre

2009-02-01

295

The periodic table of n-categories for low dimensions I: degenerate categories and  

E-print Network

The periodic table of n-categories for low dimensions I: degenerate categories and degenerate-mail: eugenia@math.uchicago.edu, gurski@math.uchicago.edu July 2005 Abstract We examine the periodic table the first few entries in the "Periodic Table" of n- categories. This table was first described by Baez

Cheng, Eugenia

296

Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration  

PubMed Central

A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse “knock-in” model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct. PMID:22110650

Shu, Xinhua; Luhmann, Ulrich F. O.; Aleman, Tomas S.; Barker, Susan E.; Lennon, Alan; Tulloch, Brian; Chen, Mei; Xu, Heping; Jacobson, Samuel G.; Ali, Robin; Wright, Alan F.

2011-01-01

297

Ovarian cancer revealed by paraneoplastic cerebellar degeneration: a case report  

PubMed Central

The prevalence of paraneoplastic cerebellar degeneration (PCD) associated with gynecological cancer is rare. Here, we reported the first case of ovarian cancer revealed by PCD in our institute. we describe a 80- year –old Moroccan female presented with subacute vestibular and cerebellar syndromes, she had an inguinal lymphadenopathy,with high levels of Anti-YO. Rapid progression and absence of known etiologies point towards a probable paraneoplastic origin of the syndrome in this patient. The exact incidence of PNS among those diagnosed with cancer remains uncertain, it is important to report this cases in the literature to help early diagnosis and appropriate treatment, which are able to stabilize the neurological symptoms. PMID:25360186

Elomrani, Fadwa; Ouziane, Imane; Boutayeb, Saber; Bensouda, Youssef; Mrabti, Hind; Errihani, Hassan

2014-01-01

298

Energy estimate and fundamental solution for degenerate hyperbolic Cauchy problems  

NASA Astrophysics Data System (ADS)

The aim of this paper is to give an uniform approach to different kinds of degenerate hyperbolic Cauchy problems. We prove that a weakly hyperbolic equation, satisfying an intermediate condition between effective hyperbolicity and the C? Levi condition, and a strictly hyperbolic equation with non-regular coefficients with respect to the time variable can be reduced to first-order systems of the same type. For such a kind of systems, we prove an energy estimate in Sobolev spaces (with a loss of derivatives) which gives the well-posedness of the Cauchy problem in C?. In the strictly hyperbolic case, we also construct the fundamental solution and we describe the propagation of the space singularities of the solution which is influenced by the non-regularity of the coefficients with respect to the time variable.

Ascanelli, Alessia; Cicognani, Massimo

299

Carbon Nanotube Capacitance Model in Degenerate and Nondegenerate Regimes  

NASA Astrophysics Data System (ADS)

In this work, fundamental results on carrier statistics in a carbon nanotube treated as a one-dimensional material are presented. Also the effect of degeneracy on the capacitance of the carbon nanotube channel in a carbon nan-otube field effect transistor is discussed. A quantum capacitance as well as a classical capacitance is revealed. Furthermore it is shown that for low gate voltage, the total capacitance is equivalent to the classical capacitance but for high gate voltage it is equivalent to the quantum capacitance. We predict that in the nondegenerate regime, the total capacitance is equivalent to the classical capacitance and that the quantum capacitance can be neglected, whereas only quantum capacitance needs to be taken into account in the calculation of the total capacitance in the degenerate regime.

Ahmadi, M. T.; Webb, J. F.; Amin, N. A.; Mousavi, S. M.; Sadeghi, H.; Neilchiyan, M. R.; Ismail, R.

2011-06-01

300

Today and Future of Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 in developed countries. Understanding of the pathologic process, genetic mechanisms, and risk factors of this disease has the benefit of seeking newer and more effective treatment options. Current clinical therapy for AMD shows a dramatic change from a decade ago. Anti-VEGF drug therapy is regarded as the more effective treatment for neovascular AMD now, especially combining PDT therapy. In the future, the genetic and biochemical therapies may be the promising treatments for AMD. This paper will focus on the progress of pathology, candidate genes of AMD, risk factors, and the existing drugs or surgical therapies available, in order to present some new directions of care with the prospect of improved vision in many patients suffered from AMD. PMID:24558588

Liu, Kang; Xie, Bolin

2012-01-01

301

Studying Age-Related Macular Degeneration Using Animal Models  

PubMed Central

ABSTRACT Over the recent years, there have been tremendous advances in our understanding of the genetic and environmental factors associated with the development of age-related macular degeneration (AMD). Examination of retinal changes in various animals has aided our understanding of the pathogenesis of the disease. Notably, mouse strains, carrying genetic anomalies similar to those affecting humans, have provided a foundation for understanding how various genetic risk factors affect retinal integrity. However, to date, no single mouse strain that develops all the features of AMD in a progressive age-related manner has been identified. In addition, a mutation present in some background strains has clouded the interpretation of retinal phenotypes in many mouse strains. The aim of this perspective was to describe how animals can be used to understand the significance of each sign of AMD, as well as key genetic risk factors. PMID:24978866

Fletcher, Erica L.; Jobling, Andrew I.; Greferath, Ursula; Mills, Samuel A.; Waugh, Michelle; Ho, Tracy; de Iongh, Robb U.; Phipps, Joanna A.; Vessey, Kirstan A.

2014-01-01

302

Experiments with Ultracold Quantum-degenerate Fermionic Lithium Atoms  

NASA Technical Reports Server (NTRS)

Experimental methods of laser and evaporative cooling, used in the production of atomic Bose-Einstein condensates have recently been extended to realize quantum degeneracy in trapped Fermi gases. Fermi gases are a new rich system to explore the implications of Pauli exclusion on scattering properties of the system, and ultimately fermionic superfluidity. We have produced a new macroscopic quantum system, in which a degenerate Li-6 Fermi gas coexists with a large and stable Na-23 BEC. This was accomplished using inter-species sympathetic cooling of fermionic 6Li in a thermal bath of bosonic Na-23. We have achieved high numbers of both fermions (less than 10(exp 5) and bosons (less than 10(exp 6), and Li-6 quantum degeneracy corresponding to one half of the Fermi temperature. This is the first time that a Fermi sea was produced with a condensate as a "refrigerator".

Ketterle, Wolfgang

2003-01-01

303

Universal dynamics of a degenerate unitary Bose gas  

NASA Astrophysics Data System (ADS)

From neutron stars to high-temperature superconductors, strongly interacting many-body systems at or near quantum degeneracy are a rich source of intriguing phenomena. The microscopic structure of the first-discovered quantum fluid, superfluid liquid helium, is difficult to access owing to limited experimental probes. Although an ultracold atomic Bose gas with tunable interactions (characterized by its scattering length, a) had been proposed as an alternative strongly interacting Bose system, experimental progress has been limited by its short lifetime. Here we present time-resolved measurements of the momentum distribution of a Bose-condensed gas that is suddenly jumped to unitarity, where . Contrary to expectation, we observe that the gas lives long enough to permit the momentum to evolve to a quasi-steady-state distribution, consistent with universality, while remaining degenerate. Investigations of the time evolution of this unitary Bose gas may lead to a deeper understanding of quantum many-body physics.

Makotyn, P.; Klauss, C. E.; Goldberger, D. L.; Cornell, E. A.; Jin, D. S.

2014-02-01

304

Next generation therapeutic solutions for age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the primary cause of blindness among the elderly worldwide. To date, no cure is available, and the available palliative treatments only showed limited efficacy in improving visual acuity. The etiology of AMD remains elusive but research over the past decade has uncovered characteristic features of the disease. Known as the hallmarks of AMD, these features include (A) oxidative stress and RPE cytotoxicity; (B) loss of macromolecular permeability and hydraulic conductivity: (C) inflammation; (D) choroidal neovascularization and vascular leakage; and (E) loss of neuroprotection. Recent breakthrough in understanding the pathogenesis of AMD has spawned an array of novel therapeutic agents designed to address these hallmarks. Here we review the features of AMD and highlight the most promising therapeutic and diagnostic approaches based on the patents published from 2008 to 2011. Most likely, a next generation treatment for AMD will be developed from these emerging efforts. PMID:24040506

Cunnsamy, Khrishen; Ufret-Vincenty, Rafael; Wang, Shusheng

2013-01-01

305

Functional consequences of locus coeruleus degeneration in Alzheimer's disease.  

PubMed

Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients, and its prevalence is expected to soar in coming decades. Neuropathologically, AD is characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, and cholinergic neuronal loss. In addition to the hallmark of memory loss, the disease is associated with other neuropsychiatric and behavioral abnormalities, including psychosis, aggression, and depression. Although cholinergic cell loss is clearly an important attribute of the pathological process, another well-described yet underappreciated early feature of AD pathogenesis is degeneration of the locus coeruleus (LC), which serves as the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The purpose of this review is to explore the extent to which LC loss contributes to AD neuropathology and cognitive deficits. PMID:18537547

Weinshenker, David

2008-06-01

306

Stem cells as tools in regenerative therapy for retinal degeneration  

PubMed Central

Objectives Regenerative medicine intends to provide therapies for severe injuries or chronic diseases where endogenous repair does not sufficiently restore the tissue. Pluripotent stem cells (SC), with their capacity to give rise to specialized cells, are the most promising candidates for clinical application. Despite encouraging results, a combination with up-to-date tissue engineering might be critical for ultimate success. Design The focus is on the use of SC for regeneration of retinal degenerations. Cell populations include embryonic, neural, and bone marrow-derived SC and engineered grafts will also be described. Results Experimental approaches have successfully replaced damaged photoreceptors and retinal pigment epithelium using endogenous and exogenous SC. Conclusions SC have the potential to significantly impact retinal regeneration. A combination with bioengineering may bear even greater promise. However, ethical and scientific issues have yet to be solved. PMID:19365041

Enzmann, Volker; Yolcu, Esma; Kaplan, Henry J.; Ildstad, Suzanne T.

2011-01-01

307

The physical properties of double degenerate common proper motion binaries  

NASA Technical Reports Server (NTRS)

Spectral types and spectrophotometry are presented for 21 double degenerate (DD) common proper motion binaries, along with estimates of their colors, absolute visual and bolometric magnitudes, and cooling ages. The oldest pairs in the sample are 9 x 10 to the 9th yr; the differential cooling ages range from 0.01 to 0.84. The median and mean separations of the DD pairs are 426 and 407 Au, respectively, both apparently smaller than the WD+MS values. The average UVW motions and velocity dispersions are significantly larger than the average velocities and dispersions associated with selected samples of single white dwarfs and MS+WD binaries when the latter are restricted to the same color/Mv range as the DD systems. This may be a result of the dynamical inflation of the velocity dispersion of DD systems due to their extremely ancient total stellar ages.

Sion, Edward M.; Oswalt, Terry D.; Liebert, James; Hintzen, Paul

1991-01-01

308

670-nm light treatment reduces complement propagation following retinal degeneration  

PubMed Central

Aim Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. Methods Sprague–Dawley (SD) rats were pretreated with 9 J/cm2 670-nm light for 3 minutes daily over 5 days; other animals were sham treated. Animals were exposed to white light (1,000 lux) for 24 h, after which animals were kept in dim light (5 lux) for 7 days. Expression of complement genes was assessed by quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Counts were made of C3-expressing monocytes/microglia using in situ hybridization. Photoreceptor death was also assessed using outer nuclear layer (ONL) thickness measurements, and oxidative stress using immunohistochemistry for 4-hydroxynonenal (4-HNE). Results Following light damage, retinas pretreated with 670-nm light had reduced immunoreactivity for the oxidative damage maker 4-HNE in the ONL and outer segments, compared to controls. In conjunction, there was significant reduction in retinal expression of complement genes C1s, C2, C3, C4b, C3aR1, and C5r1 following 670 nm treatment. In situ hybridization, coupled with immunoreactivity for the marker ionized calcium binding adaptor molecule 1 (IBA1), revealed that C3 is expressed by infiltrating microglia/monocytes in subretinal space following light damage, which were significantly reduced in number after 670 nm treatment. Additionally, immunohistochemistry for C3 revealed a decrease in C3 deposition in the ONL following 670 nm treatment. Conclusions Our data indicate that 670-nm light pretreatment reduces lipid peroxidation and complement propagation in the degenerating retina. These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy. PMID:23181358

2012-01-01

309

Telomerase reactivation reverses tissue degeneration in aged telomerase deficient mice  

PubMed Central

An ageing world population has fueled interest in regenerative remedies that may stem declining organ function and maintain fitness. Unanswered is whether elimination of intrinsic instigators driving age-associated degeneration can reverse, as opposed to simply arrest, various afflictions of the aged. Such instigators include progressively damaged genomes. Telomerase deficient mice have served as a model system to study the adverse cellular and organismal consequences of wide-spread endogenous DNA damage signaling activation in vivo1. Telomere loss and uncapping provokes progressive tissue atrophy, stem cell depletion, organ system failure, and impaired tissue injury responses1. Here, we sought to determine whether entrenched multi-system degeneration in adult mice with severe telomere dysfunction can be halted or possibly reversed by reactivation of endogenous telomerase activity. To this end, we engineered a knock-in allele encoding a 4-hydroxytamoxifen (4-OHT)-inducible telomerase reverse transcriptase-Estrogen Receptor (TERT-ER) under transcriptional control of the endogenous TERT promoter. Homozygous TERT-ER mice display short dysfunctional telomeres and sustain increased DNA damage signaling and classical degenerative phenotypes upon successive generational matings and advancing age. Telomerase reactivation in such late generation TERT-ER mice extends telomeres, reduces DNA damage signaling and associated cellular checkpoint responses, allows resumption of proliferation in quiescent cultures, and eliminates degenerative phenotypes across multiple organs including testes, spleens and intestines. Notably, somatic telomerase reactivation reversed neurodegeneration with restoration of proliferating Sox2+ neural progenitors, DCX+ newborn neurons, and Olig2+ oligodendrocyte populations. Consistent with the integral role of SVZ neural progenitors in generation and maintenance of olfactory bulb interneurons2, this wave of telomerase-dependent neurogenesis resulted in alleviation of hyposmia and recovery of innate olfactory avoidance responses. Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk1,3 and the dramatic reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity. PMID:21113150

Jaskelioff, Mariela; Muller, Florian L.; Paik, Ji-Hye; Thomas, Emily; Jiang, Shan; Adams, Andrew; Sahin, Ergun; Kost-Alimova, Maria; Protopopov, Alexei; Cadinanos, Juan; Horner, James W.; Maratos-Flier, Eleftheria; DePinho, Ronald A.

2010-01-01

310

Protective Effect of Ligustrazine on Lumbar Intervertebral Disc Degeneration of Rats Induced by Prolonged Upright Posture  

PubMed Central

Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1?, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease. PMID:24872832

Liang, Qian-Qian; Ding, Dao-Fang; Xi, Zhi-Jie; Chen, Yan; Li, Chen-Guang; Liu, Shu-Fen; Lu, Sheng; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun

2014-01-01

311

Ghost Sites  

NSDL National Science Digital Library

There is much on the Net that is living and vibrant, but there is also much that is dead, stuffed, or embalmed, as Steve Baldwin, former Pathfinder (discussed in the November 14, 1997 ScoutReport) writer likes to say. At this site Baldwin tracks notable embalmed, dead, or dying web sites. Each issue of Ghost Sites reviews five to ten such sites. Sites discussed include the latest Pathfinder out-of-date update on the Unibomber, the stillborn MecklerWeb, and Electric Minds (discussed in the November 22, 1996 Scout Report), abandoned by Howard Rheingold. Sites are rated from Dying in I.C.U. to Site is Stuffed, Embalmed and Ready for Internet Museum. Ironically, several of the sites discussed have been resurrected or metamorphosed since they were discussed, proving, if nothing else, that anything is possible in cyberspace. Note that clicking on discussed sites opens a new browser window.

312

A plant Y chromosome-STS marker encoding a degenerate retrotransposon.  

PubMed

The dioecious plant Silene latifolia has both X and Y sex chromosomes. Male-specific random amplified polymorphic DNA (RAPD) fragments were analyzed to identify Y-chromosome-linked sequences. One of the RAPD fragments, MS4, was converted into a more reliable and reproducible sequence-tagged site (STS) marker. A set of MS4 STS primers was used to amplify two genomic DNA fragments (MS4a and MS4b) from a male plant and one (MS4a) from a female plant, which indicates that MS4b is located on the Y chromosome. Sequence analysis revealed that MS4a encoded a gag protein of a Ty3-gypsy-like retrotransposon. A 147-bp region from the middle of MS4a was deleted in MS4b. The MS4b sequence was not detected in the most closely related dioecious species, S. dioica. This suggests that a retrotransposon with the MS4b sequence has degenerated recently on the Y chromosome. PMID:12589074

Obara, Mari; Matsunaga, Sachihiro; Nakao, Shunsuke; Kawano, Shigeyuki

2002-12-01

313

Elastin-Mediated Choroidal Endothelial Cell Migration: Possible Role in Age-Related Macular Degeneration  

PubMed Central

Purpose Endothelial cell (EC) migration is a key event in angiogenesis, and is likely to play an important role in choroidal neovascularization in age-related macular degeneration (AMD). Altered elastin metabolism has been described in AMD, and the present study sought to determine the effects of elastin-derived peptides (EDPs) on choroidal EC migration and proliferation. Methods Migration of the chorioretinal EC line Rf/6a and a primary culture of human choroidal ECs through polycarbonate membrane inserts was quantified in the presence of elastin bioactive hexapeptides (BPs), EDPs, bovine serum albumin (BSA), or balanced salt solution. Proliferation assays and in vitro wound closure experiments were also performed in the presence of elastin fragments or balanced salt solution (control). Elastin overlay experiments were performed on sections of human eyes. Results For both Rf/6a and human primary choroidal ECs exposed to EDPs or BPs, the number of ECs that migrated through the polycarbonate membrane was significantly higher than ECs exposed to balanced salt solution alone or to BSA (P < 0.05) in all experiments. In contrast, the rate of EC proliferation did not significantly change in comparison to controls. Elastin binding sites were identified on choroidal ECs in human eyes. Conclusions Elastin fragments increase choroidal EC migration, whereas they do not appear to increase or decrease EC proliferation. Local or systemic abnormalities in elastin physiology may participate in pathologic neovascular membrane formation in AMD. PMID:18708613

Skeie, Jessica M.; Mullins, Robert F.

2008-01-01

314

Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant  

PubMed Central

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family–based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA. PMID:24216480

Song, You-Qiang; Karasugi, Tatsuki; Cheung, Kenneth M.C.; Chiba, Kazuhiro; Ho, Daniel W.H.; Miyake, Atsushi; Kao, Patrick Y.P.; Sze, Kit Ling; Yee, Anita; Takahashi, Atsushi; Kawaguchi, Yoshiharu; Mikami, Yasuo; Matsumoto, Morio; Togawa, Daisuke; Kanayama, Masahiro; Shi, Dongquan; Dai, Jin; Jiang, Qing; Wu, Chengai; Tian, Wei; Wang, Na; Leong, John C.Y.; Luk, Keith D.K.; Yip, Shea-ping; Cherny, Stacey S.; Wang, Junwen; Mundlos, Stefan; Kelempisioti, Anthi; Eskola, Pasi J.; Mannikko, Minna; Makela, Pirkka; Karppinen, Jaro; Jarvelin, Marjo-Riitta; O'Reilly, Paul F.; Kubo, Michiaki; Kimura, Tomoatsu; Kubo, Toshikazu; Toyama, Yoshiaki; Mizuta, Hiroshi; Cheah, Kathryn S.E.; Tsunoda, Tatsuhiko; Sham, Pak-Chung; Ikegawa, Shiro; Chan, Danny

2013-01-01

315

Rotational vertebral artery occlusion secondary to adjacent-level degeneration following anterior cervical discectomy and fusion.  

PubMed

Rotational vertebral artery occlusion (RVAO), or bow hunter's syndrome, most often occurs at the C1-2 level on physiological head rotation. It presents with symptoms of vertebrobasilar insufficiency (VBI). Several previously published studies have reported on subaxial sites of vertebral artery (VA) compression by head rotation. The authors report a case of subaxial spine RVAO due to adjacent-segment degeneration. A 52-year-old man presented with dizziness when rotating his head to the left. Twenty years earlier, he had undergone a C4-5 anterior cervical discectomy and fusion (ACDF) for a herniated disc. Imaging studies including a dynamic CT angiography and dynamic catheter angiography revealed occlusion of the left VA at the C3-4 level when the patient turned his head to the left, in the setting of an aberrant vertebrobasilar system. Successful treatment was achieved by surgical decompression of the left VA and C3-4 ACDF. Expedited diagnosis and treatment are dependent on the recognition of this unusual manifestation of RVAO, especially when patients present with nonspecific symptoms of VBI. PMID:24745352

Buchanan, Colin C; McLaughlin, Nancy; Lu, Daniel C; Martin, Neil A

2014-06-01

316

Recent Patents on Emerging Therapeutics for the Treatment of Glaucoma, Age Related Macular Degeneration and Uveitis  

PubMed Central

Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis.

Vadlapudi, Aswani Dutt; Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K.

2014-01-01

317

Distinct Pathways Mediate Axon Degeneration during Apoptosis and Axon-Specific Pruning  

PubMed Central

Neurons can activate pathways that destroy the whole cell via apoptosis or selectively degenerate only the axon (pruning). Both apoptosis and axon degeneration require Bax and caspases. Here we demonstrate that despite this overlap, the pathways mediating axon degeneration during apoptosis versus axon pruning are distinct. While caspase-6 is activated in axons following nerve growth factor (NGF) deprivation, microfluidic chamber experiments reveal that caspase-6 deficiency only protects axons during axon-specific but not whole-cell (apoptotic) NGF deprivation. Strikingly, axon-selective degeneration requires the apoptotic proteins Caspase-9 and Caspase-3 but, in contrast to apoptosis, not Apaf-1. Additionally, cell bodies of degenerating axons are protected from caspase activation by protea some activity and XIAP. Also, mature neurons restrict apoptosis but remain permissive for axon degeneration, further demonstrating the independent regulation of these two pathways. These results reveal insight into how neurons allow for precise control over apoptosis and axon-selective degeneration pathways, thereby permitting long-term plasticity without risking neurodegeneration. PMID:23695670

Cusack, Corey L.; Swahari, Vijay; Henley, W. Hampton; Ramsey, J. Michael; Deshmukh, Mohanish

2014-01-01

318

Age-related macular degeneration: Beyond anti-angiogenesis  

PubMed Central

Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate vascular maturation, rather than its arrest or destruction. This would neutralize hypoxia, thus removing the stimulus that drives neovascularization and in turn the need for repeated lifelong intravitreal therapy. A pro-angiogenic approach would eliminate neovascular leakage and ultimately complete repair and preserve the neurosensory retina. PMID:24426775

2014-01-01

319

Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement  

PubMed Central

Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5–11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term. PMID:23341635

Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komaromy, Andras M.; Hauswirth, William W.; Aguirre, Gustavo D.

2013-01-01

320

Altered Knee Joint Mechanics in Simple Compression Associated with Early Cartilage Degeneration  

PubMed Central

The progression of osteoarthritis can be accompanied by depth-dependent changes in the properties of articular cartilage. The objective of the present study was to determine the subsequent alteration in the fluid pressurization in the human knee using a three-dimensional computer model. Only a small compression in the femur-tibia direction was applied to avoid numerical difficulties. The material model for articular cartilages and menisci included fluid, fibrillar and nonfibrillar matrices as distinct constituents. The knee model consisted of distal femur, femoral cartilage, menisci, tibial cartilage, and proximal tibia. Cartilage degeneration was modeled in the high load-bearing region of the medial condyle of the femur with reduced fibrillar and nonfibrillar elastic properties and increased hydraulic permeability. Three case studies were implemented to simulate (1) the onset of cartilage degeneration from the superficial zone, (2) the progression of cartilage degeneration to the middle zone, and (3) the progression of cartilage degeneration to the deep zone. As compared with a normal knee of the same compression, reduced fluid pressurization was observed in the degenerated knee. Furthermore, faster reduction in fluid pressure was observed with the onset of cartilage degeneration in the superficial zone and progression to the middle zone, as compared to progression to the deep zone. On the other hand, cartilage degeneration in any zone would reduce the fluid pressure in all three zones. The shear strains at the cartilage-bone interface were increased when cartilage degeneration was eventually advanced to the deep zone. The present study revealed, at the joint level, altered fluid pressurization and strains with the depth-wise cartilage degeneration. The results also indicated redistribution of stresses within the tissue and relocation of the loading between the tissue matrix and fluid pressure. These results may only be qualitatively interesting due to the small compression considered. PMID:23424607

Dabiri, Y.; Li, L. P.

2013-01-01

321

Altered knee joint mechanics in simple compression associated with early cartilage degeneration.  

PubMed

The progression of osteoarthritis can be accompanied by depth-dependent changes in the properties of articular cartilage. The objective of the present study was to determine the subsequent alteration in the fluid pressurization in the human knee using a three-dimensional computer model. Only a small compression in the femur-tibia direction was applied to avoid numerical difficulties. The material model for articular cartilages and menisci included fluid, fibrillar and nonfibrillar matrices as distinct constituents. The knee model consisted of distal femur, femoral cartilage, menisci, tibial cartilage, and proximal tibia. Cartilage degeneration was modeled in the high load-bearing region of the medial condyle of the femur with reduced fibrillar and nonfibrillar elastic properties and increased hydraulic permeability. Three case studies were implemented to simulate (1) the onset of cartilage degeneration from the superficial zone, (2) the progression of cartilage degeneration to the middle zone, and (3) the progression of cartilage degeneration to the deep zone. As compared with a normal knee of the same compression, reduced fluid pressurization was observed in the degenerated knee. Furthermore, faster reduction in fluid pressure was observed with the onset of cartilage degeneration in the superficial zone and progression to the middle zone, as compared to progression to the deep zone. On the other hand, cartilage degeneration in any zone would reduce the fluid pressure in all three zones. The shear strains at the cartilage-bone interface were increased when cartilage degeneration was eventually advanced to the deep zone. The present study revealed, at the joint level, altered fluid pressurization and strains with the depth-wise cartilage degeneration. The results also indicated redistribution of stresses within the tissue and relocation of the loading between the tissue matrix and fluid pressure. These results may only be qualitatively interesting due to the small compression considered. PMID:23424607

Dabiri, Y; Li, L P

2013-01-01

322

Prevalence of lumbar disc degeneration observed by magnetic resonance in symptomless women.  

PubMed

302 women aged 16-80 without symptoms of spinal disease had their lumbar intervertebral discs examined by magnetic resonance. The prevalence of one or more degenerate discs increased linearly with age but disc degeneration was already present in over one-third of women aged 21-40; these young women may prove to be at special risk of disc prolapse later in life. The high prevalence of symptomless disc degeneration must be taken into account when magnetic resonance is used for assessment of spinal symptoms. PMID:2878228

Powell, M C; Wilson, M; Szypryt, P; Symonds, E M; Worthington, B S

1986-12-13

323

Initial evolution of supports of solutions of quasilinear parabolic equations with degenerate absorption potential  

SciTech Connect

The propagation of supports of solutions of second-order quasilinear parabolic equations is studied; the equations are of the type of nonstationary diffusion, having semilinear absorption with an absorption potential which degenerates on the initial plane. We find sufficient conditions, which are sharp in a certain sense, on the relationship between the boundary regime and the type of degeneration of the potential to ensure the strong localization of solutions. We also establish a weak localization of solutions for an arbitrary potential which degenerates only on the initial plane. Bibliography: 12 titles.

Stepanova, Ekaterina V; Shishkov, Andrey E

2013-03-31

324

Models of collective cell spreading with variable cell aspect ratio: A motivation for degenerate diffusion models  

NASA Astrophysics Data System (ADS)

Continuum diffusion models are often used to represent the collective motion of cell populations. Most previous studies have simply used linear diffusion to represent collective cell spreading, while others found that degenerate nonlinear diffusion provides a better match to experimental cell density profiles. In the cell modeling literature there is no guidance available with regard to which approach is more appropriate for representing the spreading of cell populations. Furthermore, there is no knowledge of particular experimental measurements that can be made to distinguish between situations where these two models are appropriate. Here we provide a link between individual-based and continuum models using a multiscale approach in which we analyze the collective motion of a population of interacting agents in a generalized lattice-based exclusion process. For round agents that occupy a single lattice site, we find that the relevant continuum description of the system is a linear diffusion equation, whereas for elongated rod-shaped agents that occupy L adjacent lattice sites we find that the relevant continuum description is connected to the porous media equation (PME). The exponent in the nonlinear diffusivity function is related to the aspect ratio of the agents. Our work provides a physical connection between modeling collective cell spreading and the use of either the linear diffusion equation or the PME to represent cell density profiles. Results suggest that when using continuum models to represent cell population spreading, we should take care to account for variations in the cell aspect ratio because different aspect ratios lead to different continuum models.

Simpson, Matthew J.; Baker, Ruth E.; McCue, Scott W.

2011-02-01

325

Microglial TNF-? mediates enhancement of dopaminergic degeneration by brain angiotensin.  

PubMed

In vitro and in vivo models of Parkinson's disease were used to investigate whether TNF-? plays a major role in the enhancement of the microglial response and dopaminergic degeneration induced by brain angiotensin hyperactivity. Treatment of primary mesencephalic cultures with low doses of the neurotoxin MPP(+) induced a significant loss of dopaminergic neurons, which was enhanced by cotreatment with angiotensin II and inhibited by TNF-? inhibitors. Treatment of primary cultures with angiotensin induced a marked increase in levels of TNF-?, which was inhibited by treatment with angiotensin type-1-receptor antagonists, NADPH-oxidase inhibitors and NFK-? inhibitors. However, TNF-? levels were not significantly affected by treatment with angiotensin in the absence of microglia. The microglial origin of the angiotensin-induced increase in TNF-? levels was confirmed using dopaminergic (MES 23.5) and microglial (N9) cell lines. Inhibition of the microglial Rho-kinase activity also blocked the AII-induced increase in TNF-? levels. Treatment of the dopaminergic cell line with TNF-? revealed that NFK-? activation mediates the deleterious effect of microglial TNF-? on dopaminergic neurons. Treatment of mice with MPTP also induced significant increases in striatal and nigral TNF-? levels, which were inhibited by angiotensin type-1-receptor antagonists or NFK-? inhibitors. The present results show that microglial TNF-? plays a major role in angiotensin-induced dopaminergic cell death and that the microglial release of TNF-? is mediated by activation of angiotensin type-1 receptors, NADPH-oxidase, Rho-kinase and NFK-?. PMID:24272709

Borrajo, Ana; Rodriguez-Perez, Ana I; Diaz-Ruiz, Carmen; Guerra, Maria J; Labandeira-Garcia, Jose L

2014-01-01

326

Lifespan maturation and degeneration of human brain white matter.  

PubMed

Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative magnetic resonance imaging (MRI) measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7-85). The amount of R1 change during development differs between white-matter fascicles, but in each fascicle the rate of development and decline are mirror-symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white-matter tissue properties over the lifespan. PMID:25230200

Yeatman, Jason D; Wandell, Brian A; Mezer, Aviv A

2014-01-01

327

Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans  

PubMed Central

Selenium is an essential micronutrient required for cellular antioxidant systems, yet at higher doses it induces oxidative stress. Additionally, in vertebrates environmental exposures to toxic levels of selenium can cause paralysis and death. Here we show that selenium-induced oxidative stress leads to decreased cholinergic signaling and degeneration of cholinergic neurons required for movement and egg-laying in Caenorhabditis elegans. Exposure to high levels of selenium leads to proteolysis of a soluble muscle protein through mechanisms suppressible by two pharmacological agents, levamisole and aldicarb which enhance cholinergic signaling in muscle. In addition, animals with reduction-of-function mutations in genes encoding post-synaptic levamisole-sensitive acetylcholine receptor subunits or the vesicular acetylcholine transporter developed impaired forward movement faster during selenium-exposure than normal animals, again confirming that selenium reduces cholinergic signaling. Finally, the antioxidant reduced glutathione, inhibits selenium-induced reductions in egg-laying through a cellular protective mechanism dependent on the C. elegans glutaredoxin, GLRX-21. These studies provide evidence that the environmental toxicant selenium induces neurodegeneration of cholinergic neurons through depletion of glutathione, a mechanism linked to the neuropathology of Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. PMID:22560997

Estevez, Annette O.; Mueller, Catherine L.; Morgan, Kathleen L.; Szewczyk, Nathaniel J.; Teece, Luke; Miranda-Vizuete, Antonio; Estevez, Miguel

2012-01-01

328

Hippocampal degeneration in patients with amyotrophic lateral sclerosis.  

PubMed

There is increasing appreciation of non-motor system involvement in amyotrophic lateral sclerosis (ALS), although its full extent and clinical significance remains to be established. This study tested the hypothesis that memory impairment in patients with ALS is related to hippocampal degeneration. Consecutive patients with ALS (58) and 29 matched controls participated in standardized neuropsychological assessment and magnetic resonance imaging. Patients with ALS performed worse in global cognitive functioning and executive and verbal memory tests (p < 0.05). The hippocampus was manually segmented in each hemisphere, and volumes were calculated with correction for intracranial volume. Analysis of covariance, controlled for the effect of age and education years, showed significantly smaller hippocampal volume on the right (p = 0.004) in patients with ALS. Verbal memory test performance correlated with the left hippocampal volume in patients with ALS (p < 0.05), although there was no significant correlation with tests of executive function and clinical variables underscoring the specificity of the present findings. Hippocampal volume loss and its correlation with the severity of verbal memory impairment highlight significant hippocampal involvement which can occur as a non-motor deficit in patients with ALS. PMID:25004891

Abdulla, Susanne; Machts, Judith; Kaufmann, Jörn; Patrick, Karina; Kollewe, Katja; Dengler, Reinhard; Heinze, Hans-Jochen; Petri, Susanne; Vielhaber, Stefan; Nestor, Peter J

2014-11-01

329

Phase grating in a doubly degenerate four-level system  

NASA Astrophysics Data System (ADS)

In this paper, we suggest a doubly degenerate four-level system, in which the transition takes place between the hyperfine energy 52S1/2 F = 1 and 52P3/2 F = 2 in rubidium 87 D2 line, for studying atomic phase grating based on the cross-Kerr and phase conjugation effects. The phase grating with high efficiency can be obtained by tuning phase shift ? between the coupling and probe field, when the coupling intensity is much stronger than the strength of probe field. Under different coupling intensities, a high diffraction efficiency can be maintained. A new and simple way of implementing phase grating is presented. However, in such an atomic system, two main limitations must be taken into account. First, the independence between steady state probe susceptibility and the coupling intensity, when the population decay rate is larger than the Rabi frequency of the coupling field, cannot result in diffraction grating; second, the sample to be prepared should not be too long.

Liu, Yun; Wang, Pu; Peng, Shuang-Yan

2013-10-01

330

Donor and acceptor concentrations in degenerate InN  

SciTech Connect

A formalism is presented to determine donor (N{sub D}) and acceptor (N{sub A}) concentrations in wurtzitic InN characterized by degenerate carrier concentration (n) and mobility ({mu}). The theory includes scattering not only by charged point defects and impurities, but also by charged threading dislocations, of concentration N{sub dis}. For an 0.45-{micro}m-thick InN layer grown on Al{sub 2}O{sub 3} by molecular beam epitaxy, having N{sub dis} = 5 x 10{sup 10} cm{sup -2}, determined by transmission electron microscopy, n(20 K) = 3.5 x 10{sup 18} cm{sup -3}, and {mu}(20 K) = 1055 cm{sup 2}/V-s, determined by Hall-effect measurements, the fitted values are N{sub D} = 4.7 x 10{sup 18} cm{sup -3} and N{sub A} = 1.2 x 10{sup 18} cm{sup -3}. The identities of the donors and acceptors are not known, although a comparison of N{sub D} with analytical data, and also with calculations of defect formation energies, suggests that a potential candidate for the dominant donor is H.

Look, D.C.; Lu, H.; Schaff, W.J.; Jasinski, J.; Liliental-Weber, Z.

2002-01-28

331

Review of genetics in age related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is a degenerative disease of the retina and the leading cause of blindness in industrialized countries. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. The prevalence of AMD increases with age. The adverse effect of smoking is well established. Genetic predisposition has been demonstrated by familial aggregation studies and twin studies. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. The chromosomes most commonly implicated are 1q25-31 and 10q26. In particular, variants in the gene for the complement factor H (CFH) and the genes PLEKHA1/LOC387715/HTRA1, Factor B (BF) and complement component 2 (C2) have been implicated as major risk or protective factors for the development of AMD. There have been some advances in the treatment of this condition; however, a complete cure remains remote but hopeful. Understanding the causative environmental and genetic interactions will facilitate the development of future preventive methods and treatments. PMID:18097986

Montezuma, Sandra R; Sobrin, Lucia; Seddon, Johanna M

2007-01-01

332

Biomarkers in frontotemporal lobar degenerations--progress and challenges.  

PubMed

Neuronal and glial changes associated with tau, TAR DNA binding protein of ?43 kDa (TDP-43), and fused in sarcoma (FUS) together constitute the pathologic spectrum of frontotemporal lobar degeneration (FTLD). Most patients with FTLD present with prominent behavior or language changes, sometimes accompanied by extrapyramidal symptoms or motor neuron disease. Identification of FTLD patients with mutations in genes for tau, TDP-43, and FUS lends strong support for their pathogenic roles in FTLD, and elucidation of their dysfunction will pave the way for development of substrate specific therapy. However, there remains no reliable biomarker for early detection of FTLD or prediction of underlying FTLD pathologic change. Clinical syndromes usually reflects the earliest affected brain regions where atrophy can be visualized on structural MRI, but neither clinical nor structural imaging-based biomarkers has been accurately correlated with underlying pathology on the individual patient level. Biochemical markers in the cerebrospinal fluid (CSF) have also been investigated in FTLD and related disorders, including amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP). However, their accuracy and pathologic significance need to be confirmed in future multi-center studies. Here we review the progress made in FTLD biomarkers, including clinical phenotype/feature characterization, neuropsychological analysis, CSF and plasma analytes, and patterns of brain atrophy and network dysfunction detectable on brain imaging. Given the pathologic overlap of FTLD with ALS and PSP, collaboration with specialists in those fields will be essential in the translation of promising FTLD biomarkers into clinical practice. PMID:21554923

Hu, William T; Trojanowski, John Q; Shaw, Leslie M

2011-12-01

333

Rare postpartum ruptured degenerated fibroid: a case report.  

PubMed

Spontaneous rupture of uterine fibroid is rarely encountered. We present a case of a 31-year-old who presented with acute abdominal pain at 9 weeks postpartum. On examination, the abdomen had diffuse tenderness, with rebound tenderness in the suprapubic area and in both iliac fossae. On ultrasonography, a 12.7 × 8.6 × 8.9-cm sized hyperechoic mass was visible on the posterior wall of the uterus. A large amount of fluid was visible in the paracolic gutters and the Pouch of Douglas (POD). The patient underwent an exploratory laparotomy. A ruptured, cystic degenerated uterine fibroid with active bleeding was found, as well as approximately half a liter of free, bloodstained peritoneal fluid and pus. Myomectomy was performed, followed by evacuation of the fluid and clots. The patient's postoperative course was uneventful. In conclusion, preoperative diagnosis of a perforated, uterine fibroid with spontaneous intra-abdominal hemorrhage is difficult; exploratory laparotomy is both diagnostic and therapeutic in this rare, life-threatening condition. PMID:24689652

Tan, Yiap L; Naidu, Aruku

2014-05-01

334

Degenerate four-wave mixing in triply resonant Kerr cavities  

SciTech Connect

We demonstrate theoretical conditions for highly efficient degenerate four-wave mixing in triply resonant nonlinear (Kerr) cavities. We employ a general and accurate temporal coupled-mode analysis in which the interaction of light in arbitrary microcavities is expressed in terms of a set of coupling coefficients that we rigorously derive from the full Maxwell equations. Using the coupled-mode theory, we show that light consisting of an input signal of frequency {omega}{sub 0}-{Delta}{omega} can, in the presence of pump light at {omega}{sub 0}, be converted with quantum-limited efficiency into an output shifted signal of frequency {omega}{sub 0}+{Delta}{omega}, and we derive expressions for the critical input powers at which this occurs. We find the critical powers in the order of 10 mW, assuming very conservative cavity parameters (modal volumes {approx}10 cubic wavelengths and quality factors {approx}1000). The standard Manley-Rowe efficiency limits are obtained from the solution of the classical coupled-mode equations, although we also derive them from simple photon-counting 'quantum' arguments. Finally, using a linear stability analysis, we demonstrate that maximal conversion efficiency can be retained even in the presence of self- and cross-phase modulation effects that generally act to disrupt the resonance condition.

Ramirez, David M.; Joannopoulos, J. D.; Soljacic, Marin [Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Rodriguez, Alejandro W. [Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); School of Science and Engineering, Harvard University, Cambridge, MA 02139 (United States); Hashemi, Hila; Johnson, Steven G. [Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2011-03-15

335

Neuroanatomy of Apathy and Disinhibition in Frontotemporal Lobar Degeneration  

PubMed Central

Objective To investigate the neural basis for the behavioral symptoms of frontotemporal lobar degeneration (FTLD) that cause the greatest caregiver distress. Background FTLD is a progressive neurodegenerative disease associated with behavioral disturbances. Group studies have related these behaviors to volume loss on MRI. Methods Forty caregivers of patients with the clinical diagnosis of FTLD completed the Neuropsychiatric Inventory. Twelve neuropsychiatric symptoms and the associated caregiver distress were assessed. Optimized voxel-based morphometry identified significant atrophy in subgroups of FTLD patients with isolated behavioral symptoms corresponding to the most distressing behaviors, and we correlated cortical atrophy directly with these distressing behavioral disorders in an unbiased group analysis. Results The greatest stressors for caregivers were apathy and disinhibition (p < 0.005 for both contrasts). Partially distinct areas of cortical atrophy were associated with these behaviors in both individual patients with these symptoms and group-wide analyses, including the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex in apathetic patients, and the medial orbital frontal cortex in disinhibited patients. Conclusions Caregiver stress in families of FTLD patients is due in large part to apathy and disinhibition. The anatomic distribution of cortical loss corresponding to these distressing social behaviors includes partially distinct areas within the frontal lobe. PMID:19158440

Massimo, Lauren; Powers, Chivon; Moore, Peachie; Vesely, Luisa; Avants, Brian; Gee, James; Libon, David J.; Grossman, Murray

2009-01-01

336

Degenerate four-wave mixing measurement in iodine vapor  

NASA Astrophysics Data System (ADS)

Degenerate four-wave mixing (DFWM) is a nonlinear optical process that has been developed as a detective tool for making quantitative measurements of gas dynamic properties in the various environments. This technique can be used to measure temperature and species concentration in both flames and plasma environments. The resulting coherent signal beam makes DFWM particularly attractive for luminous and harsh environments, compared to incoherent techniques, such as laser-induced fluorescence (LIF). Forward DFWM with self-stability of spilt-beam system has been demonstrated in iodine vapor. It's found that there exists no LIF because of collision quenching at atmospheric pressure and room temperature. But observed vivid DFWM spectroscopy (554-556nm) of iodine vapor at 0oC and room temperature. Furthermore, DFWM can probe non-fluorescing species. We describe a novel advanced sensor method for measuring temperature of gas flows using DFWM. This technique without suffering of severe quenching problems at atmospheric pressure is of importance to trace atom, molecular and radical in combustion diagnosis.

Wang, Wei-Bo; Chen, De-Ying; Fan, Rong-Wei; Yang, Jun

2008-12-01

337

Ocular Surface Temperature in Age-Related Macular Degeneration  

PubMed Central

Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value?>0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

Sodi, Andrea; Giacomelli, Giovanni; Corvi, Andrea; Menchini, Ugo

2014-01-01

338

Degenerate gaugino mass region and mono-boson collider signatures  

NASA Astrophysics Data System (ADS)

In this paper we discuss search strategies at the LHC for light electroweak gauginos which are mostly wino-like, Higgsino-like or an admixture. These states are typically degenerate with decay products that are less energetic and hence difficult to detect. In addition, their production cross sections at a hadron collider are suppressed compared to colored states such as the gluinos. In order to detect these states one needs to trigger on initial-or final-state radiation. Many previous analyses have focussed on mono-jet and mono-photon triggers. In this paper we argue and show that these triggers are unlikely to succeed, due to the large background from QCD backgrounds for the mono-jet searches and the fact that the pT distribution of the mono-photons are rapidly decreasing functions of pT. We show this with both an analytic calculation of photons in the initial-state radiation and also a detailed numerical analysis. We then argue that mono-Z triggers, from Z decaying into charged leptons may well provide the best search strategy, in particular for Higgsino-like and mixed cases.

Anandakrishnan, Archana; Carpenter, Linda M.; Raby, Stuart

2014-09-01

339

Radio Emission from Ultrashort-Period Double Degenerate Binaries  

NASA Astrophysics Data System (ADS)

Timing measurements of periodic X-ray pulses from two ultrashort-period double degenerate binaries, RX J1914+24 and RX J0806+15, show that the rates of change of their orbital periods are consistent with gravitational radiation losses. This contradicts the predictions of models which invoke mass transfer between the two white dwarfs. The X-ray emission is, therefore, unlikely to be powered by accretion processes. The unipolar inductor model explains the source of X-ray emission as electrical dissipation at the base of a flux tube, which connects the magnetic white dwarf to its companion. This model is most consistent with the observed X-ray pulse properties. A similar current system exists in the Jupiter-Io system, where a mildly relativistic electron current produces an auroral footprint at the base of the Io flux tube and highly polarized beamed radio emission by means of the electron cyclotron maser mechanism. Detection of radio emission from RX J1914+24 and RX J0806+15 would thus provide further support for the unipolar inductor model. We present theoretical predictions, based on a loss-cone-driven electron cyclotron maser model, of radio fluxes from systems with parameters similar to RX J1914+24 and RX J0806+15.

Willes, A. J.; Wu, K.; Kuncic, Z.

340

White matter degeneration in schizophrenia: a comparative diffusion tensor analysis  

NASA Astrophysics Data System (ADS)

Schizophrenia is a serious and disabling mental disorder. Diffusion tensor imaging (DTI) studies performed on schizophrenia have demonstrated white matter degeneration either due to loss of myelination or deterioration of fiber tracts although the areas where the changes occur are variable across studies. Most of the population based studies analyze the changes in schizophrenia using scalar indices computed from the diffusion tensor such as fractional anisotropy (FA) and relative anisotropy (RA). The scalar measures may not capture the complete information from the diffusion tensor. In this paper we have applied the RADTI method on a group of 9 controls and 9 patients with schizophrenia. The RADTI method converts the tensors to log-Euclidean space where a linear regression model is applied and hypothesis testing is performed between the control and patient groups. Results show that there is a significant difference in the anisotropy between patients and controls especially in the parts of forceps minor, superior corona radiata, anterior limb of internal capsule and genu of corpus callosum. To check if the tensor analysis gives a better idea of the changes in anisotropy, we compared the results with voxelwise FA analysis as well as voxelwise geodesic anisotropy (GA) analysis.

Ingalhalikar, Madhura A.; Andreasen, Nancy C.; Kim, Jinsuh; Alexander, Andrew L.; Magnotta, Vincent A.

2010-03-01

341

Seven New Loci Associated with Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10?8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10?8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

2013-01-01

342

Genetic & Neuronanatomic Associations in Sporadic Frontotemporal Lobar Degeneration  

PubMed Central

Genome-wide association studies have identified SNPs that are sensitive for tau or TDP-43 pathology in frontotemporal lobar degeneration (FTLD). Neuroimaging analyses have revealed distinct distributions of disease in FTLD patients with genetic mutations. However, genetic influences on neuroanatomical structure in sporadic FTLD have not been assessed. In this report we use novel multivariate tools, eigenanatomy and sparse canonical correlation analysis (SCCAN), to identify associations between SNPs and neuroanatomical structure in sporadic FTLD. MRI analyses revealed that rs8070723 (MAPT) was associated with grey matter variance in the temporal cortex. DTI analyses revealed that rs1768208 (MOBP), rs646776 (near SORT1) and rs5848 (PGRN) were associated with white matter variance in the midbrain and superior longitudinal fasciculus. In an independent autopsy series we observed that rs8070723 and rs1768208 conferred significant risk of tau pathology relative to TDP-43, and rs646776 conferred increased risk of TDP-43 pathology relative to tau. Identified brain regions and SNPs may help provide an in vivo screen for underlying pathology in FTLD and contribute to our understanding of sporadic FTLD. PMID:24373676

McMillan, Corey T.; Toledo, Jon B.; Avants, Brian B.; Cook, Philip A.; Wood, Elisabeth M.; Suh, Eunran; Irwin, David J.; Powers, John; Olm, Christopher; Elman, Lauren; McCluskey, Leo; Schellenberg, Gerard D.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Grossman, Murray

2014-01-01

343

Age-Related Macular Degeneration: Genetics and Biology Coming Together  

PubMed Central

Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. PMID:24773320

Fritsche, Lars G.; Fariss, Robert N.; Stambolian, Dwight; Abecasis, Goncalo R.; Curcio, Christine A.

2014-01-01

344

Mucoid degeneration of the anterior cruciate ligament: Management and outcome  

PubMed Central

Background: Mucoid degeneration (MD) is a rare pathological affection of the anterior cruciate ligament (ACL). Mucinous material within the substance of ACL produces pain and limited motion in the knee. This series describes the clinicoradiological presentation of patients with mucoid ACL, partial arthroscopic debridement of ACL and outcomes. Materials and Methods: During a period of 3 years, 11 patients were included based upon the clinical suspicion, magnetic resonance imaging (MRI) findings, arthroscopic features and histopathologic confirmation of MD of ACL. Result: Six patients were male and five were female with median age of 40 years (range 21-59 years). All patients complained of knee pain with median duration of 5 months (range 1-24 months). All patients had painful deep flexion with 63.6% (N = 7) reporting trivial trauma before the onset of symptoms. MRI revealed MD of ACL in all with associated cyst in three patients. Partial debridement of ACL was done in ten and complete in one patient. None of them required notchplasty. Histopathology confirmed the diagnosis in all of them. At the mean followup of 13.81 months (range 6-28 months), all patients regained complete flexion and none complained of instability. Conclusion: Prior knowledge of condition with high index of suspicion and careful interpretation of MRI can establish the diagnosis preoperatively. It responds well to partial debridement of ACL and mucinous material without development of instability. PMID:24741143

Pandey, Vivek; Suman, CPS; Sharma, Swati; Rao, Sripathi P; Kiran Acharya, KV; Sambaji, Charudutt

2014-01-01

345

Terrien's Marginal Degeneration Accompanied by Latticed Stromal Opacities  

PubMed Central

ABSTRACT Purpose We report a case of Terrien’s marginal degeneration (TMD) with a unilaterally typical narrow band of peripheral corneal stroma thinning, accompanied by the presence of an unusual network of opacities diffusing throughout the anterior stroma layers. Case Report A 43-year-old woman presented with superior nasal peripheral corneal thinning and an unusual network of polygonal stromal opacities in the anterior corneal stroma of the right eye. Latticed corneal changes were unusually extensive and distributed diffusely in the stroma. No abnormalities were found in the corneal epithelium and in the basal epithelial cells. No noticeable changes were found in the left eye. Because of a progressively worse ocular irritation of the right eye, a diagnosis of TMD was made for this patient. Conclusions This case of TMD accompanied by keratopathy was unusual. The branching stromal lattice pattern of the corneal opacities was difficult to distinguish from lattice corneal dystrophy. In this case, the polygonal stromal opacities were located in the anterior corneal stroma and therefore were distinguished from a similar manifestation in posterior crocodile shagreen. PMID:24681833

Zhang, Yibing; Jia, Hui

2014-01-01

346

Anterior opercular syndrome in frontotemporal lobar degeneration with ubiquitin-only immunoreactive neuronal changes.  

PubMed

This paper presents for the first time an anterior opercular syndrome in association with a gait disorder, dropped head syndrome, dysphagia, and sialorrhea in a neuropathologically proven case of frontotemporal lobar degeneration with ubiquitin inclusions. PMID:17539954

Rektorova, I; Matej, R

2007-06-01

347

Quantum degenerate Bose-Fermi mixture of chemically different atomic species with widely tunable interactions  

E-print Network

We have created a quantum degenerate Bose-Fermi mixture of [superscript 23]Na and [superscript 40]K with widely tunable interactions via broad interspecies Feshbach resonances. Over 30 Feshbach resonances between [superscript ...

Park, Jee Woo

348

[Correlation of the degeneration of the AC joint (acromioclavicular) and rupture of the rotator cuff].  

PubMed

During the past various factors were quoted to be causative of a degeneration of the rotator cuff. In this study 122 shoulder specimen, aged 58-95 years, were dissected. A high correlation between severe degeneration of the ac-joint and rupture of the rotator cuff was found. The correlation was even higher between distally pointing osteophytes and cuff ruptures. The results demand to clearly define the degeneration of the ac-joint and the rotator cuff in patients suffering from shoulder pain. A simultaneous occurrence has to be considered. If conservative treatment fails in patients with cuff tear and ac-joint degeneration, surgical revision is recommended. This should comprise: 1. suture of the cuff-rupture 2. excision of the coraco-acromial ligament 3. anterior acromioplasty according to Neer 4. excision of the outer end of the clavicle PMID:2149245

Jerosch, J; Müller, T; Sons, H U; Castro, W H

1990-01-01

349

Primary neuronal degeneration in the guinea pig effects on spontaneous rate-type  

E-print Network

Acoustic overexposure can cause death of cochlear nerve fibers, even if elevations in cochlear sensitivity are reversible and even if there is no hair cell loss. We hypothesized that this primary neural degeneration does ...

Furman, Adam C. (Adam Charles)

2013-01-01

350

Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice.  

PubMed

Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases. PMID:25318560

Galli, Soledad; Lopes, Douglas M; Ammari, Rachida; Kopra, Jaakko; Millar, Sarah E; Gibb, Alasdair; Salinas, Patricia C

2014-01-01

351

Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice  

PubMed Central

Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases. PMID:25318560

Galli, Soledad; Lopes, Douglas M.; Ammari, Rachida; Kopra, Jaakko; Millar, Sarah E.; Gibb, Alasdair; Salinas, Patricia C.

2014-01-01

352

Use of Immunosuppressive Agents for Treatment of Age-related Macular Degeneration (AMD) and Diabetic Retinopathy  

Cancer.gov

The National Eye Institute, Laboratory of Immunology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immunosuppressive agents for the treatment of age related macular degeneration.

353

Quantum time ordering and degeneracy. II: Coherent population transfer between degenerate states  

E-print Network

We find conditions required to achieve complete population transfer, via coherent population trapping, from an initial state to a designated final state at a designated time in a degenerate $n$-state atom, where transitions are caused by an external interaction. In systems with degenerate states there is no time ordering. Analytic expressions have been found for transition probabilities in a degenerate $n$-state atom interacting with a strong external field that gives a common time dependence to all of the transition matrix elements. Except for solving a simple $n^{th}$ order equation to determine eigenvalues of dressed states, the method is entirely analytic. These expressions may be used to control electron populations in degenerate $n$-state atoms. Examples are given for $n=2$ and $n=3$.

Kh. Yu. Rakhimov; Kh. Kh. Shakov; J. H. McGuire

2003-08-02

354

The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration  

PubMed Central

Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity. PMID:24781186

Wang, Shiuan; Tan, Kai Li; Agosto, Melina A.; Xiong, Bo; Yamamoto, Shinya; Sandoval, Hector; Jaiswal, Manish; Bayat, Vafa; Zhang, Ke; Charng, Wu-Lin; David, Gabriela; Duraine, Lita; Venkatachalam, Kartik; Wensel, Theodore G.; Bellen, Hugo J.

2014-01-01

355

Residual abilities in age-related macular degeneration to process spatial frequencies during natural scene  

E-print Network

-related macular degeneration (AMD) is the first cause of central vision loss in the elderly population many daily activities (Mangione et al., 1999), such as reading (Legge et al., 1992; Fine & Peli, 1995

Alleysson, David

356

Alpha-Synuclein Disrupted Dopamine Homeostasis Leads to Dopaminergic Neuron Degeneration in Caenorhabditis elegans  

PubMed Central

Disruption of dopamine homeostasis may lead to dopaminergic neuron degeneration, a proposed explanation for the specific vulnerability of dopaminergic neurons in Parkinson's disease. While expression of human ?-synuclein in C. elegans results in dopaminergic neuron degeneration, the effects of ?-synuclein on dopamine homeostasis and its contribution to dopaminergic neuron degeneration in C. elegans have not been reported. Here, we examined the effects of ?-synuclein overexpression on worm dopamine homeostasis. We found that ?-synuclein expression results in upregulation of dopamine synthesis and content, and redistribution of dopaminergic synaptic vesicles, which significantly contribute to dopaminergic neuron degeneration. These results provide in vivo evidence supporting a critical role for dopamine homeostasis in supporting dopaminergic neuron integrity. PMID:20174477

Pehek, Elizabeth A.; Moise, Alex R.; Huang, Ying; Palczewski, Krzysztof; Feng, Zhaoyang

2010-01-01

357

Selective degeneration of CA1 pyramidal cells by chronic application of bismuth.  

PubMed

The heavy metal bismuth induces a new type of selective neuronal degeneration that shares some common aspects with that seen following hypoxia and ischemia. Continuous application of 3 microns bismuth to organotypic cultures of rat hippocampus resulted after 2-3 weeks in selective degeneration of CA1 pyramidal cells, while CA3 pyramidal cells, dentate granule cells, and subicular neurons were resistant. With 10 microns bismuth, the majority of hippocampal neurons degenerated. The addition of 20 microns MK-801, a noncompetitive NMDA-antagonist, during the entire culturing period failed to prevent neuronal degeneration induced by 3 microns bismuth. GABA-immunoreactive interneurons were also affected by bismuth, but were generally less sensitive than CA1 pyramidal cells. Acute application of up to 100 microns bismuth did not change the electrophysiological properties of CA1 pyramidal cells. PMID:7951695

Müller, M; Rietschin, L; Grogg, F; Streit, P; Gähwiler, B H

1994-04-01

358

Reorganization of Visual Processing in Macular Degeneration Is Not Specific to the "Preferred Retinal Locus"  

E-print Network

Recent work has shown that foveal cortex, deprived of its normal bottom-up input as a result of macular degeneration (MD), begins responding to stimuli presented to a peripheral retinal location. However, these studies ...

Baker, Chris I.

359

Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration  

MedlinePLUS

... macular degeneration NIH-funded research helps unravel the biology of AMD Three studies reported in Nature Genetics ... to provide more specific clues to the underlying biology of the disease. "Compared to common variants, rare ...

360

ForPeerReview Striatal Degeneration Impairs Language Learning: Evidence from  

E-print Network

ForPeerReview Striatal Degeneration Impairs Language Learning: Evidence from Huntington's Disease. Running title: Striatum and language rule learning Keywords : Huntington's disease, striatum, language, rule learning, executive control Abbreviations: HD = Huntington's disease; TFC = total functional

Paris-Sud XI, Université de

361

Effect of trapping in a degenerate plasma in the presence of a quantizing magnetic field  

SciTech Connect

Effect of trapping as a microscopic phenomenon in a degenerate plasma is investigated in the presence of a quantizing magnetic field. The plasma comprises degenerate electrons and non-degenerate ions. The presence of the quantizing magnetic field is discussed briefly and the effect of trapping is investigated by using the Fermi-Dirac distribution function. The linear dispersion relation for ion acoustic wave is derived in the presence of the quantizing magnetic field and its influence on the propagation characteristics of the linear ion acoustic wave is discussed. Subsequently, fully nonlinear equations for ion acoustic waves are used to obtain the Sagdeev potential and the investigation of solitary structures. The formation of solitary structures is studied both for fully and partially degenerate plasmas in the presence of a quantizing magnetic field. Both compressive and rarefactive solitons are obtained for different conditions of temperature and magnetic field.

Shah, H. A.; Iqbal, M. J.; Qureshi, M. N. S. [Department of Physics, GC University, Lahore 54000 (Pakistan); Tsintsadze, N. [Department of Physics, GC University, Lahore 54000 (Pakistan); Institute of Physics, Tbilisi 0177 (Georgia); Masood, W. [Theoretical Physics Division, PINSTECH, P.O. Nilore, Islamabad (Pakistan)

2012-09-15

362

A disease-specific metabolic brain network associated with corticobasal degeneration.  

PubMed

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (?24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes. PMID:25208922

Niethammer, Martin; Tang, Chris C; Feigin, Andrew; Allen, Patricia J; Heinen, Lisette; Hellwig, Sabine; Amtage, Florian; Hanspal, Era; Vonsattel, Jean Paul; Poston, Kathleen L; Meyer, Philipp T; Leenders, Klaus L; Eidelberg, David

2014-11-01

363

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration[S  

PubMed Central

Light-induced retinal degeneration (LIRD) in albino rats causes apoptotic photoreceptor cell death. Ceramide is a second messenger for apoptosis. We tested whether increases in ceramide mediate photoreceptor apoptosis in LIRD and if inhibition of ceramide synthesis protects the retina. Sprague-Dawley rats were exposed to 2,700 lux white light for 6 h, and the retinal levels of ceramide and its intermediary metabolites were measured by GC-MS or electrospray ionization tandem mass spectrometry. Enzymes of the de novo biosynthetic and sphingomyelinase pathways of ceramide generation were assayed, and gene expression was measured. The dosage and temporal effect of the ceramide synthase inhibitor FTY720 on the LIRD retina were measured by histological and functional analyses. Retinal ceramide levels increased coincident with the increase of dihydroceramide at various time points after light stress. Light stress in retina induces ceramide generation predominantly through the de novo pathway, which was prevented by systemic administration of FTY720 (10 mg/kg) leading to the protection of retinal structure and function. The neuroprotection of FTY720 was independent of its immunosuppressive action. We conclude that ceramide increase by de novo biosynthesis mediates photoreceptor apoptosis in the LIRD model and that inhibition of ceramide production protects the retina against light stress. PMID:23468130

Chen, Hui; Tran, Julie-Thu A.; Eckerd, Annette; Huynh, Tuan-Phat; Elliott, Michael H.; Brush, Richard S.; Mandal, Nawajes A.

2013-01-01

364

Effects of aging and spinal degeneration on mechanical properties of lumbar supraspinous and interspinous ligaments  

Microsoft Academic Search

Background context: The effects of aging and spinal degeneration on the mechanical properties of spinal ligaments are still unknown, although there have been several studies demonstrating those of normal spinal ligaments.Purpose: To investigate the mechanical properties of the human posterior spinal ligaments in human lumbar spine, and their relation to age and spinal degeneration parameters.Study design\\/setting: Destructive uniaxial tensile tests

Takahiro Iida; Kuniyoshi Abumi; Yoshihisa Kotani; Kiyoshi Kaneda

2002-01-01

365

Mfrp, a gene encoding a frizzled related protein, is mutated in the mouse retinal degeneration 6  

Microsoft Academic Search

The autosomal recessive mouse mutation retinal degeneration 6 (rd6 ) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolog of the human membrane-type frizzled-related protein (Mfrp) gene that results in the skipping

Shuhei Kameya; Norman L. Hawes; Bo Chang; John R. Heckenlively; J urgen K. Naggert; Patsy M. Nishina

2002-01-01

366

Retinal Degeneration in the rd Mouse in the Absence of c-fos  

Microsoft Academic Search

PURPOSE. Apoptosis is the final common death pathway of photoreceptors in light-induced retinal degeneration and in several animal models for retinal dystrophy. To date, little is known about gene regulation of apoptosis in the retina. The expression of the immediate early gene c-fos is upregu- lated concomitant with apoptosis in light-induced photoreceptor degeneration and in the rd mouse, an animal

Farhad Hafezi; Mathias Abegg; Christian Grimm; Andreas Wenzel; Kurt Munz; Jorg Stilrmer; Debora B. Farber; Charlotte E. Rente

1998-01-01

367

Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease  

Microsoft Academic Search

Slowing or halting the progressive dopaminergic (DA) degeneration in Parkinson's disease (PD) would delay the onset and development of motor symptoms, prolong the efficacy of pharmacotherapies and decrease drug-induced side-effects. We tested the potential of two orally administered novel immunophilin ligands to protect against DA degeneration in two animal models of PD. First, in an MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model, we

Lauren C. Costantini; Douglas Cole; Ole Isacson

2001-01-01

368

Holmes' Tremor Associated with Bilateral Hypertrophic Olivary Degeneration Following Brain Stem Hemorrhage: A Case Report  

PubMed Central

Holmes' tremor is a condition characterized by a mixture of postural, rest, and action tremors due to midbrain lesions in the vicinity of the red nucleus. Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubro-olivary pathway and may present clinically as Holmes tremor. We report on a 59-year-old female patient who developed Holmes tremor in association with bilateral HOD, following brain stem hemorrhage. PMID:25340035

Kim, Min Kyu; Park, Se-Hyuck; Yoon, Dae Young

2014-01-01

369

Corneal topography in asymptomatic family members of a patient with pellucid marginal degeneration  

Microsoft Academic Search

PURPOSE: To report corneal topographic patterns in asymptomatic family members of a patient with pellucid marginal degeneration.METHODS: Computer-assisted corneal topography was used to study the corneas of five family members of a patient with pellucid marginal degeneration.RESULTS: In all five asymptomatic family members, corneal biomicroscopy was normal. Corneal topography, however, showed various abnormalities in different members of this family, particularly

Ruth M Santo; Samir J Bechara; Newton Kara-José

1999-01-01

370

The role of striatal metabotropic glutamate receptors in degeneration of dopamine neurons: Review article  

Microsoft Academic Search

Summary.  ?Degeneration of dopaminergic nigrostriatal neurons is a primary cause of Parkinson's disease. Oxidative stress, excitotoxicity\\u000a and mitochondrial failure are thought to be key mechanisms resposible for degeneration of dopaminergic cells. We found that\\u000a the selective antagonist of the mGluR5 subtype MPEP in a dose of 5?mg\\/kg diminshed basal and veratridine (100??M)-stimulated dopamine release in rat striatum in an in vivo

K. Go?embiowska; J. Konieczny; K. Ossowska; S. Wolfarth

2002-01-01

371

MRI of spinal cord and brain lesions in subacute combined degeneration  

Microsoft Academic Search

Subacute combined degeneration is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord and\\u000a even more rarely of the pyramidal and spinocerebellar tracts and cerebellum. We present the initial and follow-up MRI appearances\\u000a in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B12 deficiency. The

V. K. Katsaros; F. X. Glocker; B. Hemmer; M. Schumacher

1998-01-01

372

Methyl group deficiency in nerve tissue: A hypothesis to explain the lesion of subacute combined degeneration  

Microsoft Academic Search

Summary  The pattern of degeneration induced in the spinal cords and peripheral nerves of 4 monkeys exposed to nitrous oxide resembles\\u000a subacute combined degeneration found in man with untreated vitamin B12 deficiency. Our findings indicate that nitrous oxide directly inhibits the folate dependent methionine synthetase reaction.\\u000a This ultimately results in ‘methyl group deficiency’ with consequent defective remethylation of essential constituents of

J. J. Dinn; D. G. Weir; S. McCann; B. Reed; P. Wilson; J. M. Scott

1980-01-01

373

Expression of the neuroprotective slow Wallerian degeneration (WldS) gene in non-neuronal tissues  

Microsoft Academic Search

BACKGROUND: The slow Wallerian Degeneration (WldS) gene specifically protects axonal and synaptic compartments of neurons from a wide variety of degeneration-inducing stimuli, including; traumatic injury, Parkinson's disease, demyelinating neuropathies, some forms of motor neuron disease and global cerebral ischemia. The WldS gene encodes a novel Ube4b-Nmnat1 chimeric protein (WldS protein) that is responsible for conferring the neuroprotective phenotype. How the

Thomas M Wishart; David G Brownstein; Derek Thomson; Anca M Tabakova; Katherine M Boothe; Jack W Tsao; Thomas H Gillingwater

2009-01-01

374

Spontaneous poisoning by Solanum subinerme Jack as a cause of cerebellar cortical degeneration in cattle.  

PubMed

The present work reports cerebellar degeneration in cattle associated with the ingestion of Solanum subinerme in northern Brazil. The main clinical signs were periodic crises with loss of balance, falls, opisthotonus, and nystagmus. The histological lesions consisted of diffuse vacuolation of the perikaryon of the Purkinje neurons, followed by the loss of these cells and their substitution by Bergman glia. It is concluded that S. subinerme is another species of Solanum that causes cerebellar degeneration in cattle. PMID:24561122

Lima, Everton Ferreira; Riet-Correa, Franklin; de Medeiros, Rosane Maria Trindade

2014-05-01

375

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.  

PubMed

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness. PMID:21297615

Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D; Fowler, Benjamin J; Cho, Won Gil; Kleinman, Mark E; Ponicsan, Steven L; Hauswirth, William W; Chiodo, Vince A; Karikó, Katalin; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W; Braun, Robert E; Hinton, David R; Zhang, Qing; Grossniklaus, Hans E; Provis, Jan M; Madigan, Michele C; Milam, Ann H; Justice, Nikki L; Albuquerque, Romulo J C; Blandford, Alexander D; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R; Ambati, Balamurali K; Rudin, Charles M; Chong, Mark M W; Provost, Patrick; Kugel, Jennifer F; Goodrich, James A; Dunaief, Joshua L; Baffi, Judit Z; Ambati, Jayakrishna

2011-03-17

376

Excitotoxicity and Wallerian degeneration as a processes related to cell death in nervous system.  

PubMed

Cell death is one of the processes that are currently extensively studied. Beside the commonly used terminology regarding cell death, i.e. apoptosis, autophagy, necrosis, and cornification, in recent years there has been a growing number of additional definitions of this process, such as mitotic catastrophe, anoikis, entosis, paraptosis, pyroptosis, pyronecrosis, excitotoxicity, and Wallerian degeneration, which are described in 2009 by the Nomenclature Committee on Cell Death as atypical. The recent report of that Committee significantly alter the classification and nomenclature of the cell death processes, in which excitotoxicity and Wallerian degeneration have not been taken into account. Thus the present review describes excitotoxicity, and Wallerian degeneration, as two processes associated to cell death phenomena characteristic for nervous system. Excitotoxicity is a neuronal death caused by excessive, or prolonged activation of receptors for the excitatory amino acids. Depending on the intensity of the initiating stimulus, the excitotoxicity may overlap with other types of cell death such as apoptosis and necrosis. Wallerian degeneration is a process that results when a nerve fiber is cut or crushed, in which the part of the axon separated from the neuron's cell body degenerates distal to the injury. Wallerian degeneration is not a typical cell death mechanism, since neurons undergoing this process remain alive. PMID:24442984

Dzia?o, Joanna; Tokarz-Deptu?a, Beata; Deptu?a, Wies?aw

2013-06-01

377

Degeneration of neuronal cell bodies following axonal injury in Wld(S) mice.  

PubMed

The phenotype of Wld(S) ("slow Wallerian degeneration") mice demonstrates prolonged survival of injured axons. However, whether the Wld(S) mutation delays degeneration of the neuronal cell body following axonal injury is unclear. We used a retrograde model of axonal transport failure in Wld(S) mice to test whether the mutant Wld(S) protein has any beneficial effect on the neuronal cell body. Retrograde axonal transport was physically blocked by optic nerve crush and confirmed by the absence of Fluoro-Gold labeling in wild-type and in Wld(S) mice. After this axonal injury, there was marked protection of axonal degeneration in the Wld(S) phenotype, as confirmed by immunohistochemistry and electron microscopy. However, the Wld(S) protein, localized in the nucleus of retinal ganglion cells, did not prevent or delay degeneration of the retinal ganglion cell body, confirmed by TUNEL staining and Fluoro-Gold labeling. These results imply that, after axonal injury, Wallerian degeneration of axons and degeneration of the neuronal cell body have different mechanisms, which are autonomous and independent of each other. Although the Wld(S) phenotype can be used to demonstrate stable enucleate axons, the mutation is unlikely to protect neurons in neurodegenerative diseases in which there is failure of retrograde transport. PMID:17022038

Wang, Ai Ling; Yuan, Ming; Neufeld, Arthur H

2006-12-01

378

Sodium and potassium currents influence Wallerian degeneration of injured Drosophila axons.  

PubMed

Axons degenerate after injury and in neuropathies and disease via a self-destruction program whose mechanism is poorly understood. Axons that have lost connection to their cell bodies have altered electrical and synaptic activities, but whether such changes play a role in the axonal degeneration process is not clear. We have used a Drosophila model to study the Wallerian degeneration of motoneuron axons and their neuromuscular junction synapses. We found that degeneration of the distal nerve stump after a nerve crush is greatly delayed when there is increased potassium channel activity (by overexpression of two different potassium channels, Kir2.1 and dORK?-C) or decreased voltage-gated sodium channel activity (using mutations in the para sodium channel). Conversely, degeneration is accelerated when potassium channel activity is decreased (by expressing a dominant-negative mutation of Shaker). Despite the effect of altering voltage-gated sodium and potassium channel activity, recordings made after nerve crush demonstrated that the distal stump does not fire action potentials. Rather, a variety of lines of evidence suggest that the sodium and potassium channels manifest their effects upon degeneration through changes in the resting membrane potential, which in turn regulates the level of intracellular free calcium within the isolated distal axon. PMID:24285879

Mishra, Bibhudatta; Carson, Ross; Hume, Richard I; Collins, Catherine A

2013-11-27

379

Quality of optometry referrals to neovascular age-related macular degeneration clinic: a prospective study  

PubMed Central

Objectives To evaluate the quality of referrals to a neovascular age-related macular degeneration clinic from optometrists using the standard Rapid Access Referral Form (RARF) from the Royal College of Ophthalmologists. Design A prospective study. Prospective data were gathered from all optometry referrals using the RARF, between the periods of December 2006 to August 2009. These were assessed for accuracy of history, clinical signs and final diagnosis as compared to a macula expert. Setting Highlands NHS Trust. Participants All patients referred to the eye department at NHS Highlands Trust using the RARF. Main outcome measures The symptoms of neovascular age-related macular degeneration correctly identified by optometrists, and the signs of neovascular age-related macular degeneration correctly identified by optometrists. Results Fifty-four RARFs were received during this period, there was an overall agreement with symptomatology in 57.4% of cases. Optometrists scored less well in recognizing the clinical signs of neovascular age-related macular degeneration, with the poorest scores for recognizing macular oedema (44.4%) and drusen (51.9%). Twenty (37%) patients referred had neovascular age-related macular degeneration. Conclusions RARFs make up the minority of referrals to the neovascular age-related macular degeneration clinic. Optometrists find it difficult to accurately elicit the signs of macula disease. PMID:21912730

Muen, Wisam J; Hewick, Simon A

2011-01-01

380

Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats  

PubMed Central

Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30?s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration. PMID:23532265

Issy, A.C.; Castania, V.; Castania, M.; Salmon, C.E.G.; Nogueira-Barbosa, M.H.; Bel, E. Del; Defino, H.L.A.

2013-01-01

381

Identification of Degenerate Nuclei and Development of a SCAR Marker for Flammulina velutipes  

PubMed Central

Flammulina velutipes is one of the major edible mushrooms in the world. Recently, abnormalities that have a negative impact on crop production have been reported in this mushroom. These symptoms include slow vegetative growth, a compact mycelial mat, and few or even no fruiting bodies. The morphologies and fruiting capabilities of monokaryons of wild-type and degenerate strains that arose through arthrospore formation were investigated through test crossing. Only one monokaryotic group of the degenerate strains and its hybrid strains showed abnormal phenotypes. Because the monokaryotic arthrospore has the same nucleus as the parent strain, these results indicated that only one aberrant nucleus of the two nuclei in the degenerate strain was responsible for the degeneracy. A sequence-characterized amplified region marker that is linked to the degenerate monokaryon was identified based on a polymorphic sequence that was generated using random primers. Comparative analyses revealed the presence of a degenerate-specific genomic region in a telomere, which arose via the transfer of a genomic fragment harboring a putative helicase gene. Our findings have narrowed down the potential molecular targets responsible for this phenotype for future studies and have provided a marker for the detection of degenerate strains. PMID:25221949

Kim, Sun Young; Kim, Kyung-Hee; Im, Chak Han; Ali, Asjad; Lee, Chang Yun; Kong, Won-Sik; Ryu, Jae-San

2014-01-01

382

The cholinergic system in aging and neuronal degeneration.  

PubMed

The basal forebrain cholinergic complex comprising medial septum, horizontal and vertical diagonal band of Broca, and nucleus basalis of Meynert provides the mayor cholinergic projections to the cerebral cortex and hippocampus. The cholinergic neurons of this complex have been assumed to undergo moderate degenerative changes during aging, resulting in cholinergic hypofunction that has been related to the progressing memory deficits with aging. However, the previous view of significant cholinergic cell loss during aging has been challenged. Neuronal cell loss was found predominantly in pathological aging, such as Alzheimer's disease, while normal aging is accompanied by a gradual loss of cholinergic function caused by dendritic, synaptic, and axonal degeneration as well as a decrease in trophic support. As a consequence, decrements in gene expression, impairments in intracellular signaling, and cytoskeletal transport may mediate cholinergic cell atrophy finally leading to the known age-related functional decline in the brain including aging-associated cognitive impairments. However, in pathological situations associated with cognitive deficits, such as Parkinsons's disease, Down-syndrome, progressive supranuclear palsy, Jakob-Creutzfeld disease, Korsakoff's syndrome, traumatic brain injury, significant degenerations of basal forebrain cholinergic cells have been observed. In presenile (early onset), and in the advanced stages of late-onset Alzheimer's disease (AD), a severe loss of cortical cholinergic innervation has extensively been documented. In contrast, in patients with mild cognitive impairment (MCI, a prodromal stage of AD), and early forms of AD, apparently no cholinergic neurodegeneration but a loss of cholinergic function occurs. In particular imbalances in the expression of NGF, its precursor proNGF, the high and low NGF receptors, trkA and p75NTR, respectively, changes in acetylcholine release, high-affinity choline uptake, as well as alterations in muscarinic and nicotinic acetylcholine receptor expression may contribute to the cholinergic dysfunction. These observations support the suggestion of a key role of the cholinergic system in the functional processes that lead to AD. Malfunction of the cholinergic system may be tackled pharmacologically by intervening in cholinergic as well as neurotrophic signaling cascades that have been shown to ameliorate the cholinergic deficit at early stages of the disease, and slow-down the progression. However, in contrast to many other, dementing disorders, in AD the cholinergic dysfunctions are accompanied by the occurrence of two major histopathological hallmarks such as ?-amyloid plaques and neurofibrillary tangles, provoking the question whether they play a particular role in inducing or mediating cholinergic dysfunction in AD. Indeed, there is abundant evidence that ?-amyloid may trigger cholinergic dysfunction through action on ?7 nicotinic acetylcholine receptors, affecting NGF signaling, mediating tau phosphorylation, interacting with acetylcholinesterase, and specifically affecting the proteome in cholinergic neurons. Therefore, an early onset of an anti ?-amyloid strategy may additionally be potential in preventing aging-associated cholinergic deficits and cognitive impairments. PMID:21145918

Schliebs, Reinhard; Arendt, Thomas

2011-08-10

383

Does lumbar spinal degeneration begin with the anterior structures? A study of the observed epidemiology in a community-based population  

PubMed Central

Background- Prior studies that have concluded that disk degeneration uniformly precedes facet degeneration have been based on convenience samples of individuals with low back pain. We conducted a study to examine whether the view that spinal degeneration begins with the anterior spinal structures is supported by epidemiologic observations of degeneration in a community-based population. Methods- 361 participants from the Framingham Heart Study were included in this study. The prevalences of anterior vertebral structure degeneration (disk height loss) and posterior vertebral structure degeneration (facet joint osteoarthritis) were characterized by CT imaging. The cohort was divided into the structural subgroups of participants with 1) no degeneration, 2) isolated anterior degeneration (without posterior degeneration), 3) combined anterior and posterior degeneration, and 4) isolated posterior degeneration (without anterior structure degeneration). We determined the prevalence of each degeneration pattern by age group < 45, 45-54, 55-64, ?65. In multivariate analyses we examined the association between disk height loss and the response variable of facet joint osteoarthritis, while adjusting for age, sex, BMI, and smoking. Results- As the prevalence of the no degeneration and isolated anterior degeneration patterns decreased with increasing age group, the prevalence of the combined anterior/posterior degeneration pattern increased. 22% of individuals demonstrated isolated posterior degeneration, without an increase in prevalence by age group. Isolated posterior degeneration was most common at the L5-S1 and L4-L5 spinal levels. In multivariate analyses, disk height loss was independently associated with facet joint osteoarthritis, as were increased age (years), female sex, and increased BMI (kg/m2), but not smoking. Conclusions- The observed epidemiology of lumbar spinal degeneration in the community-based population is consistent with an ordered progression beginning in the anterior structures, for the majority of individuals. However, some individuals demonstrate atypical patterns of degeneration, beginning in the posterior joints. Increased age and BMI, and female sex may be related to the occurrence of isolated posterior degeneration in these individuals. PMID:21914197

2011-01-01

384

Macular degeneration affects eye movement behavior during visual search  

PubMed Central

Patients with a scotoma in their central vision (e.g., due to macular degeneration, MD) commonly adopt a strategy to direct the eyes such that the image falls onto a peripheral location on the retina. This location is referred to as the preferred retinal locus (PRL). Although previous research has investigated the characteristics of this PRL, it is unclear whether eye movement metrics are modulated by peripheral viewing with a PRL as measured during a visual search paradigm. To this end, we tested four MD patients in a visual search paradigm and contrasted their performance with a healthy control group and a healthy control group performing the same experiment with a simulated scotoma. The experiment contained two conditions. In the first condition the target was an unfilled circle hidden among c-shaped distractors (serial condition) and in the second condition the target was a filled circle (pop-out condition). Saccadic search latencies for the MD group were significantly longer in both conditions compared to both control groups. Results of a subsequent experiment indicated that this difference between the MD and the control groups could not be explained by a difference in target selection sensitivity. Furthermore, search behavior of MD patients was associated with saccades with smaller amplitudes toward the scotoma, an increased intersaccadic interval and an increased number of eye movements necessary to locate the target. Some of these characteristics, such as the increased intersaccadic interval, were also observed in the simulation group, which indicate that these characteristics are related to the peripheral viewing itself. We suggest that the combination of the central scotoma and peripheral viewing can explain the altered search behavior and no behavioral evidence was found for a possible reorganization of the visual system associated with the use of a PRL. Thus the switch from a fovea-based to a PRL-based reference frame impairs search efficiency. PMID:24027546

Van der Stigchel, Stefan; Bethlehem, Richard A. I.; Klein, Barrie P.; Berendschot, Tos T. J. M.; Nijboer, Tanja C. W.; Dumoulin, Serge O.

2013-01-01

385

Anatomy of Disturbed Sleep in Pallido-Ponto-Nigral Degeneration  

PubMed Central

Objective Pallido-ponto-nigral degeneration (PPND), caused by an N279K mutation of the MAPT gene, is 1 of a family of disorders collectively referred to as frontotemporal dementia and parkinsonism linked to chromosome 17. This study aims to characterize the nature of the sleep disturbance in PPND and compare these findings to those in other progressive neurological illnesses. Pathological findings are also provided. Methods Ten subjects were recruited from the PPND kindred; 5 affected and 5 unaffected. The subjects underwent clinical assessment, polysomnography, and wrist actigraphy. Available sleep-relevant areas (pedunculopontine/laterodorsal tegmentum, nucleus basalis of Meynert, thalamus, and locus ceruleus) of affected subjects were analyzed postmortem. Results The affected group's total sleep time was an average of 130.8 minutes compared to 403.6 minutes in the control group (p < 0.01). Initial sleep latency was significantly longer in affected subjects (range, 58–260 minutes vs 3–34 minutes). Affected subjects also had an increase in stage I sleep (8.5% vs 1%), and less stage III/IV sleep (8.5% vs 17%). At the time of autopsy, all cases had severe neuronal tau pathology in wake-promoting nuclei, as well as decreases in thalamic cholinergic innervations. There was no difference in orexinergic fiber density in nucleus basalis of Meynert or locus ceruleus compared to controls. Interpretation The PPND kindred showed severe sleep disturbance. Sleep abnormalities are common in neurodegenerative illnesses, but this is the first study of sleep disorders in PPND. Unlike most neurodegenerative conditions, PPND is characterized by decreased total sleep time, increased sleep latency, and decreased sleep efficiency, without daytime hypersomnolence. PMID:21681797

Wszolek, Zbigniew K.; Uitti, Ryan J.; Fredrickson, Paul; Kaplan, Joseph; Boeve, Bradley F.; Dickson, Dennis W.; Strongosky, Audrey; Lin, Siong-chi

2014-01-01

386

Nearly degenerate gauginos and dark matter at the LHC  

NASA Astrophysics Data System (ADS)

Motivated by dark-matter considerations in supersymmetric theories, we investigate in a fairly model-independent way the detection at the LHC of nearly degenerate gauginos with mass differences between a few GeV and about 30 GeV. Because of the degeneracy of gaugino states, the conventional leptonic signals are likely lost. We first consider the leading signal from gluino production and decay. We find that it is quite conceivable to reach a large statistical significance for the multijet plus missing energy signal with an integrated luminosity about 50pb-1 (50fb-1) for a gluino mass of 500 GeV (1 TeV). If gluinos are not too heavy, less than about 1.5 TeV, this channel can typically probe gaugino masses up to about 100 GeV below the gluino mass. We then study the Drell-Yan type of gaugino pair production in association with a hard QCD jet, for gaugino masses in the range of 100-150 GeV. The signal observation may be statistically feasible with about 10fb-1, but systematically challenging due to the lack of distinctive features for the signal distributions. By exploiting gaugino pair production through weak boson fusion, signals of large missing energy plus two forward-backward jets may be observable at a 4-6? level above the large SM backgrounds with an integrated luminosity of 100-300fb-1. Finally, we point out that searching for additional isolated soft muons in the range pT˜3-10GeV in the data samples discussed above may help to enrich the signal and to control the systematics. Significant efforts are made to explore the connection between the signal kinematics and the relevant masses for the gluino and gauginos, to probe the mass scales of the superpartners, in particular, the lightest supersymmetric particle dark matter.

Giudice, Gian F.; Han, Tao; Wang, Kai; Wang, Lian-Tao

2010-06-01

387

Modelling the Genetic Risk in Age-Related Macular Degeneration  

PubMed Central

Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69–2.05) than patients aged 75 and above (1.45, 95% CI: 1.36–1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11–1131.96) for individuals in the highest category (GRS 3.44–5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS ?0.05–1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available. PMID:22666427

Grassmann, Felix; Fritsche, Lars G.; Keilhauer, Claudia N.; Heid, Iris M.; Weber, Bernhard H. F.

2012-01-01

388

CSF neurofilament concentration reflects disease severity in frontotemporal degeneration  

PubMed Central

Objective Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders including frontotemporal degeneration (FTD). We investigated the clinical correlates of elevated CSF NfL levels in FTD. Methods CSF NfL, amyloid-?42 (A?42), tau and phosphorylated tau (ptau) concentrations were compared in 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) of FTD-causing mutations, 79 FTD (45 behavioral variant frontotemporal dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic dementia [SD]), 22 progressive supranuclear palsy, 50 Alzheimer’s disease, 6 Parkinson’s disease and 17 corticobasal syndrome patients. Correlations between CSF analyte levels were performed with neuropsychological measures and the Clinical Dementia Rating scale sum of boxes (CDRsb). Voxel-based morphometry of structural MR images determined the relationship between brain volume and CSF NfL. Results Mean CSF NfL concentrations were higher in bvFTD, SD and PNFA than other groups. NfL in NC2 was similar to NC. CSF NfL, but not other CSF measures, correlated with CDRsb and neuropsychological measures in FTD, and not in other diagnostic groups. Analyses in two independent FTD cohorts and a group of autopsy verified or biomarker enriched cases confirmed the larger group analysis. In FTD, gray and white matter volume negatively correlated with CSF NfL concentration, such that individuals with highest NfL levels exhibited the most atrophy. Interpretation CSF NfL is elevated in symptomatic FTD and correlates with disease severity. This measurement may be a useful surrogate endpoint of disease severity in FTD clinical trials. Longitudinal studies of CSF NfL in FTD are warranted. PMID:24242746

Scherling, Carole S.; Hall, Tracey; Berisha, Flora; Klepac, Kristen; Karydas, Anna; Coppola, Giovanni; Kramer, Joel H.; Rabinovici, Gil; Ahlijanian, Michael; Miller, Bruce L.; Seeley, William; Grinberg, Lea T.; Rosen, Howard; Meredith, Jere; Boxer, Adam L.

2014-01-01

389

Nitrated ?-Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons  

PubMed Central

Background The neuropathology of Parkinson's disease (PD) includes loss of dopaminergic neurons in the substantia nigra, nitrated ?-synuclein (N-?-Syn) enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration. Methods and Findings Nitrotyrosine (NT)-modified ?-Syn was detected readily in cervical lymph nodes (CLN) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Antigen-presenting cells within the CLN showed increased surface expression of major histocompatibility complex class II, initiating the molecular machinery necessary for efficient antigen presentation. MPTP-treated mice produced antibodies to native and nitrated ?-Syn. Mice immunized with the NT-modified C-terminal tail fragment of ?-Syn, but not native protein, generated robust T cell proliferative and pro-inflammatory secretory responses specific only for the modified antigen. T cells generated against the nitrated epitope do not respond to the unmodified protein. Mice deficient in T and B lymphocytes were resistant to MPTP-induced neurodegeneration. Transfer of T cells from mice immunized with N-?-Syn led to a robust neuroinflammatory response with accelerated dopaminergic cell loss. Conclusions These data show that NT modifications within ?-Syn, can bypass or break immunological tolerance and activate peripheral leukocytes in draining lymphoid tissue. A novel mechanism for disease is made in that NT modifications in ?-Syn induce adaptive immune responses that exacerbate PD pathobiology. These results have implications for both the pathogenesis and treatment of this disabling neurodegenerative disease. PMID:18167537

Reynolds, Ashley D.; Sherman, Simon; Pisarev, Vladimir M.; Tsiperson, Vladislav; Nemachek, Craig; Ciborowski, Pawel; Przedborski, Serge; Mosley, R. Lee; Gendelman, Howard E.

2008-01-01

390

Complement Factor D in Age-Related Macular Degeneration  

PubMed Central

Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by binary logistic regression. CFD gene copy number was analyzed by gene copy number assay. Plasma CFD was measured by an enzyme-linked immunosorbent assay. Results. Genetic association was found between CFD gene SNP rs3826945 and AMD (odds ratio 1.44; P = 0.028) in a small discovery case-control series (462 cases and 325 controls) and replicated in a combined cohorts meta-analysis of 4765 cases and 2693 controls, with an odds ratio of 1.11 (P = 0.032), with the association almost confined to females. Copy number variation in the CFD gene was identified in 13 out of 640 samples examined but there was no difference in frequency between AMD cases (1.3%) and controls (2.7%). Plasma CFD concentration was measured in 751 AMD cases and 474 controls and found to be elevated in AMD cases (P = 0.00025). The odds ratio for those in the highest versus lowest quartile for plasma CFD was 1.81. The difference in plasma CFD was again almost confined to females. Conclusions. CFD regulates activation of the alternative complement pathway, which is implicated in AMD pathogenesis. The authors found evidence for genetic association between a CFD gene SNP and AMD and a significant increase in plasma CFD concentration in AMD cases compared with controls, consistent with a role for CFD in AMD pathogenesis. PMID:22003108

Stanton, Chloe M.; Yates, John R.W.; den Hollander, Anneke I.; Seddon, Johanna M.; Swaroop, Anand; Stambolian, Dwight; Fauser, Sascha; Hoyng, Carel; Yu, Yi; Atsuhiro, Kanda; Branham, Kari; Othman, Mohammad; Chen, Wei; Kortvely, Elod; Chalmers, Kevin; Hayward, Caroline; Moore, Anthony T.; Dhillon, Baljean; Ueffing, Marius

2011-01-01

391

Fear conditioning in frontotemporal lobar degeneration and Alzheimer's disease  

PubMed Central

Emotional blunting and abnormal processing of rewards and punishments represent early features of frontotemporal lobar degeneration (FTLD). Better understanding of the physiological underpinnings of these emotional changes can be facilitated by the use of classical psychology approaches. Fear conditioning (FC) is an extensively used paradigm for studying emotional processing that has rarely been applied to the study of dementia.We studied FC in controls (n = 25), Alzheimer's disease (n =25) and FTLD (n = 25). A neutral stimulus (coloured square on a computer screen) was repeatedly paired with a 1s burst of 100 db white noise. Change in skin conductance response to the neutral stimulus was used to measure conditioning. Physiological–anatomical correlations were examined using voxel-based morphometry (VBM). Both patient groups showed impaired acquisition of conditioned responses. However, the basis for this deficit appeared to differ between groups. In Alzheimer's disease, impaired FC occurred despite normal electrodermal responses to the aversive stimulus. In contrast, FTLD patients showed reduced skin conductance responses to the aversive stimulus, which contributed significantly to their FC deficit.VBM identified correlations with physiological reactivity in the amygdala, anterior cingulate cortex, orbitofrontal cortex and insula. These data indicate that Alzheimer's disease and FTLD both show abnormalities in emotional learning, but they suggest that in FTLD this is associated with a deficit in basic electrodermal response to aversive stimuli, consistent with the emotional blunting described with this disorder. Deficits in responses to aversive stimuli could contribute to both the behavioural and cognitive features of FTLD and Alzheimer's disease. Further study of FC in humans and animal models of dementia could provide a valuable window into these symptoms. PMID:18492729

Hoefer, M.; Allison, S. C.; Schauer, G. F.; Neuhaus, J. M.; Hall, J.; Dang, J. N.; Weiner, M. W.; Miller, B. L.; Rosen, H. J.

2008-01-01

392

VAGINAL DEGENERATION FOLLOWING IMPLANTATION OF SYNTHETIC MESH WITH INCREASED STIFFNESS  

PubMed Central

Objective To compare the impact of the prototype prolapse mesh Gynemesh PS to that of two new generation lower stiffness meshes, UltraPro and SmartMesh, on vaginal morphology and structural composition. Design A mechanistic study employing a non-human primate (NHP) model. Setting Magee-Womens Research Institute at the University of Pittsburgh. Population Parous rhesus macaques, with similar age, weight, parity and POP-Q scores. Methods Following IACUC approval, 50 rhesus macaques were implanted with Gynemesh PS (n=12), UltraPro with its blue line perpendicular to the longitudinal axis of vagina (n=10), UltraPro with its blue line parallel to the longitudinal axis of vagina (n=8) and SmartMesh (n=8) via sacrocolpopexy following hysterectomy. Sham operated animals (n=12) served as controls. Main Outcome Measures The mesh-vagina complex (MVC) was removed after 12 weeks and analyzed for histomorphology, in situ cell apoptosis, total collagen, elastin, glycosaminoglycan content and total collagenase activity. Appropriate statistics and correlation analyses were performed accordingly. Results Relative to sham and the two lower stiffness meshes, Gynemesh PS had the greatest negative impact on vaginal histomorphology and composition. Compared to sham, implantation with Gynemesh PS caused substantial thinning of the smooth muscle layer (1557 ± 499?m vs 866 ± 210 ?m, P=0.02), increased apoptosis particularly in the area of the mesh fibers (P=0.01), decreased collagen and elastin content (20% (P=0.03) and 43% (P=0.02), respectively) and increased total collagenase activity (135% (P=0.01)). GAG (glycosaminoglycan), a marker of tissue injury, was the highest with Gynemesh PS compared to sham and other meshes (P=0.01). Conclusion Mesh implantation with the stiffer mesh Gynemesh PS induced a maladaptive remodeling response consistent with vaginal degeneration. PMID:23240802

Liang, Rui; Abramowitch, Steven; Knight, Katrina; Palcsey, Stacy; Nolfi, Alexis; Feola, Andrew; Stein, Susan; Moalli, Pamela A.

2012-01-01

393

Site Map  

Cancer.gov

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394

Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats  

PubMed Central

The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and a ~70% loss of the sensory axons, by 24 hours. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 hours. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 µg/µl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 hours. EB also caused an ~72% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R2 = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons. PMID:23978615

Muradov, Johongir M.; Ewan, Eric E.; Hagg, Theo

2013-01-01

395

Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration.  

PubMed

Amyotrophic lateral sclerosis (ALS) is a spontaneous, relentlessly progressive motor neuron disease, usually resulting in death from respiratory failure within 3 years. Variation in the genes SOD1 and TARDBP accounts for a small percentage of cases, and other genes have shown association in both candidate gene and genome-wide studies, but the genetic causes remain largely unknown. We have performed two independent parallel studies, both implicating the RNA polymerase II component, ELP3, in axonal biology and neuronal degeneration. In the first, an association study of 1884 microsatellite markers, allelic variants of ELP3 were associated with ALS in three human populations comprising 1483 people (P=1.96 x 10(-9)). In the second, an independent mutagenesis screen in Drosophila for genes important in neuronal communication and survival identified two different loss of function mutations, both in ELP3 (R475K and R456K). Furthermore, knock down of ELP3 protein levels using antisense morpholinos in zebrafish embryos resulted in dose-dependent motor axonal abnormalities [Pearson correlation: -0.49, P=1.83 x 10(-12) (start codon morpholino) and -0.46, P=4.05 x 10(-9) (splice-site morpholino), and in humans, risk-associated ELP3 genotypes correlated with reduced brain ELP3 expression (P=0.01). These findings add to the growing body of evidence implicating the RNA processing pathway in neurodegeneration and suggest a critical role for ELP3 in neuron biology and of ELP3 variants in ALS. PMID:18996918

Simpson, Claire L; Lemmens, Robin; Miskiewicz, Katarzyna; Broom, Wendy J; Hansen, Valerie K; van Vught, Paul W J; Landers, John E; Sapp, Peter; Van Den Bosch, Ludo; Knight, Joanne; Neale, Benjamin M; Turner, Martin R; Veldink, Jan H; Ophoff, Roel A; Tripathi, Vineeta B; Beleza, Ana; Shah, Meera N; Proitsi, Petroula; Van Hoecke, Annelies; Carmeliet, Peter; Horvitz, H Robert; Leigh, P Nigel; Shaw, Christopher E; van den Berg, Leonard H; Sham, Pak C; Powell, John F; Verstreken, Patrik; Brown, Robert H; Robberecht, Wim; Al-Chalabi, Ammar

2009-02-01

396

Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration.  

PubMed

The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C-->T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing. PMID:17186464

Friedman, James S; Chang, Bo; Kannabiran, Chitra; Chakarova, Christina; Singh, Hardeep P; Jalali, Subhadra; Hawes, Norman L; Branham, Kari; Othman, Mohammad; Filippova, Elena; Thompson, Debra A; Webster, Andrew R; Andréasson, Sten; Jacobson, Samuel G; Bhattacharya, Shomi S; Heckenlively, John R; Swaroop, Anand

2006-12-01

397

[Novel approach for management of age-related macular degeneration--antiangiogenic therapy and retinal regenerative therapy].  

PubMed

Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Even with the recent advent of several treatment options, treatment of exudative AMD, characterized by choroidal neovascularization (CNV), remains difficult. Thus, in this review article, we report on the investigation of novel approaches for the management of AMD, antiangiogenic therapy for CNV, and retinal regenerative therapy. Polyion complex(PIC) micelles have a range in size of several tens of nanometers formed through an electrostatic interaction, and accumulate in solid tumors through an enhanced permeability and retention(EPR) effect. In this study, we examined the distribution of the PIC micelles which encapsulate fluorescein isothiocyanate-labeled poly-L-lysine{FITC-P(Lys)} in experimental CNV in rats, to investigate whether PIC micelles can be used for the treatment of CNV. We demonstrated that PIC micelles accumulate in the CNV lesions and are retained in the lesions for as long as 168 hours after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving an effective drug delivery system against CNV. Although photodynamic therapy (PDT) is a very promising treatment for AMD, most patients require repeated treatments. For effective PDT against AMD, the selective delivery of a photosensitizer to the CNV lesions and an effective photochemical reaction at the CNV site are necessary. The characteristic dendritic structure of the photosensitizer prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. We present an effective PDT for AMD employing a supramolecular nanomedical device, i.e., a novel dendritic photosensitizer encapsulated in a polymeric micelle formulation. With its highly selective accumulation in CNV lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity. Our results will provide a basis for an effective approach to PDT for AMD. Spatial control of gene transfection in the body is a core issue in the gene therapy for ocular diseases including AMD. Photochemical internalization (PCI) is a technology that effects light-induced delivery of DNA directly inside cells. PCI usually requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. We have developed a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer, phthalocyanine, which provides the photosensitizing action. Subconjunctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site in rats. This PCI-mediated gene delivery system is potentially useful in gene therapy for ophthalmic diseases. Accumulation of lipofuscin is related to an increased risk of AMD. We report that a major lipofuscin component, A2E(N-retinyledin-N-retinylethanolamin), activates the retinoic acid receptor (RAR). In vivo experiments suggest that A2E accumulation results in the pro-angiogenic conversion of retinal pigment epithelial(RPE) cell phenotype. This physiological consequence of A2E accumulation may be related to a novel potential therapeutic target for CNV. To recover visual function damaged by AMD, retinal regenerative therapy is essential. We investigated whether subretinal transplantation of bone marrow mesenchymal stem cells(MSCs) promotes photoreceptor survival in a rat model of retinal degeneration. Morphological and functional studies in vivo, including histological analysis and electrophysiological studies, indicate that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function. These results suggest that MSC is a useful cell source for cell-transplantation therapy for retinal degeneration. In order to elucidate the molecular mechanisms of development of the fovea, which is composed mainly of cone photoreceptors and is susceptible to injury from AMD, we performed a co

Tamaki, Yasuhiro

2007-03-01

398

Fear of falling in age-related macular degeneration  

PubMed Central

Background Prior studies have shown age-related macular degeneration (AMD) to be associated with falls. The purpose of this study is to determine if (AMD) and AMD-related vision loss are associated with fear of falling, an important and distinct outcome. Methods Sixty-five persons with AMD with evidence of vision loss in one or both eyes and 60 glaucoma suspects with normal vision completed the University of Illinois at Chicago Fear of Falling questionnaire. Responses were Rasch analyzed. Scores were expressed in logit units, with lower scores demonstrating lesser ability and greater fear of falling. Results Compared to glaucoma suspect controls, AMD subjects had worse visual acuity (VA) (median better-eye VA?=?20/48 vs. 20/24, p?

2014-01-01

399

A twin study on age-related macular degeneration.  

PubMed Central

A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD; this included the one dizygotic pair which was discordant for basal laminar drusen. The data of this study strongly suggest a genetic predisposition to AMD. Images FIGURE 1 FIGURE 1 (cont.) FIGURE 2 FIGURE 2 (cont.) FIGURE 2 (cont.) FIGURE 3 FIGURE 3 (cont.) FIGURE 3 (cont.) FIGURE 3 (cont.) FIGURE 4 FIGURE 4 (cont.) FIGURE 5 FIGURE 5 (cont.) FIGURE 5 (cont.) FIGURE 6 FIGURE 6 (cont.) FIGURE 7 FIGURE 7 (cont.) FIGURE 8 FIGURE 8 (cont.) FIGURE 9 FIGURE 9 (cont.) FIGURE 9 (cont.) FIGURE 10 FIGURE 10 (cont.) FIGURE 11 FIGURE 11 (cont.) FIGURE 11 (cont.) FIGURE 12 FIGURE 12 (cont.) FIGURE 12 (cont.) PMID:7886884

Meyers, S M

1994-01-01

400

Complement factor I and age-related macular degeneration  

PubMed Central

Purpose The complement system has been implicated in the pathogenesis of age-related macular degeneration (AMD). Complement factor I (CFI) is a serum protease that inhibits all complement pathways. A previous multicenter study identified a single missense CFI mutation (p.Gly119Arg) in 20/3,567 (0.56%) of AMD cases versus 1/3,937 (0.025%) of controls, thus suggesting that this mutation confers a high risk of AMD. A second CFI mutation, p.Gly188Ala, was identified in one patient with AMD. Methods We screened 521 unrelated AMD cases and 627 controls for the p.Gly119Arg and p.Gly188Ala variants. All participants were Caucasian and >55 years, and recruited through Southampton Eye Unit or research clinics in Guernsey. All participants underwent dilated fundal examination by an experienced retinal specialist. SNP assays were performed using KASP™ biochemistry. Results The p.Gly119Arg mutation was identified in 7/521 AMD cases compared to 1/627 age-matched controls (odds ratio [OR] = 8.47, confidence interval [CI] = 1.04–69.00, p = 0.027). There was a varied phenotype among the seven cases with the mutation, which was present in 4/254 (1.6%) cases with active or end-stage wet AMD and 3/267 dry AMD cases (1.1%). The p.Gly188Ala substitution was identified in 1/521 cases and 1/627 controls. Conclusions Our results identified a much higher frequency of heterozygosity for p.Gly119Arg in both cases and controls than in previous studies. Of note is that our sub-cohort from Guernsey had a particularly high frequency of p.Gly119Arg heterozygosity in affected individuals (4%) compared to our sub-cohort from the mainland (0.71%). Although these data support the conclusions of van de Ven et al. that the p.Gly119Arg substitution confers a high risk of AMD, our data suggest that this missense mutation is not as rare or as highly penetrant as previously reported. There was no difference in frequency for a second CFI variant, p.Gly188Ala, between the cases and the controls. PMID:25352734

Alexander, Philip; Gibson, Jane; Cree, Angela J.; Ennis, Sarah

2014-01-01

401

Progress on retinal image analysis for age related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is the leading cause of vision loss in those over the age of 50 years in the developed countries. The number is expected to increase by ?1.5 fold over the next ten years due to an increase in aging population. One of the main measures of AMD severity is the analysis of drusen, pigmentary abnormalities, geographic atrophy (GA) and choroidal neovascularization (CNV) from imaging based on color fundus photograph, optical coherence tomography (OCT) and other imaging modalities. Each of these imaging modalities has strengths and weaknesses for extracting individual AMD pathology and different imaging techniques are used in combination for capturing and/or quantification of different pathologies. Current dry AMD treatments cannot cure or reverse vision loss. However, the Age-Related Eye Disease Study (AREDS) showed that specific anti-oxidant vitamin supplementation reduces the risk of progression from intermediate stages (defined as the presence of either many medium-sized drusen or one or more large drusen) to late AMD which allows for preventative strategies in properly identified patients. Thus identification of people with early stage AMD is important to design and implement preventative strategies for late AMD, and determine their cost-effectiveness. A mass screening facility with teleophthalmology or telemedicine in combination with computer-aided analysis for large rural-based communities may identify more individuals suitable for early stage AMD prevention. In this review, we discuss different imaging modalities that are currently being considered or used for screening AMD. In addition, we look into various automated and semi-automated computer-aided grading systems and related retinal image analysis techniques for drusen, geographic atrophy and choroidal neovascularization detection and/or quantification for measurement of AMD severity using these imaging modalities. We also review the existing telemedicine studies which include diagnosis and management of AMD, and how automated disease grading could benefit telemedicine. As there is no treatment for dry AMD and only early intervention can prevent the late AMD, we emphasize mass screening through a telemedicine platform to enable early detection of AMD. We also provide a comparative study between the imaging modalities and identify potential study areas for further improvement and future research direction in automated AMD grading and screening. PMID:24211245

Kanagasingam, Yogesan; Bhuiyan, Alauddin; Abràmoff, Michael D; Smith, R Theodore; Goldschmidt, Leonard; Wong, Tien Y

2014-01-01

402

Frontotemporal lobar degeneration: epidemiology, pathology, diagnosis and management.  

PubMed

Frontotemporal lobar degeneration (FTLD) describes a spectrum of clinically, pathologically and genetically heterogeneous neurodegenerative disorders of unknown aetiology. FTLD spectrum disorders collectively represent a leading cause of early-onset dementia, with most cases presenting between 45 and 64 years of age. FTLD is characterized by progressive changes in behaviour, executive dysfunction and/or language impairment and can be differentiated clinically into three frontotemporal dementia (FTD) syndromes as follows: (i) behavioural variant (bvFTD); (ii) semantic dementia (SD); and (iii) progressive nonfluent aphasia (PNFA). Additionally, there is a significant clinical, pathological and genetic overlap between FTD and motor neuron disease/amyotrophic lateral sclerosis (FTD-ALS) and the atypical parkinsonian syndromes, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). bvFTD is characterized by progressive behavioural impairment and a decline in executive function with frontal lobe-predominant atrophy, SD by a loss of object knowledge with prominent anomia and asymmetrical atrophy of the anterior temporal lobes and PNFA by expressive or motor speech deficits with predominantly left peri-sylvian atrophy. Recent advances in molecular biology and immunohistochemical staining techniques have further classified the FTLD spectrum disorders based upon the predominant neuropathological protein into three main categories: (i) microtubule-associated protein tau (FTLD-TAU); (ii) TAR DNA-binding protein-43 (FTLD-TDP); and (iii) fused in sarcoma protein (FTLD-FUS). Up to 40% of FTD patients report a family history of neurodegenerative illness, and one-third to one-half of familial cases of FTD follow an autosomal dominant inheritance pattern. Mutations in MAPT, PGRN, TARDBP, VCP and CHMP2B have been described, along with a recently identified C9ORF72 hexanucleotide repeat expansion. To date, there are no US FDA-approved treatments or disease-modifying therapies for FTD. Pharmacological strategies have focused on neurotransmitter replacement and modulation for the treatment of behavioural, motor and cognitive symptoms of FTD, and include selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, acetylcholinesterase inhibitors and glutamate NMDA receptor antagonists. At present, adequate management of FTD symptoms involves a combination of pharmacological therapy with behavioural, physical and environmental modification techniques. PMID:22950490

Seltman, Rachel E; Matthews, Brandy R

2012-10-01

403

The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms  

PubMed Central

Purpose To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO3)–induced retinal degeneration and on the hereditary retinal degeneration caused by the rd6 mutation. Methods Retinas from NaIO3-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, rd6 mice treated with or without DFP were analyzed by histology to assess possible protection. Results In NaIO3-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress–related gene heme oxygenase-1 and the complement gene C3. DFP treatment partially protected against NaIO3-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin (Rho) and retinal pigment epithelium–specific 65 kDa protein (Rpe65), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in rd6 mice. Conclusions The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation. Translational Relevance These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted. PMID:24049707

Hadziahmetovic, Majda; Pajic, Miroslav; Grieco, Steven; Song, Ying; Song, Delu; Li, Yafeng; Cwanger, Alyssa; Iacovelli, Jared; Chu, Sally; Ying, Gui-shuang; Connelly, John; Spino, Michael; Dunaief, Joshua L.

2012-01-01

404

The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms  

PubMed Central

Purpose To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO3)–induced retinal degeneration and on the hereditary retinal degeneration caused by the rd6 mutation. Methods Retinas from NaIO3-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, rd6 mice treated with or without DFP were analyzed by histology to assess possible protection. Results In NaIO3-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress–related gene heme oxygenase-1 and the complement gene C3. DFP treatment partially protected against NaIO3-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin (Rho) and retinal pigment epithelium–specific 65 kDa protein (Rpe65), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in rd6 mice. Conclusions The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation. Translational Relevance These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted. PMID:24049709

Hadziahmetovic, Majda; Pajic, Miroslav; Grieco, Steven; Song, Ying; Song, Delu; Li, Yafeng; Cwanger, Alyssa; Iacovelli, Jared; Chu, Sally; Ying, Gui-shuang; Connelly, John; Spino, Michael; Dunaief, Joshua L

2012-01-01

405

Sarm1-Mediated Axon Degeneration Requires Both SAM and TIR Interactions  

PubMed Central

Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile ?-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is engaged by disparate neuronal insults: SARM ablation blocks axon degeneration induced by axotomy or vincristine treatment, while SARM acts in parallel with a soma-derived caspase-dependent pathway following trophic withdrawal. SARM is a multidomain protein that associates with neuronal mitochondria. Deletion of the N-terminal mitochondrial localization sequence disrupts SARM mitochondrial localization in neurons but does not alter its ability to promote axon degeneration. In contrast, mutation of either the SAM (sterile ? motif) or TIR (Toll-interleukin-1 receptor) domains abolishes the ability of SARM to promote axonal degeneration, while a SARM mutant containing only these domains elicits axon degeneration and nonapoptotic neuronal death even in the absence of injury. Protein–protein interaction studies demonstrate that the SAM domains are necessary and sufficient to mediate SARM–SARM binding. SARM mutants lacking a TIR domain bind full-length SARM and exhibit strong dominant-negative activity. These results indicate that SARM plays an integral role in the dismantling of injured axons and support a model in which SAM-mediated multimerization is necessary for TIR-dependent engagement of a downstream destruction pathway. These findings suggest that inhibitors of SAM and TIR interactions represent therapeutic candidates for blocking pathological axon loss and neuronal cell death. PMID:23946415

Gerdts, Josiah; Summers, Daniel W.; Sasaki, Yo; DiAntonio, Aaron

2013-01-01

406

Diversity of reductive dehalogenase genes from environmental samples and enrichment cultures identified with degenerate primer PCR screens  

PubMed Central

Reductive dehalogenases are the critical enzymes for anaerobic organohalide respiration, a microbial metabolic process that has been harnessed for bioremediation efforts to resolve chlorinated solvent contamination in groundwater and is implicated in the global halogen cycle. Reductive dehalogenase sequence diversity is informative for the dechlorination potential of the site or enrichment culture. A suite of degenerate PCR primers targeting a comprehensive curated set of reductive dehalogenase genes was designed and applied to 12 DNA samples extracted from contaminated and pristine sites, as well as six enrichment cultures capable of reducing chlorinated compounds to non-toxic end-products. The amplified gene products from four environmental sites and two enrichment cultures were sequenced using Illumina HiSeq, and the reductive dehalogenase complement of each sample determined. The results indicate that the diversity of the reductive dehalogenase gene family is much deeper than is currently accounted for: one-third of the translated proteins have less than 70% pairwise amino acid identity to database sequences. Approximately 60% of the sequenced reductive dehalogenase genes were broadly distributed, being identified in four or more samples, and often in previously sequenced genomes as well. In contrast, 17% of the sequenced reductive dehalogenases were unique, present in only a single sample and bearing less than 90% pairwise amino acid identity to any previously identified proteins. Many of the broadly distributed reductive dehalogenases are uncharacterized in terms of their substrate specificity, making these intriguing targets for further biochemical experimentation. Finally, comparison of samples from a contaminated site and an enrichment culture derived from the same site 8 years prior allowed examination of the effect of the enrichment process. PMID:24312087

Hug, Laura A.; Edwards, Elizabeth A.

2013-01-01

407

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408

Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration  

PubMed Central

The disruption of the extracellular disc matrix is a major hallmark of disc degeneration. This has previously been shown to be associated with an up-regulation of major matrix metalloproteinase (MMP) expression and activity. However, until now hardly any data are available for MMP/TIMP regulation and thereby no concept exists as to which MMP/TIMP plays a major role in disc degeneration. The objective of this study was, therefore, to identify and quantify the putative up-regulation of MMPs/TIMPs on the mRNA and protein level and their activity in disc material in relation to clinical data and histological evidence for disc degeneration. A quantitative molecular analysis of the mRNA expression levels for the MMPs (MMPs-1, -2, -3, -7, -8, -9, -13) and the MMP inhibitors (TIMPs-1 and -2) was performed on 37 disc specimens obtained from symptomatic disc herniation or degeneration. In addition, disc specimens from patients without disc degeneration/herniation (=controls) were analyzed. Expression of MMPs-1, -2, -3, -7, -8, -9, -13 and TIMPs-1, -2 was analyzed using quantitative RT-PCR, normalized to the expression level of a house keeping gene (GAPDH). Gene expression patterns were correlated with MMP activity (in situ zymography), protein expression patterns (immunohistochemistry), degeneration score (routine histology) and clinical data. MMP-3 mRNA levels were consistently and substantially up-regulated in samples with histological evidence for disc degeneration. A similar but less pronounced up-regulation was observed for MMP-8. This up-regulation was paralleled by the expression of TIMP-1 and to a lesser extent TIMP-2. In general, these findings could be confirmed with regard to protein expression and enzyme activity. This study provides data on the gene and protein level, which highlights the key role of MMP-3 in the degenerative cascade leading to symptomatic disc degeneration and herniation. Control of the proteolytic activity of MMP-3 may, therefore, come into the focus when aiming to develop new treatment options for early disc degeneration. PMID:19466462

Bachmeier, Beatrice E.; Nerlich, Andreas; Mittermaier, Norbert; Weiler, Christoph; Lumenta, Christianto; Wuertz, Karin

2009-01-01

409

Association of ATP synthase alpha-chain with neurofibrillary degeneration in Alzheimer's disease.  

PubMed

Amyloid deposits and neurofibrillary tangles (NFT) are the two hallmarks that characterize Alzheimer's disease (AD). In order to find the molecular partners of these degenerating processes, we have developed antibodies against insoluble AD brain lesions. One clone, named AD46, detects only NFT. Biochemical and histochemistry analyses demonstrate that the labeled protein accumulating in the cytosol of Alzheimer degenerating neurons is the alpha-chain of the ATP synthase. The cytosolic accumulation of the alpha-chain of ATP synthase is observed even at early stages of neurofibrillary degenerating process. It is specifically observed in degenerating neurons, either alone or tightly associated with aggregates of tau proteins, suggesting that it is a new molecular event related to neurodegeneration. Overall, our results strongly suggest the implication of the alpha-chain of ATP synthase in neurofibrillary degeneration of AD that is illustrated by the cytosolic accumulation of this mitochondrial protein, which belongs to the mitochondrial respiratory system. This regulatory subunit of the respiratory complex V of mitochondria is thus a potential target for therapeutic and diagnostic strategies. PMID:12614671

Sergeant, N; Wattez, A; Galván-valencia, M; Ghestem, A; David, J-P; Lemoine, J; Sautiére, P-E; Dachary, J; Mazat, J-P; Michalski, J-C; Velours, J; Mena-López, R; Delacourte, A

2003-01-01

410

A murine rp1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration.  

PubMed

Mutations in the RP1 gene can cause retinitis pigmentosa. We identified a spontaneous L66P mutation caused by two adjacent point mutations in the Rp1 gene in a colony of C57BL/6J mice. Mice homozygous for the L66P mutation exhibited slow, progressive photoreceptor degeneration throughout their lifespan. Optical coherence tomography imaging found abnormal photoreceptor reflectivity at 1 month of age. Histology found shortening and disorganization of the photoreceptor inner and outer segments and progressive thinning of the outer nuclear layer. Electroretinogram a- and b-wave amplitudes were decreased with age. Western blot analysis found that the quantity and size of the mutated retinitis pigmentosa 1 (RP1) protein were normal. However, immunohistochemistry found that the mutant Rp1 protein partially mislocalized to the transition zone of the shortened axonemes. This mutation disrupted colocalization with cytoplasmic microtubules in vitro. In conclusion, the L66P mutation in the first doublecortin domain of the Rp1 gene impairs Rp1 protein localization and function, leading to abnormalities in photoreceptor outer segment structure and progressive photoreceptor degeneration. This is the first missense mutation in Rp1 shown to cause retinal degeneration. It provides a unique, slowly progressive photoreceptor degeneration model that mirrors the slow degeneration kinetics in most patients with retinitis pigmentosa. PMID:25088982

Song, Delu; Grieco, Steve; Li, Yafeng; Hunter, Allan; Chu, Sally; Zhao, Liangliang; Song, Ying; DeAngelis, Robert A; Shi, Lan-Ying; Liu, Qin; Pierce, Eric A; Nishina, Patsy M; Lambris, John D; Dunaief, Joshua L

2014-10-01

411

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration  

PubMed Central

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell death. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness. PMID:21297615

Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D.; Fowler, Benjamin J.; Cho, Won Gil; Kleinman, Mark E.; Ponicsan, Steven L.; Hauswirth, William W.; Chiodo, Vince A.; Karikó, Katalin; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W.; Braun, Robert E.; Hinton, David R.; Zhang, Qing; Grossniklaus, Hans E.; Provis, Jan M.; Madigan, Michele C.; Milam, Ann H.; Justice, Nikki L.; Albuquerque, Romulo J.C.; Blandford, Alexander D.; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R.; Ambati, Balamurali K.; Rudin, Charles M.; Chong, Mark M.W.; Provost, Patrick; Kugel, Jennifer F.; Goodrich, James A.; Dunaief, Joshua L.; Baffi, Judit Z.; Ambati, Jayakrishna

2011-01-01

412

Mesenchymal Stem Cells Arrest Intervertebral Disc Degeneration Through Chondrocytic Differentiation and Stimulation of Endogenous Cells  

PubMed Central

Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest degeneration in rabbit and canine intervertebral discs. In this study, we have used the mouse model to investigate the mechanism of degeneration arrest. BMSC from Egfp transgenic mice were injected into the degenerated murine intervertebral discs induced by annular puncture. We found that BMSC could arrest the progressive degeneration of the discs with significant regeneration of the nucleus pulposus (NP). In the regeneration, expression of proteoglycan genes were upregulated and extracellular matrix (ECM) progressively accumulated in the NP after BMSC injection. Combined in situ hybridization and immunohistochemistry revealed that BMSC underwent chondrocytic differentiation in the regeneration process. Interestingly, BMSC-induced an increase of endogenous notochordal cells in NP and expression of chondrocytic markers. In this study, we have firstly shown that the BMSC could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells. PMID:19584814

Yang, Fan; Leung, Victor YL; Luk, Keith DK; Chan, Danny; Cheung, Kenneth MC

2009-01-01

413

Degenerate MAGGY elements in a subgroup of Pyricularia grisea: a possible example of successful capture of a genetic invader by a fungal genome.  

PubMed

The LTR-retrotransposon MAGGY is found sporadically in isolates of Pyricularia grisea (Magnaporthe grisea). Based on a dendrogram constructed by RFLP analysis of rDNA, isolates that carry MAGGY elements were classified into a single cluster that comprised four rDNA types. However, in a few members of this cluster, exemplified by isolates from common millet (Panicum miliaceum), the MAGGY element has distinct features. Southern analysis suggested that these isolates possessed a single copy of a MAGGY-related sequence whose restriction map differed from that of MAGGY itself. Sequence analysis revealed that the MAGGY-related sequence was a degenerate form of MAGGY, characterized by numerous C:G to T:A transitions, which have often been reported to result from RIP (Repeat-induced point mutation) or RIP-like processes. However, the favored target site for C:G to T:A transitions in this fungus, determined by examining a total of 501 sites, was (A/T)pCp(A/T), which differs from that for the RIP process originally reported in Neurospora (CpA), and from that reported in Aspergillus (CpG). The fact that certain members of the cluster of MAGGY carriers retain a single copy of a degenerate MAGGY element implies that the ancestor of these isolates successfully "captured" the invading MAGGY element. PMID:10485287

Nakayashiki, H; Nishimoto, N; Ikeda, K; Tosa, Y; Mayama, S

1999-07-01

414

Diapause Formation and Downregulation of Insulin-Like Signaling via DAF-16/FOXO Delays Axonal Degeneration and Neuronal Loss  

PubMed Central

Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS) participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS) pathway protects neurons from degenerating in a DAF-16/FOXO–dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment. PMID:23300463

Calixto, Andrea; Jara, Juan S.; Court, Felipe A.

2012-01-01

415

The effective density of randomly moving electrons and related characteristics of materials with degenerate electron gas  

NASA Astrophysics Data System (ADS)

Interpretation of the conductivity of metals, of superconductors in the normal state and of semiconductors with highly degenerate electron gas remains a significant issue if consideration is based on the classical statistics. This study is addressed to the characterization of the effective density of randomly moving electrons and to the evaluation of carrier diffusion coefficient, mobility, and other parameters by generalization of the widely published experimental results. The generalized expressions have been derived for various kinetic parameters attributed to the non-degenerate and degenerate electron gas, by analyzing a random motion of the single type carriers in homogeneous materials. The values of the most important kinetic parameters for different metals are also systematized and discussed. It has been proved that Einstein's relation between the diffusion coefficient and the drift mobility of electrons is held for any level of degeneracy if the effective density of randomly moving carriers is properly taken into account.

Palenskis, V.

2014-04-01

416

Lensfibre degeneration at cataract lenses. A LM, SEM and TEM investigation.  

PubMed

The degeneration process of lensfibres in a cataractous lens, described as the biochemical changes of a part of the lensproteins, can be characterised morphologically as follows: Emulsification of a part of the lensfibre-mass and the development of open spaces between the lensfibres with the formation of vacuoles (spherical structures) with a granular or a compact contents with high contrast, which is squeezed into the intercellular space. Degeneration of the ball & socket system interdigitation and microvilli domain system and the formation of almost empty rectangular structures in somewhat radial array. Balloon-like bulging of the cytoplasm of the lenscell, degeneration of the cytoplasm membrane and visualisation of a micro-filamentous network with enclosed cell organelles. PMID:8181429

Kalicharan, D; Jongebloed, W L; Worst, J G

1993-01-01

417

Axonal protection by modulation of p62 expression in TNF-induced optic nerve degeneration.  

PubMed

p62, which is also called sequestosome 1 (SQSTM1), plays a critical role in neuronal cell death. However, the role of p62 in axonal degeneration remains unclear. We evaluated whether the modulation of p62 expression may affect axonal loss in tumor necrosis factor (TNF)-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with p62 small interfering RNA (siRNA) exerted a partial but significant protective effect against TNF-induced axonal loss. Rapamycin exerted substantial axonal protection after TNF injection. We found that the increase in p62 was significantly inhibited by p62 siRNA. Treatment with rapamycin also significantly inhibited increased p62 protein levels induced by TNF. These results suggest that the upregulation of p62 may be involved in TNF-induced axonal degeneration and that decreased p62 levels may lead to axonal protection. PMID:25150927

Kojima, Kaori; Kitaoka, Yasushi; Munemasa, Yasunari; Hirano, Ayano; Sase, Kana; Takagi, Hitoshi

2014-10-01

418

Cosmological constant in SUGRA models with Planck scale SUSY breaking and degenerate vacua  

NASA Astrophysics Data System (ADS)

The empirical mass of the Higgs boson suggests small to vanishing values of the quartic Higgs self-coupling and the corresponding beta function at the Planck scale, leading to degenerate vacua. This leads us to suggest that the measured value of the cosmological constant can originate from supergravity (SUGRA) models with degenerate vacua. This scenario is realised if there are at least three exactly degenerate vacua. In the first vacuum, associated with the physical one, local supersymmetry (SUSY) is broken near the Planck scale while the breakdown of the SU(2)W×U(1)Y symmetry takes place at the electroweak (EW) scale. In the second vacuum local SUSY breaking is induced by gaugino condensation at a scale which is just slightly lower than ?QCD in the physical vacuum. Finally, in the third vacuum local SUSY and EW symmetry are broken near the Planck scale.

Froggatt, C. D.; Nevzorov, R.; Nielsen, H. B.; Thomas, A. W.

2014-10-01

419

Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model.  

PubMed

Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post-operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze-drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p?degeneration provides a good model of disc degeneration. Furthermore, CABC-injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10-12%) viscoelastic moduli after mild degeneration within goats, though the inter-animal differences were relatively large (complex modulus ?12 to 41?kPa). Relative water content in the NP was unaffected by CABC, remaining at ?75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. PMID:23255234

Detiger, Suzanne E L; Hoogendoorn, Roel J W; van der Veen, Albert J; van Royen, Barend J; Helder, Marco N; Koenderink, Gijsje H; Smit, Theo H

2013-05-01

420

Menopause is associated with lumbar disc degeneration: a review of 4230 intervertebral discs.  

PubMed

Abstract Objective The main objective of this study was to investigate, in a population of normal postmenopausal women, the association between menopause and severity of lumbar disc degeneration from the first lumbar to the first sacral vertebra on magnetic resonance imaging. Methods Between January 2010 and May 2013, 846 normal women and 4230 intervertebral discs were retrospectively analyzed. Age, height, weight and years since menopause (YSM) were recorded. Disc degeneration was evaluated using the modified Pfirrmann grading system. Results Compared to premenopausal and perimenopausal women, postmenopausal women had more severe disc degeneration after removal of age, height and weight effects (p < 0.0001). Postmenopausal women were divided into six subgroups for every 5 YSM. When YSM was below 15 years, there was a significant difference between every two groups, i.e. groups 1-5 YSM, 6-10 YSM and 11-15 YSM (p < 0.01). A positive trend was observed between YSM and severity of disc degeneration, respectively, i.e. L1/L2 (r = 0.235), L2/L3 (r = 0.161), L3/L4 (r = 0.173), L4/L5 (r = 0.146), L5/S1 (r = 0.137) and all lumbar discs (r = 0.259) (p < 0.05 or 0.01). However, when YSM was above 15, there was no difference, i.e. groups 16-20 YSM, 21-25 YSM and 26-30 YSM (p > 0.05), and the significance correlation also disappeared (p > 0.05). Conclusion Menopause is associated with disc degeneration in the lumbar spine. The association almost entirely occurred in the first 15 years since menopause, suggesting estrogen decrease may be a risk factor for lumbar disc degeneration. PMID:25017806

Lou, C; Chen, H-L; Feng, X-Z; Xiang, G-H; Zhu, S-P; Tian, N-F; Jin, Y-L; Fang, M-Q; Wang, C; Xu, H-Z

2014-12-01

421

Non-erythropoietic erythropoietin derivatives protect from light-induced and genetic photoreceptor degeneration.  

PubMed

Given the high genetic heterogeneity of inherited retinal degenerations (IRDs), a wide applicable treatment would be desirable to halt/slow progressive photoreceptor (PR) cell loss in a mutation-independent manner. In addition to its erythropoietic activity, erythropoietin (EPO) presents neurotrophic characteristics. We have previously shown that adeno-associated viral (AAV) vector-mediated systemic EPO delivery protects from PR degeneration. However, this is associated with an undesired hematocrit increase that could contribute to PR protection. Non-erythropoietic EPO derivatives (EPO-D) are available which allow us to dissect erythropoiesis's role in PR preservation and may be more versatile and safe than EPO as anti-apoptotic agents. We delivered in animal models of light-induced or genetic retinal degeneration either intramuscularly or subretinally AAV vectors encoding EPO or one of the three selected EPO-D: the mutant S100E, the helix A- and B-derived EPO-mimetic peptides. We observed that (i) systemic expression of S100E induces a significantly lower hematocrit increase than EPO and provides similar protection from PR degeneration, and (ii) intraocular expression of EPO-D protects PR from degeneration in the absence of significant hematocrit increase. On the basis of this, we conclude that erythropoiesis is not required for EPO-mediated PR protection. However, the lower efficacy observed when EPO or S100E is expressed intraocularly rather than systemically suggests that hormone systemic effects contribute to PR protection. Unlike S100E, EPO-mimetic peptides preserve PR only when given locally, suggesting that different EPO-D have a different potency or mode of action. In conclusion, our data show that subretinal delivery of AAV vectors encoding EPO-D protects from light-induced and genetic PR degeneration. PMID:21421996

Colella, Pasqualina; Iodice, Carolina; Di Vicino, Umberto; Annunziata, Ida; Surace, Enrico M; Auricchio, Alberto

2011-06-01

422

Linearly coupled oscillations in fully degenerate pair and warm pair-ion astrophysical plasmas  

NASA Astrophysics Data System (ADS)

In this paper we study the coexisting low frequency oscillations in strongly degenerate, magnetized, (electron-positron) pair and warm pair-ion plasma. The dispersion relations are obtained for both the cases in macroscopic quantum hydrodynamics approximation. In pair-ion case, the dispersion equation shows coupling of electrostatic and (shear) electromagnetic modes under certain circumstances with important role of ion temperature. Domain of existence of such waves and their relevance to dense degenerate astrophysical plasmas is pointed out. Results are analyzed numerically for typical systems with variation of ion concentration and ion temperature.

Khan, S. A.; Ilyas, M.; Wazir, Z.; Ehsan, Zahida

2014-08-01

423

New CoreValve Evolut 23 mm technology for treatment of degenerated bioprosthesis.  

PubMed

The treatment of degenerated surgical bio-prosthetic heart valves (BHV) has been reported as a novel indication for TAVI. The intervention may be complicated by high residual transvalvular gradients and coronary ostia obstruction, especially in small size BHV. We report two cases of BHVs treated with the new CoreValve Evolut 23 mm highlighting the importance of fluoroscopic guidance, based on BHV markers, in achieving a correct TAVI implantation. The small dimensions of the new CoreValve Evolut 23 allowed us to obtain low residual gradients even in this particular subset of degenerated BHV. PMID:24021234

Zavalloni, Dennis; De Benedictis, Mauro; Pagnotta, Paolo; Scrocca, Innocenzo; Presbitero, Patrizia

2014-02-01

424

On the Properties of Time-Dependent, Force-Free, Degenerate Electrodynamics  

E-print Network

This paper formulates time-dependent, force-free, degenerate electrodynamics as a hyperbolic system of conservation laws. It is shown that this system has four characteristic modes, a pair of fast waves propagating with the speed of light and a pair of Alfven waves. All these modes are linearly degenerate. The results of this analytic study can be used in developing upwind numerical schemes for the electrodynamics of black holes and pulsar magnetospheres. As an example, this paper describes a simple one-dimensional numerical scheme based on linear and exact Riemann solvers.

S. S. Komissarov

2002-02-25

425

Dyakonov-perel electron spin relaxation in a highly degenerate wurtzite semiconductor  

SciTech Connect

The doping density dependence of the electron spin lifetime in n-type bulk GaN is investigated up to the highly degenerate regime by time-resolved Kerr-rotation spectroscopy. We find a non-monotonic doping density dependence with maximum spin lifetimes at the onset of degeneracy. The reduction of spin lifetimes in the degenerate regime shows a weak ?{sub s}?n{sub D}{sup ?2/3} density dependence, in full agreement with Dyakonov-Perel theory.

Rudolph, J.; Buß, J. H.; Hägele, D. [Arbeitsgruppe Spektroskopie der kondensierten Materie, Ruhr-Universität Bochum, Universitätsstraße 150, D-44780 Bochum (Germany); Semond, F. [Centre de Recherche sur l'Hétéro-Epitaxie et ses Applications, Centre National de la Recherche Scientifique, Sophia Antipolis, Valbonne (France)

2013-12-04

426

Degenerate rearrangement of 5-nitro-1,2,3,4,5-pentamethyl-1,3-cyclopentadiene  

SciTech Connect

Dynamic PMR spectroscopy was used to detect the degenerate rearrangement of 5-nitro-1,2,3,4,5-pentamethyl-1,3-cyclopentadiene. The rate of the 1,2 shift of the nitro group is virtually the same in solvents of different polarity. A linear correlation was found between the activation free energies of the 1,2 shift of the nitro and methyl group encompassing the degenerate rearrangements of 5-R-1,2,3,4,5-pentamethyl-1,3-cyclopentadienes and arenonium ions.

Borodkin, G.P.; Susharin, E.R.; Shakirov, M.M.; Shubin, V.G.

1986-06-20

427

Degenerate sigmatropic rearrangement of 1,2,3,4,5-pentamethyl-1,3-cyclopentadiene  

SciTech Connect

The kinetics of the degenerate rearrangement of 1,2,3,4,5-pentamethyl-1,3-cyclopentadiene, realized by a 1,2-shift of a hydrogen atom, were studied by the labeled atom method and by dynamic PMR. The results from MINDO/3 quantum-chemical calculations are consistent with this mechanism. Linear correlations relating the rate of the 1,2-shifts of the hydrogen atom in the degenerate rearrangement of the carbocations and 1,2,3,4,5-pentamethyl-1,3-cyclopentadiene to the parameters characterizing the skeleton of the rearrangement structures were obtained.

Borodkin, G.I.; Susharin, E.R.; Shakirov, M.M.; Shubin, V.G.

1986-02-10

428

Classification of nondegenerate equilibria and degenerate 1-dimensional orbits of the Kovalevskaya-Yehia integrable system  

SciTech Connect

The paper is devoted to a topological analysis of the Kovalevskaya-Yehia integrable case in rigid body dynamics. It is proved that the integral has the Bott property on isoenergy surfaces of the system; the topology of the Liouville foliation in a neighbourhood of degenerate 1-dimensional orbits and equilibria (points of rank 0) is also described. In particular, marked loop molecules are constructed for degenerate 1-dimensional orbits, and a representation in the form of an almost direct product is found for nondegenerate singularities of rank 0. Bibliography: 17 titles.

Logacheva, Nina S [M. V. Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, Moscow (Russian Federation)

2012-01-31

429

Link N and mesenchymal stem cells can induce regeneration of the early degenerate intervertebral disc.  

PubMed

Link N is a naturally occurring peptide that can stimulate proteoglycan synthesis in intervertebral disc (IVD) cells. IVD repair can also potentially be enhanced by mesenchymal stem cell (MSC) supplementation to maximize extracellular matrix (ECM) production. In a previous study, we have shown that Link N can inhibit osteogenesis and increase the chondrogenesis of MSCs in vitro. The aim of the present study was to determine the potential of MSCs and Link N alone or in combination with regard to tissue repair in the degenerate disc. Bovine IVDs with trypsin-induced degeneration were treated with MSCs, Link N, or a combination of MSCs and Link N. Trypsin-treated discs were also injected with phosphate-buffered saline to serve as a degeneration control. The ECM proteins and proteoglycans were extracted from the inner nucleus pulposus (NP) of the discs, and sulfated glycosaminoglycans (GAGs) were analyzed by the dimethyl methylene blue dye-binding assay. The expression of type II collagen was analyzed by western blot. To track the MSCs after injection, MSCs were labeled with PKH67 and observed under confocal microscopy after the 2 week culture period. The GAG content significantly increased compared with the degeneration control when degenerate discs were treated with MSCs, Link N, or a combination of both Link N and MSCs. Histological analysis revealed that the newly synthesized proteoglycan was able to diffuse throughout the ECM and restore tissue content even in areas remote from the cells. The quantity of extractable type II collagen was also increased when the degenerate discs were treated with MSCs and Link N, either alone or together. MSCs survived, integrated in the tissue, and were found distributed throughout the NP after the 2 week culture period. MSCs and Link N can restore GAG content in degenerate discs, when administered separately or together. Treatment with MSCs and Link N can also increase the expression of type II collagen. The results support the concept that biological repair of disc degeneration is feasible, and that the administration of either MSCs or Link N has therapeutic potential in early stages of the disease. PMID:24786145

Mwale, Fackson; Wang, Hong Tian; Roughley, Peter; Antoniou, John; Haglund, Lisbet

2014-11-01

430

Intervertebral disk degeneration in dogs: consequences, diagnosis, treatment, and future directions.  

PubMed

Evidence of intervertebral disk degeneration (IVDD) is extremely common in dogs, and its prevalence increases with age. It has many important consequences because degeneration of the intervertebral disks often is a prelude to disk herniation, which can injure the spinal cord, spinal nerves, or both. This review summarizes the advances in diagnosis and treatment of IVDD that have been made since the 1950s when the first detailed description of the degenerative changes was published. It also discusses new approaches to treatment of the associated spinal cord injury and new methods by which to classify injury severity that are currently under development. PMID:24010573

Jeffery, N D; Levine, J M; Olby, N J; Stein, V M

2013-01-01

431

Adenosine 5'-triphosphate (ATP) inhibits schwann cell demyelination during Wallerian degeneration.  

PubMed

Adenosine 5'-triphosphate (ATP) is implicated in intercellular communication as a neurotransmitter in the peripheral nervous system. In addition, ATP is known as lysosomal exocytosis activator. In this study, we investigated the role of extracellular ATP on demyelination during Wallerian degeneration (WD) using ex vivo and in vivo nerve degeneration models. We found that extracellular ATP inhibited myelin fragmentation and axonal degradation during WD. Furthermore, metformin and chlorpromazine, lysosomal exocytosis antagonists blocked the effect of ATP on the inhibition of demyelination. Thus, these findings indicate that ATP-induced-lysosomal exocytosis may be involved in demyelination during WD. PMID:24363123

Shin, Youn Ho; Chung, Hyung-Joo; Park, Chan; Jung, Junyang; Jeong, Na Young

2014-04-01

432

Challenging transfemoral valve-in-valve implantation in a degenerated stentless bioprosthetic aortic valve.  

PubMed

Bioprosthetic heart valves are often preferred over mechanical valves as they may preclude the need for anticoagulation. Reoperation is the standard treatment for structural failure of bioprosthetic valves; however, it carries significant risk especially in inoperable elderly patients. Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) seems to be an effective and promising procedure in patients with degenerated bioprosthetic aortic valves avoiding the risks associated with the use of cardioplegia and redo cardiac surgery. We report an interesting case of a high-risk 74-year-old patient with a degenerated Sorin Freedom Solo stentless valve treated successfully with ViV TAVR. PMID:25091103

Halapas, A; Chrissoheris, M; Spargias, Konstantinos

2014-08-01